WCLC2016 Abstract Book VF WEB RevDec12

Volume 12, Issue S1, January 2017
WCLC 2016 Abstracts
IASLC 17 TH WORLD CONFERENCE

ON LUNG CANCER
DECEMBER 4−7, 2016 | VIENNA, AUSTRIA
NOW
THERE’S
OPDIVO is the only PD-1 inhibitor that delivered superior

OS vs. chemotherapy in two Phase III studies designed
to include PD-L1 expressors and non-expressors with
previously treated NSCLC1
OPDIVO is indicated for the treatment of locally advanced or metastatic

non-small cell lung cancer (NSCLC) after prior chemotherapy in adults1
OS – overall survival; PD-1 – programmed death-1; PD-L1 – programmed death-ligand 1

Reference: 1. OPDIVO Summary of Product Characteristics.
ABBREVIATED SMPC
▼ This medicinal product is subject to additional monitoring. This will allow quick monotherapy, an increase in progression-free survival (PFS) for the combination of
identification of new safety information. Healthcare professionals are asked to nivolumab with ipilimumab is established only in patients with low tumour PD-L1
report any suspected adverse reactions. See section 4.8 in the SmPC for how to expression (see sections 4.4 and 5.1 in the SmPC). Non-Small Cell Lung Cancer
report adverse reactions. (NSCLC) OPDIVO is indicated for the treatment of locally advanced or metastatic
NAME OF THE MEDICINAL PRODUCT: OPDIVO 10 mg/mL concentrate for non-small cell lung cancer (NSCLC) after prior chemotherapy in adults. Renal
solution for infusion. Pharmacotherapeutic Group: Antineoplastic agents, Cell Carcinoma (RCC) OPDIVO as monotherapy is indicated for the treatment of
monoclonal antibodies. ATC code: L01XC17. QUALITATIVE AND QUANTITATIVE advanced renal cell carcinoma after prior therapy in adults. CONTRAINDICATIONS:
COMPOSITION: Each mL of concentrate contains 10 mg of nivolumab. One vial Hypersensitivity to the active substance or to any of the excipients listed in section
of 4 mL contains 40 mg of nivolumab. One vial of 10 mL contains 100 mg of 6.1 in the SmPC. MARKETING AUTHORISATION HOLDER: Bristol Myers Squibb
nivolumab. Nivolumab is produced in Chinese hamster ovary cells by recombinant Pharma EEIG, Uxbridge Business Park, Sanderson Road, Uxbridge UB8 1DH,
DNA technology. List of excipients: Sodium citrate dihydrate, Sodium chloride, United Kingdom CONTACT IN AUSTRIA: Bristol-Myers Squibb GesmbH, Vienna,
Mannitol (E421), Pentetic acid (diethylenetriaminepentaacetic acid), Polysorbate Tel. +43 1 60143 -0 NR, prescription only. DATE OF LAST REVISION: July 2016
80, Sodium hydroxide (for pH adjustment), Hydrochloric acid (for pH adjustment) Further information, especially in regards to special warnings and precautions
Water for injections. THERAPEUTIC INDICATIONS: Melanoma OPDIVO as for use, Interactions with other medicinal products or other forms of interaction,
monotherapy or in combination with ipilimumab is indicated for the treatment of pregnancy and lactation as well as undesirable effects are to be extracted from the
advanced (unresectable or metastatic) melanoma in adults. Relative to nivolumab published Summary of Product Characteristics (SmPC).
1506AT16PR11523-04 10/16 © 2016 Bristol-Myers Squibb Company
105795 WCLC Vienna JTO Advert_OPDIVO v2.0 2016.10.06.indd 1 06/10/2016 14:40

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
BOOK OF ABSTRACTS INDEX
Invited Speaker Sessions Mini Oral Abstract Sessions
Plenary Sessions S2 Monday, December 5, 2016 S174
Education Sessions S9 Tuesday, December 6, 2016 S191
Scientific Sessions S36 Wednesday, December 7, 2016 S219
Meet the Expert Sessions S77
Pro-Con Sessions S95
Interactive Sessions S98 Poster Sessions
Nurses Session S100 Poster Session 1

Monday, December 5, 2016 S231
Patient Advocacy Session S108
Poster Session 2
Young Investigator Session S116
Tuesday, December 6, 2016 S408
Joint IASLC - Chinese Society for
Poster Session 3
Clinical Oncology - Chinese Alliance
Wednesday, December 7, 2016 S587
Against Lung Cancer Session S120
Publish Only S760

Oral Abstract Sessions
Monday, December 5, 2016 S125
Tuesday, December 6, 2016 S141

Disclosure Summary S810
Wednesday, December 7, 2016 S159
Author Index S862
Copyright © 2016 by the International Association for the Study of Lung Cancer S1
on June 1, 2013, banning smoking in airports, train stations, stadiums, schools,

PLENARY SESSIONS playgrounds, hospitals, government institutions, beaches, and places of
employment. Tougher smoking fines were signed into law by President
SESSION PL02b: TOBACCO CONTROL Vladimir Putin on October 21, 201 The importance of smoke-free policies for
cancer prevention is high. SHS is a definite cause of cancer and is defined as
MONDAY, DECEMBER 5, 2016 - 09:00-10:20 Class 1 carcinogen by the International Agency for Research on Cancer. The
number of cancers caused by SHS can be calculated, but smoke-free policies
have other cancer prevention benefits. They discourage young people from
PL02B.04 TOBACCO CONTROL starting to smoke, encourage smokers to quit, and help former smokers stay
Luke Clancy off smoking and promote an attitude of denormalisation of smoking. Smoking
Tobaccofree Research Institute Ireland, Dublin/Ireland has often been regarded as a normal social activity despite the fact that it
Tobacco Control Tobacco is the biggest preventable cause of cancer in the is addictive, is a cause of great inequality, and contributes significantly to
world. Estimates suggest that approximately one-third of all cancers are disease, disability, and death. Smoke-free policies can achieve their positive
caused by tobacco use. Although 80%–90% of all lung cancers are attributable effect by educating about the health benefits, limiting opportunities to
to tobacco, it also has a causative role in malignancies of the mouth, larynx, smoke, and promoting an attitude of denormalisation of smoking.
pharynx, nose and sinuses, oesophagus, stomach, liver, pancreas, kidney, Keywords: Tobacco Contro, Smokefree, Tobacco Taxation, Smoking Cessation
bladder, cervix, and bowel as well as on one type of ovarian cancer and some
types of leukaemia. Tobacco is a widely and legally available product which,
through the drug nicotine, is highly addictive and is promoted by a powerful
and highly profitable industry. It has several marketing advantages over
other addictive drugs. Other addictive drugs are mostly illegal, their method SESSION PL03: PRESIDENTIAL SYMPOSIUM
of administration is often by injection, they are socially disruptive, and they TUESDAY, DECEMBER 6, 2016 - 08:35-10:25
have very low social acceptability. In contrast, tobacco use has been the norm
in the past and still has social acceptability in certain societies. Thousands
of harmful chemicals are present in tobacco and particularly in tobacco
smoke, which has documented serious adverse health effects. There are 70
PL03.02 LUNG CANCER STAGING – CHANGING THE CLINICAL
known carcinogens in cigarette smoke including nitrosamines, polycyclic PRACTICE
aromatic hydrocarbons, benzene, cadmium, toluidine, and vinyl chloride Ramon Rami-Porta
Industry access to policymakers Tobacco control policies, and therefore the Thoracic Surgery, Hospital Universitari Mutua Terrassa, and Ciberes Lung Cancer
health of the public, suffer when policy-makers maintain connections with Group, Terrassa/Spain
the Transnational Tobacco Companies (TTC), as this provides a direct avenue Introduction At the time of the 17th World Conference on Lung Cancer, the 8th
for policy influence. TTCs still meet with and hope to influence government edition of the tumor, node and metastasis (TNM) classification of lung cancer
officials responsible for tobacco control policy in many countries. This is in will have been published by the Union for International Cancer Control, the
direct violation of those countries commitments under the FCTC which is American Joint Committee on Cancer and the International Association for
a legally binding WHO treaty. Through these contacts, industry has been the Study of Lung Cancer (IASLC) in their respective staging manuals. The
able to offer ‘help’ to national governments to negotiate e.g. a later excise innovations introduced, based on the analyses of the new IASLC database
harmonization deadline and influence the speed of increase to meet these that includes 70,967 evaluable patients with non-small cell lung cancer
requirements. Political links such as this contravene the FCTC Article 5.3, and 6,189 with small cell lung cancer are described in the table. (1-9) These
which seeks to protect policymaking from industry influence. What can we innovations will lead to some changes in clinical practice that are worth
do to reduce death and disability from Tobacco use? The prevalence—at reflecting on. Table. Innovations introduced in the 8th edition of the TNM
approximately 29% of the adult population—remains stubbornly high in classification of lung cancer.
Europe and is increasing among females in some European countries. This
despite the fact that effective and cost effective interventions to control
and eliminate tobacco use exist and are well known. The World Health Descriptor 8th edition
Organization (WHO) has validated several strategies which are effective
in curtailing the use of tobacco .These approaches include using increased T component
price, through taxation, as a tool to reduce tobacco use. The use of smoke-
>/= 1cm T1a
free legislation to prevent exposure to second-hand smoke (SHS) in the
workplace is also important in preventing cancer because SHS is also a known >1 – 2cm T1b
carcinogen. The banning of advertising, sponsorship, and promotion of
tobacco is an effective and a widespread intervention to help reduce tobacco >2 – 3cm T1c
use and the use of strong antismoking advertising has also been shown to be
effective. WHO recommends the monitoring of smoking and the provision of >3 – 4cm T2a
cessation programs to help smokers stop smoking. This treatment of tobacco
dependence is particularly covered by Article 14 of the FCTC. In Art.14 of the >4 – 5cm T2b
FCTC governments are urged to ‘facilitate accessibility and affordability
for treatment of tobacco dependence’ (World Health Organization, 2015). >5 – 7cm T3
According to the 2014 FCTC implementation report, the implementation
of services to support cessation of tobacco use in line with Article 14 can >7cm T4
and should be significantly improved (World Health Organization, 2014).
Brochus <2cm from carina T2
Yet there seems to date to be little progress. Price as a control intervention
The relationship between a rise in price and a fall in tobacco consumption
Total atelectasis/pneumonitis T2
is clear; however, a number of important aspects of this relationship must
be considered. Lower socioeconomic groups and younger people are most Diaphragm inasion T4
sensitive to price increase as a deterrent, whereas in higher socioeconomic
groups, price is not necessarily a determining factor. The use of price as an Mediastinal pleura invasion -
instrument to reduce tobacco use is usually opposed by the tobacco industry
and its allies. The industry and its representatives usually try to persuade
finance ministers that a price increase will lead to a loss of revenue through
an increase in smuggling, although the evidence from many studies is that
a rise in tobacco price leads to an increase in revenue and a reduction in
cigarette consumption. Taxation is an effective, highly cost-effective and very M component
powerful tool available to governments if they want to prevent cancer and
Metastases in thoracic cavity M1a
the many other diseases which are caused by tobacco. Smoke free policies
Since Ireland introduced its comprehensive national smoke-free legislation
Single extrathoracic metastasis M1b
in 2004, many European countries have followed Ireland’s lead, but not all of
those have introduced laws as comprehensive as Ireland’s. Nevertheless, all 27 Multiple extrathoracic metastases M1c
EU member state countries have initiated some form of smokefree strategy.
To date, 14 EU member states have enacted laws which ban smoking in all Other innovations in classification
indoor workplaces including bars, restaurants, and clubs; however, a number
of countries with significant populations such as Germany and Poland have
only limited smoke-free laws. It is encouraging that Russia, where smoking
prevalence is very high (more than 50%), introduced its smoke-free measure
S2 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

Chansky K, Crowley J et al. The IASLC Lung Cancer Staging Project: proposals
Second primaries One TNM for each for the revisions of the N descriptors in the forthcoming 8th edition of the TNM
classification for lung cancer. J Thorac Oncol 2015; 10: 1675-1684. 4. Eberhardt
Separate tumor nodules T3, T4 and M1a
WEE, Mitchell A, Crowley J et al. The IASLC lung cancer staging project:
proposals for the revisions of the M descriptors in the forthcoming 8th edition
Multifocal adenocarcinomas with ground Highest T (#/m) and
of the TNM classification for lung cancer. J Thorac Oncol 2015; 10: 1515-1522. 5.
glass opacity/lepidic features global N and M
Goldstraw P, Chansky K, Crowley J et al. The IASLC lung cancer staging project:
Pneumonic type adenocarcinoma T3, T4 and M1a proposals for the revision of the stage grouping in the forthcoming (8th)
edition of the TNM classification of lung cancer. J Thorac Oncol 2016; 11: 39-51.
The T component: Tumor size is a much more relevant prognostic factor than 6. Nicholson AG, Chansky K, Crowley J et al. The International Association
in previous editions and is now a descriptor in all T categories. Therefore, for the Study of Lung Cancer Lung Cancer Staging Project: proposals for
tumor size measurement should be carefully performed because small the revision of the clinical and pathologic staging of small cell lung cancer
changes in size mean important changes in prognosis. (2) In part-solid tumors, in the forthcoming eighth edition of the TNM classification for lung cancer.
only the solid/invasive part counts to measure tumor size. (7) The fact that J Thorac Oncol 2016; 11: 300-311. 7. Travis WD, Asamura H, Bankier A et al.
adenocarcinoma in situ –Tis(AIS) – and minimally invasive adenocarcinoma The IASLC Lung Cancer Staging Project: proposals for coding T categories
–T1mi– have their own coding in the TNM classification will increase their for subsolid nodules and assessment of tumor size in part-solid tumors in
awareness. (7) These, together with the smallest coded solid tumors, those the forthcoming eighth edition of the TNM classification of lung cancer. J
of one cm or less in largest dimension –T1a– can become the base from which Thorac Oncol 2016; 11: 1204-1223. 8. Detterbeck FC, Nicholson AG, Franklin
to study therapeutic options, such as sublobar resections, stereotactic WA et al. The IASLC Lung Cancer Staging Project: summary of proposals for
radiotherapy, radiofrequency ablation; tumor biology, including tumor revisions of the classification of lung cancers with multiple pulmonary sites
growth, tumor density and intensity of the standardized uptake value, as well of involvement in the forthcoming eighth edition of the TNM classification. J
as molecular profile and genetic signatures. Visceral pleural invasion and its Thorac Oncol 2016; 11: 539-650. 9. Detterbeck FC, Chansky K, Groome P et al.
two categories (PL1: invasion beyond its elastic layer; and PL2: invasion of the The IASLC Lung Cancer Staging Project: methodology and validation used in
pleural surface) have been confirmed as important prognostic factors. (2) This the development of proposals for revision of the stage classification of NSCLC
means that pathologists should intensively investigate the identification of in the forthcoming (eighth) edition of the TNM classification of lung cancer. J
visceral pleural invasion, and, if it is not evident by the standard hematoxylin Thorac Oncol 2016; 11: 1433-1446. 10. Travis WD, Brambilla E, Rami-Porta R et al.
and eosine stains, elastic stains should be used, as recommended in the 7th Visceral pleural invasion: pathologic criteria and use of elastic stains. Proposal
edition of the TNM classification. (10) The N component: Although there will for the 7th edition of the TNM classification for lung cancer. J Thorac Oncol
be no changes in the N categories, the analyses for the 8th edition have shown 2008; 3: 1384-1390.
that quantification of nodal disease has prognostic implications. This had Keywords: lung cancer staging, TNM classification, adenocarcinoma in situ,
already been evident in the 7th edition, when it was found that the number lung cancer
of involved nodal zones was prognostic. The analyses for the 8th edition
have considered the number of involved nodal stations and have found that
the more nodal stations involved, the worse the prognosis; and that the
prognosis of tumors with involvement of multiple N1 stations was similar
PL03: PRESIDENTIAL SYMPOSIUM
to that of tumors with single station N2 without concomitant N1 disease TUESDAY, DECEMBER 6, 2016 - 08:35-10:25
(skip metastases). (3) The findings of the 7th edition already raised the issue
of indicating upfront resection in patients with tumors with single N2 zone
involvement, because their prognosis was the same as that of tumors with PL03.03 RANDOMISED PHASE III STUDY OF OSIMERTINIB VS
multiple N1 zones. The question will be raised again in the light of the results PLATINUM-PEMETREXED FOR EGFR T790M-POSITIVE ADVANCED
of the 8th edition. However, in both occasions, the quantification of nodal NSCLC (AURA3)
disease derived from pathological staging of those tumors that had been Vassiliki Papadimitrakopoulou1, Yi Long Wu2, Myung-Ju Ahn3, Suresh
resected and the resection had been accompanied by a properly performed Ramalingam4, Marina Garassino5, Hye Ryun Kim6, Frances Shepherd7, Hiroaki
systematic nodal dissection. This is difficult to replicate at clinical staging, Akamatsu8, Willemijn Theelen9, Chee Khoon Lee10, Martin Sebastian11, Alison
the moment at which therapeutic decisions are made, unless a transcervical Templeton12, Marcelo Marotti12, Serban Ghiorghiu12, Tony Mok13
mediastinoscopic lymphadenectomy is performed. This lymphadenectomy 1
Thoracic/Head and Neck Medical Oncology, the University of Texas, MD Anderson
has been found to be equivalent to that performed at the time of resection, Cancer Center, Houston/TX/United States of America, 2Guangdong Lung Cancer
either by thoracoscopic or open surgery, and is the only pre-resection test Institute, Guangdong General Hospital and Guangdong Academy of Medical
that can define single station or single zone N2 disease reliably. The M Sciences, Guangzhou/China, 3Samsung Medical Center, Seoul/Korea, Republic of,
4
component: There is no change in the metastasis within the thoracic cavity Emory University, Winship Cancer Institute, Atlanta/GA/United States of America,
5
(M1a), but single extrathoracic metastases have better prognosis than Medical Oncology Department, Thoracic Oncology Unit, Fondazione IRCCS Istituto
multiple extrathoracic metastasis in one or in several organs, and different Nazionale Dei Tumori, Milan/Italy, 6Department of Internal Medicine, Division of
Medical Oncology, Yonsei University College of Medicine, Seoul/Korea, Republic
categories have been defined for them: M1b for single and M1c for multiple
of, 7Princess Margaret Cancer Center, Toronto/ON/Canada, 8Third Department of
extrathoracic metastases. (4) The fact that single extrathoracic metastasis Internal Medicine, Wakayama Medical University, Wakayama/Japan, 9Department
have their own category will facilitate the redefinition of oligometastatic of Thoracic Oncology, the Netherlands Cancer Institute, Amsterdam/Netherlands,
and oligoprogressive disease, the establishment of therapeutic protocols 10
Clinical Research Unit, St George Hospital, Clinical Research Unit, Kogarah/NSW/
with radical intention, and the investigation of all therapeutic modalities Australia, 11University Hospital Frankfurt, Goethe University, Frankfurt Am Main/
to eliminate the advance disease. However, clinical staging will have to be Germany, 12 Astrazeneca, Cambridge/United Kingdom, 13Key Laboratory of South
precise and will have to determine the number and the organ location of China, Department of Clinical Oncology, the Chinese University of Hong Kong, Sha
the metastatic deposits. The stages: Some TNM subsets have moved from Tin/Hong Kong Prc
one stage to another and new stages and sub-stages have been created to
accommodate groups of tumors with similar prognosis. (5) As it occurred This abstract is under embargo until December 6, 2016 at 07:00 CET.
with the 7th edition, the question of how to treat patients whose tumors have
changed stage will be raised at multidisciplinary team meetings. Taxonomic
changes do not necessarily mean an automatic change in therapy if the clinical
trials performed to test therapeutic options did not include the tumors that PL03: PRESIDENTIAL SYMPOSIUM
are now included in the selected stages for study. Therefore, in the absence TUESDAY, DECEMBER 6, 2016 - 08:35-10:25
of results from clinical trials, clinical judgment will have to determine what
the best options are for a given patient with a given tumor. Lung cancer with
multiple lesions: The 8th edition will provide a set of rules with the intention PL03.05 BRAIN: A PHASE III TRIAL COMPARING WBI AND
to classify lung cancers with multiple lesions in a homogeneous way. (8) It is CHEMOTHERAPY WITH ICOTINIB IN NSCLC WITH BRAIN
our responsibility to follow the rules to collect prospective data uniformly and METASTASES HARBORING EGFR MUTATIONS (CTONG 1201)
validate the given recommendations with international data. Conclusion: The Yi Long Wu1, Jin -Ji Yang2, Caicun Zhou3, Jifeng Feng4, Shun Lu5, Yong Song6,
8th edition will help us refine prognosis both at clinical and pathologic staging Cheng Huang7, Gang Wu8, Ying Cheng9, Li Zhang10, Chengping Hu11, Gongyan
and stratify tumors in future clinical trials, but will require more attention Chen12, Li Zhang13, Xiaoqing Liu14, Hong-Hong Yan1, Fenlai Tan15, Yi-Sheng
from us at measuring tumor size, at determining nodal disease, at searching Huang16
1
for metastases, and at using clinical judgment to indicate treatment. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong
References: 1. Rami-Porta R, Bolejack V, Giroux DJ et al. The IASLC lung cancer Academy of Medical Sciences, Guangzhou/China, 2Guangdong General Hospital,
staging project: the new database to inform the eighth edition of the TNM Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences,
classification of lung cancer. J Thorac Oncol 2014; 9: 1618-1624. 2. Rami-Porta Guangzhou/China, 3Department of Medical Oncology, Shanghai Pulmonary
Hospital, Tongji University School of Medicine, Shanghai/China, 4 Medical Oncology,
R, Bolejack V, Crowley J et al. The IASLC lung cancer staging project: proposals
Jiangsu Cancer Hospital, Nanjing/China, 5Shanghai Lung Cancer Center, Shanghai
for the revisions of the T descriptors in the forthcoming 8th edition of the TNM Chest Hospital, Shanghai Jiao Tong University, Shanghai/China, 6Department
classification for lung cancer. J Thorac Oncol 2015; 10: 990-1003. 3. Asamura H, of Respiratory Medicine, Nanjing Military General Hospital, Nanjing/China,
7
Fujian Cancer Hospital, Fujian/China, 8Wuhan Union Hospital, Wuhan/China, 1
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,
9
Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun/China, 10 Medical MD/USA; 2Hospital Universitario Insular de Gran Canaria, Las Palmas/Spain;
Oncology, Sun Yat-Sen University Cancer Center, Guangzhou/China, 11Department 3
Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston,
of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha/ ON/Canada; 4Westmead Hospital and the University of Sydney, Sydney, NSW/
China, 12Harbin Medical University Cancer Hospital, Harbin/China, 13Department Australia; 5Jász-Nagykun-Szolnok County Hospital, Szolnok/Hungary; 6Országos
of Respiratory Medicine, Peking Union Medical College Hosptial, Peking Union Korányi TBC és Pulmonológiai Intézet, Budapest/Hungary; 7Meir Medical Center,
Medical College&chinese Academy of Medical Sciences, Beijing, China., Beijing/ Kfar-Saba/Israel; 8Davidoff Cancer Center, Petah Tikva University, Petah Tikva/
China, 14Department of Pulmonary Oncology, 307 Hospital of the Academy of Israel; 9Southern Medical Day Care Centre, Wollongong, NSW/Australia; 10St.
Military Medical Sciences, Cancer Center, Beijing/China, 15Betta Pharmaceuticals James’s Hospital and Cancer Trials Ireland (formerly ICORG – All Ireland Cooperative
Co.,ltd, Beijing/China, 16 Zhongshan Chenxinghai Hospital, Zhongshan/China Oncology Research Group), Dublin/Ireland; 11The Royal Marsden Hospital, Sutton,
Surrey/UK; 12MedStar Franklin Square Hospital, Baltimore, MD/USA; 13Okayama
University Hospital, Okayama/Japan; 14 Merck & Co., Inc., Kenilworth, NJ/USA; 15Lung
This abstract is under embargo until December 6, 2016 at 07:00 CET. Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German
Center for Lung Research (DZL), Grosshansdorf/Germany
TUESDAY, DECEMBER 6, 2016 - 08:35-10:25
This abstract is under embargo until December 7, 2016 at 07:00 CET.
PL03.07 FIRST-LINE CERITINIB VERSUS CHEMOTHERAPY IN

PATIENTS WITH ALK-REARRANGED (ALK+) NSCLC: A RANDOMIZED,
PHASE 3 STUDY (ASCEND-4) SESSION PL04A: IMMUNE CHECKPOINT INHIBITORS IN ADVANCED NSCLC
Gilberto De Castro Jr 1, Daniel Shao-Weng Tan2, Lucio Crinò3, Yi Long Wu4, Luis WEDNESDAY, DECEMBER 7, 2016 - 08:45-09:40
Paz-Ares5, Jürgen Wolf6, Sarayut Geater 7, Sergey Orlov8, Diego Cortinovis9,
Chong-Jen Yu10, Maximilian Hochmair 11, Alexis Cortot12, Chun-Ming Tsai13, PL04A.02 OAK, A RANDOMIZED PH III STUDY OF ATEZOLIZUMAB
Denis Moro-Sibilot14, Rosario García Campelo15, Fabrice Branle16, Paramita
VS DOCETAXEL IN PATIENTS WITH ADVANCED NSCLC: RESULTS
Sen17, Tracey Mcculloch17, Jean-Charles Soria18
1 FROM SUBGROUP ANALYSES
Instituto Do Câncer Do Estado de São Paulo, São Paulo/Brazil, 2National
Cancer Center, Singapore/Singapore, 3 Azienda Ospedale Perugia, Perugia/Italy, Shirish Gadgeel1, Fortunato Ciardiello2, Achim Rittmeyer3, Fabrice Barlesi4,
4
Guangdong General Hospital, Guangzhou/China, 5University Hospital 12 Octubre, Diego Cortinovis5, Carlos Barrios6, Toyoaki Hida7, Keunchil Park8, Dariusz
Madrid/Spain, 6University Hospital Cologne, Cologne/Germany, 7Prince of Songkla Kowalski9, Manuel Cobo Dols10, Joseph Leach11, Jonathan Polikoff 12, Christina
University, Songkhla/Thailand, 8State Pavlov Medical University, St Petersburg/ Matheny13, Pei He13, Marcin Kowanetz13, Daniel Chen13, Daniel Waterkamp13,
Russian Federation, 9 Az. Ospedaliera San Gerardo, Monza/Italy, 10 National Taiwan Marcus Ballinger 13, Alan Sandler 13, David R. Gandara14, Joachim Von Pawel15
University Hospital, Taipei City/Taiwan, 11Otto Wagner Hospital, Department 1
Karmanos Cancer Institute/wayne State University, Detroit/MI/United States of
of Respiratory and Critical Care Medicine, Vienna/Austria, 12Lille University
America, 2 Seconda Università Degli Studi Di Napoli, Napoli/Italy, 3Lungenfachklinik
Hospital, Lille/France, 13Taipei Veterans General Hospital, Taipei/Taiwan, 14 CHU
Immenhausen, Immenhausen/Germany, 4 Aix-Marseille University; Assistance
de Grenoble, Cedex/France, 15Complejo Uni. Hosp. A Coruna (Antes Hospital Juan
Publique Hôpitaux de Marseille, Marseille/France, 5Medical Oncology Unit, Aou
Canalejo), Coruña/France, 16Novartis Pharma Ag, Basel/Switzerland, 17Novartis
San Gerardo, Monza/Italy, 6Medicine, Pucrs School of Medicine, Porto Alegre/
Pharmaceutical Corporation, East Hanover/NJ/United States of America, 18Institut
Brazil, 7Aichi Cancer Center Hospital, Nagoya/Japan, 8Samsung Medical Center,
Gustave Roussy, Villejuif/France
Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of, 9 Oncology
Centre - Institute M. Sklodowska- Curie, Warsaw/Poland, 10 Medical Oncology
Section, Hospital Regional Universitario Carlos Haya, Málaga/Spain, 11Pra Health
Sciences, Raleigh/NC/United States of America, 12 Southern California Permanente
Medical Grou, San Diego/CA/United States of America, 13Genentech, Inc, South
San Francisco/CA/United States of America, 14Division of Hem-Oncology, UC
Davis Comprehensive Cancer Center, Sacramento/CA/United States of America,
15
Asklepios-Fachkliniken München-Gauting, Gauting/Germany
PL03.09 PHASE 3 STUDY OF GANETESPIB, A HEAT SHOCK PROTEIN
90 INHIBITOR, WITH DOCETAXEL VERSUS DOCETAXEL IN
ADVANCED NON-SMALL CELL LUNG CANCER (GALAXY-2) PL04: IMMUNE CHECKPOINT INHIBITORS IN ADVANCED NSCLC
WEDNESDAY, DECEMBER 7, 2016 - 08:45-09:40
Rathi Pillai1, Dean Fennell2, Vladimir Kovcin3, Tudor Ciuleanu4, Rodryg
Ramlau5, Dariusz Kowalski6, Michael Schenker 7, Branislav Perin8, Ilker Yalcin9,
Florentina Teofilovici9, Vojo Vukovic9, Suresh Ramalingam10 PL04A.03 DURVALUMAB IN ≥3RD-LINE LOCALLY ADVANCED OR
1
Hematology and Medical Oncology, Winship Cancer Institute, Emory University, METASTATIC, EGFR/ALK WILD-TYPE NSCLC: RESULTS FROM THE
Atlanta/GA/United States of America, 2Cancer Research Uk Centre, University of
Leicester & Leicester University Hospitals, Leicester/United Kingdom, 3Medical
PHASE 2 ATLANTIC STUDY
Center Bezanijska Kosa, Belgrade/Serbia, 4Institute of Oncology Ion Chiricuta and Marina Garassino 1, Johan Vansteenkiste2, Joo-Hang Kim3, Hervé Léna4,
Umf Iuliu Hatieganu, Cluj Napoca/Romania, 5Department of Oncology, Poznan Julien Mazières5, John Powderly6, Phillip Dennis7, Yifan Huang7, Catherine
University of Medical Sciences, Poznan/Poland, 6Department of Lung Cancer and Wadsworth8, Naiyer Rizvi9
Chest Tumours; the Maria Sklodowska-Curie Memorial Cancer Centre and Institute 1
Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan/Italy, 2University Hospitals
of Oncology, Warsaw/Poland, 7Oncolab, Craiova/Romania, 8 Clinic for Thoracic
KU Leuven, Leuven/Belgium, 3CHA Bundang Medical Center, CHA University,
Oncology, Institute for Pulmonary Diseases of Vojvodina, Faculty of Medicine,
Gyeonggi-Do/Korea, Republic of, 4 CHU Rennes - Hôpital Pontchaillou, Rennes/
University of Novi Sad, Sremska Kamenica/Serbia, 9Synta Pharmaceuticals,
France, 5CHU de Toulouse - Hôpital Larrey, Toulouse/France, 6Carolina Biooncology
Lexington/MA/United States of America, 10Winship Cancer Institute, Emory
Institute, Huntersville/NC/United States of America, 7Astrazeneca, Gaithersburg/
University, Atlanta/GA/United States of America
MD/United States of America, 8 Astrazeneca, Alderley Park/United Kingdom,
9
Columbia University Medical Center, New York/NY/United States of America

SESSION PL04a: IMMUNE CHECKPOINT INHIBITORS IN

ADVANCED NSCLC
PL04: IMMUNE CHECKPOINT INHIBITORS IN ADVANCED NSCLC
WEDNESDAY, DECEMBER 7, 2016 - 08:45-09:40 WEDNESDAY, DECEMBER 7, 2016 - 08:45-09:40
PL04A.01 HEALTH-RELATED QUALITY OF LIFE FOR PL04A.04 MULTICENTRIC FRENCH HARMONIZATION STUDY FOR
PEMBROLIZUMAB VS CHEMOTHERAPY IN ADVANCED NSCLC WITH PD-L1 IHC TESTING IN NSCLC
PD-L1 TPS ≥50%: DATA FROM KEYNOTE-024 Julien Adam1, Isabelle Rouquette2, Diane Damotte3, Cécile Badoual4, Claire
1 2 3 4 Danel5, Francesca Damiola6, Frédérique Penault-Llorca7, Sylvie Lantuejoul6
Julie R. Brahmer, Delvys Rodríguez-Abreu, Andrew G. Robinson, Rina Hui, 1
Tibor Csőszi,5 Andrea Fülöp,6 Maya Gottfried,7 Nir Peled,8 Ali Tafreshi,9 Sinead Department of Pathology, Gustave Roussy Cancer Campus, Villejuif/France,
2
Department of Pathology, Institut Universitaire Du Cancer de Toulouse-Oncopole,
Cuffe,10 Mary O’Brien,11 Suman Rao,12 Katsuyuki Hotta,13Anne C. Deitz,14
Centre Hospitalier Universitaire de Toulouse, Toulouse/France, 3Department of
Gregory M. Lubiniecki,14 Jin Zhang,14 Reshma Rangwala,14 Martin Reck15 Pathology, Hopital Cochin Aphp, and Centre de Recherche Des Cordeliers, Inserm

Umrs 1138, Paris Descartes 5 University, Paris/France, 4Department of Pathology, NSCLC.7 The advent of Precision Medicine has highlighted the crucial role of
Hopital Européen Georges-Pompidou AP-HP and Inserm U 970, Team 10, Paris the pathologist. Instead of the image of a pathologist looking at microscope
Descartes 5 University, Paris/France, 5Department of Biopathology, Hôpital Bichat- slides in isolation in a basement office, he or she plays a crucial role as an
Claude Bernard, AP-HP, and Faculté de Médecine, Université Paris Diderot, Inserm
integral part of the diagnostic and therapeutic team involved in every aspect
Umr 1152, Paris/France, 6Biopathology, Cancer Institute Léon Bérard, Lyon/France,
7
Department of Biopathology, Centre Jean Perrin, Clermont-Ferrand, France, Ea of patient management. The pathologist assumes further responsibilities
4677 “Ertica”, University of Auvergne, Clermont-Ferrand/France such as tissue procurement and optimal utilization, triaging scant resources
for clinical trial requirements, involvement in molecular testing, performing
requested or required immunostaining, establishing tissue repositories etc.
This abstract is under embargo until December 7, 2016 at 07:00 CET. Previously clinical decision making required the pathologist only to make a
diagnosis of SCLC or NSCLC. Precision Medicine has highlighted the
importance of accurate classification of NSCLC. Classification is required for
mutation testing, therapy selection (or exclusion) and entry onto histology
dependent clinical trials. While the introduction of immunostains has greatly
facilitated the classification of poorly differentiated NSCLC, the SEER
SESSION PL05: CLOSING PLENARY SESSION: A LIFE IN THO- database indicates that up to 14% of NSCLC may remain unclassified
RACIC ONCOLOGY - REFLECTIONS FROM GIANTS ON MILES- throughout the USA. For these reasons we developed a molecular classifier for
NSCLC that can be applied to formalin fixed paraffin embedded (FFPE)
TONES IN THE TREATMENT ADVANCES IN LUNG CANCER materials and small core biopsies.8 The assay is highly accurate and
WEDNESDAY, DECEMBER 7, 2016 - 16:00-18:00 quantitative, and also provides information on grading and survival. While
SCLC languished for three decades, its recent designation as a recalcitrant
cancer by the US Congress has resulted in a dramatic resurrection of interest,
PL05.01 PATHOLOGY funding and achievement.9 This has highlighted the importance of preclinical
Adi Gazdar models for SCLC.10, 11 I feel very humbled and privileged to have lived through
Hamon Center for Therapeutic Oncology Research, University of Texas and contributed to the seminal advances in our understanding of the biology
Southwestern Medical Center, Dallas/TX/United States of America and therapy of lung cancer. This would not have been possible without the
many wonderful and talented people I have worked with. I am reminded of the
While many regard a pathologist as a physician involved in laboratory quote of Isaac Newton: “If I have seen further than others, it is because I have
diagnosis, by definition Pathology is the science or the study of the origin, stood on the shoulders of giants”.References
nature and course of diseases. This broader definition of pathology, which 1. Matthews MJ, Kanhouwa S, Pickren J, et al. Frequency of residual and
basically encompasses all of the study of medicine, is what first attracted me metastatic tumor in patients undergoing curative surgical resection for lung
to the field. After my residency I joined the NCI as a research pathologist cancer. Cancer chemotherapy reports Part 3 1973;4:63-67.
studying viral oncology in rodents. However a few years later John Minna gave 2. Gazdar AF, Carney DN, Russell EK, et al. Establishment of continuous,
me the opportunity to return to the study of human cancer when he was clonable cultures of small-cell carcinoma of lung which have amine precursor
appointed the head of the NCI-VA Medical Oncology Branch in Washington, uptake and decarboxylation cell properties. Cancer Res 1980;40:3502-3507.
DC, with a focus on lung cancer therapy. Our branch was fortunate to have an 3. Gazdar AF, Carney DN, Nau MM, et al. Characterization of variant subclasses
outstanding lung pathologist, Mary Matthews who taught me most of what I of cell lines derived from small cell lung cancer having distinctive biochemical,
know about lung pathology. Mary also had a profound effect on the morphological, and growth properties. Cancer Res 1985;45:2924-2930.
understanding and treatment of lung cancer. In 1973 she established that 4. Borromeo MD, Savage TK, Kollipara RK, et al. ASCL1 and NEUROD1 Reveal
small cell lung cancer (SCLC) was almost always metastatic at the time of Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct
diagnosis, and that surgery was unlikely to be curative.1These observations, Genetic Programs. Cell reports 2016;16:1259-1272.
plus the finding that SCLC showed initial responses to the therapy then 5. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation
currently available, helped establish the fundamental distinction of lung with clinical response to gefitinib therapy. Science 2004;304:1497-1500.
cancers into SCLC and NSCLC categories. The Mary Matthew award for 6. Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor
Pathology and Translational Research is one of the distinguished awards of mutations in lung cancer. Nat Rev Cancer 2007;7:169-181.
the IASLC and I was fortunate and honored to be the fourth recipient in 2003. 7. Shigematsu S, Lin L, Takahashi T, et al. Clinical and biological features
John Minna assembled an outstanding group of physicians/scientist many of associated with Epidermal Growth Factor Receptor gene mutations in lung
whom became pioneers in the field of lung cancer. Of interest, all three past cancers. J Natl Cancer Inst 2005;97:339-346.
and present Chief Executive Officers of the IASLC, Heine Hansen, Paul Bunn 8. Girard L, Rodriguez-Canales J, Behrens C, et al. An Expression Signature as
and Fred Hirsch, spent time at the NCI-VA Medical Oncology Branch. John an Aid to the Histologic Classification of Non-Small Cell Lung Cancer. Clin
preached that new approaches for the therapy of lung cancer were needed, Cancer Res 2016.
that this would require understanding biology, and to understand biology we 9. Gazdar AF, Minna JD. Developing New, Rational Therapies for Recalcitrant
needed preclinical models. My job was to establish such models and help Small Cell Lung Cancer. J Natl Cancer Inst 2016;108.
“translate” them into clinical care. By the early 1980s we had established and 10. Gazdar AF, Hirsch FR, Minna JD. From Mice to Men and Back: An
characterized large banks of SCLC cell lines and demonstrated that they Assessment of Preclinical Model Systems for the Study of Lung Cancers. J
expressed the entire neuroendocrine (NE) cell program.2 The cell lines were Thorac Oncol 2016;11:287-299.
widely distributed to the scientific community, and in the absence of reliable 11. Gazdar AF, Savage TK, Johnson JE, et al. The comparative pathology of
tumor tissue sources, became the major source of biologic and molecular genetically engineered mouse models for neuroendocrine carcinomas of the
knowledge of SCLC. Within that decade our group, largely from the use of cell lung. J Thorac Oncol 2015;10:553-564.
lines, described chromosome 3p loss, MYC family amplification, RB1 and TP53 Keywords: Molecular biology, Translational medicine, Pathology, lung cancer
loss as being characteristics of SCLC and also discovered the MYCL oncogene.
The NCI-VA Medical Oncology Branch later relocated to the Bethesda Naval
Hospital, MD. In 1991, John Minna accepted a position at the University of
Texas Southwestern Medical Center, Dallas, and I was his first recruitment. PL05: CLOSING PLENARY SESSION: A LIFE IN THORACIC ONCOLOGY - REFLECTIONS FROM
GIANTS ON MILESTONES IN THE TREATMENT ADVANCES IN LUNG CANCER
Thus, during my long career I have only had two employers! I believe this WEDNESDAY, DECEMBER 7, 2016 - 16:00-18:00
continuity has helped establish strong, long term collaborations and boosted
overall productivity. One of the interests of Mary Matthews and me was the
heterogeneity of SCLC. It became obvious to us that the so-called oat cell PL05.02 SURGERY
variant was an ischemic artifact. However we were intrigued by the plasticity Peter Goldstraw]
of SCLC, with a substantial percentage of cases having abnormal (“variant”) Academic Department of Thoracic Surgery, National Heart and Lung Institute,
morphologies or combined with NSCLC elements, especially after therapy.3 Imperial College, Dartmouth/United Kingdom
The variant morphology and its relationship to NEUROD1 as the driver
transcription factor (as opposed to ASCL1 as the driver in typical or “classic” The speaker began his training in Cardiothoracic surgery in 1973 and was
SCLC) has recently been highlighted.4 By the mid 1980s, advances in SCLC appointed as a Consultant in 1979. He will introduce this topic by describing
biology and therapy had hit a stonewall, and funding dried up. It was time to a typical case undergoing surgical treatment for lung cancer in the 1970s,
move onto NSCLC! We established a large collection of NSCLC cell lines and the patient journey and outcomes at that time. From that basis he will detail
these also formed much of the basis of our understanding of this disease, the changes in the surgical treatment of lung cancer in the last 40 years. This
although tumor tissues were much more readily available. While cell lines have will include: · Changes in the epidemiology of lung cancer. · Improvements
their pluses and minuses, they are excellent for identifying driver mutations in pre-operative selection. · Improvements in the staging process prior to
and testing targeted therapies. They contributed to the identification of the surgery, during surgery and post-surgery. · Differences in surgical approach
role of EGFR mutations in lung cancer.5, 6 Soon after this discovery we used our and the anatomical extent of resection. · Changes in the stage classification
international fellows and contacts to perform the first large multinational over that period. · The establishment of effective adjuvant therapy. ·
study of geographic and ethnic variations in mutation frequencies, and also Improved outcomes in morbidity, mortality and survivorship. None of these
demonstrated that mutations were largely absent in tumors other than improvements has been of itself a game changer but collectively they amount
to a fundamental change in the surgical management of this disease. A brief International patterns of radiotherapy practice for non-small cell lung cancer.
mention will be made of advances in the surgical treatment of other thoracic Semin Radiat Oncol. 2015;25(2):143-50.
malignancies. Keywords: lung cancer, radiation oncology, history
Keywords: lung cancer, surgery, staging, results
PL05: CLOSING PLENARY SESSION: A LIFE IN THORACIC ONCOLOGY - REFLECTIONS FROM

PL05: CLOSING PLENARY SESSION: A LIFE IN THORACIC ONCOLOGY - REFLECTIONS FROM GIANTS ON MILESTONES IN THE TREATMENT ADVANCES IN LUNG CANCER
GIANTS ON MILESTONES IN THE TREATMENT ADVANCES IN LUNG CANCER WEDNESDAY, DECEMBER 7, 2016 - 16:00-18:00
PL05.04 TRANSLATIONAL LUNG CANCER RESEARCH

PL05.03 RADIO-ONCOLOGY Nagahiro Saijo
David Ball Japanese Society of Medical Oncology, Tokoyo/Japan
Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne/Australia
Lung cancer is a leading cause of cancer death in the world. The survival
When I commenced training in radiation oncology in 1973, there were no CT benefit of chemotherapy was rarely observed in NSCLC until the development
scanners, calculations were done with slide rules, and chemotherapy, let of Cisplatin. Platinum doublets including 2nd/3rd generation cytotoxic drugs
alone combined modality therapy, had no established role in the treatment of showed minor prolongation of survival but the effect reached a plateau.
non-small cell lung cancer. An influential trial published in the Lancet in 1971(1) JCOG conducted key RCTs to develop new standards against SCLC but a
had shown no difference in survival whether patients were randomized breakthrough has not been observed yet. Two recent major therapeutic
to radiotherapy, chemotherapy, a combination of the two or a policy of advancements in NSCLC are immunotherapies to inhibit immune checkpoints
wait-and–see. Yet within 30 years, the standard of care for patients with and development of targeted drugs for driver mutations.
inoperable lung cancer being treated for cure, both small cell and non-small
cell, had, ironically, become, and remains, concomitant chemotherapy and Translational Research in Immune Checkpoint inhibitors
radiotherapy. The outlook for patients generally regarded as incurable at Immunotherapy of cancer has a long history without success because of
the outset of my career is that up to one in three selected patients can now wrong strategy of immune stimulation with non-specific immunostimulators,
expect to live five years as a result of chemoradiation. Patients with stage biological response modifiers and recently by peptide antigens. After
I non-small cell lung cancer can have their cancer successfully ablated by introduction of idea on immune checkpoint inhibition by Dr. James Allison,
non-invasive stereotactic radiotherapy in 90% of cases. The developments the studies of this fields were dramatically activated. Currently two anti-PD-1
which led to these changes can be grouped according to three main themes: antibodies such as Nivolumab and Pembrolizumab have been approved for
the impact of the computer revolution; a better understanding of the natural the treatment of NSCLC based on reproducible effects of tumor shrinkage
history and biology of the disease, and the introduction of mutimodality and survival benefit. In second line treatment, both antibodies significantly
therapy. The computer revolution: imaging, treatment planning and delivery improved survival compared with standard care of cytotoxic chemotherapy
Better identification and delineation of the tumor are critical to the success irrespective of patient selection. Recent press release announced that
of radiotherapy, in particular avoidance of the catastrophic “geographic Nivolumab failed to demonstrate benefit for PFS compared to cytotoxic
miss”. Without computers, the CT and hybrid PET/CT scanners could not have chemotherapy (CheckMate-026), on the other hand Pembrolizumab
been possible. These dramatically improved the accuracy of staging as well demonstrated superior PFS and OS (KEYNOTE-024). Both of the trials patient
as providing 3D information on the relationship of the soft tissue target to selection was done based on PD-L1 expression in lung cancer cells. In spite
the nearby dose-limiting organs at risk. As computing power increased it of positive data on survival, RR in various trials against advanced NSCLC
became possible to create 4D images of moving tumours, and to image the with or without prior chemotherapy ranges from 15-25% for both drugs
target with on-board CT scanners attached to the linac immediately before and median survival is almost same in anti-PD1 Ab and cytotoxic drugs.
treatment, so making image guided stereotactic ablative radiotherapy The most important issue will be how to concentrate responsive patient
possible. Powerful computerised treatment planning systems are now able population or how to eliminate in effective patients. Although there is a
to create complex dose distributions conforming to the irregularities of any tendency of correlation between PD-L1 expression and objective response/
target volume, and to provide dose-volume metrics predictive of risks of survival, responders to Ab are experienced even in PD-L1 negative patients.
normal tissue damage. Improved understanding of the natural history and biology There are many problems in PD-L1 screening. There is no comparative data
of the disease The recognition that the central nervous system is a sanctuary of various PD-1 tests used in various clinical trials. Each PD-1 test uses
site which can harbour metastatic disease leading to treatment failure in different antibody. Each test uses a different definition and cut off point
spite of successful chemotherapeutic eradication of extracranial disease, that defines PD-1 positivity. There is no data on best sample, paraffin-fixed
particularly in small cell lung cancer, led to the introduction of prophylactic vs fresh tissue, primary site tumor vs metastatic tissue. PD-1 expression is
cranial irradiation. The British study of continuous hyperfractionated not stable and influenced by many factors. There is no reliable validation
accelerated radiotherapy (CHART) which was given over 12 days to patients and standardization. In tumor cells, mutation burden may influence on
with inoperable non-small cell lung cancer resulted in better survival than antigenicity. In colorectal cancer, microsatellite instability has related with
treatment given over six weeks, even though the total dose was lower. This response to anti-PD-1 antibody, but it is not yet clear whether mutation
trial provided clinical support for the notion of treatment induced accelerated burden really increases antigenicity. CD8 lymphocytes infiltration is also
repopulation, and reinforced the principle that total treatment times should considered to be one of the biomarkers for anti-PD-1 Ab response. However, it
be kept short in both small cell and non-small cell lung cancer, both when is too objective and seems to be quite difficult to quantify CD 8 lymphocytes
radiotherapy is used alone, and when in combination with chemotherapy. infiltration. The most important thing will be the function of killer T
Multimodality therapy The limitations of single modality therapy for a disease lymphocytes which can respond to target antigens and to kill tumor cells. The
with a high propensity for developing genetically determined resistance have best method may be quantitative measurements of cytotoxicity in killer T cell
long been recognised, and have stimulated the development of strategies on tumor cells. The techniques to demonstrate this process are mandatory for
simultaneously employing non-cross resistant therapies to maximise tumor successful patient selection in the treatment with anti-PD-1 antibody.
cell kill, in line with the principles espoused by Goldie and Coldman.(2) The use
of concomitant platinum based chemotherapy with high dose radiotherapy Translational Drug Development for Precision Medicine
is now well established by meta analysis as improving survival of both non- Recent development of molecular target drugs in lung cancer really reflects
small cell and small cell lung cancers, but it is also more toxic. Amelioration of progress of translational studies. EGFR-TKIs are one of the most important
these toxicities represents a major challenge for the future. Future directions drugs and changed concept of treatment of lung cancer. Finding on many rare
It is likely that the technical progress in radiation treatment planning and driver mutations forced to reclassify lung cancer to various genomic subtypes.
delivery is close to a plateau, and that future progress will depend more on Innovative technologies for genomic medicine changes one size fit medicine
understanding the biology of the disease and its response, and that of the to precision medicine. For discovery of drugs to each genomic subtype of lung
normal tissues, to radiation damage. Biomarkers of response and toxicity, so cancer, nationwide and global screening network should be mandatory.
spectacularly harnessed to advantage by our medical oncology colleagues, In Japan LC-SCRUM Japan leaded by Dr. Koichi Goto, National Cancer Center
are desperately needed to tailor the radiotherapy prescription to the Hospital East, started in February 2013 to find out new seeds against lung
needs of each individual and their cancer. Finally, it is evident that in many cancer by the support of government.. At the beginning, tumor tissues were
jurisdictions, including industrialised wealthy nations, that many patients are analyzed for ALK/ROS1/RET fusions using RT-PCR in EGFR –Mt negative
either receiving substandard radiotherapy that might increase their chances patients and the detected fusions were confirmed by FISH. From March 2015,
of cure, or are not receiving treatment at all.(3) Unless these problems can multiplex diagnostic kit using NGS was introduced and this project expanded
be addressed, the benefits of the remarkable advances in technology and as SCRUM-Japan including other histological types of lung cancer such as SQ
biology documented above will shamefully be restricted to only a fraction and SM as well as GI malignancy.
of those afflicted with locoregional disease. 1. Durrant KR, Berry RJ, Ellis F, 14 pharmaceutical companies started to support this project. No. of
Ridehalgh FR, Black JM, Hamilton WS. Comparison of treatment policies institutions joined in the network increased to 200 In Non-SQ NSCLC, 159 and
in inoperable bronchial carcinoma. Lancet. 1971;1(7702):715-9. 2. Goldie JH, 96 for SQ and SM, respectively on March, 2016. More than 2,500 samples were
Coldman AJ, Gudauskas GA. Rationale for the use of alternating non-cross- analyzed. Rare mutations including ROS(91), RET(54) and ALK(40) fusions,
resistant chemotherapy. Cancer Treat Rep. 1982;66(3):439-49. 3. Vinod SK. ERB2 mutation/amplification(48), BRAF mutation(16), MET amplification/

ex14 skip(16) and PIK3A mutation(22) have been screened in 287 Non-SQ- and histology. In parallel, the adjuvant UFT meta-analysis also confirmed
NSCLC patients and 67(23%) have been accrued to more than 12 clinical trials. a significant advantage of the drug compared to control in 2003 Japanese
In LURET trials against RET fusion gene + patients, 19 patients have been patients (p<0.001). The individual-data-based meta-analysis was updated
accrued and 17 are eligible. The response rate of vandetanib was 53%and in 2007. It confirmed the significant effect of postoperative chemotherapy,
PFS was 4.7 months. In 0012-01 trial against ROS fusion gene + patients, 129 with or without postoperative radiotherapy. Neoadjuvant chemotherapy:
patients (74 from china, 26 from Japan, 15 from Taiwan and 12 from Korea) Several phase II trials have been carried out in the 80’s to evaluate the benefit
has been accrued. Response rate of crizotinib was 69%in 127 evaluable of preoperative chemotherapy in operable NSCLC with encouraging results. In
patients. J-AlEX trial was a phase III randomized controlled trial comparing the mid 90’s, two randomized phase III trials had a significant impact on the
alectinib(ALE) and crizotinib(CRI) in ALK-positive NSCLC. Response rates for medical community due to their impressive results. Both trials randomized 60
ALE and CRI were 85.4% and 70.2% respectively. PFS was not reached and 10.2 stage IIIA patients and were interrupted after positive interim results were
months(P<0.0001), respectively. Other clinical trials are ongoing. observed. Only two published randomized phase III studies comparing front-
Samples from SQ and SM are increasing and interesting mutations and line surgery to pre-operative chemotherapy followed by surgery accrued the
amplifications have been detected in these materials. number of patients that were initially planned: a French study that included
Accordingly this nationwide and population enrichment screening system 373 patients and the Medical Research Council LU22 trial that included
enabled various rare driver mutations to be efficiently detected in lung cancer, 519 patients. None of the large randomized studies could demonstrate a
contributing to the rapid accrual of matched patients in translational clinical significant advantage in favor of pre-operative chemotherapy. A recent
trials. individual patient data-based meta-analysis of pre-operative chemotherapy
trials has included 2385 patients from 15 trials. A HR of 0.87 (CI 95%:
0.7_–0.96, p=0.007) was observed, equivalent to an absolute improvement in
survival of 5% at five years, similar to the benefit observed with postoperative
PL05: CLOSING PLENARY SESSION: A LIFE IN THORACIC ONCOLOGY - REFLECTIONS FROM
chemotherapy. Preoperative or postoperative chemotherapy? A comparison
WEDNESDAY, DECEMBER 7, 2016 - 16:00-18:00 of preoperative versus postoperative chemotherapy has been did not show
any difference. In fact, the key issue may be to determine which patients
should be treated with adjuvant and/or neo-adjuvant therapy. The neo-
PL05.05 CHEMOTHERAPY adjuvant approach offers a unique opportunity to test new drugs and to
Thierry Le Chevalier compare the tumor characteristics prior to and following induction therapy.
Medicine, Gustave Roussy Hospital, Villejuif/France Developing molecular based therapeutic strategies will certainly be one of
the major challenges over the next few years. Several randomized adjuvant
Chemotherapy has long been the only available systemic treatment for studies have recently been initiated in Europe and in America, based on the
Non-Small Cell lung Cancer. In the late 70’s, there were a multitude of triplets molecular characteristics of patients tumor. In conclusion, chemotherapy
and quadruplets with response rates ranging from 20-35% in patients with remains the main systemic treatment for most patients with lung cancer and
stage IV disease. In 1980, cisplatin, a cytotoxic agent initially developed the only one able to increase the cure rate. Unfortunately, very few drugs
for germ-cell tumors, showed some activity, mostly when combined with a have been developed in the last decade in spite of a clear unmet medical
vinca-alkaloïd or with etoposide. At the time Vinorelbine was registered by need. A better individual selection of drugs/drug combinations according to
the FDA in 1994, alone or in combination with cisplatin, only 3 drugs were pharmacogenomic data might encourage the community to optimize the use
approved for NSCLC, nitrogen mustard, methotrexate and doxorubicin! of cytotoxic agents.
Metastatic Disease: The individual data-based meta-analysis published in Keywords: Chemotherapy NSCLC
1995 established the superiority of chemotherapy over supportive care in
patients with advanced NSCLC. These results have been recently updated and
confirmed in 2714 patients from 16 trials with an overall survival benefit of
9% at 1 year. Chemotherapy also improves quality of life and symptom control PL05: CLOSING PLENARY SESSION: A LIFE IN THORACIC ONCOLOGY - REFLECTIONS FROM
in patients with good performance status. It is classically recommended WEDNESDAY, DECEMBER 7, 2016 - 16:00-18:00
to use platin compounds (mostly cisplatin and carboplatin) in combination
with third generation agents including vinorelbine, gemcitabine, taxanes
(paclitaxel, docetaxel, nab-paclitaxel) or pemetrexed (in non-squamous PL05.07 A WISE MAN’S CONCLUSION
NSCLC). Integrating palliative care at an early stage of the treatment also Lawrence Einhorn
prolongs survival and improves quality of life. Second line chemotherapy Medicine, Indiana University, Indianapolis/IN/United States of America
with docetaxel or pemetrexed has also been demonstrated active even if the
benefit on overall survival remains modest. The use of biological markers The past decade has seen more advances in diagnosis and management of
such as ERCC1, RRM1, beta-tubulin or thymidilate synthase has not yet proven lung cancer than were available in the previous 30 years. Fifty years ago, the
efficacy on the choice of cytotoxic agents. Maintenance: Up to 2009, it was association of cigarette smoking in lung cancer was firmly established by
generally accepted that 4 to 6 cycles of induction chemotherapy followed the Surgeon General’s report in the United States. During the past decade,
by a rest till progression were the standard. The switch to a new drug as major efforts by IASLC and other organizations have greatly reduced the
maintenance after 4 cycles of a platin-based doublet showed a benefit for use of tobacco and, thus, we will be seeing a decrement in morbidity and
PFS and OS. Maintenance is now considered a standard in the management mortality from lung cancer. However, in the United States last year, there
of metastatic NSCLC. Chemo-radiotherapy for locally advanced disease: were still 228,000 new cases and 160,000 deaths from lung cancer. It remains
The benefit obtained with radiotherapy and chemotherapy given the number one cause of cancer death in both American men and women,
sequentially in locally advanced inoperable NSCLC is modest but significant and the same is true in most developed and developing countries. Over 28%
and well established. Several randomized trials comparing radiotherapy- of all cases of cancer death in the United States are due to lung cancer. IASLC
chemotherapy given sequentially or concomitantly have suggested a better has been a leader in updating the TNM classification for non-small cell lung
outcome when both modalities were given early and simultaneously. A meta- cancer. This allows for uniformity of data results in surgical and adjuvant
analysis based on individual patient data from published and unpublished studies. Cisplatin-based adjuvant chemotherapy has been demonstrated
randomised trials which compared radiotherapy alone with the same to improve the surgical cure rate by 5-10%. In the future, we hope to be able
radiotherapy combined with concomitant cisplatin- or carboplatin-based to identify by molecular, rather than just clinical characteristics, those
chemotherapy was recently performed. The analysis was based on 9 trials patients with resected lung cancer who are cured with surgery and do not
including 1764 patients. The hazard ratio of death among patients treated need to be subjected to adjuvant chemotherapy, as has been similarly
with radio-chemotherapy compared to radiotherapy alone was 0.89 (CI 95%: accomplished in breast cancer. Also, we hope to have better definition of
0.81-0.98; P = 0.02) corresponding to an absolute benefit of chemotherapy tumors that are inherently platinum resistant and, therefore, would need
of 4% at 2 years. There was some evidence of heterogeneity among trials and alternative strategies to try to improve the surgical cure rate. For the last
sensitivity analyses did not lead to consistent results. The available data are two decades of the 20th century, chemotherapy has been the backbone for
insufficient to accurately define the size of such a potential treatment benefit treatment of stage IVB lung cancer. Most studies have been built around
and the optimal schedule of chemotherapy in combination with radiotherapy. platinum combination chemotherapy. Earlier studies pre-platinum utilized
Adjuvant chemotherapy: In the meta-analysis published in 1995, a 13% inactive drugs such as cyclophosphamide and doxorubicin. In the 1980s,
reduction in the risk of death was observed, suggesting an absolute benefit cisplatin and etoposide was a common platinum doublet, and in the 1990’s,
of 5% at 5 years with adjuvant chemotherapy. These results constituted the carboplatin + paclitaxel. A review of phase III trials in North America from
rationale for a new generation of randomized studies with platinum-based 1973-1994 demonstrated very sobering results. Thirty-three trials in 8,434
regimens. The LACE meta-analysis, which was reported at ASCO 2006, pooled patients were performed and 23 of these 33 included a platinum compound.
a total of 4584 patients accrued in the five largest cisplatin-based adjuvant Only 5 of the 33 trials demonstrated a statistically significant difference
trials launched after the results of the meta-analysis. It confirmed the in survival with a median increase of 2 months (range 0.7 to 2.7 months).
benefit of adjuvant chemotherapy with a 5.3% improvement of survival at 5 It thus became clear that we need to personalize therapy rather than
years (p=0.0043). Disease-free survival was also improved (5.2% at 5 years, giving all patients the same chemotherapy. Modest success was seen by
p<0.0001). There was a negative effect of adjuvant chemotherapy for stage adding Bevacizumab to carboplatin + paclitaxel. Major advances have been
IA. The risk reduction was 8% for stage IB, 17% for stages II and III. The effect made during the past decade with the identification of specific mutations
of chemotherapy did not vary according to age, gender, PS, type of surgery that can be therapeutically exploited. EGFR and ALK were the first to be
identified and subsequently ROS-1. Molecular targeted agents demonstrated

spectacular responses in the great majority of patients, compared to the
usual 25% brief responses that were achieved previously with platinum-based
combination chemotherapy. These driver mutations were predominantly in
adenocarcinomas and non-smokers or never smokers. More recent mutations
have included smokers and non-smokers such as BRAF V600E and MET Exon-
14 skipping mutation which can be seen in smokers as well as non-smokers.
During the past five years, immunotherapy has been an exciting new addition
to the armamentarium for treatment of patients with metastatic lung
cancer. Immune checkpoint inhibitors are still in the nascent phase and the
optimal duration of therapy for stage IVB disease, combination with other
immunotherapeutic agents, chemotherapy, or radiotherapy, as well as use
of adjuvant therapy, will be awaited with eager anticipation. Exciting new
technology such as CRISPR-cas9 to gene edit PD-1 holds great potential future
promise to make these immune checkpoint inhibitors more effective in a
larger percentage of patients with lung cancer, as well as those responses
being more durable.
Keywords: lung cancer, chemotherapy, immunotherapy, new agents

differences. We analyzed urine samples from 300-700 subjects per group for
EDUCATION SESSIONS total nicotine equivalents, total NNAL, PheT, 3-PheOH, SPMA, HPMA, and
HMPMA. The results demonstrated that African Americans, although smoking
SESSION ED01: BIOLOGY OF LUNG CANCER fewer cigarettes per day than any of the other groups except Latinos, had
significantly higher levels of total nicotine equivalents, total NNAL, PheT,
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 3-PheOH, and SPMA compared to Whites while Japanese Americans had
significantly lower levels of most of these biomarkers than Whites. The
relatively low level of urinary total nicotine equivalents in the Japanese
ED01.02 TOBACCO CARCINOGENS AND LUNG CANCER American smokers was related to a high prevalence of CYP2A6 polymorphisms
SUSCEPTIBILITY in this group (10). CYP2A6 is the primary catalyst of nicotine metabolism and
Stephen Hecht 1, S. Lani Park2, Steven Carmella1, Daniel Stram2, Christopher the CYP2A6 alleles common in Japanese Americans code for low activity and
Haiman2, Loic Le Marchand3, Sharon Murphy1, Jian-Min Yuan4 non-functional enzyme. Therefore, Japanese Americans on the average have
1
Masonic Cancer Center, University of Minnesota, Minneapolis/MN/United States of more unchanged nicotine circulating and will not need to obtain as much
America, 2University of Southern California Keck School of Medicine, Los Angeles/ nicotine per cigarette. The biomarker profiles of Native Hawaiians and Latinos
CA/United States of America, 3Cancer Research Center of Hawai’I, University of did not clearly relate to their relative lung cancer risks, but Native Hawaiians
Hawai’I, Honolulu/AL/United States of America, 4University of Pittsburgh Cancer had high levels of the acrolein biomarker HPMA compared to other groups
Institute, University of Pittsburgh, Pittsburgh/PA/United States of America while those of Latinos were low. These results provide important new data
pertinent to the relatively high risk of African Americans and the lower risk of
While cigarette smoking is clearly the major cause of lung cancer, only 11% of
Japanese Americans for lung cancer. Collectively, our results support the use
female and 24% of male lifetime smokers will get lung cancer by age 85 or
of urinary nicotine metabolites, total NNAL, and PheT as biomarkers of lung
greater, and this relatively small percentage is not due to competing causes of
cancer risk in cigarette smokers. Further studies are required to produce a
death from smoking (1) The major goal of the research approach discussed in
reliably predictive algorithm for lung cancer susceptibility in cigarette
this presentation is to identify individuals who are highly susceptible to the
smokers. These studies are likely to require the analysis of DNA adduct levels
carcinogenic effects of cigarette smoke. These individuals would be
and to incorporate genetic and epigenetic information. Reference List 1.
candidates for intensive lung cancer surveillance and screening, increasing the
International Agency for Research on Cancer (2004) Tobacco Smoke and
probability of detection of a tumor at an early stage. We are not proposing
Involuntary Smoking. In IARC Monographs on the Evaluation of Carcinogenic
methods for early detection of tumors such as the identification of
Risks to Humans, vol. 83 pp 174-176, IARC, Lyon, FR. 2. Tammemagi, C. M., Pinsky,
metabolites or proteins characteristic of lung tumors, but rather early
P. F., Caporaso, N. E., Kvale, P. A., Hocking, W. G., Church, T. R., Riley, T. L.,
identification of susceptible individuals. While there are already algorithms
Commins, J., Oken, M. M., Berg, C. D., and Prorok, P. C. (2011) Lung cancer risk
relating various parameters to lung cancer susceptibility, they are mostly
prediction: prostate, lung, colorectal and ovarian cancer screening trial
retrospective in nature, with pack-years of cigarette smoking being a major
models and validation. J. Natl. Cancer Inst. 103, 1058-1068. 3. Weissfeld, J. L., Lin,
prognostic factor (2,3). Thus, these algorithms are typically applied to
Y., Lin, H. M., Kurland, B. F., Wilson, D. O., Fuhrman, C. R., Pennathur, A.,
subjects who are older, when the process may be more advanced. Our ultimate
Romkes, M., Nukui, T., Yuan, J. M., Siegfried, J. M., and Diergaarde, B. (2015)
goal is to develop a risk model that is prospective in nature. Overall, there
Lung cancer risk prediction using common SNPs located in GWAS-identified
would be a greater probability of success if one could identify high risk
susceptibility regions. J Thorac. Oncol. 4. Hecht, S. S. (1999) Tobacco smoke
individuals early in the carcinogenic process. Even if this were effective in only
carcinogens and lung cancer. J. Natl. Cancer Inst. 91, 1194-1210. 5. Rodgman, A.
10% of tobacco users, the outcome could be prevention of more than 15,000
and Perfetti, T. (2009) The Chemical Components of Tobacco and Tobacco Smoke.
lung cancer deaths per year in the U.S. alone and massive financial savings.
CRC Press, Boca Raton, FL. 6. Hecht, S. S., Yuan, J.-M., and Hatsukami, D. K.
Among the more than 7,000 identified chemical compounds in cigarette
(2010) Applying tobacco carcinogen and toxicant biomarkers in product
smoke, there are 72 fully characterized carcinogens among which at least 20
regulation and cancer prevention. Chem. Res. Toxicol. 23, 1001-1008. 7. Yuan, J.
are known to cause lung tumors in laboratory animals (4,5). Important among
M., Butler, L. M., Stepanov, I., and Hecht, S. S. (2014) Urinary tobacco
the lung carcinogens are polycyclic aromatic hydrocarbons (PAH) such as
smoke-constituent biomarkers for assessing risk of lung cancer. Cancer Res. 74,
benzo[a]pyrene, tobacco-specific nitrosamines such as
401-411. 8. Hecht, S. S., Murphy, S. E., Stepanov, I., Nelson, H. H., and Yuan, J.-M.
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and volatiles such as
(2012) Tobacco smoke biomarkers and cancer risk among male smokers in the
1,3-butadiene. Other related volatile compounds that may contribute to the
Shanghai Cohort Study. Cancer Lett. 334, 34-38. 9. Haiman, C. A., Stram, D. O.,
carcinogenic process include acrolein, crotonaldehyde, and benzene. Perhaps
Wilkens, L. R., Pike, M. C., Kolonel, L. N., Henderson, B. E., and Le Marchand, L.
the most important compound in tobacco smoke is nicotine – while not a
(2006) Ethnic and racial differences in the smoking-related risk of lung cancer.
carcinogen, it is the addictive constituent of smoke that causes people to
N. Engl. J. Med. 354, 333-342. 10. Park, S.-L., Tiirikainen, M., Patel, Y., Wilkens, L.
continue to inhale this incredibly unhealthy mixture. In pursuit of our goal of
R., Stram, D. O., Le Marchand, L., and Murphy, S. E. (2016) Genetic
identifying smokers susceptible to lung cancer, we have focused on several
determinants of CYP2A6 activity across racial/ethnic groups with different
tobacco smoke toxicant and carcinogen parent substances and metabolites in
risk of lung cancer and effect on their smoking behavior. Carcinogenesis in
urine (6). Thus, we and others have developed and applied analytically
press.
validated mass spectrometric methods for total nicotine equivalents (the sum
of nicotine and six metabolites: nicotine glucuronide, cotinine, cotinine Keywords: tobacco carcinogens, polycyclic aromatic hydrocarbons,
glucuronide, 3’-hydroxycotinine and its glucuronide, and nicotine-N -oxide); 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of
NNK; phenanthrene tetraol (PheT) and 3-hydroxyphenanthrene (3-PheOH),
metabolites of a representative PAH; S -phenylmercapturic acid (SPMA), a
metabolite of the carcinogen benzene; 3-hydroxypropylmercapturic acid ED01: BIOLOGY OF LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
(HPMA), a metabolite of acrolein; and 3-hydroxy-1-methylpropylmercapturic
acid (HMPMA), a metabolite of crotonaldehyde. We have collaborated with
epidemiologists to evaluate the relationship of these urinary metabolites to ED01.03 INSIGHTS FROM TCGA
cancer, as determined in prospective cohort studies. These studies collect and
Bharath Ganesh1, Siddhartha Devarakonda2, Ramaswamy Govindan3
store bio-samples from large numbers of healthy subjects, then follow the 1
Internal Medicine, St. Luke’S Hospital, Chesterfield/AL/United States of America,
subjects until sufficient numbers of cancer cases occur for statistical analysis. 2
Medical Oncology, Washington University School of Medicine, Saint Louis/United
Samples from the cases and matched controls without cancer are retrieved States of America, 3Medical Oncology, Washington University School of Medicine,
from biorepositories and analyzed for specific biomarkers. The results of Saint Louis/MO/United States of America
these studies have been reviewed (7,8). In summary, statistically significant
relationships of urinary total cotinine (cotinine plus its glucuronide, the major Advances in sequencing technologies have made it possible to characterize
metabolite of nicotine), total NNAL, and PheT with lung cancer risk were and catalogue genomic alterations in several cancers in an unbiased manner.
observed among male smokers in Shanghai. Urinary total cotinine and total Multiple individual groups and large-scale consortia such as The Cancer
NNAL were related to lung cancer risk in a study of male and female smokers in Genomic Atlas (TCGA), have sequenced close to a thousand lung cancer
Singapore, and total NNAL in serum was related to lung cancer risk in a study samples to date. 1-8 Apart from furthering our understanding of the frequently
of male and female smokers in the U.S. (7,8). Levels of urinary SPMA , HPMA, altered pathways in common histological subtypes of lung cancer, data from
and HMPMA were not independently related to lung cancer in the Shanghai these studies have also highlighted the molecular heterogeneity underlying
study. These results indicate that total cotinine, total NNAL, and PheT are this disease. Investigators from TCGA initially reported genomic,
possible biomarkers of lung cancer risk. We are also collaborating with transcriptomic, methylation and copy-number alterations in 230
scientists from the Multiethnic Cohort study, a prospective cohort study adenocarcinoma (LUAD) and 178 squamous cell carcinoma (SQCC)
investigating the association of genetic and lifestyle factors with chronic samples.1,2 An updated analysis, that included a total of 660 LUAD and 484
diseases in a population with diverse ethnic backgrounds. They have reported SQCC samples, was subsequently published in early 2016.9 While the majority
that, for the same number of cigarettes smoked, and particularly at lower of lung cancer patients have a history of cigarette smoking, nearly 10% of
levels of smoking, African Americans and Native Hawaiians have a higher risk patients are lifelong never-smokers.3Lung cancers that arise in smokers
for lung cancer than Whites while Latinos and Japanese Americans have a exhibit some of the highest mutational burdens across all human cancers (8-10
lower risk (9). We are investigating the mechanistic basis for these remarkable mutations/Mb). The vast majority of these mutations are C>A transversions.
On the contrary, tumors from never smokers demonstrate a much lower advances in genome sequencing, molecularly targeted therapies and
mutational burden (0.8-1 mutations/Mb) and are enriched for C>T transitions. immunotherapies . 12References 1. Network CGAR. Comprehensive molecular
1,2
Single nucleotide variations (SNVs) and copy number alterations (CNAs) profiling of lung adenocarcinoma. Nature 2014;511:543-50. 2. Network CGAR.
While both LUAD and SQCC show frequent inactivation of the tumor Comprehensive genomic characterization of squamous cell lung cancers.
suppressors TP53 and CDKN2A, these alterations are considerably more Nature 2012;489:519-25. 3. Govindan R, Ding L, Griffith M, et al. Genomic
common in SQCCs. CDKN2A harbors the loci for two isoforms, p14ARF and landscape of non-small cell lung cancer in smokers and never-smokers. Cell
p16INK4A, and is inactivated in SQCC through homozygous deletion (29%), 2012;150:1121-34. 4. Imielinski M, Berger AH, Hammerman PS, et al. Mapping
methylation (21%), inactivating mutations (18%), or exon 1b skipping (4%). the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell
1,2
These findings indicate a strong selective pressure for the loss of these 2012;150:1107-20. 5. George J, Lim JS, Jang SJ, et al. Comprehensive genomic
tumor suppressors in NSCLC. The pattern of oncogenic alterations varies profiles of small cell lung cancer. Nature 2015;524:47-53. 6. Rudin CM, Durinck
considerably between LUAD and SQCC. While LUADs typically showed S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a
activating RTK/RAS/RAF pathway mutations, these mutations are highly frequently amplified gene in small-cell lung cancer. Nat Genet 2012;44:1111-6. 7.
infrequent in SQCCs - which predominantly showed alterations in oxidative Peifer M, Fernández-Cuesta L, Sos ML, et al. Integrative genome analyses
stress response (NFE2L2, KEAP1 and CUL3) and squamous differentiation identify key somatic driver mutations of small-cell lung cancer. Nat Genet
pathways (SOX2, TP63, NOTCH1, etc.) in 44% of samples. 1,2KRAS is the most 2012;44:1104-10. 8. Seo JS, Ju YS, Lee WC, et al. The transcriptional landscape
commonly mutated oncogene in LUAD, followed by EGFR, BRAF, PIK3CA, and and mutational profile of lung adenocarcinoma. Genome Res 2012;22:2109-19.
MET. The majority of EGFR mutations in LUAD are targetable (L858R or exon 19 9. Campbell JD, Alexandrov A, Kim J, et al. Distinct patterns of somatic genome
deletion) with tyrosine kinase inhibitors (TKIs).1In contrast, such alterations alterations in lung adenocarcinomas and squamous cell carcinomas. Nat
are absent in SQCC. Two SQCC samples however demonstrated L861Q Genet 2016;48:607-16. 10. Katayama R, Shaw AT, Khan TM, et al. Mechanisms
mutations in EGFR, which are potentially targetable with TKIs. 1,2 Although of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl
SQCC and LUAD shared several CNAs at the chromosomal arm level, Med 2012;4:120ra17. 11. Choi YL, Soda M, Yamashita Y, et al. EML4-ALK
amplification of 3q was frequent in SQCC. This region harbors important mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med
oncogenes such as SOX2, PIK3CA, and TP63. LUADs frequently showed 2010;363:1734-9. 12. McGranahan N, Furness AJ, Rosenthal R, et al. Clonal
amplifications in genes such as NKX2-1, TERT, MDM2, KRAS, and neoantigens elicit T cell immunoreactivity and sensitivity to immune
EGFR.1,2Oncogenic activation of kinases such as ALK, ROS1, and RET through checkpoint blockade. Science 2016;351:1463-9.
rearrangement has been well described in LUAD, and these fusions are
targetable with TKIs. These fusions were seen in 1-2% (ALK : 3/230, ROS1: Keywords: TCGA, Genomics, sequencing
4/230, and RET: 2/230 samples) of LUADs. 1,2 Transcriptome analysis
Deregulated splicing can be a consequence of mutations that alter splice-sites
within a gene or splicing factors. Mutations in the proto-oncogene MET that
lead to exon 14 skipping, and abnormal splicing of proto-oncogenes such as
CTNNB1 as a result of U2AF1 mutation have been described in LUAD. 1
Transcriptome analyses have also enabled a reclassification of LUADs and SESSION ED02: PALLIATIVE CARE IN LUNG CANCER:
SQCCs into three and four distinct subtypes, respectively. LUAD samples can A GLOBAL CHALLENGE
be categorized as terminal respiratory unit (enriched for EGFR mutations and
fusions; favorable prognosis), proximal-inflammatory (NF1 and TP53
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
co-mutation), or proximal-proliferative (KRAS and STK11 alterations) subtypes.
Similarly, SQCCs can be classified as classical, basal, secretory, or primitive.
Alterations in genes that participate in the oxidative stress response ED02.03 PALLIATIVE CARE IN INDIA
pathway, hypermethylation, and chromosomal instability are characteristic Gouri Shankar Bhattacharyya1, K Govindbabu2, Hemant Malhotra3, Purvish
of the classical subtype (associated with heavy smoking and poor prognosis). Parikh4
1,2
Key pathogenic alterations TCGA analysis revealed alterations in well 1
In-Charge, Medical Oncology, Fortis Hospital, Anandapur, Kolkata, Kolkata/India,
known oncogenic drivers involving RAS signaling pathway in 62% of LUAD.. 2
Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore/India,
3
These samples with readily identifiable oncogenic driver alterations were Head, Division of Medical Oncology, RK Birla Cancer Center, SMS Medical College
collectively labeled ‘oncogene-positive’. Additional analyses of the ‘oncogene- Hospital, Jaipur/India, 4Icon-Aro, Mumbai/India
negative’ sample cohort showed enrichment for RIT1, and NF1 mutations.
A cancer diagnosis is one of the most feared events rarely diagnosed before
Given the role of RIT1 and NF1 in RTK/RAS/RAF signaling, samples with these
the late 20th century now competes with the Cardio-vascular disease, stroke,
mutations were reclassified as oncogene positive, increasing the overall
respiratory failure. The last half century has produced substantial advances in
percentage of oncogene positive samples in LUAD to 76%. Nearly 69% of SQCC
the treatment and early detection of few types of cancer and atleast modest
samples showed alterations in genes regulating PI3K/AKT, or RTK/RAS
gain in many other. Yet the reality is that half of the patients diagnosed with
signaling. 1,2 The inability to readily identify an oncogenic driver in nearly a
cancer will die within the first couple of years. With people living longer, the
third of sequenced lung cancer samples highlights the need for greater
continued use of tobacco products, infectious disease that transmit cancer
powering of subsequent studies to identify novel low frequency genomic
causing virus, and epidemic of obesity and arm-chair lifestyle, the cancer
alterations. For instance, previously uncharacterized alterations in the RTK/
burden is projected to increase substantially over the decade. The delivery of
RAS/RAF pathway were observed in RASA1, SOS1 in the updated TCGA analysis
high quality cancer care across the care continuum from diagnosis and
which analyzed a much larger cohort of samples.9 Overall, despite showing a
treatment to maintaining the health of survivors and providing end-of-life
few similarities between LUAD and SQCC, investigators of TCGA reported
care consistent with patients’ needs, values, and preferences. The provision of
prominent differences between the genomic landscapes of these subtypes.
patient-centered care planning, palliative care, and psychosocial care; the
These subtypes have more of their alterations in common with other cancers
prevention and management of long-term and late effects of cancer
than with one another. SQCCs more closely resembled head and neck
treatment; and family caregiver support should span the cancer care
squamous cell and bladder cancer, while LUAD resembled glioblastoma
continuum from diagnosis through end-of-life care. The full cancer care
multiforme and colorectal cancer in this regard. 9 Immunotherapies The vast
continuum also includes the domains of prevention and risk reduction and
majority of lung cancers do not harbor alterations that are targetable by TKIs.
1,2 screening. Cancer care for older adults, as noted throughout this report, is
Immune checkpoint inhibitors are approved for use in patients with
especially complex. Age is one of the strongest risk factors for cancer. The
metastatic NSCLC. There is a clear need to develop optimal predictive
majority of cancer diagnoses and cancer deaths occur in individuals 65 years
biomarkers to identify those who are likely to respond to immune checkpoint
and older, and the majority of cancer survivors are in this age range. There are
inhibitors. Mutational burden has been correlated with better response to
many important considerations to understanding the prognoses of older
checkpoint inhibitors. Furthermore, using exome and transcriptome
adults with cancer and formulating their care plans, such as altered
sequencing and sophisticated bioinformatics, it is now possible to identify
physiology, functional and cognitive impairment, multiple coexisting
mutated and expressed genes that could potentially serve as a trigger for
morbidities, increased side effects of treatment, distinct goals of care, and
immune response (so called neoantigens) once immune checkpoints like
the increased need for of social support. Their ability to participate in clinical
programmed death-1 or programmed death ligand-1 are inhibited.. Swanton
trials has been limited, and thus the evidence base for informing treatment
and colleagues performed a neoantigen and clonality analysis on TCGA
decisions in this population is lacking. The current health care delivery system
samples to examine characteristics such as neoantigen burden and
is poorly prepared to address these concerns comprehensively. Thus, meeting
intratumor heterogeneity (ITH), and their impact on survival. In LUAD, a
the needs of the aging population will be an integral part of improving the
higher neoantigen burden was significantly associated with longer survival.
quality of cancer care. Lung cancer is one of the commonest cancer causing
Although not statistically significant, there was a trend towards longer
death and it presents late. It is an extremely symptomatic disease and
survival in molecularly homogeneous tumors (<1% ITH) as opposed to
majority of the patients succumb to this disease. It is innately human to
heterogeneous tumors. The updated TCGA analysis showed that 47% of LUAD
comfort and provide care to those suffering from cancer particularly who are
and 53% of SQCC samples exhibited at least five predicted neoantigens.
close to death. Yet what seems evident as an individual’s personal level has by
Efforts are ongoing to develop personalized vaccine therapy using predicted
and large no guided policy all over the world. There is no argument that
neoantigens in lung cancer and other malignancies. Outcomes for patients
palliative care should be integrated into cancer care from diagnosis to death.
with advanced lung cancer are likely to improve in the near future with further
Palliative care provides a specialized holistic approach to providing medical

care with serious illness and the focus of Palliative Care is on providing relief Department of Palliative Medicine, Selayang Hospital, Batu Caves/Malaysia
from symptom and improving the quality of life of patients. Palliative Care is
not End-of-Life or hospice but encompasses both. There is a dichotomy in the Southeast Asia comprises of 10 main countries including Malaysia, Indonesia,
principle of medical care in cancer which single mindedly focuses on attempts Thailand, Philippines, Singapore, Brunei, Cambodia, Laos, Myanmar and
to cure every patient at every stage. Recognition of the importance of Vietnam. The concept of palliative care first developed around the mid-
symptom control and other aspects of Palliative care from diagnosis through 1980s in Singapore and the Philippines and later in the 1990s in Malaysia,
dying process has been growing. Patients should not have to choose between Thailand and Indonesia. In other countries such as Brunei, Cambodia,
treatment with curative intent or comfort care. There is need for both in Myanmar, Vietnam and Laos palliative care has only been developing more
varying degrees throughout the course of cancer whether the eventual rapidly over the past 10 years. Levels of development of palliative care in
outcome is survival or death. The goal is to maintain the best possible quality Southeast Asia are highly variable depending very much upon factors such
of life allowing the patients to choose whatever treatment they so wish while as availability of medical resources, funding, geography, demographics and
also meeting the needs of advanced disease through adequate symptom the priorities of the country’s leadership. In 2011, the Worldwide Palliative
control. This goal is most often not met. For atleast half of those patients Care Alliance(WPCA) mapped out the global development of palliative care
dying from cancer - most of whom are elderly and many vulnerable - death dividing countries into 4 categories. Category 1 where there is no known
entails a spectrum of symptoms including pain, labored breathing, distress, development of palliative care, category 2 where development is at the level
nausea, confusion, and other physical and psychological conditions that go of capacity building, category 3 where there is isolated provision of palliative
untreated and vastly diminishes the quality of remaining days. The patient is care services and category 4 where services are approximating integration
not the only one who suffers; family, care givers undergo unreleaved emotion into mainstream medicine. Among these countries, only Singapore and
and financial burden. This cannot be ignored within the context of the Malaysia have achieved category 4 status while majority are in category 3
patients’ who are terminally ill. A major problem in Palliative care is the under (Indonesia, Thailand, Philippines, Myanmar, Cambodia, Brunei and Vietnam).
recognization, under diagnosis and thus undertreatment of the patients with Regardless of the level of development, challenges faced in developing
significant stress ranging from existentional anguish, axiety and depression. palliative care in Southeast Asia are common throughout and include first
Living with and eventually dying from a chronic illness runs substantial cost and foremost barriers of drug availability and fear of using opioids amongst
for patients, family, society and cost of those dying from cancer are 20% public as well medical practitioners. Apart from this is the challenge of public
higher than average costs. Inadequacy of Palliative and End-of-Life care perceptions towards death and dying which have made development of this
springs not from a single cause of a sector of society the separation of discipline difficult. Even till today there are many misconceptions regarding
palliative and hospice care from potentially life prolonging treatment within the role and concept of palliative care amongst healthcare professionals. For
the health care system, which is both influenced by and affects countries that are more advanced in their development, the key challenge
reimbursement policy; inadequate training of health care personnel in now is how to continue development in a sustainable manner and how to
symptom management and other palliative care skills; inadequate standards improve and maintain standards of care. In Malaysia, palliative care began in
of care and lack of accountability in caring for dying patients; disparities in the early 1990s with the development of voluntary organisations providing
care, even when available, for ethnic and socioeconomic segments of the homecare services for patients with terminal cancer. In 1995 the concept was
population; lack of information resources for the public dealing with palliative introduced into government hospitals and soon received nationwide support
and end-of-life care; lack of reliable data on the quality of life and the quality by the Ministry of Health in Malaysia. In 2005, the subspecialty of palliative
of care of patients dying from cancer (as well as other chronic diseases); and medicine was established and a formalised training programme for medical
low level of public sector investment in palliative and end-of-life care research specialists was developed. At present there are a total of 18 trained palliative
and training. This is not to suggest that there is no relevant ongoing research medicine specialists in Malaysia with 2 more in training. In 2014, an advanced
or relevant question or training program - there are - but the efforts are not diploma programme for nurses, physiotherapists and occupational therapists
coordinated and there is no focus for these activities in the Government was developed in the Ministry of Health which has now trained 38 nurses
agencies. What has resulted is under funding, lack of training and lack of and paramedics who have now become permanent stakeholders in palliative
research, leadership, with no sustained program for developing and care service provision and development. Apart from this, non-governmental
disseminating Palliative treatment. Care for those approaching death is an organisations also serve as a backbone to community palliative care services
integral and important part of health care. Everyone dies, and those at this in Malaysia and there are currently 25 services throughout the country
stage of life deserve attention that is as thorough, active, and conscientious providing homecare. It is with such initiatives that Malaysia hopes to create a
as that granted to those for whom cure or longer life is a realistic goal. Care for sustainable and credible workforce to continue the development and growth
those approaching death should involve and respect both patients and those of palliative care throughout the nation and possibly the region.
close to them. Particularly for patients with a grim prognosis, clinicians need
Keywords: palliative care, opioid availability, end-of-life care, advanced cancer
to consider patients in the context of their families and close relationships
and to be sensitive to their culture, values, resources, and other
characteristics. Good care at the end of life depends on strong interpersonal
skills, clinical knowledge, and technical proficiency , and it is informed by ED02: PALLIATIVE CARE IN LUNG CANCER: A GLOBAL CHALLENGE
scientific evidence, values, and personal and professional experience. Clinical MONDAY, DECEMBER 5, 2016 - 11:00-12:30
excellence is important because the frail condition of dying patients leaves
little margin to rectify errors. Changing individual behavior is difficult, but
ED02.05 PALLIATIVE CARE IN IRAN
changing an organization or a culture is potentially a greater challenge—and
often is a precondition for individual change. Deficiencies in care often reflect Reza Malayeri
flaws in how the health care system functions, which means that correcting Palliative Care Unit, Firoozgar Hospital, Tehran/Iran
problems will require change at the system level. The health care community
It is well known that palliative care is a necessity in cancer patients, as early on
has special responsibility for educating itself and others about the
as the time of diagnosis. In adult oncology, there is evidence to suggest early
identification, management, and discussion of the last phase of fatal medical
specialist palliative care improves HRQOL, mood, treatment decision-making,
problems. Although health care professionals may not have a central presence
health-care utilization, advanced care planning, patient satisfaction, and
in the lives of some people who are dying, many others draw heavily on
end-of-life care (1). Early admission to community-based palliative care also
physicians, nurses, social workers, and others for care—and caring. Thus,
reduces the use of Emergency departments by cancer patients in the 90 days
health care professionals are inescapably responsible for educating
before death (2). Palliative care for cancer patients is rather new in Iran and
themselves and helping to educate the broader community about good care
has a history of less than 7 years. Here we give an overview on the status of
for dying patients and their families. More and better research is needed to
palliative care in Iran. We also present the demographics of our patients in the
increase our understanding of the clinical, cultural, organizational, and other
first and largest palliative care ward in Iran over the last two years. Iran has a
practices or perspectives that can improve care for those approaching death.
population of around 80 million people. In Iran, cancer is known as the third
The knowledge base for good end-of-life care has enormous gaps and is
cause of death. Adult morbidity rate of cancer in different regions of Iran is
neglected in the design and funding of biomedical, clinical, psychosocial, and
estimated 48-112 cases per million people among the females and 51-144 cases
health services research. Time is now to integrate Palliative care with
per million people among the males (3). Also, mortality rate related to cancer
mainstream care in cancer.
was about 53500 people in 2014 (4). The majority of cancer patients expire
Keywords: Palliative-care, Cancer-care, Improving Cancer-care, End-of-Life- in the intensive care units (ICU), whereas bed occupancy of ICUs is in crises,
care being about 100% in Iran. For each ICU bed, 4 people are applicants (5). We
currently have around 8 active palliative care units for cancer patients and one
palliative care ward in Iran, all run by charities. In these palliative care units,
we have oncologists, palliative care specialists, pain specialists, psychologists,
ED02: PALLIATIVE CARE IN LUNG CANCER: A GLOBAL CHALLENGE spiritual care specialists, social workers and dieticians. A total number of 3677
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
patients, ages between 16 and 94 (Median 61), of whom 3277 (89%) with a
similar age distribution had a cancer diagnosis were referred to our palliative
ED02.04 PALLIATIVE CARE IN SOUTH-EAST ASIA care unit in Firoozgar Hospital, which is run by the Ala Charity, in Tehran in
the last three years. 1770 female (54%) and 1457 male (46%) advanced cancer
Richard Lim
patients were referred. A number of 388 (12%) patients had breast cancer,
339 (10%) had hematologic malignancies, 312 (10%) had esophageal or gastric in the region, took on the challenge of fighting tobacco across the region in
cancer, 311 (10%) had colorectal cancer, 105 (3%) had a cancer of the CNS, 101 collaboration with regional and international partners. KHCC became the
(3%) had lymphoma, 93 (3%) had renal cancer, 87 patients (3%) had ovarian regional host for Global Bridges (an international TDT healthcare alliance
cancer, 81 (2%) had lung cancer, 54 patients (2%) had prostate cancer and 50 co-founded by the Mayo Clinic, the American Cancer Society, and the
(2%) had pancreatic cancer. The other 40% of the cancer patients had either University of Arizona). The main mission of this collaboration is to address the
less frequent cancers or their exact cancer site was not recorded. In most implementation of article 14 of the FCTC agreement and design and
countries, the gap between death and specific therapies is considered as an implement effective programmes to promote the cessation of tobacco use
indicator of the quality of physician services and more length of time will and provide adequate treatment for tobacco dependence (TDT). This will also
be a better indicator for physician services, while cancer patients in health serve to address one of the six strategies recommended by the WHO; Offer
system of Iran receive specific treatment and chemotherapy even to moment help to quit tobacco use. Tobacco dependence in the region is severe. The high
of death. To consider countless benefits of home care and the patients’ desire number of cigarettes smoked per capita and the significant exposure to SHS
to receive services at home, if we can provide the conditions that at least 20% make people less capable of quitting on their own. Availing TDT across the
of end stage cancer patients receive home based palliative care, 1000 deaths region would respond to the high demand for such service (more than 65% of
will occur at home yearly, and 1000 ICU beds will be released for use for other smokers are interested in quitting) and help curb the expected epidemic of
patients with better prognosis for survival (5). For this reason, the Ala charity NCDs. Long term, quitting tobacco generally reduces the risk of disease and
has also started free of charge home care services in Isfahan and Tehran. Iran, premature death by 90% for those who quit before the age of 30 and by 50%
like many other countries, needs many more palliative care units as well as for those who quit before the age of 50. In addition, TDT will optimize the
an expansion of home based palliative care services to advanced and very management of certain NCDs such as cancer resulting in better treatment
advanced cancer patients. As palliative medicine is not financially lucrative, outcomes and long-term survivals. Over the past 5 years, KHCC developed
charities play a major role in setting up, maintaining and expanding these partnership with countries across the Middle East and worked on training
units.References: healthcare providers (HCPs) on how to treat tobacco dependence (figure 1).
More than 2000 HCPS were trained to date (figure 2). Furthermore, 4 hubs
Salins N, Ramanjulu R, Patra L, Deodhar J, Muckaden MA. Integration of Early designated for TDT training were established in Oman, Egypt, Tunisia and
Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Morocco. In addition, an evidence-based TDT training curriculum specifically
Critical Review of Evidence. Indian J Palliat Care. (2016) 22:252-7 designed for the Middle East was developed and in the process of being made
available in 3 languages; Arabic, English and French. In conclusion, tobacco
McNamara BA, Rosenwax LK, Murray K, Currow DC. Early admission to
dependence represents a major threat to the health and wellbeing of the
community-based palliative care reduces use of emergency departments in
people in the Middle East. Significant rise in NCDs including cancer is
the ninety days before death. J Palliat Med. (2013) ;16:774-9
expected over the next few years. Many collaborative initiatives are underway
Mousavi SM, Gouya MM, Ramazani R, et al. Cancer incidence and mortality in to address this sever epidemic.
Iran. Annals of Oncology. (2009) ;20:556–63.
World Health Organization. Cancer country profiles in Iran 2014. Geneva:

WHO; 2014. [cited 29 August 2015]. Avilable from: http://www.who.int/cancer/
country-profiles/en/
Heydari H. Home-based Palliative Care: A Strategy for Keeping Intensive Care

Unit Beds Vacant. Int J Community Based Nurs Midwifery. (2016);4:186-7.
Keywords: Palliative medicine, cancer, Iran
SESSION ED03: GLOBAL TOBACCO CONTROL POLICIES:

ADVANCES & CHALLENGES
MONDAY, DECEMBER 5, 2016 - 14:30-15:45
ED03.01 TOBACCO CONTROL IN THE MIDDLE EAST

Feras Hawari
The King Hussein Cancer Foundation, Amman/Jordan
Despite many countries signing and ratifying the Framework Convention on

Tobacco Control (FCTC), the prevalence of tobacco continues to be on the rise
in the Middle East. For example, in countries like Jordan and Tunisia, tobacco
prevalence among males is close to 5o% and in Jordan specifically it is
estimated to increase to 88% over the next 5 years according to the World
Health Organization (WHO). In 2008 it was estimated that five million people
died due to tobacco related illnesses. This number is expected to increase to
eight million in the year 2030 with individuals from low- and middle-income
countries making up approximately 80% of these deaths. Tobacco is a risk
factor for all major non-communicable diseases (NCDs) such as cardiovascular
diseases, cancer, pulmonary diseases and diabetes mellitus. The developing
countries and the Middle East in particular is bracing for at least a 25%
increase in such diseases over the next few years. The world economic forum
estimates that the cost for such chronic disabling diseases will exceed USD 15
trillion with cancer costs specifically reaching close to USD 3 trillion. The WHO
outlined six strategies that, when implemented simultaneously, will result in
significant reduction in tobacco prevalence and its related morbidity and
mortality. Those strategies known as MPOWER (Monitor tobacco use and Keywords: Middle East, Training, tobacco, treatment
prevention policies, Protect people from tobacco smoke, Offer help to quit
tobacco use, Warn about the dangers of tobacco, Enforce bans on tobacco
advertising, promotion and sponsorship, Raise taxes on tobacco) when
implemented in a country like Jordan, for example, close to 180,000 deaths can ED03: GLOBAL TOBACCO CONTROL POLICIES: ADVANCES & CHALLENGES
be prevented over 5 years. Despite the documented benefits of these six MONDAY, DECEMBER 5, 2016 - 14:30-15:45
strategies, compliance with implementing them across the Middle East
remains low. Only few countries have pictorial warnings, exposure to second ED03.02 THE AUSTRALIAN TOBACCO CONTROL STRATEGY:
hand smoke (SHS) is high, tobacco prices remain low and smoking cessation
LESSONS LEARNED
services are scarce. As the population in the Middle East age and with the
ongoing rise in tobacco prevalence and obesity, cancer is expected to be on Mike Daube
top of the list of diseases causing death and disability in the region. For that Faculty of Health Sciences, Curtin University, Perth/WA/Australia
reason, King Hussein Cancer Center (KHCC), one of the leading cancer centers

This presentation will outline the developments that have led the about it and all those with investments, including those through compulsory
international tobacco industry to describe Australia as “the darkest pension schemes have a role to play. It’s up to us to keep tobacco control on
market in the world”. This will be presented in the context of international the agenda and in public dialogue. A tobacco free future that will allow our
developments, with implications and recommendations for other countries, children and the generations to come to enjoy long and healthy lives should
and researchers, clinicians, health professionals,health organisations and be our shared hope. If you are interested in supporting this work, please come
governments There will be discussion of the origins and early history of along to the Tobacco Free Portfolios workshop on the morning of Wednesday
tobacco control in Australia; the components of comprehensive tobacco 7th December. Further details available at www.tobaccofreeportfolios.org
control programs; policy-relevant research; successes, failures and
distractions; and the roles of key organisations and individuals. This will be Keywords: Cross sector collaboration, tobacco, Tobacco Control, advocacy
followed by an outline of major developments, including the establishment of
a consensus approach; national and local approaches; activity by key groups;
progress across a range of key areas including public education, advocacy,
tobacco advertising bans, taxation, health warnings, smoke-free, exposing
tobacco industry activities, cessation supports; and other measures. There SESSION ED04: BRONCHOPULMONARY CARCINOIDS
will be discussion of the Australian world-leading tobacco plain packaging MONDAY, DECEMBER 5, 2016 - 14:30-15:45
legislation, which is now being replicated in many other countries, and the
very encouraging resultant trends. The Australian experience and successes
will be presented in a global context, with recognition that the tobacco ED04.01 SURGERY IN BRONCHOPULMONARY TYPICAL AND
industry will always oppose any measures that might reduce smoking ATYPICAL CARCINOIDS
and is constantly looking for new ways to resist action and promote its
products. From this conclusions will be drawn and recommendations made Pier Luigi Filosso 1, Alberto Sandri2, Francesco Guerrera2
1
for all concerned to reduce smoking, with consideration of next possible Thoracic Surgery, University of Torino, Torino/Italy, 2University of Torino, Torino/
developments. Italy
Keywords: Plain packaging, The world’s darkest market, Tobacco Control, Complete surgical resection of the tumor is the treatment of choice for
advocacy Bronchopulmonary Carcinoids (BCs). The goal is to resect the lesion, saving
as much lung parenchyma as possible. The type of surgical approach and
resection are strictly depend on: a) tumor’s location, b) tumor’s histology and
c) presence of lymphnodal metastases. In case of peripheral small BC (Figure
ED03: GLOBAL TOBACCO CONTROL POLICIES: ADVANCES & CHALLENGES 1), the type of surgical resection (wide wedge resection vs segmentectomy
MONDAY, DECEMBER 5, 2016 - 14:30-15:45 or lobectomy) is still matter of debate. Few scientific evidences (1,2) report
that a wedge resection could be safely proposed since, in multivariate
ED03.04 TRUMPING BIG TOBACCO analysis, long-term survival is not compromised when this approach is used.
However, those studies are retrospective, sometimes with limited data
Bronwyn King
on the patients’ follow-up and the number of wedge resections is limited:
CEO, Tobacco Free Portfolios, Melbourne/Australia therefore it is very difficult to draw definitive conclusions with those
potential biases. The statement that a wedge resection should be reserved
I never would have imagined my work as a doctor would take me to corporate
to a small peripheral N0 Typical Carcinoid (TC) seems to be more prudent. An
boardrooms across the globe, from Melbourne to London, Paris, New York
anatomical resection (segmentectomy/lobectomy) should be proposed in
and more. But then I never would have imagined I would be invested in the
case of an Atypical Carcinoid (AC), or whenever the tumor can not be resected
tobacco industry either. In my early time as a doctor, I did a placement on
in a less invasive manner (e.g: centroparenchymal lesion or when the lobe is
the lung cancer ward of the Peter MacCallum Cancer Centre in Melbourne.
totally occupied by the tumor – Figure 2-). The aim to preserve as much lung
Despite being able to offer the very best medicine available, the majority
tissue as possible is the cause of the development of tissue-sparing surgical
of my patients died, many of them in their 50’s and 60’s, some as young as
techniques (the so called “bronchial sleeve resections” and the “sleeve
40. It was shocking to bear witness to the true impact of tobacco. Whilst
lobectomies”). The first contemplates a bronchial resection with the tumor,
the treatment and care of patients is paramount, we must deal with the
without any lung parenchyma exeresis; in the latter, a formal lobectomy
source of the problem – tobacco and the companies that manufacturer it.
with bronchoplastic procedure, is performed to avoid major pulmonary
Once I discovered that through my compulsory pension fund, I was invested
resections (e.g.: bilobectomy or pneumonectomy). An intraoperative frozen
in and actually owned a part of a several tobacco companies, I couldn’t just
section of the bronchial margin has to be performed in all bronchoplastic
do nothing – I had to take action. In my quest to disentangle the Australian
procedures to confirm that no neoplastic cells are present in the anastomosis
pension sector from tobacco I’ve become well informed about tobacco and
(3). Contrariwise, a pneumonectomy should be reserved to patients with
the extent of the ‘tobacco epidemic’, as it is referred to by the World Health
a “destroyed lung”, usually caused by long-term obstructive pneumonia, a
Organisation. The numbers astound me. Six million deaths per year are
phenomena caused by an endobronchial tumor growth which completely
attributed to tobacco and we are on track for one billion tobacco related
obstructs the bronchial lumen, or when a tissue sparing resection can
deaths this century. Many, including investors (both individual mums and
not be safely performed. The type of surgical approach (thoracotomy vs.
dads as well as big financial institutions), aren’t actually aware of the extent
minimally invasive one) must be decided based on tumor’s size and location,
of their tobacco exposure. Tobacco stocks are generally picked up in standard
as well as the type of surgical resection planned. In general, VATS approach
products. Often, tobacco companies have not been selected specifically for
is currently indicated for small and peripheral BCs, while a posterolateral
investment, but they are wrapped up within default investment products,
thoracotomy is generally used when a bronchoplastic procedure must be
so they still find a way into your portfolio. I founded Tobacco Free Portfolios
performed. Lymphadenectomy, and in particular, systematic hilar and
to collaboratively engage with leaders of the finance sector to encourage
mediastinal lymphadenectomy, must be always performed, in accordance
tobacco free investment. Finance executives have been alarmed also, at the
with the European Society of Thoracic Surgeons (ESTS) recommendations
scale of the tobacco problem and have deeply considered the role they can
for intraoperative lymph node assessment (4). A minimum of six nodal
play in addressing this pressing global issue. One by one, they have acted
stations, three of which mediastinal, have to be harvested, including the
and are now proud to lead organisations that are tobacco free. There are
subcarenal ones. Lymph nodal metastases, in fact, may be present in up
now 35 tobacco free pension funds in Australia – just over 40% of all funds.
to 25% of TCs and in less than 50% of ACs (5,6). In case of N positive (N+)
Many more will soon follow. Each tobacco free announcement is met with
BCs, and whenever feasible, upfront surgery may be proposed: a complete
resounding public support. Tobacco Free Portfolios recently took a global
resection (R0) must be performed, whilst debulking interventions are not
step and we were delighted to work with the global insurance giant AXA
recommended. A satisfactory overall survival for BCs with lymph nodal
who announced a tobacco free decision in May 2016, divesting $1.8B Euro of
metastases has been reported in several papers (7,8): those patients, in
tobacco assets. More organisations are soon to follow suit. That is the way
fact, survive longer than those with N+ NSCLC. An endobronchial resection
of the future. Affiliations with the tobacco industry are no longer wanted.
(usually through rigid bronchoscopy) has been sometimes advocated for
There are very few individuals or organisations that actively seek to be a part
purely endobronchial tumors (3): it is mandatory to determine whether
of the tobacco industry. The associations are often so deep and longstanding
the tumor may present with an extrabronchial growth, in which case a
that it can seem overwhelming – but they must be addressed and they must
local treatment alone is not sufficient, and should be followed by surgery
be undone. Momentum for tobacco-free investment continues to grow
(with or without bronchoplastic techniques). A palliative endobronchial
steadily and I can confidently say that the conversation in Australian has
treatment may be offered to those patients unfit for surgery, in which
largely moved from ‘should we go tobacco-free?’ to ‘how can we go tobacco-
severe obstructive phenomena caused by the endoluminal tumor growth
free?’ This is a pleasing development and a terrific case study, however, there
cause infective and respiratory consequences. Post-resectional tumor
is still much to do to accelerate action across the globe. The good news is
relapses may occur approximately in 20% of ACs and in 5% TCs (3,8): the risk
that conversations I have in Vienna, Paris, Singapore, London and New York
of recurrence is strictly dependent from the histologic tumor subtype, the
are received with exactly the same concern as the conversations I have in
presence of lymph nodal metastases and the completeness of resection (9,10).
Melbourne, Sydney and Canberra. The devastating impact of tobacco is felt
Most recurrences are distant (liver, adrenal gland, bone), but sometimes,
everywhere on Earth. Tobacco is everyone’s problem, not just the doctors that
local relapses (lung and/or mediastinum) have also been reported. Surgery,
provide the care and treatment. We should all feel obliged to do something
with the same aim of the elective one, may be offered to those patients, SESSION ED05: THE 8TH EDITION OF THE TNM STAGING
improving their survival.References 1 Yendamuri S, Gold D, Jayaprakash V,
SYSTEM
Dexter E, Nwogu C, Demmy T: Is sublobar resection sufficient for carcinoid
tumors? Ann Thorac Surg. 2011;92:1774-1778 2 Ferguson MK, Landreneau MONDAY, DECEMBER 5, 2016 - 16:00-17:30
RJ, Hazelrigg SR, Altorki NK, Naunheim KS, Zwischenberger JB, Kent M, Yim
AP: Long-term outcome after resection for bronchial carcinoid tumors.
Eur J Cardiothorac Surg. 2000;18:156-61 3 Detterbeck FC: Management of ED05.01 WHAT’S NEW IN LUNG CANCER STAGING?
carcinoid tumors. Ann Thorac Surg 2010;89:998-1005 4 Lardinois D, De Leyn Hisao Asamura
P, Van Schil P, Porta RR, Waller D, Passlick B, Zielinski M, Lerut T, Weder W: Division of Thoracic Surgery, Keio University School of Medicine, Tokyo/Japan
ESTS guidelines for intraoperative lymph node staging in non-small cell
lung cancer. Eur J Cardiothorac Surg. 2006;30:787-792 5 Lim E, Yap YK, De The tumor, node and metastasis (TNM) classification for malignant tumors
Stavola BL, Nicholson AG, Goldstraw P: The impact of stage and cell type on has been periodically revised in the International Union for Cancer Control
the prognosis of pulmonary neuroendocrine tumors. J Thorac Cardiovasc (UICC) and American Joint Committee on Cancer (AJCC). As for lung cancer,
Surg. 2005;130:969-972 6 Daddi N, Ferolla P, Urbani M, Semeraro A, Avenia N, the process of revision is quite unique compared with malignancies of other
Ribacchi R, Puma F, Daddi G: Surgical treatment of neuroendocrine tumors organs in that the corresponding professional society, the International
of the lung. Eur J Cardiothorac Surg. 2004;26:813-817 7 Filosso PL, Ferolla P, Association for the Study of Lung Cancer (IASLC), has been playing a principal
Guerrera F, Ruffini E, Travis WD, Rossi G, Lausi PO, Oliaro A; European Society role in database construction, making revision agenda, simulation, and
of Thoracic Surgeons Lung Neuroendocrine Tumors Working-Group Steering validation as a proposal to UICC and AJCC. The agenda articles have been
Committee: Multidisciplinary management of advanced lung neuroendocrine already published for T, N, M, and stage grouping in the official journal
tumors. J Thorac Dis. 2015;7(Suppl 2):S163-S171 8 Filosso PL, Oliaro A, Ruffini of IASLC. In brief, the IASLC database included 77,156 evaluable patients
E, Bora G, Lyberis P, Asioli S, Delsedime L, Sandri A, Guerrera F: Outcome diagnosed with lung cancer from 1999 to 2010, originating from 35 different
and prognostic factors in bronchial carcinoids: a single-center experience. databases in 16 countries of 5 continents. Among these, the data of 3905
J Thorac Oncol. 2013;8:1282-1288 9 Caplin ME, Baudin E, Ferolla P, Filosso P, patients were given by electric data capturing. In the T descriptors, new
Garcia-Yuste M, Lim E, Oberg K, Pelosi G, Perren A, Rossi RE, Travis WD; ENETS tumor-size groups were created: T1a </= 1cm; T1b >1-2 cm; T1c >2-3cm; T2a
consensus conference participants: Pulmonary neuroendocrine (carcinoid) >3-4cm; T2b >4-5cm; T3 >5-7cm; and T4 >7cm. Endobronchial l ocation <2cm
tumors: European Neuroendocrine Tumor Society expert consensus and from the carina has better prognosis than any other T3 descriptor and will
recommendations for best practice for typical and atypical pulmonary be classified as T2. Total atelectasis/pneumonitis will be classified as T2
carcinoids. Ann Oncol. 2015;26:1604-1620 10 Öberg K, Hellman P, Ferolla P, because it has a T2 prognosis. Diaphramatic invasion will be T4. Visceral
Papotti M; ESMO Guidelines Working Group: Neuroendocrine bronchial and pleural invasion remains the same, and mediastinal pleura invasion, seldom
thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment used, disappears as a T descriptor. The N component remains the same, but
and follow-up. Ann Oncol. 2012;23 Suppl 7:vii120-vii123 the number of involved nodal stations has prognostic impact. Therefore,
it was proposed to divide N1 into N1a (single station N1) and N1b (multiple
station N1), N2 into N2a1 (single station N2 without pN1 involvement), N2a2
(single station N2 with pN1 involvement) and N2b (multiple station N2) for
testing. For the M component, M1a (intrathoracic metastases) remains the
same, but extrathoracic metastases are divided into single extrathoracic
metastasis (new M1b) and multiple extrathoracic metastases in a single or
multiple organs (M1c). Regarding stages, stage IA is divided into IA1, IA2 and
IA3 to accommodate T1a, T1b and T1cN0M0 tumors; all N1 disease are stage IIB
except for T3-T4N1M0 that are IIIA; a new stage IIIC is created for T3-T4N3M0
tumors; and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). The
8th edition of the TNM classification of lung cancer defines new tumor-size
groups, confirms the prognostic relevance of quantifying nodal disease,
establishes a new category for single extrathoracic metastasis, and creates
new stage groupings. Looking at these, the importance of the accurate
measurement of tumor diameter and accurate counting of the swollen nodes
and lesions of distant disease has been raised. In this way it improves our
understanding of the anatomic extent of the tumor, enhances ,our capacity
to indicate prognosis at clinical and pathologic staging, and increases the
possibilities of research by facilitating tumor stratification for future clinical
trials.
Keywords: Prognosis, TNM classification, Staging, lung cancer
ED05: THE 8TH EDITION OF THE TNM STAGING SYSTEM

MONDAY, DECEMBER 5, 2016 - 16:00-17:30
ED05.02 UPDATE ON THE MESOTHELIOMA STAGING SYSTEM

Valerie Rusch
Surgery, Memorial Sloan-Kettering Cancer Center, New York/NY/United States of
America
The initial TNM staging classification for malignant pleural mesothelioma

(MPM), published in the 6th edition of the UICC and AJCC staging manuals,
was derived from analyses of small retrospective surgical series. It has
been criticized for being insufficiently evidence-based and difficult to
apply to clinical staging. To identify potential deficits in the MPM staging
classification, the IASLC Staging and Prognostic Factors Committee (ISPC),
in collaboration with members of the International Mesothelioma Interest
Group (IMIG), initiated a large multinational database in 2009. This approach
was modeled on methods used by the IASLC to revise the lung cancer
staging system. Data were submitted on 3,101 patients from 15 centers on 4
continents, all of whom had some form of surgical management, and an initial
analysis was published in 2012. Overall survival (OS) data largely supported
continued use of the original MPM staging classification but identified several
important areas for improvement, particularly for the T and N components.
To address issues raised by this initial analysis, a second iteration of the IASLC
MPM database was started in 2013 to inform revisions for the 8th edition of
the AJCC / UICC staging systems. The data dictionary was revised to provide
more granular information for the T, N and M descriptors and a new electronic
data capture (EDC), housed at the biostatistical center CRAB (Cancer Research
Keywords: Lung, Neuroendocrine Tumors, Surgery, Outcome
and Biostatistics, Seattle, WA, USA), was developed. Additional investigators

who could provide valid information on patients with tumors staged clinically ED05: THE 8TH EDITION OF THE TNM STAGING SYSTEM
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
and managed non-surgically were recruited. Data to inform revisions for the
8th edition of the MPM staging classification originated from 29 centers
on 4 continents and included 3,519 cases of which 2,460 passed the initial ED05.03 THE THYMIC EPITHELIAL TUMOR STAGING SYSTEM
eligibility screen. As planned, this dataset included both patients managed
Kazuya Kondo
surgically and non-surgically. OS examined for T categories according to the
epartment of Oncological Medical Services, tokushima University Graduate
d
current 7th edition staging classification showed a clear difference between
School, Tokushima/Japan
all clinically staged categories except for T1a versus T1b and T3 versus T4.
Pathological staging failed to demonstrate a survival difference between Thymic epithelial tumors are rare tumors. The clinical staging system for
adjacent categories with the exception of T3 versus T4. Performance improved thymoma was introduced first by Bergh and associates in 1978 and later
with collapse of T1a and T1b into a single T1 category. Analyses suggested modified by Wilkins and Castleman (1), and was almost established by
that all current T descriptors should be maintained. Tumor thickness and Masaoka and associates in 1981 (2). In France, multiple centers have adopted
morphology were also significantly associated with OS. Consequently, a the Groupe d’Etudes des Tumeurs Thymiques (GETT) staging system (1). The
recommendation was made to collapse both clinical and pathological T1a and Masaoka classification is the most widely accepted now and is an excellent
T1b into a T1 category. Because simple measurement of pleural thickness had predictor of the prognosis of thymoma (3, 4). And a modification of this
prognostic significance, it was felt that this should be examined further with classification was suggested by Koga et al. in 1994 (5) The International
a view to incorporation into future revisions of the staging classification. Thymic Malignancies Interest Group (ITMIG) has chosen to use the Masaoka-
With respect to the N categories (as defined in the 7th edition staging Koga stage classification system (1). There has never been an official TNM
classification), there was no significant difference in OS between cN0, cN1 and system classification of thymic epithelial tumor by American Joint Committee
cN2, likely reflecting the inaccuracies of current methods for clinical lymph on Cancer/Union for International Cancer Control (AJCC/UICC) stage
node staging in MPM. For pathologically staged tumors, patients with pN1 or classification due to their relative rarity. Yamakawa and Masaoka presented
pN2 tumors had a worse OS than those with pN0 tumors but no OS difference a tentative TNM system classification of thymoma in 1991. Then Tsuchiya
was noted between those with pN1 and pN2. Exploratory analyses found et al. (1994) in National Cancer Center Hospital of Japan, the WHO (2004)
that tumors with both pN1 and pN2 nodal involvement had a poorer OS than and Bedini et al.(2005) in National Cancer Institute of Italy proposed a TNM
those with pN2 only. Consequently, a recommendation was made to collapse staging system (1). The ITMIG and the International Association for the Study
N1 and N2 into a new N1 category and to relabel the current N3 category as of Lung Cancer (IASLC) simultaneously set out to accomplish a staging system
N2. Larger numbers of well staged cases are needed to determine whether for thymic epithelial neoplasms, and subsequently joined forces in 2010,
this new N1 category should be subdivided in the future according to the partnering to create a Thymic Domain of the Staging and Prognostic Factors
number of involved lymph node stations. Of the 3,519 submitted cases, 84 Committee (TD-SPFC), charged with the development of proposals to AJCC/
were cM1 at diagnosis. Median OS for cM1 was significantly worse than for T4 UICC for the eight edition of the stage classification system. The ITMIG and
or N3 (as defined in the 7th edition) supporting inclusion of only cM1 in the IASLC assembled and analyzed a worldwide database of 10,808 patients with
stage IV group. Exploratory analyses suggested a possible difference in OS for thymic malignancies from 105 sites. They made a stage classification that was
single versus multiple site cM1 but additional data are needed in the future to tumor, node, metastasis (TNM) based, and applicable to thymoma as well as
determine the validity of this finding. Candidate stage groups were developed thymic carcinoma (6-9) (Tables). The T component is divided into 4 categories
using a recursive partitioning and amalgamation (RPA) algorithm applied to (Table 1). A tumor is classified in a particular “level” if one or more structures
all cM0 cases. Based on these analyses, optimal stage groupings proposed in that level is involved, regardless of whether other structures of a lower
for the 8th edition of the staging classification were: stage IA (T1N0), stage IB level are involved or not. The encapsulation of the tumor is not included,
(T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4) and because this did not have a clinically significant difference of prognosis in
stage IV (any M1). These new stage groupings are substantially different from the retrospective database. The T1 includes tumors that were classified as
what is currently used in the 7th edition. The IASLC database is the largest stage I or II in the Masoaka or Masaoka-Koga stage classification systems.
available multinational database in this rare malignancy and has provided The involvement of the pericardium pathologically is designated as T2, and
the first evidence-based revisions of the TNM classification for MPM leading several neighboring organs (potentially resectable) are included in the T3
to substantial changes in the T and N components and the stage groupings. category because they had similar prognosis. The T4 includes several organs
Continued efforts to accrue to this database will be important to inform with more extensive local invasion (potentially unresectable). The TD-SPFC
further changes for the 9th edition of the staging classification.1-7 decided to subcategorize T1 into T1a (no mediastinal pleural involvement) and
T1b (involvement of the mediastinal pleura) to gain more prospective data
Reference List
for further testing, as there is a slight difference in cumulative incidence of
(1) Rusch VW, The International Mesothelioma Interest Group. A proposed recurrence in patients from Japan submitted by the Japanese Association for
new international TNM staging system for malignant pleural mesothelioma. Research in the Thymus (6, 7). Lymph node involvement is common in thymic
Chest 1995;108:1122-8. carcinoma (more than 27%) but is relatively uncommon in thymoma (2%)
(4). The N component is divided into 3 categories (Table 1). No lymph node
(2) Rusch VW, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Initial metastasis is classified as N0. Lymph nodes are assigned in 2 groups according
analysis of the International Association for the Study of Lung Cancer to their proximity to the thymus: anterior (perithymic) (N1) and deep cervical
Mesothelioma Database. J Thorac Oncol 2012;7:1631-9. or thoracic nodes (N2). The anterior region (N1) encompasses the space
surrounding the thymus that is bordered by the hyoid bone and diaphragm
(3) Pass HI, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. craniocaudally, the medial edge of the carotid sheaths and mediastinal
Supplementary prognostic variables for pleural mesothelioma: A report from pleura laterally, the sternum anteriorly, the pericardium and great vessels
the IASLC Staging Committee. J Thorac Oncol 2014;9(6):856-64. posteriorly in the middle, and extending to the level of the phrenic nerves
posterolaterally. The deep region (N2) describes the space distant to the
(4) Pass HI, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. The
anterior region within the mediastinum. It is situated posterior to the anterior
IASLC Mesothelioma Database: Improving staging of a rare disease through
mediastinum, anterior to the esophagus, and among the pulmonary hila; it
international participation. J Thorac Oncol. In press 2016.
extends into the neck on either side of the anterior cervical nodes. Involved
(5) Nowak AK, Chansky K, Rice DC, Pass HI, Kindler HL, Shemanski L, et al. nodes outside these regions are outside the N category and considered a
The IASLC Mesothelioma Staging Project: Proposals for revisions of the T distant metastasis (M1) (6, 8, 9). The M component is divided into 3 categories
descriptors in the forthcoming eighth edition of the TNM classification for (Table 1). Absence of tumor outside the primary mass (or nodal metastases) is
mesothelioma. J Thorac Oncol. In press 2016. classified as M0. M1a is used to designate pleural or pericardial nodules. M1b
designates pulmonary intraparenchymal nodules or distant metastases (6,
(6) Rice DC, Chansky K, Nowak AK, Pass HI, Kindler HL, Shemanski L, et al. 8). The TNM categories are organized into distinct stage groups as shown in
The IASLC Mesothelioma Staging Project: Proposals for revisions of the N Table 2. Stages I, II, IIIa, and IIIb are determined primarily by the T component.
descriptors in the forthcoming eighth edition of the TNM classification for Stages IVa and IVb are determined by the presence of N1 or M1a disease for IVa
malignant pleural mesothelioma. J Thorac Oncol. In press 2016. and N2 or M1b disease for IVb (6-9).
(7) Rusch VW, Chansky K, Kindler HL, Nowak A, Pass HI, Rice DC, et al. (See Table next page)
The IASLC Malignant Mesothelioma Staging Project: Proposals for the M
descriptors and for revision of the TNM stage groupings in the forthcoming
(eighth) edition of the TNM classification for mesothelioma. J Thorac Oncol. In
press 2016.
ED05: THE 8TH EDITION OF THE TNM STAGING SYSTEM

MONDAY, DECEMBER 5, 2016 - 16:00-17:30
ED05.04 WHAT’S NEW IN ESOPHAGEAL CANCER STAGING?

Thomas Rice
Thoracic and CV Surgery, Cleveland Clinic, Cleveland/OH/United States of America
What’s New in Esophageal Cancer Staging? Thomas W. Rice, MD The 8th

edition cancer staging manuals will be published later this year,1,2 and the
new staging recommendations will go into effect January 1, 2017. Staging
cancer of the esophagus and esophagogastric junction for the 8th edition of
the AJCC/UICC manuals was developed on a strong 7th edition foundation.3,4
A greatly enhanced Worldwide Esophageal Cancer Collaboration (WECC)
database, with a substantial increase in both numbers of patients (22,654)
entered and variables (39) collected,5-7 permitted a more dynamic and
dependable Random Forest–based machine learning analysis. Random
Forest analyses provided risk-adjusted survival estimates for all patients,
from which distinctive and homogeneous stage groups with monotonically
decreasing survival were identified.8-10 Cancer Categories There were no
major changes in cancer categories; however, there were some important
refinements for T, N, grade, and location. Subcategorization of pT1 into pT1a
and pT1b enhanced and improved Stage I grouping. Regional lymph nodes
(N) were clarified in a new and simplified map. Undifferentiated cancers now
require additional analyses to expose histopathologic cell type. If glandular
origin can be determined, the cancer is staged as Grade 3 adenocarcinoma; if
squamous origin can be determined or if the cancer remains undifferentiated
after full analysis, it is staged as Grade 3 squamous cell carcinoma. Cancer
location, not important for adenocarcinoma stage grouping, in conjunction
with grade is necessary to subgroup only pT3N0M0 squamous cell carcinoma.
The definition of the esophagogastric junction was revised; cancers
involving the esophagogastric junction with epicenters 2 cm or less into
the gastric cardia are staged as adenocarcinomas of the esophagus, while
those with more than 2-cm involvement are staged as stomach cancers.
Stage Groupings Pathologic Stage Grouping (pTNM) Historically, pathologic
stage after esophagectomy alone has been the sole basis for all cancer
staging, regardless of classification (c, yc, yp, r, and a). Today, pathologic
stage has lost some of its clinical relevance for advanced-stage cancer as
neoadjuvant therapy replaces esophagectomy alone. However, it remains
important for early-stage cancers and as a key reference point. Dissimilar
stage group composition and survival profiles necessitated separate staging
groupings for adenocarcinoma and squamous cell carcinoma. Neoadjuvant
Pathologic Stage Grouping (ypTNM) New to the 8th edition is stage grouping
of patients with esophageal cancers who have had neoadjuvant therapy
and pathologic review of the resection specimen (ypTNM). Drivers of this
addition include absence of equivalent pathologic (pTNM) categories for the
peculiar neoadjuvant pathologic categories (ypT0N0-3M0 and ypTisN0-3M0),
dissimilar stage group compositions, and markedly different survival profiles.
Grade and location play no role in neoadjuvant pathologic stage grouping.
The groupings are identical for both histopathologic cell types. Clinical
Stage Grouping (cTNM) Also new to the 8th edition is clinical stage grouping
(cTNM) prior to treatment decision. Clinical staging is done typically in the
absence of complete histologic cancer data, because clinical TNM categories
are typically defined by imaging and examination of needle aspiration and
biopsy specimens. Dissimilar stage group composition and survival profiles
necessitated clinical stage grouping (cTNM) distinct from pathologic stage
References 1. Detterbeck FC, Nicholson AG, Kondo K, Van Schil P, Moran C. grouping (pTNM). There is separate clinical staging for adenocarcinoma and
The Masaoka-Koga Stage Classification for Thymic Malignancies Clarification squamous cell carcinoma. How to proceed with TNM-8? 8th edition staging
and Definition of Terms. J Thorac Oncol. 2011;6: S1710–S1716. 2. Masaoka A, for cancer of the esophagus and esophagogastric junction are data driven and
Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special expanded from pathologic stage (pTNM) to include also pathologic stage after
reference to their clinical stages. Cancer 1981;48:2485–92. 3. Detterbeck neoadjuvant therapy (ypTNM) and clinical stage (cTNM) before treatment
FC, Parsons AM. Thymic tumors. Ann Thorac Surg 2004;77:1860-9. 4. Kondo decision. Critical evaluation of 8th edition staging, intensive data collection,
K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 in-depth analyses, and further consensus appraisal are necessary to proceed
patients from Japan. Ann Thorac Surg 2003;76:878–84. 5. Koga K, Matsuno from the 8th to the 9th edition.References 1) American Joint Committee on
Y, Noguchi M, et al. A review of 79 thymomas: modification of staging system Cancer Staging Manual. 8th ed. In press. 2) TNM classifications of malignant
and rappraisal of conventional division into invasive and non-invasive tumors. International Union Against Cancer. 8th ed. In press. 3) Edge SB,
thymoma. Pathol Int 1994;44:359–67. 6. Detterbeck FC, Stratton K, Giroux Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. American
D, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal Joint Committee on Cancer Staging Manual. 7th ed. New York: Springer-
for an Evidence-Based Stage Classification System for the Forthcoming (8th) Verlag; 2010. 4) Sobin LH, Gospodarrowicz MK, Wittekind C, editors. TNM
Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: classifications of malignant tumors. International Union Against Cancer. 7th
S65–S72 7.Nicholson AG, Detterbeck FC, Marino M, et al.,The ITMIG/IASLC ed. Oxford, England: Wiley-Blackwell; 2009. 5) Rice TW, Chen L-Q, Hofstetter
Thymic Epithelial Tumors Staging Project: Proposals for the T component WL, et al. Worldwide Esophageal Cancer Collaboration: pathologic staging
for the Forthcoming (8th) Edition of the TNM Classification of Malignant data. Dis Esophagus. In press. 6) Rice TW, Lerut TEMR, Orringer MB, et al.
Tumors. J Thorac Oncol. 2014;9: S73–S80 8. Kondo K, Schil PV, Detterbeck FC, Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging
et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposals data. Dis Esophagus. In press. 7) Rice TW, Apperson-Hansen C, DiPaola LM,
for the N and M Components for the Forthcoming (8th) Edition of the TNM et al. Worldwide Esophageal Cancer Collaboration: clinical staging data.
Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S81-S87 9. Bhora Dis Esophagus. In press. 8) Rice TW, Ishwaran H, Hofstetter WL, Kelsen DP,
FY, Chen DJ, Detterbeck FD,et al., The ITMIG/IASLC Thymic Epithelial Tumors Blackstone EH. Recommendations for pathologic staging (pTNM) of cancer of
Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the esophagus and esophagogastric junction for the 8th edition AJCC/UICC
the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J staging manuals. Dis Esophagus. In press. 9) Rice TW, Ishwaran H, Kelsen DP,
Thorac Oncol. 2014;9: S88–S96 Hofstetter WL, Blackstone EH. Recommendations for neoadjuvant pathologic
staging (ypTNM) of cancer of the esophagus and esophagogastric junction for
Keywords: Thymoma, TNM Staging System, Thymic carcinoma
the 8th edition AJCC/UICC staging manuals. Dis Esophagus. In press. 10)Rice
TW, Ishwaran H, Blackstone EH, Hofstetter WL, Kelsen DP. Recommendations

for clinical staging (cTNM) of cancer of the esophagus and esophagogastric Zoledronic acid versus placebo in the treatment of skeletal metastases in
junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus. In patient with lung cancer and other solid tumors: a phase III, double-blind,
press. randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors
Study Group. J Clin Oncol. 2003;21(16):3150-7. [10] Cassileth BR, Deng GE,
Keywords: AJCC, cTNM, pTNM, ypTNM Gomez JE, Johnstone PA, Kumar N, Vickers AJ. Complementary therapies and
integrative oncology in lung cancer. ACCP evidence-based clinical practice
guidelines (2nd edition). Chest. 2007;132(Suppl3):340S-54.
Keywords: pain- pathophysiology and management, pathophysiology of pain,

principles of pain management
SESSION ED06: SYMPTOM MANAGEMENT IN LUNG
CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 ED06: SYMPTOM MANAGEMENT IN LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
ED06.03 PAIN MANAGEMENT ED06.04 BIOLOGY AND MANAGEMENT OF TUMOR CACHEXIA

Vera Hirsh Jeffrey Crawford
Department of Medical Oncology, McGill University, Royal Victoria Hospital, Medicine, Duke Cancer Institute, Durham/NC/United States of America
Montreal/Canada
The International Consensus Conference definition of cancer cachexia is a
Introduction: Pain is the most common symptom in cancer patients and it multifactorial syndrome defined by an ongoing loss of skeletal muscle mass
is also the most common symptom in lung cancer patients.[1]The majority with or without fat mass that cannot be fully reversed by conventional
of patients with lung cancer present with advanced stage of the disease nutritional support and leads to progressive functional impairment.1 As
at diagnosis. Symptoms may result from local effects of the tumor, from clinicians, we define cachexia clinically based on weight loss of 5% or greater
regional or distant spread or from distant effects not related to metastases- or body mass index <20 kg/m2, with 2% weight loss. On physical exam, we
paraneoplastic syndromes. Pain in these patients may be associated recognize cachexia based on gross loss of muscle mass and weakness, often
with depression, fatigue [2] and may affect quality of life and patients’ associated with physical findings such as temporal wasting. However,
performance status. Early palliative care including pain management may these patients with physical stigmata of cachexia are a small subgroup of
increase their survival. [3] Pain can be classified by type of pain or according the total population. If one assesses objective measures of muscle mass,
to the origin of the pain. The location or origin of the pain determines the approximately half of patients with advanced lung cancer will have muscle
type of pain, thoracic or extrathoracic. Pain: Pain is often multifactorial in wasting at diagnosis and 2/3 of patients will develop it during their treatment
origin and needs to be addressed in each aspect. It can be acute or chronic. course. This muscle wasting or sarcopenia, occurs across all weight groups,
Acute pain can be caused by hemorrhage into a tumor, bone pain secondary including those with normal weight, overweight and obesity.2 These patients
to a pathological fracture, visceral pain, ie. from acute intestinal obstruction would not be recognized clinically to be cachetic. Yet, they have significant
or perforation of a viscous. Its duration is limited and predictable. Chronic clinical consequences from muscle wasting. The use of standardized CT for
pain is differentiated by its longevity. It is estimated that approximately the quantitative assessment of skeletal muscle and other body tissues has
75% of cancer patients live with chronic pain. [4] It must be approached helped us better understand the importance of muscle and its impact on
with dual aim: relieving the pain as well as preventing further recurrences cancer outcomes.3 Muscle wasting is associated with an increased risk of
of pain. Pathophysiology of Pain: Physiological pain is termed nociceptive dose limiting chemotherapy toxicity, shorter time to disease progression
pain due to the stimulation of the sensory nociceptors located in tissues and reduced overall survival. Clinically, the cancer patient with cachexia
when damaged. They are somatic, visceral, neuropathic and psychogenic undergoes a progressive decline in muscle mass with associated anorexia,
pains. [5] Neuropathic pain is associated with a loss of opioid receptors in fatigue and reduced quality of life. Patient reported outcomes include
sensory afferents and an increased release of glutamate in the dorsal horn. weakness, declining muscle strength, reduced mobility and impact on physical
The resultant hyperexcitability causes spontaneous pain and hyperalgesia performance. At a molecular level, this loss of muscle mass is associated with
and allodynia in areas adjacent to the nerve damage. There are three main a number of biochemical changes in enzymes, regulatory proteins, altered
causes of pain in patients with advanced lung cancer: Skeletal metastatic metabolism, increased markers of inflammation and impaired immunity.
disease 34%, Pancoast tumor 31%, chest wall disease 21%. [6] Principles The driving force for muscle wasting in cancer patients is the competition for
of Pain Management: The World Health Organization analgesic ladder for nutrients between the cancer and the host often complicated by decreased
cancer pain relief provides a stepwise approach to managing pain in cancer protein/caloric intake. However, the mechanisms that both incite and
patients. [7] Step 1 includes paracetamol or non-steroidal anti-inflammatory promote the ongoing process of muscle loss are complex and include factors
drugs. Step 2- weak opioids, ie. codeine. Step 3- strong opioids, ie. morphine. associated with direct muscle atrophy, including the release of cytokines
Non-opioid and adjuvant treatments can be added to steps 2 and 3. Different such as tumor necrosis alpha and interleukin 6, as well as myostatin and
routes of the administration of analgesics and their side effects management activin. One strategy that might ameliorate the cachexia process include
will be described. Their advantages and disadvantages of each route of therapeutic approaches that block these cytokine mediated pathways and
administration will be pointed out. The need of adjuvant treatments such several agents are in development.4 Another approach has been to try to
as tricyclic antidepressants and anticonvulsants, corticosteroids, topical increase muscle growth signaling through anabolic pathways such as selective
analgesics, treatments of nausea, constipation, etc., are an integral part androgen receptor modulators (SARM) and ghrelin minetics. A first in class
of pain management. Interventional procedures help reduce the doses of SARM, enobosarm has shown promising results with improvement of muscle
analgesics and their side effects. [8] Special mention will be about skeletal mass and physical function in patients with cachexia.5 Subsequent phase III
metastases and bone targeted agents such as zoledronic acid and denosumab, trials in patients with advanced lung cancer receiving chemotherapy have
which have shown ability to reduce the pain and analgesic consumption in shown increase in muscle mass in the enobosarm treatment group versus
lung cancer patients. [9] Complementary therapies which help to control pain placebo, but physical function testing using stair climb measurement were
will also be mentioned.ie. Acupuncture,[10] psychological methods of care, etc. inconsistent.6 Meanwhile, trials of anamorelin, a ghrelin receptor agonist
Conclusion: An active multidisciplinary approach is required to manage pain have also demonstrated improvement in skeletal muscle mass. In phase III
in patients with advanced lung cancer. Multifactorial pain is frequent and may trials in patients with advanced lung cancer and cachexia, improvement in
require several different analgesics, along with general palliative care and skeletal muscle mass has been seen along with positive effects on improved
even special interventional procedures. Patients with advanced lung cancer appetite and weight gain. Again, functional improvement as measured
live longer as there are more treatment options. It is of utmost importance by hand grip strength was not observed.7 It is not clear why there is a lack
to preserve a good quality of life with a better performance status to enable of association of these promising agents that increase muscle mass, with
them to receive now further available therapies. [1] Caraceni A, Portenoy functional improvement. This may reflect issues regarding the patient
RK. An international survey of cancer pain characteristics and syndromes. population, the objective test being used, the duration of treatment or other
IASP Task Force on Cancer Pain. Pain. 1999;82 (32) :263-74. [2] Laird BJ, Scott factors. However, these phase III trials in advanced lung cancer represent
AC, Colvin LA, et al. Pain, depression, and fatigue as a symptom cluster in an important step forward in our understanding of cachexia and possible
advanced cancer. J. Pain Symptom Manage. 2011;42(1): 1-11. [3] Temel JS, Greer therapeutic interventions. Currently, as we are moving forward with the
JA, Muzikansky A, et al. Early palliative care for patients with metastatic non- development of new agents for cachexia, it is important for us to recognize
small-cell lung cancer. N Engl J Med. 2010;363(8):733-42. [4] Ferrell BR, Juarez the magnitude of the problem in our patients. Until CT imaging becomes a
G. Borneman T. Use of routine and breakthrough analgesia in care. Oncol Nurs standard clinical technique for assessment of muscle mass, we need to rely
Forum. 1999;26(10):1655-61. [5] Portenoy RK, Lesage P. Management of cancer on our standard clinical approaches of history and physical exam. Perhaps
pain. Lancet. 1999;353 (9165):1695-700. [6] Watson PN, Evans RJ. Intractable most importantly, is our documentation of the degree of weight loss in our
pain with lung cancer. Pain. 1987; 29(2):163-73. [7] Geneva W. World Health patients as a routine measure at baseline and during treatment just as we
Organisation. Cancer Pain Relief. 1996 [8] Vranken JH, Zuurmond WW, de Lange assess other patient reported outcomes such as pain, fatigue and functional
JJ. Continuous brachial plexus block as treatment for the Pancoast syndrome. status. Incorporating weight loss along with body mass index can be a
Clin J Pain . 2000;16(4):327-33 [9] Rosen LS, Gordon D, Tchekmedyian S, et al. very powerful tool for predicting outcome and survival for our patients.8
Moreover, it can help us address potential interventions that may be of sedation.

benefit for them. While current pharmacologic interventions are of limited
benefit, exercise and nutritional support are both important interventions
for our patients, along with continuing monitoring of appetite, weight and
functional performance during treatment.9 Cancer treatment itself can be
associated with an increase in muscle mass, particularly in patients whose
tumors respond well to therapy. However, for those patients who progress
through therapy, the toxicity of our treatment only compounds the ongoing
cachexia process. Better cancer therapeutics combined with optimum
supportive care remain the goal of management. 1. Fearon K, Strasser F, Anker
SD, et al. Definition and classification of cancer cachexia: an international
consensus. Lancet Oncol. 2011 May;12(5):489-95. 2. Prado CM, Lieffers JR,
McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity
in patients with solid tumours of the respiratory and gastrointestinal tracts:
a population-based study. Lancet Oncology. 2008; 9(7):629-35. 3. Prado CM,
Antoun S, Sawyer MB, Baracos VE. Two faces of drug therapy in cancer: drug-
related lean tissue loss and its adverse consequences to survival and toxicity.
Curr Opin Clin Nutr Metab Care. 2011;14:250–254. 4 Cohen S, Nathan JA,
Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising
therapies. Nat Rev Drug Discov. 2015 Jan;14(1):58-74. 5. Dobs AS, Boccia RV,
Croot CC, et al. Effects of enobosarm on muscle wasting and physical function
in patients with cancer: a double-blind, randomised controlled phase 2 trial.
Lancet Oncol. 2013 Apr;14(4):335-45. 6. Crawford J, Prado C, Johnston M, Gralla
R, Taylor R, Hancock M, Dalton J. Study design and rationale for the phase 3
clinical development program of enobosarm, a selective androgen receptor
modulator, for the prevention and treatment of muscle wasting in cancer
patients (POWER Trials). Cur Oncol Rep (2016) 18:37. 7. Temel JS, Currow DC,
Fearon K, et al. Phase III trials of anamorelin in patients with advanced non-
small cell lung cancer (NSCLC) and cachexia (ROMANA 1 and 2). J Clin Oncol 33,
2015 (suppl; abstr 9500) 8. Martin L, Senesse P, Gioulbasanis I, Antoun S, et
al. Diagnostic criteria for the classification of cancer-associated weight loss.
J Clin Oncol. 2015 Jan 1;33(1):90-9. 9. Crawford J. Clinical results in cachexia
therapeutics. Current Opinion in Clinical Nutrition & Metabolic Care. 19(3):199-
204, May 2016. Management of depression The patient had multiple reasons for being
severely depressed: her mother was experiencing lung cancer at the same time
Keywords: Cacexia, muscle wasting, sarcopenia ; the patient was concerned about becoming increasingly a burden for her
family; she was aware of her worsening condition and realizing that her life
would end soon; she was extremely anxious to have to die in intractable pain.
The management of the patient’s depression included the following: monthly
ED06: SYMPTOM MANAGEMENT IN LUNG CANCER consultation with an onco-psychiatrist and weekly visits to a psychologist-
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
social worker ; psychotropic drugs ; several sessions of hypnosis. Palliative
sedation That the control of the patient’s pain and/or dyspnea might require
ED06.06 DECISIONS IN CASE OF INTRACTABLE SYMPTOMS palliative sedation has been discussed since 2010 (time of worsening of her
Jean Klastersky 1, Bénédicte Michel2, Isabelle Libert3, Aspasia Georgala2, symptoms) between the patient, her family and the caregivers. The patient
Myriam Obiols2, Florence Lewis3, Dominique Lossignol3 and her family spoke openly about end-of-life issues, always emphasizing
1 not to let the patient die in severe pain. After making the decision to resort
Medicine, Institut Jules Bordet, Brussels/Belgium, 2Medicine, Institut Jules Bordet
- Centre Des Tumeurs de L’Ulb, Bruxelles/Belgium, 3Institut Jules Bordet - Centre Des to sedation in case of intractable symptoms, the patient and her family
Tumeurs de L’Ulb, Bruxelles/Belgium expressed a sense of relief that her suffering could and would be alleviated.
When the patient expressed unbearable pain and dyspnea, the mobile
Case report: A 55-year-old lady was diagnosed with small cell lung cancer in nursing team started her on midazolam, scopolamine and methadone by
late 2008. She had been a long-time cigarette smoker without, any other sub-cutaneous route, with no clear-cut response; the patient was brought
significant medical history. She was a housewife, deeply religious and to the hospital, where the same medications were given intravenously, with
dedicated mother to 2 children. As a first treatment for her cancer, she the addition of haloperidol. No attempt to lift the sedation process (respite
received radiotherapy on the right apex and mediastinum, concomitantly with sedation) was made, according to the patient’s will. The patient was able to
chemotherapy (cisplatin plus etoposide), early in 2009. Six months later, she rest comfortably and died peacefully after 2 days, with her family at her side.
presented a very painful right shoulder and chest wall. Chemotherapy was Discussion In case of dyspnea due to lung cancer progression, corticosteroids,
resumed, with some improvement of the pain, but late in 2009, radiotherapy morphine and oxygen are used since many years ; novel options were
had to be administered to the chest for uncontrolled pain; oral etoposide was introduced timidly during the last years. These new options include non-
given without much benefit. The pain progressively increased and the patient invasive ventilation, high-flow oxygen and rational use of medications usually
was complaining of increasing shortness of breath. As the tumour was clearly prohibited in patients with respiratory distress, such as benzodiazepines,
progressing, in 2010, with further lung, bone and liver involvement, a decision antidepressants and synthetic opioids [1]. The World Health Organization
was made to discontinue any specific oncological treatment. Both symptoms (WHO) scale for cancer-related pain proves to be an effective approach to
pain and dyspnea increased in intensity and became uncontrollable late in pain management in cancer patients [2], and many variations based on it
2010; the patient and her family requested sedation at any cost. The patient have been proposed [3]. However, these approaches represent pragmatic and
was started on palliative sedation and died peacefully after 2 days; with her empiric attitudes that are rarely evaluated in prospective studies. There is
family present. Supportive and palliative treatments for pain Table 1 also a lack of consensus about the use of co-analgesia and other supportive
summarizes the time evolution of the patient and the corresponding approaches for refractory pain [5]; although pragmatic recommendations
interventions as far as analgesics and co-analgesics are concerned. exist, a comprehensive algorithm for the management of refractory pain is
Management of dyspnea over the course of her disease, the patient still lacking. Based on the experience in our supportive care unit, we proposed
experienced progressive dyspnea which could be managed with oxygen, a comprehensive model for the progressive management of pain in cancer
corticoids, benzodiazepines and bronchodilatating aerosols, as well as patients (Figure 1). Finally, the approach to pain (or other symptoms) that
physical therapy and hypnosis. Dyspnea became major and beyond control is beyond medical control, fortunately a relatively rare situation, has not
the day prior to the last hospitalization and was a reason for accelerated been clearly defined [6;7]. Palliative sedation or euthanasia is always an
emotionally and ethically challenging event for all involved and implies to
meet the needs of the patient and family but also those of the caregivers [8;
9; 10] and requires repeated and professional counselling with the patient
and family as well as regular debriefing sessions with the medical and nursing
teams. Although the decision to offer and provide palliative sedation or
euthanasia (if requested by the patient and not illegal) is never easy, it should
be seen, however, as the medical duty to safeguard the patient’s autonomy,
the principle of individual freedom to make choices.
(See Figure next page)

epithelial tumor which consist of densely packed small cells with scant
cytoplasm, finely dispersed granular chromatin and absent or inconspicuous
nucleoli. In contrast LCNEC is made of large cells and should show both
neuroendocrine morphology (rosettes, palisades) and immunohistochemical
neuroendocrine markers (at least one). Both SCLC and LCNEC can be pure or
combined with NSCLC components but keep their diagnostic priority (SCLC-
or LCNEC- combined). Carcinoid tumors are neuroendocrine malignancies
accounting for <1% of all lung cancer, divided in two categories with highly
different frequencies, the typical and atypical carcinoid, the last being
extremely rare. Typical carcinoids are carcinoid tumors with <2mm2 and
lacking necrosis. They measure ≥0.5 cm in size. Atypical carcinoids are
carcinoid tumors with 2-10 mitoses per 2mm2 and/or foci of necrosis. Despite
the grouping of these tumors together, it is clear that the carcinoids have
major clinical, epidemiologic, histologic and genetic differences compared to
the high grade SCLC and LCNEC. Carcinoid patients are significantly younger,
have a better prognosis and lack the strong association with smoking that
applies for SCLC and LCNEC. Also compared to carcinoid tumors, SCLC
and LCNEC have much higher mitotic rates (more than 11 per 2mm2), more
necrosis and can show combinations with other lung cancer types including
adenocarcinoma or squamous cell carcinoma, which testify of a common
progenitor cell derivation, not shared by carcinoid which is never mixed with
a non-neuroendocrine (NE) tumor type. Carcinoid tumors also have very few
genetic abnormalities compared to SCLC and LCNEC which show the highest
rate of mutations per megabase among all cancer3,4,5 . While in many cases,
SCLC and carcinoid tumors can be diagnosed on good quality tumor material
with a high quality H&E stained section and in well preserved cytological
samples, immunohistochemistry (IH)/neuroendocrine markers can be very
helpful in diagnosing pulmonary NE tumors especially in small biopsies with
crushed artefact. Endocrine morphology and neuroendocrine IH markers
are both required for the diagnosis of LCNEC. The cases with one missing
(endocrine morphology or NE markers) are considered as large cell carcinoma
in the absence of other differentiation marker on resection specimens, and as
non-small cell lung carcinoma on small samples (cytology or biopsy) Mitotic
counts are still retained to differentiate typical carcinoids (less than 2 mitoses
per mm2) from atypical carcinoids (2 to 10 per 2mm2) and from high grade
NE tumors SCLC and LCNEC (more than 11 mitoses per 2 mm2 , for being more
reproducible than KI-67 evaluation. The role of Ki-67 is mainly to separate
the high grade SCLC (more than 50%) and LCNEC (more than 40%) from the
References 1. Cabezón-Gutiérrez L, Khosravi-Shahi P, Custodio-Cabello carcinoid tumors (from 1 to 15%) especially in small biopsies with crushed and/
S, Muñiz-González F, del Puerto Cano-Aguirre M, Alonso-Viteri S. Opioids or necrotic tumor cells. It is recommended to avoid the diagnosis of SCLC or
for management of episodic breathlessness or dyspnea in patients with LCNEC for tumors with less than 50% and 40% MIB1/KI67 index respectively.
advanced disease. Support Care Cancer 2016;24:4045-55 2. Meuser T, Pietruck Data are conflicting regarding the use of KI-67 in separating typical from
C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during cancer atypical carcinoid tumors, so it is not recommended in this setting. Careful
pain treatment following WHO-guidelines: a longitudinal follow-up study counting of mitoses is essential as it is the most important histologic criteria
of symptom prevalence, severity and etiology. Pain 2001; 93:247-57 3. Zech for separating typical from atypical carcinoid and the carcinoids from the
DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health high grade SCLC and LCNEC. Due to recognition of the potential overlap in the
Organization Guidelines for cancer pain relief: a 10-year prospective study. morphology of LCNEC and basaloid squamous cell carcinoma, it can be helpful
Pain 1995; 63:65-76 4. Swarm RA, Abernethy AP, Anghelescu DL, et al. Adult to confirm negative squamous markers (i.e. p40) in TTF-1 negative tumors that
cancer pain. J Natl Compr Canc Netw 2010;8:1046-86 5. Lee M, Silverman otherwise meet criteria for LCNEC. Many recent progress have been made
SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid on the comprehensive genomic profiles of SCLC 3,4 , LCNEC 5 and carcinoids
–induced hyperalgesia. Pain Physician 2011; 14:145-61 6. Council on Scientific 6
. Although sharing NE features, these 3 tumors group show substantial
Affairs, American Medical Association. Good care of the dying patient. JAMA and significant differences.Recent comprehensive genomic analyses have
1996;275:474-8 7. Field MJ, Cassel CK, eds. Approaching death: improving care established the genomic profile of SCLC 3,6. Their unique and remarkable
at the end of life. Washington DC: : National Academy Press, 1997 8. de Graeff characteristic is the universal bi-allelic alteration of both TP53 and RB1 gene
A, Dean M. Palliative sedation therapy in the last weeks of life : a literature (100% for P53 and 93% for RB1) by different alterations of each of the 4 alleles:
review and recommendations for standards. J Palliat Med 2007; 10:67-85 9. non synonymous mutations, damaging mutations by complex genomic
Olsen ML, Swetz KM, Mueller PS. Ethical decision-making with end-of-life rearrangements. Locally clustered mutations, indicative of functional
care: palliative sedation and withholding or withdrawing life-sustaining selection, occurred on CREBBP (15%) and EP300 (13%) genes, inactivating
treatments. Mayo Clinic Proc 2010;85:949-54 10. Lossignol D. End-of-life their histone acetylase functions. Notch family genes inactivating their
sedation: is there an alternative? Curr Opin Oncol. 2015;27(4): 358-64 protein functions occurred in 25% of SCLC 4. Notch is considered as a master
regulator of NE differentiation. LCNEC genomics share characteristic features
Keywords: sedation, euthanasia, Pain, dyspnea
with SCLC for a part of LCNEC (SCLC-like LCNEC) or with AD /SQC for another
part (about 25%). Mutations pattern and frequency of combined cases
imply a considerable plasticity of theses tumours which might represent an
evolutionary trunk branching SCLC to NSCLC. Carcinoid is a unique example of
a tumor driven entirely by chromatin modifiers and remodeling genes, which
are not mutant in SCLC. In summary, 51% of carcinoid carried mutations in
SESSION ED07: CLASSIFICATION AND DRUGGABLE chromatin remodeling genes. In addition, the eukaryotic translation initiation
TARGETS OF THORACIC TUMORS factor (EIF1AX) was mutated in 9% of cases, genes of the E3 ubiquitin ligases
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 system were mutated or rearranged in 18%. Altogether 73% of carcinoids
have driver genes that are candidates for targeted therapy 6. New evidence
is provided that carcinoid is not an early progenitor of high grade NE tumors
SCLC and LCNEC.References: 1. Travis WD, Brambilla E, Burke A, Marx A,
ED07.02 THE 2015 WHO CLASSIFICATION OF NEUROENDOCRINE
Nicholson A. WHO Classification of the Tumours of the Lung, Pleura, Thymus and
TUMORS Heart. 4th Edition. Lyon: IARC Press; 2015. 2. Clinical Lung Cancer Genome
Elisabeth Brambilla Project (CLCGP), Network Genomic Medicine (NGM). A genomics-based
Dacp (Pathology), CHU Grenoble, Grenoble/France classification of human lung tumors. Sci Transl Med. 2013;5(209):209ra153.
doi:10.1126/scitranslmed.3006802. 3. Peifer M, Fernández-Cuesta L, Sos ML,
France Neuroendocrine lung tumors were considered as separate entities in et al. Integrative genome analyses identify key somatic driver mutations of
the previous WHO classification 2004: the carcinoid tumors, small cell lung small-cell lung cancer. Nat Genet. 2012;44(10):1104-1110. doi:10.1038/ng.2396.
carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) were 4. George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small
grouped separately. However, in the current WHO 2015 classification, they cell lung cancer. Nature. 2015;524(7563):47-53. doi:10.1038/nature14664. 5.
are grouped together 1. They are listed in the order of their frequency with Fernandez-Cuesta L, Peifer M, George J, et al. Genomic Characterization of
SCLC first as it is the most common. SCLC (15% of lung tumors) is a malignant
Large-Cell Neuroendocrine Lung Tumors. J Thorac Oncol. 2015;10(9 - WCLC non-small cell lung cancer. An extensive body of literature mainly composed of
2015 Abstracts: PDF Only):S185. doi:10.1097/01.JTO.0000473439.77589.a7. 6. retrospective studies supports the use of radical anatomical segmentectomy
Fernandez-Cuesta L, Peifer M, Lu X, et al. Frequent mutations in chromatin- for peripheral cT1N0M0 non-small lung cancer with less than 2 cm in diameter,
remodelling genes in pulmonary carcinoids. Nat Commun. 2014;5:3518. certainly for older patients with limited cardiopulmonary function. However,
doi:10.1038/ncomms4518. caution should be taken to promote a widespread indication for intentional
segmentectomy in young good surgical candidates until the results of
Keywords: Neuroendocrine tumors, lung cancer, Pathology, genetic the ongoing randomised controlled trials become available. 3,4 The role of
minimally invasive surgery: Minimally invasive anatomical resection for lung
cancer carried out by means of video-assisted thoracic surgery (VATS) has
been increasingly carried out during the past years. A systematic review and
meta-analysis of randomized and nonrandomized trials published in 2009
reported an improved five-year survival and reduced systemic recurrences in
SESSION ED08: EARLY-STAGE NSCLC: STATE-OF-THE-ART patients who received VATS lobectomy. 5 A multicentric propensity-matched
TREATMENT AND PERSPECTIVES analysis of more than 1000 patients, of which 700 had undergone VATS
lobectomy confirms, that thoracoscopic lobectomy is associated with lower
TUESDAY, DECEMBER 6, 2016 - 14:30-15:45 morbidity as compared with thoracotomy. The positive impact of minimally
invasive surgery in the treatment of lung cancer particularly applies to the
elderly. 6 Regarding long-term survival after video-assisted thoracoscopic
ED08.01 SURGERY OF EARLY-STAGE NSCLC lobectomy a meta- showed a survival benefit in the favour of VATS with a
Michael Mueller difference in survival of 5% at five years. The reason for this observed
Thoracic Surgery, Otto Wagner Teaching Hospital, Sigmund Freud University,
Vienna/Austria survival benefit may be attributed to a less pronounced compromise of the
immunocompetence after the surgical trauma. 7 The role of mediastinal lymph
General considerations: Early stage lung cancer - a term in transition Generally node dissection: The rationale for a formal mediastinal lymph node dissection
early stage lung cancer is understood as stage I and stage II non-small lung is multifold. The distribution pattern of mediastinal lymph node metastasis
cancer. An alternative understanding of early stage lung cancer is resectable is not predictable and skip metastasis are seen in up to 30% of patients. Even
disease. However, both definitions are imprecise and subject to development small tumours may present with unexpected N2 disease with an incidence of
and Expertise. 1. Defining early stage lung cancer as resectable disease 6-10%. The operative morbidity is not significantly influenced by a systematic
depends on regional philosophies and local expertise and therefore is the mediastinal lymph node dissection. Recommended standard of mediastinal
most unreliable and variable definition. The term resectability focuses on the lymph node dissection is the removal of all mediastinal tissue containing
T factor of the tumour and describes the ability of the surgeon to achieve lymph nodes in a systematic Approach within anatomical landmarks. The
radical resection. In contrast operability includes any potential regional and most recent randomized controlled trial published in 2011 did not find a
systemic spread and focuses more on the N and M descriptors. 2. Defining survival benefit by complete mediastinal lymphadenectomy in patients
early stage lung cancer based on mediastinal nodal involvement neglects with early stage lung cancer, but the results should not be generalized to
the fact, that single station N2 (N2a) is associated with the same five-year patients staged only radiographically or those with higher stage tumours.
survival as multistation N1 (N1b). This touches on the term locally advanced The recommendation from this study is that a formal mediastinal en-bloc
disease, which in fact also means different things for different people. For the dissection may still affect survival and certainly optimally stages patients.
oncologist locally advanced disease usually means N2 involvement with the In the subgroup analysis no difference between VATS and open lobectomy
consequent call for chemotherapy. For the surgeon locally advanced disease was observed for number of lymph nodes harvested and regarding long-term
primarily addresses the T factor and is used for T3 or T4 tumours, indicating survival.8 As minimally invasive surgery along with unilateral mediastinal
more extended resections in the absence of N2 disease. In summary, terms lymphadenectomy generally prolongs operation times and the requirement
like early stage, locally advanced stage or advanced stage should be avoided of single lung ventilation the advantages for the elderly population has to
since they do not properly describe a clinical situation nor are they guiding be questioned and discussed individually. An alternative to thoracoscopic
therapy. If the term early stage lung cancer should be maintained for any unilateral lymphadenectomy is offered by video-assisted mediastinal
reason, there is need for revisions. The five-year survival of stage I and stage lymphadenectomy through the neck (VAMLA). The approach is similar
II non-small lung cancer is a range of less than 30 to more than 90% and the to transcervical mediastinoscopy and allows for a radical bloc dissection
survival expectedly mainly depends on nodal involvement. The estimated of all mediastinal lymph node stations. Besides the benefit of bilateral
median five-year survival of patients with Screening detected T1N0 NSCLC lung ventilation during this phase of the operation a bilateral mediastinal
is a reported 92%. Even nodal negativeT3 tumours are associated with lymphadenectomy offers improved surgical radicality. Alternatives to surgical
almost 60% five year survival following radical resection. On the other hand resection and the role of primary radiotherapy: In patients unfit for surgery
involvement of multiple N1 lymph nodes results in a much worse prognosis SABR is the treatment of choice for peripherally located stage I non-small cell
of about 35%. However, for this presentation the current definition of lung cancer. If SABR is not
stage I and stage II non-small lung cancer was used. Preoperative staging:
Resectability of lung cancer for technical reasons in general, and in early stage available a hypofractionated radiotherapy is advocated. A systematic Review
lung cancer in particular, very rarely is an issue. Oncological operability has comparing outcomes of SABR and surgery in patients with severe COPD
to be defined preoperatively along international guidelines. The European revealed a higher 30 day mortality following surgery but similar overall
Society of Thoracic Surgeons (ESTS) recently has ublished revised guidelines survival at one and three years. 9 In a meta-analysis of 19 out of 318 papers
for preoperative mediastinal lymph nodes staging for non-small cell lung with the best evidence addressing a comparison of SABR and surgical wedge
cancer. Only one selected group of patients with tumours of less than 3 resection both methods proved as reasonable alternatives to lobectomy in
cm in diameter (cT1) in the outer third of the lung without signs of nodal high risk surgical patients. In this analysis SABR was associated with reduced
involvement at CT scan, PET scan or PET CT (cN0) may directly undergo local recurrence compared to wedge resection and should be considered when
surgical resection. All other clinical situations require invasive preoperative wedge resection is planned due to anatomical location and size of the primary
staging by bronchoscopy plus EBUS/EUS. If the absence of nodal involvement tumour in a patient who is high risk for surgery. 10 Although local tumour
is verified by EBUS/EUS this patient may also directly undergo surgery. In the control may be comparable or even superior to extra-anatomic surgical
presence of radiologically suspect mediastinal lymph nodes and negative resection a quite high rate of late radiological changes after stereotactic
EBUS/EUS further confirmation is recommended using mediastinoscopy or ablative radiotherapy for early stage lung cancer has to be considered. At one
thoracoscopy. If mediastinal nodal involvement is histologically verified by year follow-up the predicted probability of having expected or pronounced
any means the patient has to undergo multimodality treatment. All clinical radiological changes after SABR were 65 and 22%. These changes included
findings are to be discussed in an interdisciplinary tumour board for proper phenomena like mass-like appearance, radiation fibrosis, and rib fractures,
therapy planning. 1Surgical therapy of early stage NSCLC: Surgery remains the cornerstone which sometimes are difficult to differentiate from tumour recurrence.
of treatment of early stage non-small lung cancer for patients willing to Summary: The ACCP guidelines address the question, who had to be
accept the procedure-related risks. Goal of any surgical intervention for early considered a high risk candidate for surgery. With the advent of minimally
stage lung cancer is the complete resection of the primary tumour together invasive resection, the criteria to classify a patient as too ill to undergo an
with regional lymphatic nodes. The standard for any resection with curative anatomic lung resection are being redefined. Surgical resection remains the
intent is defined by anatomical lung resection. In early stage lung cancer the primary and preferred approach to the treatment of stage I and II NSCLC in
predominant type of resection is lobectomy or bilobectomy, sometimes along patients with good or low surgical risk. Primary radiation therapy remains the
with bronchoplastic or angioplastic procedures or extended resections for primary curative intent approach for patients who refuse surgical resection
locally invading T3 tumours. Pneumonectomy particularly in the treatment or are determined by a multidisciplinary team to be inoperable. 11References:
1. Revised ESTS guidelines for preoperative mediastinal lymph node staging for
of early stage lung cancer is rarely used. Gold standard of surgical resection
non-small-cell lung cancer. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B,
for lung cancer is lobectomy. This standard is based on a prospective multi- Rami-Porta R, Turna A, Van Schil P, Venuta F, Waller D, Weder W, Zielinski M. Eur J
institutional randomized trial comparing limited resection with lobectomy Cardiothorac Surg. 2014 May;45(5):787-98 2. Randomized trial of lobectomy versus
for peripheral T1N0 non-small cell lung cancer published in 1995. 2 In the limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group.
absence of more recent prospective randomised trials lobectomy still must be Ginsberg RJ; Rubinstein LV. Ann Thorac Surg. 1995; 60(3):615-22; discussion 622-3
considered the surgical procedure of choice for patients with peripheral T1N0 3. Tsutani Y, Miyata Y, Nakayama H, et al. Oncologic outcomes of segmentectomy

compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity

score-matched analysis in a multicenter
study. J Thorac Cardiovasc Surg 2013;146:358-64. 4. Zhao X, Qian L, Luo Q, et al.

Segmentectomy as a safe and equally effective surgical option under complete
video-assisted thoracic surgery for patients of stage I non-small cell lung cancer.
J Cardiothorac Surg 2013;8:116, 5. Yan TD, Black D, Bannon PG, McCaughan BC.
Systematic review and metaanalysis of randomized and non-randomized Trials on
safety and efficacy of videoassisted thoracic surgery lobectomy for early-stage
non-small cell lung cancer. J Clin Oncol 2009; 27: 2553–2562 6. Thoracoscopic
lobectomy is associated with lower morbidity compared with thoracotomy.
Villamizar NR, Darrabie MD, Burfeind WR, Petersen RP, Onaitis MW, Toloza E,
Harpole DH, D’Amico TA. J Thorac Cardiovasc Surg. 2009 Aug;138(2):419-25. 7.
Long-term survival in video-assisted thoracoscopic lobectomy vs open lobectomy
in lung-cancer patients: a meta-analysis. Taioli E, Lee DS, Lesser M, Flores R. Eur J
Cardiothorac Surg. 2013 Feb 14. 8. Darling GE, et al. Randomized trial of m diastinal
lymph node sampling versus complete lymphadenectomy during pulmonary
resection in the patient with N0 or N1 less than hilar) non-small cell carcinoma. J
Thorac Cardiovasc Surg 011;141:662-70 9. Early and locally advanced non-small-cell
lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, Treatment
and follow-up. J. Vansteenkiste, D. De Ruysscher, W. E. E. Eberhardt, E. Lim, S.
Senan, E. Felip & S. Peters, on behalf of the ESMO Guidelines
Working Group 10. Mahmood S, Bilal H, Faivre-Finn C, Shah R. Is stereotactic

ablative radiotherapy equivalent to sublobar resection in high-risk surgical
patients with stage I non-small-cell lung cancer? Interact Cardiovasc Thorac Surg.
2013 Nov;17(5):845-53. 11. Treatment of stage I and II non-small cell lung cancer:
Diagnosis and management of lung cancer, 3rd ed: American College of Chest
Physicians evidence-based clinical practice guidelines.Howington
JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Chest. 2013 May;143(5 Suppl)
Keywords: early stage lung cancer, thoracic surgery, VATS lobectomy, VAMLA
ED08: EARLY-STAGE NSCLC: STATE-OF-THE-ART TREATMENT AND PERSPECTIVES

ED08.02 THE ROLE OF RADIOTHERAPY IN EARLY-STAGE NSCLC

Suresh Senan
Radiation Oncology, VU University Medical Center, Amsterdam/Netherlands The observed rates for a second primary lung cancer following SABR appear
similar to those following surgery [Verstegen N, 2015]. In this situation, a
Radiotherapy is a curative treatment for early-stage NSCLC. Following subsequent course of SABR can generally be performed safely. Operable
hypofractionated radiotherapy in 15 once-daily fractions of 4 Gy to biopsy- patients The role of SABR in fit patients remains a topic of active debate.
proven tumors, a prospective multicenter study reported a 3-year local control Indirect comparisons of outcomes following the two modalities have
rate of 82.7% (95% CI = 69.7% to 90.5%) [Cheung PC, 2014]. In the past decade, revealed conflicting results. The role of SABR in surgical patients is currrently
stereotactic ablative radiotherapy (SABR or SBRT) has become established being investigted in 3 prospective randomized studies (NCT02468024,
as the guideline-recommended standard of care for medically inoperable NCT02629458, NCT01753414), with a fourth study (VALOR) scheduled to open
patients with a peripheral early-stage NSCLC, as 5-year local control rates shortly.
of 90% have been reported [Louie AV, 2015]. SABR is usually delivered in 3-8
fractions, utilizes small margins for positional uncertainty, 4-dimensional Keywords: stereotactic radiotherapy, Early-stage lung cancer, follow-up,
computed tomography (4DCT) for treatment planning, multiple conformal toxicity
beams or arcs for delivery, and cone-bean CT scans for daily setup. Where
facilities for SABR are unavailable, hypofractionated radiotherapy delivered
using 4DCT planning remains an acceptable curative treatment. Diagnosis
Population studies reveal that a significant proportion of elderly patients, TUESDAY, DECEMBER 6, 2016 - 14:30-15:45
as well as those with severe co-morbidities, do not receive any treatment.
Guidelines recommend that a tissue diagnosis be obtained before initiating
treatment for early-stage NSCLC, but also permit the use of SABR following ED08.03 ADJUVANT CHEMOTHERAPY OF COMPLETELY RESECTED
review by an expert tumor board, in tumors where the calculated probability Glenwood Goss
of malignancy is high [Vansteenkiste J, 2014; Callister ME, 2015]. However, Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa,
any decision to proceed to a FDG-PET directed SABR approach in less fit Ottawa/ON/Canada
patients must take into account the likelihood of benign disease. Given a high
incidence of pulmonary tuberculosis, guidelines for Asia have recommended Adjuvant Chemotherapy of Completely Resected NSCLC Glenwood D. Goss
performing early non-surgical biopsies in Asian patients [Bai C, 2016]. Lung cancer remains the leading cause of cancer death world-wide and
Toxicity Treatment-related grades 3-4 toxicity are uncommon following accounts for approximately 28% of all cancer deaths (1,2). Surgical resection is
SABR to peripheral lung tumors, while local control rates are approximately the cornerstone of therapy for early stage disease, but relapse is high with
90% [Louie AV 2015]. Commonly reported toxicities are chest wall pain, rib 30-60% of patients with resected NSCLC still dying of their disease. Despite
fractures, and except in patients who have pre-existing interstitial lung the results of a 1995 meta-analysis demonstrating a non-significant 5%
disease (ILD), the incidence of high-grade radiation pneumonitis is low. survival advantage at five years with the addition of adjuvant cisplatin-based
A systematic literature review of SABR in patients with ILD reported a chemotherapy, no large randomized studies conclusively demonstrated a
treatment-related mortality in 15% [Chen H, Proc ASTRO 2016]. Follow-up benefit following resection until 2003(3). Five large randomized trials were
Guidelines recommend 6-monthly CT scans for up to 3 years following SABR, undertaken to determine if adjuvant platinum-based chemotherapy after
followed by annual scans thereafter. The assessment of radiological changes curative surgery for NSCLC conferred a survival advantage: ALPI; IALT; JBR10;
can be challenging in a sub-group of patients during long-term follow-op, and CALGB 9633; and ANITA (4,5,6,7,8). Three of these five trials showed
the so-called high-risk radiological features [HRF] can identify patients in statistically significant improvements in overall survival, ranging from 4%
whom a biopsy is warranted [Figure 1, Huang K, 2014]. The HRF’s identified in [IALT] to 15% [JBR10] at 5 years, corresponding to an absolute improvement in
the literature are an enlarging opacity at primary site, a sequential enlarging relapse-free survival from 49% to 61%. Of the two trials that did not
opacity, enlarging opacity after 12-months, a bulging margin, loss of linear demonstrate improved survival, one [ALPI] suffered from poor compliance to
margin, loss of air bronchogram and cranio-caudal growth [Huang K, 2014]. the treatment regimen (69%), and the second was a smaller trial (n=344)
Initial reports on surgery for local failures following SABR indicate that this limited to patients with stage IB disease [CALGB 9633], which was likely
salvage procedure can be performed safely [Allibhai Z, 2012; Hamaji M, 2015; underpowered to detect a statistically significant improvement in overall
Verstegen N, Proc ELCC 2015]. survival. Interestingly, despite being limited to patients with stage IB disease,
CALGB 9633 did demonstrate an overall survival hazard ratio comparable to
the other adjuvant trials (HR=0.8) that included patients with more advanced
disease, despite not achieving statistical significance. Since the publication of
original adjuvant chemotherapy trials, a number of meta-analyses have Group. Adjuvant chemotherapy, with or without postoperative radiotherapy,
confirmed the benefit of adjuvant platinum-based chemotherapy after in operable non-small-cell lung cancer: two meta-analyses of individual
surgical resection for NSCLC(9,10). In these meta-analyses, all-stage (IB-IIIA) patient data. Lancet 2010; 375: 1267-77. 11. Wakelee H, Dubey S, Gandara D et
hazard ratios were in the range of HR=0.86, corresponding to an absolute al. Optimal adjuvant therapy for non-small cell lung cancer – how to handle
benefit for chemotherapy on overall survival of 4-5% at 5 years. The benefit, stage I disease. Oncologist 2007; 12: 331-7. 12. Arriagada R, Dunant A, Pignon JP,
however, was demonstrated to be stage dependent (albeit using older staging et al. Long-Term Results of the International Adjuvant Lung Cancer Trial
criteria versions), with the benefit only reaching statistical significance for Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer
stages II and III. While the role of adjuvant chemotherapy in stage I disease is JCO January 1, 2010 vol. 28no. 1 35-42 13. Butts C, Ding K, Seymour L,et al.
controversial (11), subgroup analyses in a number of trials in high-risk patients Randomized Phase III Trial of Vinorelbine Plus Cisplatin Compared With
with stage IB disease (tumours≥4cm) suggests that there may be an overall Observation in Completely Resected Stage IB and II Non–Small-Cell Lung
survival advantage with adjuvant chemotherapy in this subgroup of patients, Cancer: Updated Survival Analysis of JBR-10. Journal of Clinical Oncology,
comparable to those observed in stage II and III disease [Strauss 2008]. In 2009 January 1, 2010 vol. (28) 1 29-34. 14. H.A. Wakelee1, S.E. Dahlberg2, S.M. Keller
the long term follow up of the IALT study (with a median follow up of 7.5 years) te al. E1505: Adjuvant chemotherapy +/bevacizumab for early stage NSCLC:
was reported. Results showed a beneficial effect of adjuvant chemotherapy Outcomes based on chemotherapy subsets. ASCO Annual Meeting, 2016 Abstr
on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on 8507: E1505 Chemotherapy subsets. 15. Booth CM, Shepherd FA, Peng Y et al.
disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there Adoption of adjuvant chemotherapy for NSCLC: a population-based outcome
was a significant difference between the results of overall survival before and study. J Clin Oncol 2010; 28: 3472-8.
after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95%
CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were Keywords: adjuvant chemotherapy, early stage non small cell lung cancer
observed for disease-free survival. The analysis of non-lung cancer deaths for
the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06) suggesting
that those patients receiving adjuvant chemotherapy had a higher death rate
from non- lung causes after 5 years(12). However these conclusions were not TUESDAY, DECEMBER 6, 2016 - 14:30-15:45
support by the findings of Butts and colleagues reporting on JBR10 with a
median follow-up was 9.3 years (range, 5.8 to 13.8). Adjuvant chemotherapy
continued to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = ED08.04 PERSPECTIVES OF TARGETED THERAPIES AND
.04). There was a trend for interaction with disease stage (P = .09; HR for stage IMMUNOTHERAPY IN COMPLETELY RESECTED NSCLC
II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = Heather Wakelee
.87). Adjuvant chemotherapy resulted in significantly prolonged disease Department of Medicine, Division of Oncology, Stanford Cancer Institute/Stanford
specific survival (HR, 0.73; 95% CI, 0.55 to 0.97;P = .03). Observation was University School of Medicine, Stanford/CA/United States of America
associated with significantly higher risk of death from lung cancer (P = .02),
with no difference in rates of death from other causes or second primary The use of four cycles of cisplatin-based adjuvant chemotherapy is now
malignancies between the arms. They concluded that prolonged follow-up of the standard of care for patients with resected stage II and IIIA NSCLC and
patients from the JBR.10 trial continues to show a survival benefit for is commonly used for patients with larger (at least 4 cm in size) stage IB
adjuvant chemotherapy(13). Recently in a post hoc analysis of ECOG 1505, a tumors. The survival benefit with adjuvant chemotherapy though is limited
trial of adjuvant chemotherapy +/- bevacizumab for early stage NSCLC, with meta-analyses revealing a 4-5% absolute survival benefit at 5 years for
Wakelee and colleagues had the opportunity to compare four different patients receiving adjuvant cisplatin-based chemotherapy.1,2Some recent
cisplatin doublet regimens namely, cisplatin with one of vinorelbine, attempts to improve outcomes with the addition of other agents to cisplatin
docetaxel, gemcitabine or pemetrexed. Median follow-up time for each doublets (or as longer term therapy) have been disappointing. The addition
chemotherapy doublet was: vinorelbine 54.3 months; docetaxel 60.3 months; of bevacizumab to chemotherapy in the ECOG-ACRIN E1505 adjuvant trial
gemcitabine 57.0 months; and pemetrexed 40.6 months respectively. The failed to show a benefit in disease free survival (DFS) or overall survival
arms were well balanced for the major prognostic factors apart from smoking (OS). 3The use of the MAGE-A3 vaccine in the MAGRIT trial was similarly
where the rate was slightly lower in the pemetrexed arm. There was no negative.4 With knowledge about molecular drivers of NSCLC and targeted
difference in the median number of cycles between arms. Both in the treatment options in advanced disease, multiple studies are either completed
nonsquamous and squamous subgroups there was no difference in overall or underway to study molecularly targeted agents in earlier stages of lung
survival (nonsquamous logrank p=0.18 and squamous p=0.99) and disease free cancer, particularly with epidermal growth factor receptor (EGFR) tyrosine
survival (nonsquamous p=0.54 and p=0.83). The authors concluded that there kinase inhibitors (TKIs). In metastatic NSCLC the EGFR TKIs produce superior
did not appear to be a difference in outcome between cisplatin doublet response and progression free survival (PFS) compared with platinum doublet
regimens(14). Despite the established benefit of adjuvant chemotherapy after chemotherapy in treatment naïve patients with tumors with activating EGFR
curative surgery for NSCLC there is still much to be done with approximately mutations (EGFRmut).5,6Similar outcomes with significant response and PFS
50 % of patients still dying from disease. Furthermore, not all patients with improvements with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib
early stage disease are eligible or willing to undergo chemotherapy following compared to chemotherapy have been reported in patients with tumors
complete surgical resection [Booth 2010]. As such, the long-term prognosis of harboring translocations of ALK.7 Encouraging data from retrospective and
patients with NSCLC, even among those with early stage disease, remains non-randomized trials looking at adjuvant EGFR TKI use led to randomized
poor. Therefore it is imperative that we find new and better therapies to trials. Earlier trials that did not select based on EGFRmut status were
improve upon the results of surgical resection and adjuvant chemotherapy. negative, but more recent trials have been more encouraging. The phase III
.References: 1. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: RADIANT trial selected patients with resected early stage NSCLC for EGFR
American Cancer Society; 2012. 2. Jemal A, Siegel R, Ward E et al. Cancer expression by IHC/FISH, but not by EGFR mutation status, and randomized
Statistics 2007. CA Cancer J Clin 2007; 57: 43-66. 3. L. A. Stewart, S. Burdett, J. them to adjuvant erlotinib or placebo. 8 The primary end point was DFS in
F. Tierney, J. Pignon on behalf of the NSCLC Collaborative Group: Surgery and the full data set, with secondary analyses focused on patients with tumors
adjuvant chemotherapy (CT) compared to surgery alone in non-small cell lung harboring del19 or L858R EGFR mutations. No differences were found in
cancer (NSCLC): A meta-analysis using individual patient data (IPD) from DFS or OS based on treatment arm for the nearly 1000 patients who were
randomized clinical trials (RCT). Journal of Clinical Oncology, 2007 ASCO enrolled. In the EGFRmut subset (N=161) DFS did favor erlotinib (HR 0.61,
Annual Meeting Proceedings (Post-Meeting Edition).Vol 25, No 18S (June 20 95% CI = 0.384-0.981, p = 0.0391), but this was not considered statistically
Supplement), 2007: 7552 4. Scagliotti GV, Fossati R, Torri V et al. Randomized significant, as the primary endpoint of the trial was negative. The overall
study of adjuvant chemotherapy for completely resected stage I, II, or IIIA survival results, while still immature, were not in favor of the erlotinib
non-small-cell lung cancer. J Natl Cancer Inst 2003; 95: 1453–61. 5. Arriagada R, arm, even in the EGFRmut subset. The conclusion from this study is that
Bergman B, Dunant A et al. Cisplatin-based adjuvant chemotherapy in adjuvant EGFR TKI therapy requires further investigation and should not be
patients with completely resected non-small-cell lung cancer. N Eng J Med considered a standard treatment option at this time. Multiple ongoing trials
2004; 350: 351-60. 6. Winton T, Livingston R, Johnson D et al. Vinorelbine plus are exploring adjuvant EGFR TKI (and adjuvant ALK TKI) therapy for resected
cisplatin vs observation in resected non-small-cell lung cancer. N Eng J Med early stage NSCLC patients with tumors harboring the appropriate molecular
2005; 352: 2589-97. 7. Strauss GM, Herdone JE, Maddaus et al. Adjuvant marker.(Table 1) The ongoing trials are looking not only at whether or not
paclitaxel plus carboplatin compared with observation in stage IB non-small an OS benefit can be obtained with adjuvant molecularly targeted therapy
cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, but also duration of therapy and the potential to use EGFR TKIs instead of
Radiation Therapy Oncology Group, and North Central Cancer Treatment chemotherapy in selected patients. The largest United States study is the NCI
Group Study Groups. J Clin Oncol 2008; 26: 5043-51. 8. Douillard JY, Rosell R, De National Clinical Trials Network (NCTN) ALCHEMIST trial. The study is open to
Lena M et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with resected early stage (IB-IIIA) NSCLC who are screened for EGFR
patients with completely resected stage IB-IIIA non-small cell lung cancer activating mutations and ALK translocations. Patients with tumors harboring
(Adjuvant Navelbine International Trialist Association [ANITA]): a randomized EGFR mutations or ALK translocations enter the appropriate sub-study
controlled trial [published erratum appears in Lancet Oncol 2006; 7: 797]. and, after completion of all planned adjuvant chemotherapy or radiation
Lancet Oncol 2006; 7: 719-27. 9. Pignon JP, Tribodet GV, Scagliotti G et al. Lung therapy, are randomized to targeted TKI therapy or placebo for 2 years. Both
adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative sub-studies will enroll approximately 400 patients (410 EGFR; 378 ALK) and
Group. J Clin Oncol 2008; 26: 3552-9. 10. NSCLC Meta-analyses Collaborative are powered for an OS endpoint. Patients without actionable mutations can
enroll on the ANVIL sub-study looking at adjuvant nivolumab, a PD-1 targeted

agent.(Table 1) Globally most targeted therapy adjuvant trials are being SESSION ED10: LOCALLY ADVANCED NSCLC:
conducted in Asia, particularly China and Japan. ADJUVANT (C-TONG 1104) STATE-OF-THE-ART TREATMENT
trial in China and IMPACT WJOG6410L in Japan are phase III trials for patients
with resected stage II-IIIA EGFRmut NSCLC comparing gefitinib to cisplatin/
vinorelbine using DFS as the primary endpoint.(Table 1) Other trials outlined
in Table 1 are exploring variations on this theme using gefitinib or icotinib
and either after or instead of adjuvant chemotherapy. The PD-1 inhibitors ED10.02 THE ROLE OF SURGERY IN STAGE III NSCLC
nivolumab and pembrolizumab are approved for the second line treatment Walter Klepetko
of advanced stage NSCLC and will likely be utilized in first-line in the near Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria
future.9-11 Based on their promise in advanced stage NSCLC, multiple trials
with PD-1 and PD-L1 agents are ongoing. Most studies are for patients who Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease
have completed adjuvant chemotherapy (though some allow chemotherapy characterized by either locally advanced tumor infiltration and/or mediastinal
naïve patients) and they predominantly randomize patients to approximately lymph node involvement. Due to improvements in chemo (CT)- and combined
1 year of PD-1 or PD-L1 inhibitor therapy. Most include testing for PD-L1 chemoradiation (CRT) therapy protocols, patients with locally advanced
expression, but do not exclude patients with low tumor levels of PD-L1. Many stage III NSCLC become potential candidates for curative resection more
are placebo controlled.(Table 1) Chemotherapy has helped improve outcomes frequently. According to the TNM-7 classification, stage III NSCLC can be
but continued investigations with novel approaches will be necessary to defined by the following T and N subsets: stage IIIA: T3 N1-2, T4 N0-1, T1-2 N2;
continue to improve cure rates for patients with resected early stage NSCLC. stage IIIB: T4 N2, T1-4 N3. Five-year survival of stage III is generally around 25%
The use of molecularly targeted agents for patients with tumors containing taken all different therapy strategies together. Several studies have shown
EGFRmut or ALK translocations are promising with validation studies ongoing that induction treatment before surgery is beneficial in resectable cases
and the hope of immunotherapy is being investigated as well in multiple and selected patients undergoing radical resection may have encouraging
global trials. Table 1. Ongoing Phase III Targeted and Immunotherapy Adjuvant 5-year survival rates up to 60%. However, to date, no worldwide consent
Trials exists on the general role of surgery in curative attempt. Furthermore,
it is still unclear if resectable patients might have greater benefit from
Trial Description Primary Endpoint(s) induction CT compared to combined induction CRT and if concomitant CRT
should be preferred over a sequential treatment. Only a small number of
C-TONG 1104
*gefitinib vs. cisplatin/vinorelbine 3-year DFS prospective phase II/III trials are available addressing these issues. A phase
NCT01405079
III trial comparing induction CRT plus surgery (S) with definitive CRT in
GASTO1002 patients with stage IIIA/N2 published in 2009 has questioned the role of
*Chemo then icotinib vs obs 5-year DFS
NCT01996098 surgery since there was no difference in overall survival (OS) between the
BD-IC-IV-59 two groups [1]. However, the 30-day mortality was unacceptably high (26%)
*Chemo then icotinib vs. placebo 2-year DFS
NCT02125240 in the subgroup of patients undergoing pneumonectomy and thus patients
WJOG6401L with CRT and lobectomy had significantly improved OS compared to those
*Gefitinib vs. cisplatin/vinorelbine 5-year DFS with CRT alone. Moreover, several other retrospective series have reported
IMPACT
encouraging long-term survival in selected patients undergoing induction
ALCHEMIST *Erlotinib vs. placebo: ALK^
OS treatment followed by radical surgery. The benefit of adding sequential RT
A081105/E4512 crizotinib vs placebo
to CT prior to surgery (S) in stage IIIA/N2 has been investigated in a recent
ALCHEMIST/ &EGFR/ALK wildtype; US NCI phase III trial [2]. Patients undergoing CRT/S had a non-significant superior
OS/DFS
ANVIL NCTN, Nivolumab vs obs median OS of 37 months compared to 26 months with CT/S. Both groups had
Restricted to PD-L1+ Global, similar disease free survival (DFS) and it was concluded that RT did not add
Impower010 DFS
Atezolizumab vs. placebo any benefit to induction CT prior to surgery. However, those with CRT/S had
MEDI4736 &Global, MEDI4736 vs placebo DFS an objective response, pathological complete response, a R0 resection rate
and a mediastinal downstaging more frequently and less local progression
&ETOP/EORTC, Pembrolizumab vs
Keynote-091 DFS compared to CT/S. The question whether to apply RT concomitantly or
placebo
sequentially to CT has been investigated in a recent meta-analysis [3]. Pooled
All EGFR studies include stage II-IIIA All PD-1/PD-L1 studies open to IB (4cm) data from six prospective trials suggested that concomitant CRT, as compared
– IIIA after adjuvant chemotherapy N: Number of estimated enrollment DFS: with sequential CRT, improved survival of patients with locally advanced
disease-free survival; OS: overall survival *EGFR deletion 19 or exon 21 L858R NSCLC, primarily because of a better locoregional control. However, these
mutation only ALK^ : Positive for ALK translocation by FISH &- regardless of patients were treated without surgery and caution should be taken when
PD-L1 status US NCI NCTN: United States National Cancer Institute, National transferring these conclusions to the neoadjuvant setting before surgery.
Clinical Trials NetworkReferences: 1. Pignon JP, Tribodet H, Scagliotti GV, From the surgical point of view, patients with local tumor invasion (T3-4
et al: Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE N0-1 including Pancoast tumors) have to be treated by different oncological
Collaborative Group. J Clin Oncol, 2008 2. Group NM-aC, Arriagada R, Auperin principles than those with mediastinal lymph node (LN) involvement (N2).
A, et al: Adjuvant chemotherapy, with or without postoperative radiotherapy, In patients with T3 tumors invading the chest wall, diaphragm, mediastinal
in operable non-small-cell lung cancer: two meta-analyses of individual pleura, phrenic nerve or parietal pericardium and N1 involvement, primary
patient data. Lancet 375:1267-77, 2010 3. Wakelee HA, Dahlberg SE, Keller SM, resection can be undertaken. Induction therapy may improve local control
et al: Randomized phase III trial of adjuvant chemotherapy with or without rates in larger tumors but it remains unclear if systemic treatment is
bevacizumab in resected non-small cell lung cancer (NSCLC): Results of E1505. beneficial prior to or after local resection. Intraoperative frozen section
Journal of Thoracic Oncology Proceedings WCLC 2015:Abstr: Plen04.03, 2015 of resection margins should be mandatory and reconstruction of resected
4. Vansteenkiste JF, Cho BC, Vanakesa T, et al: Efficacy of the MAGE-A3 cancer structures with synthetic material may be necessary. T4 tumors with invasion
immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3- to the mediastinal structures or vertebral bodies are a unique subset of
positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, locally advanced NSCLC and multidisciplinary treatment can be challenging.
placebo-controlled, phase 3 trial. Lancet Oncol 17:822-835, 2016 5. Mok TS, Well selected patients may benefit from multimodality therapy including
Wu YL, Thongprasert S, et al: Gefitinib or Carboplatin-Paclitaxel in Pulmonary surgery and should be treated in well experienced centers [4, 5]. In patients
Adenocarcinoma. N Engl J Med, 2009 6. Sequist LV, Yang JC, Yamamoto N, et with suspected N2 disease, invasive staging for histological confirmation
al: Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With has been widely accepted as a standard procedure [6]. In case of multilevel
Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol, 2013 7. and/or bulky N2 disease, surgery should be avoided due to the expected poor
Solomon BJ, Mok T, Kim DW, et al: First-line crizotinib versus chemotherapy in outcome. However, it has been well shown that patients in good performance
ALK-positive lung cancer. N Engl J Med 371:2167-77, 2014 8. Kelly K, Altorki NK, status with single or two level N2 disease with good response after induction
Eberhardt WE, et al: Adjuvant Erlotinib Versus Placebo in Patients With Stage therapy may have improved OS when undergoing curative resection [7, 8].
IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, On the other hand, patients with persistent N2 disease after induction
Phase III Trial. J Clin Oncol 33:4007-14, 2015 9. Brahmer J, Reckamp KL, Baas P, treatment tend to have worse OS and high recurrence rates and thus should
et al: Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell not undergo surgery. This finding strengthens the impact of invasive re-
Lung Cancer. N Engl J Med 373:123-35, 2015 10. Borghaei H, Paz-Ares L, Horn L, staging after induction treatment as proposed by recent staging guidelines.
et al: Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell In conclusion, selected patients with stage III NSCLC may have beneficial
Lung Cancer. N Engl J Med 373:1627-39, 2015 11. Herbst RS, Baas P, Kim DW, et outcome after surgery combined with CT or CRT. However, this holds truth
al: Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, only for cases with response to induction treatment, nodal downstaging
advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled and when R0 resection is deemed achievable. Surgery should be avoided
trial. Lancet 387:1540-50, 2016 in patients with multilevel/bulky N2 disease or persistent mediastinal LN
after induction treatment due to the expected poor outcome. The optimal
Keywords: Adjuvant therapy, immunotherapy, targeted therapy sequence and modality of induction treatment has yet to be defined in larger
prospective trails.References: [1] Albain KS, Swann RS, Rusch VW, Turrisi
AT, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or
without surgical resection for stage III non-small-cell lung cancer: a phase prescription defined by the maximal doses achievable to normal tissues.
III randomised controlled trial. Lancet. 2009;374:379-86. [2] Pless M, Stupp More recently, several clinical studies investigated the role of proton beam
R, Ris HB, Stahel RA, Weder W, Thierstein S, et al. Induction chemoradiation therapy in NSCLC. A dosimetric advantage of proton- over conventional
in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. photon radiotherapy is mediated by its unique properties: low doses upon
Lancet. 2015;386:1049-56. [3] Aupérin A, Le Péchoux C, Rolland E, Curran WJ, tissue penetration, maximal dose deposition towards the end of the beam’s
Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential path (Bragg peak) and finite range with minimal dose beyond the tumor.
radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. Retrospective data and phase II studies suggested promising survival rates,
2010;28:2181-90. [4] Collaud S, Fadel E, Schirren J, Yokomise H, Bolukbas S, and reduced pulmonary and esophageal toxicity with protons. However, the
Dartevelle P, et al. En Bloc Resection of Pulmonary Sulcus Non-small Cell Lung results of recent phase III trial did not confirm the superiority of this method
Cancer Invading the Spine: A Systematic Literature Review and Pooled Data over IMRT (9). In summary, recent diagnostic and therapeutic advances
Analysis. Ann Surg. 2015;262:184-8. [5] Rusch VW. Management of Pancoast the use of radiation in stage III NSCLC allow for more accurate treatment
tumours. Lancet Oncol. 2006;7:997-1005. [6] De Leyn P, Dooms C, Kuzdzal planning, more precise dose delivery and managing tumor and organ motion.
J, Lardinois D, Passlick B, Rami-Porta R, et al. Revised ESTS guidelines for Some of these developments have been adopted in clinical practice, despite
preoperative mediastinal lymph node staging for non-small-cell lung cancer. relatively few evidence of their advantages in terms of better local control and
Eur J Cardiothorac Surg. 2014;45:787-98. [7] Friedel G, Budach W, Dippon J, survival. The paucity of phase III trials testing new radiotherapy approaches
Spengler W, Eschmann SM, Pfannenberg C, et al. Phase II trial of a trimodality is partly due to relying on better dose distribution and reduced exposure
regimen for stage III non-small-cell lung cancer using chemotherapy as of normal tissues, making comparisons with less advanced techniques an
induction treatment with concurrent hyperfractionated chemoradiation with ethical dilemma (10).References 1. Bradley JD, Paulus R, Komaki R, et al.
carboplatin and paclitaxel followed by subsequent resection: a single-center Standard-dose versus high-dose conformal radiotherapy with concurrent
study. J Clin Oncol. 2010;28:942-8. [8] Hancock J, Rosen J, Moreno A, Kim AW, and consolidation carboplatin plus paclitaxel with or without cetuximab
Detterbeck FC, Boffa DJ. Management of clinical stage IIIA primary lung for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a
cancers in the National Cancer Database. Ann Thorac Surg. 2014;98:424-32; randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187-
discussion 32. 99. 2. Saunders M, Dische S, Barrett A, et al. Continuous hyperfractionated
accelerated radiotherapy (CHART) versus conventional radiotherapy in non-
Keywords: non small cell lung cancer, stage III, induction therapy small-cell lung cancer: a randomised multicentre trial. Lancet 1997;350:161–5.
3. Baumann M, Herrmann T, Koch R, et al. Final results of the randomized
phase III CHARTWEL-trial (ARO 97–1) comparing hyperfractionated-
accelerated versus conventionally fractionated radiotherapy in non-small
ED10: LOCALLY ADVANCED NSCLC: STATE-OF-THE-ART TREATMENT
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 cell lung cancer (NSCLC). Radiother Oncol 2011;100:76–85. 4. Mauguen
A, Le Pećhoux C, Saunders MI, et al. Hyperfractionated or accelerated
radiotherapy in lung cancer: an individual patient data meta-analysis. J
ED10.03 NEW DEVELOPMENTS IN RADIOTHERAPY OF STAGE III Clin Oncol 2012;30:2788–97. 5. Chang JY, Dong L, Liu H, et al. Image-guided
NSCLC radiation therapy for non-small cell lung cancer. J Thorac Oncol 2008;3:177–86.
Jacek Jassem 6. Sonke JJ, Belderbos J. Adaptive radiotherapy for lung cancer. Semin
Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk/ Radiat Oncol 2010;20:94-106. 7. Bezjak A, Rumble RB, Rodrigues G, and al.
Poland Intensity-modulated radiotherapy in the treatment of lung cancer. Clin
Oncol 2012;24:508–20. 8. De Ruysscher D, van Baardwijk A, Steevens J, et
NSCLC accounts for 80-85% of all lung cancers, and stage III disease al. Individualised isotoxic accelerated radiotherapy and chemotherapy are
constitutes about 40% of the total cases. The main treatment modality associated with improved long term survival of patients in stage III NSCLC: a
in these patients is radiotherapy, usually combined with concurrent prospective population-based study. Radither Oncol 2012;102:228-233. 9. ZX
chemotherapy. Five-year overall survival in stage III disease is merely 10-15%. Liao, J. JJ Lee, R Komaki, et al. Bayesian randomized trial comparing intensity
Radiotherapy of thoracic tumors poses several challenges, such as tissue modulated radiation therapy versus passively scattered proton therapy for
heterogeneity, tumor and organ motion and changing anatomy over the locally advanced non-small cell lung cancer. J Clin Oncol 2016;34(15S):435s. 10.
treatment course. Main approaches addressing these problems include Dziadziuszko R, Jassem J. Randomized clinical trials using new technologies
dose intensification, altered fractionation and advanced radiotherapy in radiation oncology: ethical dilemma for medicine and science. J Thor Oncol
techniques. Until recently, dose escalation was considered the main means 2007;7:3-4.
to increase radiotherapy efficacy. Despite encouraging results of phase I–II
studies, the results of recent RTOG trial 0617 were disappointing (1). This
study compared high-dose radiotherapy (74 Gy/37 fractions) to a standard-
dose (60 Gy/30 fractions) concurrently with weekly paclitaxel/carboplatin, ED10: LOCALLY ADVANCED NSCLC: STATE-OF-THE-ART TREATMENT
with or without cetuximab. Surprisingly, median overall survival in the
high-dose arms was significantly shorter (20 months vs. 29 months in the
standard-dose arms; p=0.004) (1). It was speculated that the inefficacy ED10.04 NEW DEVELOPMENTS FOR SYSTEMIC THERAPIES IN
of high-dose radiotherapy could be due to long overall treatment time STAGE III NSCLC
and accelerated tumor repopulation. Shortening treatment time may be
Everett Vokes
accomplished by accelerated radiotherapy. A phase III study investigating
Medicine, University of Chicago, Chicago/IL/United States of America
continuous hyperfractionated accelerated radiotherapy (CHART; 54 Gy/36
fractions of 1.5 Gy delivered 3 times daily over 12 consecutive days) showed Concomitant chemoradiotherapy is currently the most widely accepted
increased efficacy compared to conventional fractionation (2). A CHARTWEL standard of care for patients with locoregionally advanced NSCLC. Induction
study, using the same fractionation but with weekend breaks, was not chemotherapy represents an evidence-based alternative and is a particular
superior to conventional fractionation (3). A meta-analysis of 10 trials attractive prior to surgery in patients with marginally resectable disease
(2000 patients) demonstrated an absolute 5-year survival benefit of 2.5% (1). Over the past two decades, the regimens of cisplatin and etoposide and
with hyperfractionated and/or accelerated radiotherapy over conventional carboplatin and paclitaxel with concurrent radiotherapy, respectively have
fractionation, at the expense of significantly increased grade 3–4 acute been most widely used, with cisplatin and vinorelbine with radiotherapy as
esophagitis (4). Important developments in lung radiotherapy represent new possible alternative. More recently interest in the cisplatin/pemetrexed/
imaging techniques. PET-CT, currently a routine procedure, allows better radiotherapy combination has gained interest based on the superior toxicity
patient selection for radical radiotherapy and facilitates selective irradiation and efficacy profile of this regimen in the stage IV setting for patients with
of involved volumes (5). Image guided radiation therapy (IGRT), such as non-squamous cell malignancies (2). In addition, it is possible to administer
daily volumetric kilovoltage cone-beam computed tomography (CBCT), this combination of drugs at systemic doses together with radiotherapy
provides actual positional information, allowing for online repositioning (3). In the randomized phase III PROCLAIM study, this regimen was directly
and more precise tumor localization. Image-guided adaptive radiotherapy compared with etoposide and cisplatin. The goal of this trial was to establish
(IGART) additionally accounts for changes and deformations occurring superiority of this regimen. The trial was closed prior to full enrollment with
during the radiotherapy course, thus allowing treatment re-planning (6). approximately 300 patients per arm evaluated, due to futility for superiority.
Currently, dose delivery in NSCLC is commonly accomplished by intensity Median survival for both study groups was very similar at 26.8 and 25.0
modulated radiotherapy (IMRT). This technique improves the conformality months, respectively and better than statistically assumed (4). Additional
of radiotherapy by modulating the radiation beam intensity profile, chemoradiotherapy regiments of current interest include the addition of
and allows decreasing the mean lung dose, particularly in patients with the PARP inhibitor veliparib to chemoradiotherapy as recently presented
larger tumor volumes (7). The problem of intrafraction motion in thoracic (5). Over the last decade, systemic therapy for patients with metastatic lung
malignancies has been traditionally managed by extension of treatment cancer has been transformed through the use of tumor mutation analyses and
margins, leading to excessive radiation to normal tissues. Currently, tumor targeted therapies as well as the emergence of immune-oncology. However,
motion may be managed individually by respiratory-correlated 4-dimensional application of these strategies to the stage III setting has been slow and no
CT (4DCT) based on the acquisition of organ and tumor imaging data at definitive data exist currently to support these strategies in the curative
extreme phases of the breathing cycle. An innovative option allowing for intent setting. The addition of cetuximab to chemoradiotherapy did not result
safe dose intensification is isotoxic therapy (8). This approach includes dose

in a survival benefit in RTOG 0612 (6). There are, however several ongoing David R. Gandara1, Sanjay Popat2, Barbara Melosky3
trials that will be described, including RTOG 1306-Alliance 31101. In this trial 1
UC Davis Comprehensive Cancer Center/USA 2Royal Marsden Hospital, London/UK;
3
patients with EGFR mutation or an alk translocation are randomized to either Department of Medical Oncology, BC Cancer Agency Vancouver Centre, Vancouver/
induction chemotherapy with the appropriate targeted agent (erlotinib Canada
and crizotinib, respectively) followed by concurrent chemoradiotherapy or
concurrent chemoradiotherapy alone. This trial is actively accruing patients. Oncogene-driven lung cancer remains the embodiment of personalized
Regarding immune-oncology, a trial evaluating a liposome-based MUC vaccine medicine. Since the first description of EGFR activating mutations found in
(tecemotide) has been completed. MUC1 is a mucinous glycoprotein that patients with what was then called bronchiolalveolar carcinoma of the lung
is overexpressed and aberrantly glycosylated in NSCLC and a vaccination (BAC) in 2004, the topic of oncogene-driven lung cancer has grown rapidly
strategy was supported by preclinical studies as well as clinical data in a stage and expanded to now encompass a number of additional mutation- and
III subgroup analysis of an earlier exploratory trial. Butts et al (7) reported fusion-related entities. Recent updates to molecular testing guidelines, such
on a randomized trial in which patients completing locoregional sequential as those of IASLC, have added several new oncogenes to the initial EGFR and
or concurrent therapy were randomized to placebo versus tecemotide ALK recommendations, including ROS1 and RET fusions, MET amplification
vaccination therapy reporting a trend for improved overall survival that was or mutation, and HER2 mutations (1,2,3). Although the efficacy of tyrosine
statistically significant in the subset analysis of patients receiving concurrent kinase inhibitors (TKI) in the treatment of some of these disease subsets
radiotherapy as their primary therapy. Further investigations of this agent is well established, the treatment decision-making process at the time of
however were halted following emergence of additional negative data from each relapse is becoming more complex as our knowledge of resistance
a Japanese phase II trial that remains unpublished. Regarding PD-1 or PD-L1 pathways grows and more treatment options become available, with 2nd
inhibitors, trials have recently been activated investigating the addition and 3rd generation drugs now in play. Subtping of progressive disease (PD)
of such agents in the consolidation setting following primary treatment of in oncogene-driven lung cancer into systemic PD versus oligo-PD or CNS-
patients with unresectable SCLC. For example, in the ‘Pacific’ trial patients santuary PD can assist in determining the most appropriate therapeutic
are randomized in a 2-1 fashion to durvalumab for up to 12 months or placebo. approach, as shown in Figure 1 below(4). Further, the methods by which we
In the Alliance, a trial looking at induction chemotherapy with atezolizumab assess tumor at the time of initial or re-biopsy are also rapidly evolving, from
is currently in the process of activation. Here patients will receive induction single gene or multiplexed gene panels to highly sensitive and specific next
chemotherapy with atezolizumab for up to four cycles followed by generation sequencing (NGS). Lastly, we and others (4,5) have proposed
concurrent chemoradiotherapy and additional adjuvant immune therapy. algorithms for possible substitution of plasma cell free DNA by NGS platforms
These strategies are well supported by preclinical data showing irradiation for tissue re-biopsy or for serial monitoring in plasma, as demonstrated in
upregulating PD1 expression on myeloid and tumor cells and synergistic Figure 2.
amplification of radiation antitumor effects by PD-L1 blockade (8). Updated In this presentation we will present a step-wise approach to molecular testing
information on these trials and relevant preclinical data will be presented. and personalizing treatment for patients with oncogene-driven NSCLC,
References: 1. Schild SE, Vokes EE. Pathways to improving combined modality focusing on EGFR-mutated and ALK-rearranged subsets, since the treatment
therapy for stage III nonsmall-cell lung cancer. Ann Oncol 2016 Apr;27(4):590- paradigms are most well established. We will emphasize some of the real
9. 2. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold world challenges faced by treating physicians. Decision criteria for selecting
C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, the best first-line therapy will be reviewed, the importance of re-biopsy upon
Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara disease progression to determine the most appropriate next-line therapy
D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus highlighted, and third line therapy and beyond discussed. The emerging role
pemetrexed in chemotherapy-naive patients with advanced-stage non-small- of liquid biopsy for assessment of plasma cell free DNA will be discussed, as
cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. 3. Govindan R, Bogart well as a rationale for substituting liquid biopsy for initial or repeat tumor
J, Stinchcombe T, Wang X, Hodgson L, Kratzke R, Garst J, Brotherton T, Vokes biopsy in some clinical settings. Algorithms designed to facilitate treatment
EE. Randomized phase II study of pemetrexed, carboplatin, and thoracic decision-making will be presented. Two examples in EGFR-mutated lung
radiation with or without cetuximab in patients with locally advanced cancer are shown below.
unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial
30407. J Clin Oncol. 2011 Aug 10;29(23):3120-5. 4. Senan S, Brade A, Wang LH, Figure 1: Algorithm for management by Progressive Disease Subtyping
Vansteenkiste J, Dakhil S, Biesma B, Martinez Aguillo M, Aerts J, Govindan
R, Rubio-Viqueira B, Lewanski C, Gandara D, Choy H, Mok T, Hossain A, Iscoe EGFR-mutated NSCLC
N, Treat J, Koustenis A, San Antonio B, Chouaki N, Vokes E. PROCLAIM:
Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin
Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy
in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol.
2016 Mar 20;34(9):953-62. 5. Cristea MC, Miao, J, Argiris A, Chen AM, Daly ME,
Decker RH, Garland LL, Wang D, Koczywas M, Moon J, Kelly K, Gandara DR.
SWOG S1206: A dose-finding study of veliparib added to chemoradiotherapy
with carboplatin and paclitaxel for unresectable stage III non-small cell
lung cancer. J Clin Oncol. 2016 34:(suppl; abstr 8537). 6. Bradley JD, Paulus
R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K,
Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB,
Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose
versus high-dose conformal radiotherapy with concurrent and consolidation
carboplatin plus paclitaxel with or without cetuximab for patients with
stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised,
two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99.
7. Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M,
Nawrocki S, Ciuleanu TE, Bosquée L, Trigo JM, Spira A, Tremblay L, Nyman J, Figure 2: Algorithm for Re-Biopsy and/or Plasma cf DNA Analysis
Ramlau R, Wickart-Johansson G, Ellis P, Gladkov O, Pereira JR, Eberhardt WE,
Helwig C, Schröder A, Shepherd FA; START trial team. Tecemotide (L-BLP25) In EGFR-mutated NSCLC
versus placebo after chemoradiotherapy for stage III non-small-cell lung
cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol.
2014 Jan;15(1):59-68. 8. Deng L, Liang H, Burnette B, Beckett M, Darga T,
Weichselbaum RR, Fu YX. Irradiation and anti-PD-L1 treatment synergistically
promote antitumor immunity in mice. J Clin Invest. 2014 Feb;124(2):687-95.
Keywords: radiation sensitization, Stage III NSCLC, concurrent

chemoradiotherapy
SESSION ED11: ADVANCED NSCLC:

STATE-OF-THE-ART TREATMENT
ED11.01 SYSTEMIC THERAPY FOR ADVANCED ONCOGENE-DRIVEN

NSCLC
References restaurants in Austria. Smoking is otherwise banned in all other enclosed

places in these countries as well. It is well known that raising the price of
1. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins tobacco products is the best tobacco control measure, we therefore compared
RB, Kwiatkowski DJ, Saldivar JS, Squire J et al: Molecular testing guideline tax rates and prices of popular cigarette brands. Although EU member states
for selection of lung cancer patients for EGFR and ALK tyrosine kinase must comply with EU tax regulation requirements, recently joined members
inhibitors: guideline from the College of American Pathologists, International are allowed several years to converge, therefore significant differences may
Association for the Study of Lung Cancer, and Association for Molecular be observed in this manner between discussed countries. Countries generally
Pathology. Journal of thoracic oncology : official publication of the International apply combined taxation policy on cigarettes in agreement with Article 6
Association for the Study of Lung Cancer 2013, 8(7):823-859. of the WHO Framework Convention on Tobacco Control Guideline: apart
from the value added tax (VAT), the excise duty consists of an ad valorem
2. Leighl NB, Rekhtman N, Biermann WA, Huang J, Mino-Kenudson M,
and a specific element In 2015, the average 20 piece pack price (in Euro) was
Ramalingam SS, West H, Whitlock S, Somerfield MR: Molecular Testing for
4.6 in Austria, 3 in the Czech Republic, 3.2 in Hungary, 3.2 in Poland and 2.8
Selection of Patients With Lung Cancer for Epidermal Growth Factor Receptor
in Romania. Regulating the distribution and limiting the access to certain
and Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: American
tobacco products is an important tool in tobacco control, and even more so
Society of Clinical Oncology Endorsement of the College of American
in the prevention of youth smoking. The sale of tobacco products to minors
Pathologists/International Society for the Study of Lung Cancer/Association
is generally prohibited under 18 years (in Austria, under 16 years), however
of Molecular Pathologists Guideline. Journal of Clinical Oncology 2014.
there are noteworthy differences where vending machines are concerned,
3. Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, e.g. in Austria these are allowed to operate. Sale of cigarettes over the
L. R., ... & Grant, S. C. Non–small cell lung cancer, version 2.2013. Journal of the internet is legal in the Czech Republic. Directly accessible distribution of
National Comprehensive Cancer Network, 2013, 11(6), 645-653. tobacco products is allowed in Poland and Romania. Hungary applies the
highest degree on distribution restriction: tobacco may only be purchased in
4. Gandara DR, Li T, Lara PN, Kelly K, Riess JW, Redman MW, Mack PC: Acquired supervised tobacco stores, vending machines and internet sale are prohibited.
resistance to targeted therapies against oncogene-driven non-small-cell lung Advertising and tobacco industry sponsorship activities are uniformly
cancer: approach to subtyping progressive disease and clinical implications. forbidden in these countries. Yet another important issue of tobacco control
Clinical lung cancer 2014, 15(1):1-6. is the accessibility and financial support of smoking cessation programs.
Austria focuses its efforts on youth smoking prevention, nevertheless
5. Oxnard, G. R., Thress, K. S., Alden, R. S., Lawrance, R., Paweletz, C. P., cessation programs are also coordinated nationally. The Czech Republic lays
Cantarini, M., ... & Jänne, P. A. Association between plasma genotyping and great effort on disseminating brief intervention practice among physicians
outcomes of treatment with osimertinib (AZD9291) in advanced non–small- and nurses. Health insurance covers smoking cessation programs, however
cell lung cancer. Journal of Clinical Oncology, 2014, JCO667162. pharmacotherapies are excluded. The National Health Fund partially covers
smoking cessation programs in Poland. Romania has established specialized
quit centers whose activities are partially covered by health insurance. In
Hungary, the Methodological Centre coordinates cessation activity in nearly
one hundred pulmonary outpatient clinics around the country, offering
SESSION ED12: REGIONAL TOBACCO CONTROL POLICIES: individual and group cessation counseling. Counseling is covered by health
ADVANCES & CHALLENGES insurance, excluding pharmacotherapy. In addition, telephone counseling
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 and cessation support is also available free of charge. Regarding e-cigarettes,
diverse regulatory schemes are detected across Europe. In Hungary, the
distribution of nicotine containing e-cigarette cartridges fall under the
drugs act, whereas the same regulation applies to the use as to regular
ED12.01 TOBACCO CONTROL POLICIES IN EASTERN EUROPE cigarettes. The latter is observed also in Poland. Promotion and distribution
Gábor Kovács, Zsuzsa Cselkó of e-cigarettes is prohibited in Austria. In the Czech Republic however, both
National Korányi Institute for TB and Pulmonology, Budapest/Hungary advertising and distribution is analogues to that of regular cigarettes. The
Association of European Cancer Leagues (ECL) assesses European countries’
According to the regional distribution of the World Health Organization efforts in tobacco control every three years using the Tobacco Control Scale
(WHO), Europe extends from the Atlantic Ocean to Central Asia, (TCS). The TCS quantifies the implementation of tobacco control policies
encompassing states of the former Soviet Union. In political terms however, based on six strategies described by the World Bank: price increases,
Eastern Europe refers to countries located on the eastern border of the public information campaigns, bans on advertising and promotion, smoke
European Union (EU). Consequently, in our presentation we focus on how free work and other public places, health warnings and treatment to help
smoking status has changed in some of the policy-wise emerging countries smokers stop. It is informative to observe the 2013 ranking of the discussed
located here – namely the Czech Republic, Hungary, Poland and Romania – and countries: the Czech Republic had a continuously deteriorating position and
how these data compare to Austria’s indicators. We present data on smoking ranked 31st, while Austria earned the 34th, Poland the 20th and Romania the
prevalence and trends, restricting use, taxation and average cigarette prices, 19th position among the 34 surveyed countries. Hungary has significantly
as well as the distribution of tobacco products in specific countries. Reference improved its position between 2010 and 2013, and due to fierce government
is made to restricting advertising and tobacco industry sponsorship activities. measures in recent years it ranked 11th as compared to the previous 27th spot.
Smoking cessation support practice is another important aspect, while References: 1. World Health Organization Framework Convention on Tobacco
electronic cigarette (e-cigarette) regulation is a relatively new issue. Table 1 Control Implementation Database. 2. Ng, M., et al.: Smoking Prevalence and
presents smoking prevalence and trends of specific countries. Cigarette Consumption in 187 Countries, 1980-2012. JAMA. 2014;311(2):183-192.
doi:10.1001/jama.2013.284692
CZE HUN POL ROM AUT
Keywords: tobacco control policies, smoking prevalence
1980 26,2 34,8 42,5 26,8 27,8
1996 26,6 31,1 33,7 30,6 29,6

ED12: REGIONAL TOBACCO CONTROL POLICIES: ADVANCES & CHALLENGES
2006 26,3 32,9 30,5 26,7 32,5 WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
2012 24,4 28,5 27,6 27,5 32,3

ED12.02 TOBACCO CONTROL: THE TURKISH EXPERIENCE
Table 1. Smoking prevalence (%) (+15 years old) It is striking that while the Nazmi Bilir
proportion of smokers has decreased in Hungary and Poland, an opposite
Public Health, Hacettepe University, Ankara/Turkey
tendency may be observed in Austria. Smoking prevalence stagnated in
Romania and the Czech Republic. It is noteworthy that the proportion of Turkey has been a tobacco producing country since Ottoman time. At that
women smokers is high in Austria (28.3%), in Hungary (25.8%) and in Poland time tobacco production mostly was in the hands of foreign companies.
(24.1%). Smoke-free laws were adopted in the beginning of this Century in Following the establishment of Turkish Republic in 1923, the State
North America and Western Europe, and soon resulted in decreasing the Monopoly on tobacco was established and tobacco production and sales was
proportion of smokers. Although there were smoking and trade control nationalized by the government, therefore production and sales of tobacco
laws earlier in the presented countries, effective legislation has only been was planned and implemented by the State Monopoly (TEKEL). Only domestic
promulgated a few years ago and in some countries it hasn’t even been tobacco products were on sale in the country, and importation and sales of
published. Hungary applies total ban on smoking in enclosed public places foreign tobacco products was not allowed. TEKEL provided tobacco products
(with the exception of psychiatric units) since 2011. In Poland, a partial ban for the smokers, but did not make any effort to increase its use; i.e. did not
is in place, smoking is allowed in certain restaurants. The Czech Republic make any advertisement of tobacco. The tobacco monopoly has been the
exercises a slightly more liberal regulation regarding restaurants. A partial only responsible body on tobacco production and sales, until 1980’s. In 1984
ban exists in Romania in restaurants and there may be designated smoking the law passed at the Parliament allowing importation of foreign cigarettes
areas in enclosed places where smoking is prohibited. Smoking is allowed in into the country, and then tobacco advertisements started. In 1987 Minister

of Health invited some interested scientists to discuss the way to control 2015,1) Japan was scored “No or weak policy” for smoke-free policies, mass
tobacco use in the country. The first tobacco control law was drafted by the media and advertising bans, “Minimal policy” for health warnings, and
Ministry and adopted at the Parliament in 1991; but vetoed by the President. “Moderate policy” for cessation program and taxation. In order to accelerate
Same year another law passed from the Parliament to allow multinational tobacco control activities, evidence-based official summary report on
tobacco companies to establish tobacco production factories in the country. health effects of tobacco products and effectiveness of tobacco control is
As the result of these changes, tobacco use started to increase, more than needed. A report of Surgeon General in the US 2) and Monograph series from
the population increase (Table 1) (1). The first large-scale survey in 1988 (2) on International Agency for Research on Cancer 3) are the examples. In these
tobacco use revealed that 63% of males and 24% of females smoke. Table 1. reports, causal relationship was judged systematically considering scientific
Cigarette sales, Turkey, 1925 - 2011 As reaction to these developments, a civil evidences through systematic review comprehensively based on certain
society organization was established in 1993; “National Coalition on Tobacco criteria. A causal conclusion conveys the inference that changing a given
or Health, SSUK”. By this way an organized fight against the multinational factor will actually reduce a population’s burden of disease, either by reducing
tobacco companies started. In 1995 a large scale survey on tobacco use the overall number of cases or by making disease occur later than it would
among role model groups revealed that 43% of physicians, almost 50% of have. So far in Japan, although such official summary reports were published
teachers, 27% of members of the Parliament and 24% of religious leaders were three times, judgement on the causal relationship was not included. Here
smoking (3). At the same time, draft tobacco control law was in the agenda we report the 4th version of the report which contain judgement on the
of the Parliament. SSUK worked closely with some of the “sensitive” MP’s, causal relationship between smoking and various diseases.4) Methods Health
participated in the Parliamentary Commissions to discuss the draft tobacco effect of active and passive cigarette smoking was categorized into 4 levels
control law, and visited Head of the Parliament, Parliamentary Groups of (sufficient/suggestive causal relation, insufficient evidence and suggestive
the political parties. At the end of these efforts, Tobacco Control Law was no causal relation). Causal relationship was judged comprehensively in terms
adopted by the Parliament in November 1996. The Law banned smoking at of consistency, strength, time-relation, biological plausibility, dose-response
some of the indoor public places, i.e. heath and education facilities and public relation and risk reduction after cessation, which are similar to US Surgeon
transport, banned all kinds of advertisement and promotion of tobacco General Report.5) It was judged by each corresponding writer of the disease
products, banned selling of tobacco products to children, etc. After more than first, then discussed in the committee and determined by consensus.
10 years of implementation, the Law was amended in 2008, to cover all indoor Effectiveness of tobacco control activities and economic impact was also
public places, including restaurants, cafes and tea houses etc. as smoke-free. evaluated. Results Based on the previous evidence reports (domestic and
In the meantime, the WHO, FCTC was adopted and MPOWER policies were international), health effects of active cigarette smoking were evaluated for
announced. At that time National Tobacco control Program and Action Plan cancer, cardiovascular diseases, respiratory diseases, reproductive effects,
was prepared; and several studies were performed to demonstrate the results and other effects, such as diabetes and dental diseases. Health effects of
of smoke-free implementation. Three kinds of studies were done (4): · Indoor passive smoking and adolescence use was also evaluated. It is judged that the
air quality measurements: PM2.5 levels at various indoor public places were evidence is sufficient to infer a causal relationship with active smoking (Level
measured before and after the implementation of smoke-free law, (in offices, 1) for cancer of the lung, oral cavity/pharynx, larynx, nasal cavity, esophagus,
shops, restaurants, etc.) and considerable decrease were observed (Figure stomach, liver, pancreas, bladder and cervix uteri. For cardiovascular
1). · Complaints of the workers at hospitality workplaces: Some symptoms diseases, ischemic heart disease, stroke, abdominal dissecting aneurysm and
(watering in eyes, stuffy nose, cough, etc) of the same workers at the peripheral arteriosclerosis, and for respiratory diseases, chronic obstructive
restaurants and cafes were inquired before and after the implementation of pulmonary diseases (COPD), decline of pulmonary function and deaths due
the smoke-free law at the same places, and good reductions in the presence to tuberculosis are judged as Level 1. Active smoking of pregnant women is
of symptoms were observed. · Health consequences of passive exposure to judged as causally related to preterm delivery, low birth weight, fetus growth
tobacco smoke: Admissions due to acute cardiovascular and/or respiratory retardation and sudden infant deaths syndrome (SIDS). For other diseases,
conditions to the emergency medical services were evaluated before and type 2 diabetes mellitus, periodontitis and nicotine dependency are judged
after the implementation of smoke-free policies, and some reductions were as Level 1. For passive smoking, it is judged to be sufficiently causally related
observed, particularly among males. Figure 1. Indoor air quality of some (level 1) for lung cancer and ischemic heart disease and stroke in adulthood.
indoor public places before and after the implementation of smoke-free Odor annoyance and nasal irritation as acute effect for respiratory system,
policies In conclusion, implementation of comprehensive tobacco control and asthma and sudden infant death syndrome (SIDS) for children are judged
measures help to improve indoor air quality; reduces the health complaints as level 1. For smoking in adolescence, deaths due to all cause deaths, cancer
of the workers at hospitality workplaces and reduces the emergency and circulatory disease and increased risk of cancer incidence are judged
admissions due to acute cardiovascular and respiratory conditions. Also as level 1. Tobacco control activities were summarized according to the
smoking prevalence was reduced during the 20 years period between 1993 MPOWER. <M> Although prevalence of current smokers has decreased (32.2%
(before the introduction of first tobacco control law) and 2012 (5 years after for males and 8.5% for females in 2014), pace of decrease slowed recently.
the comprehensive tobacco control law). In addition to smoke-free policy, <P> Although the Health Promotion Act (2003) and revision of the Industrial
Turkey is implementing more than 80% of tax to tobacco products, bans all Safety and Health Act (2015), which mandates company to protect workers
kinds of advertisement and promotion of tobacco products and sponsorship from passive smoking with best efforts, have made some progress to promote
by tobacco industry, monitors tobacco use prevalence at 4 years intervals smoke-free environment, especially in schools, hospitals and governmental
(Global Adult Tobacco Surveys in 2008 and 2012, and was planned in 2016) offices, problems still remain in other places, such as restaurants and bars.
(5)
, prohibits selling of tobacco products to children less than 18 years of age <O> Cessation support in the community and workplace, cessation support
and provides free treatment for tobacco dependency. As a result, Turkey was using OTC cessation medicines at pharmacy and cessation treatment using
declared as the single country in the world implementing all six MPOWER health insurance are the 3 pillow conducted in Japan. <W> Warning labels
measures with great success, and was awarded by WHO. Political commitment on tobacco packages in Japan uses only characters and too many words,
of the government and active participation of civil society and the academia which results in few impact on smokers. Almost no mass media campaign
were the major keys to success (6).References 1. Tobacco and Alcohol Market has been conduct to provide information to the public. <E> Regulation to
Regulatory Authority. 2. PIAR. Public Research on Smoking Habits and tobacco industry mostly relies on voluntary basis and their CSR activities
Campaign against Smoking in Turkey, Ministry of Health, 1988. 3. Bilir N, Güçiz have been conducted with no regulation. <R> Although after recent tax
B, Yıldız AN. Smoking Behaviors and Attitudes, Ankara, Hacettepe Public increases, tax rate became almost in the middle among developed countries
Health Foundation, International Development Research Centre, Ankara, and tobacco consumption decreased, tobacco price is still low (Fig 1).6-8) It is
1997. 4. Expansion of Smoke-free Public Places and Workplaces, Evaluation of summarized that activities were weak for smoke-free policies, mass media
Impact of Tobacco Control Policies, Turkey; Project conducted by Society of advertising bans and health warnings in Japan. Regarding smoke-free policy,
Public Health Specialists, in collaboration of Ministry of Health, H. Özcebe, N. Tokyo Olympic/Paralympic 2020 will be the best occasion to further promote
Bilir and D. Aslan, Ankara 2011. 5. Global Adult Tobacco Survey, Turkey Report, the policy at national level. Conclusion Evidence-based summary reports
Ministry of Health, 2012. 6. Bilir, N, Özcebe H, Ergüder T and Mauer-Stender K., should be effectively used in order to accelerate tobacco control activities
Tobacco Control in Turkey; Story of Commitment and Leadership, WHO Euro, in Japan.References 1) WHO Tobacco Free Initiative (TFI). 2015. ‘Tobacco
2012. control country profiles’, Accessed 2016/01/31. http://www. who. int/tobacco/
surveillance/policy/country_profile/en/ 2) The Health Consequences of
Keywords: Tobacco Control, Turkey, indoor air quality Smoking - 50 Years of Progress A Report of the Surgeon General. Atlanta, GA:
U.S. Department of Health and Human Services, Centers for Disease Control
and Prevention, Coordinating Center for Health Promotion, National Center
for Chronic Disease Prevention and Health Promotion, Office on Smoking and
ED12: REGIONAL TOBACCO CONTROL POLICIES: ADVANCES & CHALLENGES
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 Health, 2014. 3) IARC. IARC Monographs on the Evaluation of Carcinogenic
Risks to Humans, Vol 100E, Personal Habits and Indoor Combustions. Lyon,
France: International Agency for Research on Cancer; 2012 4) Committee
ED12.05 TOBACCO CONTROL POLICIES IN JAPAN on the health effect of smoking. Smoking and Health – report from the
Tomotaka Sobue committee on the health effect of smoking, 2016. 5) The Health Consequences
Department of Social and Environmental Medicine, Osaka University, Osaka/Japan of Smoking: A Report of the Surgeon General. In: Service USPH, ed. Atlanta,
GA: U.S. Department of Health and Human Services, Centers for Disease
Background: Although Japan ratified the FCTC in 2004, progress in tobacco Control and Prevention, National Center for Chronic Disease Prevention
control is still limited. In the WHO report on the global tobacco epidemic,
and Health Promotion, Office on Smoking and Health, 2004. 6) Ministry of 2013); Mexico (21.7% in 2008-2011 to 23.6% in 2014); Peru (from 44.5% in
Finance. Tax and stamp revenue settlement amount investigation. List of 1998 to 21.1% in 2010 and 13.3% in 2013); Uruguay (from 34% in 1998 to 23.5%
statistical tables. 7) Ministry of Internal Affairs and Communications. White in 2011)5 – 11. Discussion: According to the 2014 FCTC Progress Report12, the
paper for local finance. 8) Tobacco Institute of Japan. Statistical data on implementation degree of the articles among the countries varied from <20%
cigarette. Time trend table for sales performance by fiscal year. Fig 1. Trends of to more than >75% in most cases. One-third of all FCTC signing countries have
tax income, tobacco consumption and smoking rate in Japan.6-8) not enacted anti-tobacco legislation or reached the full implementation of
at least two important time-bound articles: tobacco advertising ban and
health warnings on cigarette packages and at the selling points. Our data also
showed uneven degrees of implementation among the studied countries.
One of the underlying causes for slow implementation in some countries, like
Mexico and Argentina, is the strong political lobby by the tobacco industry.
In our study, Argentina has come in third in smoking prevalence, with a 22.1%
smoking rate among adults, due to the strong pressure upon legislators by
the tobacco industry that so far has prevented the FCTC ratification by the
Congress. Nevertheless, the Argentinean political environment was more
sensitive than the Mexican, to the persistent anti-smoking advocacy by
the medical associations and organizations of the civil society. Therefore,
some of the FCTC tobacco control policies were enacted by legislators in 2011
and implemented in 2013. Mexico, however, was the one with the poorest
implementation of tobacco control policies and the highest in smoking
prevalence among adults (23,60%), seconded by Uruguay (23.5%), where the
past administration has neither enforced the already existing tobacco-control
policies, nor promoted new ones, such as heavy taxes upon tobacco products.
One of the important measures recommended by the FCTC - which has proved
to be effective in smoking prevention among children and teenagers - is
high taxation (over 75%) of tobacco products12. Conclusion: The degree of
compliance with the terms of the Convention seems to have a direct impact
on the reduction of smoking rates in the countries studied. Other solutions
should contemplate tobacco farmers, whose fear of shifting to new unfamiliar
cultures is exploited by the tobacco industry to prevent FCTC ratification in
Keywords: evidence-based policy, health effects, summary report
many countries. But farmers should not stop growing tobacco plants, but just
shift to transgenic tobacco farming13. Transgenic tobacco is being successfully
tested for expression of for more than fifteen human therapeutic proteins,
ED12: REGIONAL TOBACCO CONTROL POLICIES: ADVANCES & CHALLENGES including antibodies, antigens for vaccines, and autoimmune inhibitor
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 factors. (14-17). Pharmaceutical companies could benefit from the existing
agricultural tradition of tobacco farming in Brazil, Argentina, and elsewhere
by fostering the commercial production of those molecules. Transgenic
ED12.06 TOBACCO CONTROL POLICIES IN LATIN AMERICA
tobacco is improper for smoking and could also have the nicotine gene
Nise Yamaguchi1, Norma Pilnik2, Jaime De La Garza3, Luis Ashton4, Abel knocked out to discourage misuse. Therefore, the pharma industry could open
Garcia5, Eduardo Bianco6, Gregorio Kevorkof 7 new roads to smoking eradication while preserving the economic activity and
1
Clinical Oncology and Tumor Immunology, Hospital Albert Einstein, São Paulo/ profitability of traditional tobacco farmers. Effective tobacco control requires
Brazil, 2Internal Medicine Oncology Department, School of Medicine Cordoba a close cooperation between health institutions, medical societies, NGOs, and
University, Cordoba/Argentina, 3Thoracic Oncology Unit and Laboratory of
the press - and the regular funding of surveillance programs and educational
Personalized Medicine, National Cancer Institute, Mexico City/Mexico, 4 Auna,
campaigns. Smoking prevention programs must be part of the educational
Lima/Peru, 5Cancer Prevention and Control, National Institute of Neoplastic
Diseases, Lima/Peru, 6Tobacco Epidemic Center, Montevideo/Uruguay, 7Internal curricula from the pre-school onwards.
Medicine, National University of Cordoba, Cordoba/Argentina
Keywords: anti-smoking policies, smoking rates, biofarming, Tobacco Control
Introduction: Smoking is the single most important cancer risk factor and
accounts for 26% of all cancer deaths and 84% of lung cancer deaths in Latin
America1. Lung cancer is one of the most preventable cancer types; and
doctors of all expertise are essential to impart to patients and their families
the idea of smoking prevention, thereby contributing to the reduction of
mortality from lung cancer. There are around 145 million smokers age 15 years SESSION ED13: TREATMENT OF MALIGNANT PLEURAL
or older in Latin American. Adult smoking prevalence varies from 35% in Chile
MESOTHELIOMA
and 30% in Bolivia to 11% in Panama and 11∙7% in El Salvador2, 3. The continuing
popularity of smoking among adolescents is particularly worrisome as WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
smoking rates among teens and young adults predict future lung cancer
rates. Smoking rates among young people aged 13–15 years are now higher
than in adults in many Latin American countries. Prevalence among female ED13.02 TISSUE-BASED BIOMARKERS
adolescents has surpassed their male counterparts in Argentina, Brazil, Glen Reid1, Steven Kao2, Nico Van Zandwijk1
Chile, Mexico, and Uruguay. Unless these high rates of smoking are curtailed, 1
Asbestos Diseases Research Institute, Sydney/Australia, 2Medical Oncology, Chris
cancer mortality rates will continue to rise3. We have assessed the impact O’Brien Lifehouse, Sydney/Australia
on smoking rates of anti-tobacco policies adopted by five Latin American
countries, in compliance to the WHO’s Framework Convention on Tobacco Introduction: Malignant pleural mesothelioma (MPM) is difficult to diagnose
Control (FCTC). Argentina, Brazil, Mexico, Peru, and Uruguay were used as and accurate prediction of patient outcomes still relies on a range of clinical
case studies to illustrate the challenges and ways in which governments and scores. Despite extensive efforts in the last decade, there are few tumour-
civil society organizations can effectively work together to reduce lung cancer based molecular markers that can accurately contribute to diagnosis and
deaths and other tobacco-related diseases. Since the endeavor for approving prediction of disease course. Recent reports describing the mutational
anti-tobacco policies was met with a strong lobby against it in these and transcriptional landscape of MPM tumours have revealed a number
countries, different degrees of compliance with the FCTC terms were reached. of changes that may yield clinically useful biomarkers following further
We analyzed reports issued by local governments and epidemiologic surveys development and validation studies. Diagnosis: The definitive MPM diagnosis
found in the literature. Tobacco farming in Latin-America has increased in relies on a tissue biopsy and demonstration of invasion. Diagnostic markers
recent years, representing almost 16% of the global production. Argentina consist of a combination the expression of mesothelial-specific proteins
and Brazil are among the ten largest world producers and the cultivated and absence of markers of adenocarcinoma. Recent advances have shown
area in Latin America reaches 13.55% of the global land dedicated to tobacco that the mutation of the tumour suppressor BAP1 leads to loss of nuclear
farming worldwide. The prices paid by the tobacco industry to farmers are staining, and that this is highly specific for discriminating mesothelioma
also increasing since 2007, and the sector employs 650,000 people. Tobacco from benign conditions. As in some cases MPM has neither BAP1 mutation
farming is also present in Colombia, Dominican Republic, Honduras, Ecuador, nor loss of nuclear staining, sensitivity is lacking, but this can be improved
Guatemala, Mexico, Nicaragua and Paraguay4. Therefore, tobacco control by incorporating detection of CDKN2A genomic loss using FISH. Assessment
policies must necessarily include solutions to help tobacco growers to escape of additional mutations and fusion genes recently identified in MPM may
from the influence of the tobacco industry without loss of income and jobs. represent useful markers for future development. Characteristic changes
Results: We have found a differential decrease (and increase) in smoking in microRNA expression are present in MPM, and these form the basis of a
among the population of the studied countries in the last decades: Argentina: highly accurate molecular test for the differential diagnosis of MPM from
(from 29% in 2007 to 22.1% in 2014); Brazil (from 34.8% in 1989 to 14.7% in other tumours affecting the pleura. Prognosis: Clinical and pathological

parameters remain the best predictors of disease outcome, and although complete resection (R0) was not achievable. The anatomical location of
some molecular markers have demonstrated prognostic significance, these the mesothelioma simply does not allow a resection with save margins of
are yet to be validated. Histopathological subtype is an accurate prognostic normal tissue. Therefore additional therapies were looked for and a different
indicator, with the epithelioid subtype associated with significantly better number of approaches have been taken. To answer the question if any
outcomes than the non-epithelioid biphasic and sarcomatoid types. The systemic induction therapy is considered the best, this can be answered
variation within epithelioid tumours is well recognised, and epithelioid with a clear No. reasons for this is the lack of randomized studies in this
tumours with a pleomorphic morphology have poor prognosis, similar to patient population and the fact that patients with MPM are grouped
patients with non-epithelioid tumours. Recent results from transcriptomic together despite differences in pathology, surgical approach (EPP vs
analyses have revealed subsets within epithelioid and non-epithelioid Pleurectomy decortication) and biological behavior. There has been a number
tumours which more accurately describe prognosis. These include the of preferential approaches with chemotherapy in this disease ranging from
two-cluster C1/C2 classification system based on a 3 gene predictor, and Induction chemotherapy; Intracavitary therapy and Adjuvant chemotherapy.
the 4 clusters (sarcomatoid, epithelioid, biphasic-epithelioid and biphasic- (table) In the case of induction therapy it is clear that one aims at reducing
sarcomatoid) derived from RNA-seq analysis. MicroRNA expression has also the tumor bulk and to prevent metastases during surgery. The preferred
been linked to outcome. Early studies revealed prognostic significance of treatment is cisplatin with pemetrexed since this is considered to be the
miR-29c-3p, with higher levels corresponding to longer survival. More recently, standard of this disease.(1) Other regimens have been tested in small extend
microRNA expression profiles differing between long and short survivors but usually involved. The use of intra-cavitary treatment has attracted
yielded a 6-microRNA score that predicted outcome in two surgical series. attention since MPM cells show the tendency to stay localized in the thoracic
Whether TCGA data confirm these observations remains to be determined. cavity for a relative long period. The administration of a local cytotoxic drug
In addition to RNA and protein biomarkers, the cellular composition of would allow an improvement in local control and limited systemic effects.
tumours influences patient outcomes. It is likely that the mix of cell types Cisplatin has been used frequently during surgery and were combined with
within tumour samples also contributes to biomarker expression, especially heating of the lavage fluid to 40 0 Celsius. (2) Special precautions for this so-
for RNA extracted from whole tumours. For some proteins, differential called Hyperthermic lavage approach have to be taken in the operating suite
expression in the stromal and tumour compartments is of prognostic value, with protection of the staff to avoid exposure to the drugs. In general the
for example in the case of SPARC expression. The importance of the immune lavage procedure adds another hour to the debulking surgery. Measurements
cell infiltrate was recently investigated in a large number of epithelioid of platin adducts in the blood during this procedure have shown that there is
samples revealing that greater numbers of tumour-infiltrating CD4+ and no important systemic levels measured. Unfortunately there has not been any
CD8+ T lymphocytes (TILs), as well as fewer tumour-associated macrophages comparison of these approaches. Most series only report the feasibility of the
(TAMs) of the M2-type correlate with survival. In addition, the ratio of the treatment with sometimes impressive survival figures. These are partly due
TAMs/TILs was also shown to predict outcome in epithelioid MPM. Other to the strong selection of patients for the studies. A relative new approach is
cell populations associated with vascular and lymphatic invasion are also the use of a platin containing fibrin glue that can be applied to the thoracic
linked to survival. Prediction: Unlike lung cancer, few actionable mutations wall after debulking using a spray system. The initial results indicate that
are present in MPM that predict sensitivity to targeted agents, and clinical the treatment is fast and serial biopsies show that the effect is sustained for
trials with these drugs have yielded disappointing results. Markers for single many weeks.(3) Finally, adjuvant therapies can be applied. In this field, there
agent chemotherapy and the standard cisplatin/pemetrexed doublet have are no data to support any specific treatment and the choices are generally
also been investigated in retrospective studies attempting to link patient defined based on the study protocol. No prospective trials have been reported
outcomes with gene (mRNA and protein) expression and polymorphisms.
Multiple reports have linked levels of TS protein, but not mRNA, to outcomes Most of the studies are trimodality therapies where RT is an important part
with pemetrexed-based chemotherapy. As expected from a multi-targeted of the protocol. One typical example is the EORTC study where the feasibility
agent, other levels of other proteins such as folypoly-glutamate synthase of trimodality therapy in a phase II trial (EORTC 08031) with clearly defined
(FGPS) and the reuced folate carrier (RFC) were also associated with tumour timelines was tested(5). Patients with pathologically proven mesothelioma
response and patient outcomes. However, a subsequent study with a similar received induction chemotherapy (3 courses cisplatin and pemetrexed )
number of patients suggested that both TS and FPGS lack predictive value. followed by EPP within 21–56 days after the last dose of chemotherapy in
With respect to DNA repair genes involved in cisplatin activity, ERCC1 and the absence of progressive disease and unacceptable toxicity. A ‘‘success of
others have been evaluated, but results are again inconclusive. The picture treatment’’ was defined as a patient who had received the full protocol and
is complicated by assessment of target genes in patients treated with two was alive after 90 days without progressive disease and without grade 3 or
interacting agents (with or without subsequent surgery), and the true value 4 toxicity. Of the 57 patients included, 42 had EPP (73.7%) after induction
of these genes awaits carefully controlled prospective analyses. The recent therapy. The 90-day mortality was 6.5% with an overall survival time of 18.4
breakthrough success of immune checkpoint inhibiting antibodies targeting months and progression-free median survival time of 13.9 months. Only 24
CTLA4 and the PD-1/PD-L1 axis in melanoma and lung cancer has seen these (42.1%) patients met the definition of success, thereby failing the primary
agents applied to MPM patients. With response rates of around 25% for PD-1 endpoint. This study shown how difficult it is to complete a trimodality study
targeting antibodies pembrolizumab and nivolumab in MPM, new predictive in this patient group and only when a standard is defined, proper comparative
markers are needed to improve patient selection and for health economics studies can be performed. Other important studies addressing the neo-
reasons. Although the Keynote trial included patients based on positivity of adjuvant approach are presented in the table.
PD-L1 staining, PD-L1 status appears to have little value in predicting response
1.Baas P, Fennel D, Kerr K, van Schil PE. Malignant Pleural Mesothelioma:
rate. Ongoing research into immune cell involvement may shed more light
Guidelines for Diagnosis, treatment and follow-up. Annals Oncology 2015
on this. Future directions: Continuing research in this area should learn from
2.Sugarbaker DJ, Gill RR, Yeap BY, Wolf AS, DaSilva MC, Baldini EH, Bueno R,
limitations of the biomarker studies of the last decades to improve the search
Richards WG. Hyperthermic intraoperative pleural cisplatin chemotherapy
for useful molecular markers. Large prospective trials are needed to carefully
extends interval to recurrence and survival among low-risk patients with
evaluate predictive markers. Alternative approaches such as the analysis of
malignant pleural Mesothelioma undergoing surgical macroscopic complete
live cell populations taken from fine-needle aspirates and investigation of
resection. J Thorac Cardiovasc Surg. 2013 Apr;145(4):955-63.
circulating tumour cells and tumour-derived markers in the circulation (DNA,
3.Opitz I. Use of fibrin glue in malignan pleural mesothelioma, presented at
exosomes) may yield novel markers. Conclusions: Extensive research into
the xxth IMIG conference Birmingham UK
tumour-based markers for MPM is gradually making progress. New markers
4.Van Schil P, Baas P, Gafaar R, Maat AP, van der Pol M, Hassan B et al.
to assist in diagnosis and prognosis have been identified, but the selection
Trimodality therapy for malignant pleural mesothelioma: results from an
of accurate predictive markers has so far remained elusive. Next-generation
EORTC phase II multicentre trial.
sequencing has identified multiple new candidate markers requiring further
5.Weder W, Stahel RA, Bernhard J, Bodis S, Vogt P, Ballabeni P, et al.
investigation, and may provide breakthroughs in the future.
Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural
Keywords: predictive markers, diagnosis, Prognosis pneumonectomy in malignant pleural mesothelioma. Ann Oncol 2007;18:1196-
202
6.Cao C, Tian D, Manganas C, Matthews P, Yan TD. Systematic review of
trimodality therapy for patients with malignant pleural mesothelioma. Ann
ED13: TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA Cardiothor Surg 2012;1:428-37
(See Table next page)
ED13.04 SYSTEMIC INDUCTION THERAPY OF MALIGNANT PLEURAL
MESOTHELIOMA
Paul Baas
Thoracic Oncology, Netherlands Cancer Institute, Amsterdam/Netherlands
Over the last 3 decades clinical researchers have focused on the optimal
treatment of patients with mesothelioma (MPM). In the 80’s surgery had
become a standard approach in some centers but it became clear that a
# Completed Completed Completed Outcome

Study type drugs
pts Chemotherapy Surgery Radiotherapy (mOS)
SAKK 17/04 Lancet 23/27 in 2nd
Neo-adj 151 Cis/pem 145 125 7.6-9.4
Onc 2015;16;1651 stage
Frederico BMC
Neo-adj 54 Cis/pem 96% 83% 41% 15.5
Cancer 2013;13;22
Krug JCO
Neo-adj 77 Cis/pem 83% 74% 52% 16.8
2009;27;3007
Weder JCO
Neo-adj 20 Cis/gem 90% 80% n.a. 23
2004;22;3451
Van Schil ERJ
Neo-adjuvant 59 Cis/pem 93% 79% 65% 18.4
2010;36;1362
Richards JCO Cispl 50-
intracavitary 61 n.a. 72% n.a. 9.0
2006;24;1561 225
Tilleman JTCS
intracavitary 121 Cispl 225 n.a 79% n.a. 12.8
2009;138;405
Keywords: surgery; mesothelioma; chemotherapy
ED13: TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA

III trial (Polaris), comparing first line Cis/Pem with ADI-PEG 20 or placebo,
ED13.05 SYSTEMIC THERAPY OF INOPERABLE MALIGNANT will start in 2017 for biphasic (mixed) or sarcomatoïd MPM only because they
PLEURAL MESOTHELIOMA exhibit ASS-1 defect twice more frequently than epithelioïd subtype. Finally,
Arnaud Scherpereel other innovative drugs also candidates for first line treatment in combination
with Cis/Pem, after preliminary positive clinical trials, include gene therapy,
Pulmonary and Thoracic Oncology, Hospital of the University (CHRU) of Lille, Lille/
France cell therapy using chimeric antigen receptors (CARs) or dendritic cells (DC), or
oncovirotherapy, and will be assessed as first line treatment in MPM very soon
To date, the treatment of malignant pleural mesothelioma (MPM), a rare and or later. For example, the European “DENIM” phase III trial will test DC based
aggressive tumor usually induced by previous asbestos exposure, relies mostly immunotherapy with allogenic tumor cell lysate as maintenance treatment
on chemotherapy and best supportive care (BSC). But medical treatment has after Cis/Pem chemotherapy in MPM patients. But, as in lung cancers,
been so far quite deceptive with median overall survival (mOS) about one year immune checkpoint inhibitors (ICI) seem to represent presently the most
at its best for the last 13 years with recommended first line chemotherapy by exciting tool for MPM patients. In fact, even if a recent, large phase II trial
cisplatin (or carboplatin) and pemetrexed in patients fitted for it. The optimal (n=564; “Determine”) with anti-CTLA-4 mAb (tremelimumab) versus placebo
duration of first line chemotherapy is unknown but a maximum of 6 cycles is in 2nd/3rd line treatment did not meet its first endpoint (mOS) (21), early
recommended. There was no evidence supporting maintenance treatment by data of a phase Ib basket trial with anti-PD-1 mAb (pembrolizumab) showed
pemetrexed or other drug. Pathogenesis of MPM includes overexpression of promising response rate (RR) of 28% and DCR of 76% in PD-L1 positive MPM
growth factors, many genetic and epigenetic alterations and/or mutations of (22). Other trials with checkpoint inhibitors are ongoing with anti-PD-1 alone
malignant cells responsible for cell proliferation and resistance to apoptosis, (nivolumab, pembrolizumab), or a combination of anti-PD-1 (nivolumab) or
pleural inflammation and local immunosuppression induced by the tumor and anti-PD-L1 (durvalumab) and anti-CTLA-4 (tremelimumab or ipilimumab) as
favoring its growth. These elements provide the rationale for many targeted first or 2nd/3rd lines treatment. Interestingly, new clinical trials are already
therapies and immunotherapy. But so far, very few drugs exhibited sufficient underway to assess value of ICI, such as nivolumab + ipilimumab combo,
value to deserve further trials. Thus, first trials assessing anti-angiogenic drugs versus Cis/Pem as first line treatment. In conclusion, the triplet cisplatin/
in MPM did not support their use in this cancer despite the key role of VEGF. pemetrexed/bevacizumab may be a new first line standard of care for patients
A phase III testing thalidomide as maintenance treatment after cisplatin/ eligible for bevacizumab, and not candidate to multimodal treatment trials.
pemetrexed (Cis/Pem) was negative, as well as phase II trial of bevacizumab Second line and further lines treatments are very limited with no validated
(anti-VEGF antibodies) combined with first line cisplatin/gemcitabine. But options except pemetrexed in case of late relapse after platinum/pemetrexed.
other phase II trials evaluating bevacizumab with Cis or Carbo/Pem were But exciting drugs and strategies were tested in this testing, in particular ICI.
promising with progression-free survival (PFS) of 6.9 months. Therefore, a But remaining key questions include which predictive biomarkers for these
phase III randomized (1:1) « MAPS » trial recruited 448 unresectable MPM innovative, thrilling but expensive treatments to target the best patients
patients to test Cis/Pem with (arm B) or without (arm A) bevacizumab. for each drug? And how to potentially combine these drugs versus, or in
Arm B non-progressive patients received bevacizumab maintenance until combination with, standard chemotherapy? Thus real hopes seem closer for
progression or toxicity. Median overall survival (mOS) was significantly longer our MPM patients with new systemic treatments.
in the B arm: 18.8 [95%CI: 15.9-22.6] vs. 16.1 months [14.0-17.9] in the A arm,
(adj.HR= 0.76, p=0.012). Thus, bevacizumab addition to Cis/Pem provided a Keywords: Mesothelioma, chemotherapy, Immunotherapy, systemic
significantly longer survival in MPM patients with acceptable toxicity, making treatment
this triplet a new treatment paradigm for this cancer. Moreover, there was
no detrimental effect of bevacizumab on quality of life (QoL) despite its
higher specific but manageable toxicity. There was no significant difference ED13: TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA
between arms for the percentages of drug delivery or of second line treatment WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
to explain why adding bevacizumab to Cis/Pem significantly increased mOS,
even if MAPS standard arm patients had a longer OS than patients from
historical series or previous trials. Based on the same rationale than the ED13.06 MESOTHELIOMA IN A SETTING OF GERMLINE BAP1
MAPS trial, nintedanib, a drug targeting VEGF, FGF and PDGF receptors, is MUTATIONS
currently tested versus placebo in MPM patients treated by first line Cis/ Michele Carbone 1, Harvey Pass2, Haining Yang1
Pem chemotherapy in a large phase II/III randomized trial. Early I or II trials 1
Thoracic Oncology, University of Hawaii Cancer Center, Hawaii/HI/United States
assessing drugs targeting mesothelin, a mesothelial cell surface molecule of America, 2Department of Cardiothoracic Surgery, NYU Langone Medical Center,
overexpressed in (mostly epithelioïd) MPM, showed promising results in New York/NY/United States of America
combination with first-line Cis/Pem, justifying further, randomised and
larger studies. Thus, very interesting trials are ongoing with anti-mesothelin Individuals that are born with germline BAP1 mutations are affected by the
monoclonal antibodies (mAbs) alone (amatuximab, a chimeric IgG1 antibody), BAP1 cancer syndrome. All individuals affected by this cancer syndrome have
or planned with immunotoxins (mAbs combined with anti-tubulin (anetumab developed one or more malignancies in the course of their life. Mesothelioma,
ravsantine) or Listeria toxins (CRS-207) versus placebo combined with Cis/ uveal and cutaneous melanomas –tumors often associated with exposure to
Pem too. For non-epithelioïd MPM patients, another hope might come from environmental carcinogens-, are the most common malignancies, although
the dependence to arginin exhibited by argininosuccinate synthetase -1 (ASS- almost any tumor type has been detected in carriers of this cancer syndrome.
1) tumors such as mesothelioma, and the good results of Pegylated Arginine In addition, BAP1 mutant carriers develop multiple benign melanocytic
Deiminase (ADI-PEG 20) alone or in combination with Cis/Pem, assessed in tumors –histologically different from other SPITZ-like tumors- that we have
the phase I « TRAP » trial recently presented by Szlosarek and al. A phase II/ called melanocytic BAP1 associated intradermal tumors (MBAITs) that can

alert the physician that the patients is a carrier of the BAP1 cancer syndrome. ED14: SMALL CELL LUNG CANCER
Most malignancies develop after the 4th decade of life, although cancers in
individuals as young as 19 years old have been detected. Because many of
these malignancies, for example melanomas, can be cured by early detection, ED14.02 THORACIC RADIOTHERAPY OF SCLC
it is important to identify BAP1 mutant carriers that can be screened for
Berend Slotman
early detection and curative resection. Moreover, carriers of germline BAP1
Radiation Oncology, VU University Medical Center, Amsterdam/Netherlands
mutation may be at increased risk of developing mesothelioma and melanoma
following exposure to low doses of asbestos, sunlight and X-Rays, thus Limited stage: Small cell lung cancer (SCLC) comprises 10-15% of all lung
cancer preventive measures can be implemented. When cancer develops in tumors and is associated with an aggressive clinical behavior. Two out of three
a setting of BAP1 germline mutations, these patients have a much better patients presents with hematogenous metastases at diagnosis (extensive
prognosis compared to patients with the same malignancies when they occur stage (ES)). For patients without hematogenous metastases (limited stage
sporadically (i.e., not in carriers of BAP1 mutations). Familial mesotheliomas (LS)), chemoradiotherapy is the standard treatment. Although radiotherapy
in these individuals occur in either the pleura or peritoneum (frequency ratio after chemotherapy has the theoretical benefit of treating smaller target
1:1) at a median age of 56.3 years, have a male-to-female ratio of 0.73:1, and volumes with less toxicity, concurrent chemoradiotherapy has shown to be
are associated with prolonged survival of 5 to 10 or more years, compared superior. Moreover, earlier use of radiotherapy during chemotherapy leads
with a median age at diagnosis of 72, a pleural-to-peritoneal ratio of 86:14, a to better results. The absolute benefit of early versus late radiotherapy was
male-to-female ratio of 4:1, and a median survival of less than 1 year in sporadic about 10% for patients who had received cisplatinum-based chemotherapy
mesothelioma. About 100 families with this mutated BAP1 cancer syndrome [1]. Turrisi et al. [2] demonstrated that twice daily radiotherapy starting with
have been described in the United States, Europe, and New Zealand. Genetic a first course of chemotherapy resulted in improved survival rates. Median
studies demonstrated that these mutations are transmitted across multiple survival was 23 months for patients who received twice-daily radiotherapy
generations over the course of several centuries, and some US families (45Gy/30fractions/3weeks) versus 19 months for once daily treated patients
carrying BAP1 mutations descend from a Swiss family that immigrated in the (45Gy/25fractions/5weeks). The corresponding 5 years survival rates were
US in the early 1700s. An International Consensus Meeting sponsored by the 26% and 16%. However, more Grade 3-4 oesophagitis was seen during
IASLC supported medical screening for at-risk people who are carriers of BAP1 twice-daily treatment (32% versus 16%). Only a minority of patients in the
germline mutations as follows: (1) annual dermatological screening for early US and Europe receive twice daily radiotherapy. Recently the results of
detection of melanoma at age 18 or younger; (2) annual eye examination/ the CONVERT trial, in which once-daily radiotherapy (70Gy) was compared
ophthalmoscopy for uveal melanoma at age 18 or younger; and (3) skin and with twice daily radiotherapy (45 Gy) were presented [3]. Radiotherapy was
eye examinations every 6 months after age of 30, when the frequency of initiated at the 2nd course of 4-6 cycles of cisplatin/etoposide. There was
cancer among carriers of germline BAP1 mutations starts to increase. It no statistically significant difference in overall survival between the two
was also recommended that genetic counseling should be offered to all arms. Overall survival at 2 years was 56% for patients treated twice-daily
individuals tested for BAP1. Moreover, those with BAP1 germline mutations versus 51% for patients treated once-daily (p= 0.15) [3]. There was also no
should be ncouraged to participate in studies to improve early detection of significant difference in time to progression. There were no differences in a
mesothelioma (Carbone M. et al., Journal of Thoracic Oncology 11, 1246-1262, 2016). acute toxicity, except for Grade 3-4 neutropenia, which occurred more often
Keywords: BAP1, mesothelioma, germline in the twice-daily treatment arm (74% versus 65%). There were no differences
in Grade 3-5 oesophagitis (19%) and pneumonitis (2%). The authors concluded
that survival in both study arms was higher than reported previously and that
radiation related toxicities were lower than expected, probably related to
the use of modern radiotherapy techniques. The results of the study support
the use of either twice daily or once daily as standard of care for patients with
limited stage disease and in good performance score. In RTOG0538 study,
SESSION ED14: SMALL CELL LUNG CANCER which also compares 70 Gy once-daily and 45 Gy twice-daily radiotherapy,
WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45 radiotherapy commences with the first or second course of chemotherapy.
The results of this study are eagerly awaited [4]. Extensive stage: In the EORTC
study on prophylactic cranial irradiation (PCI) for ES-SCLC, it was noted that
ED14.01 CHEMOTHERAPY OF SMALL CELL LUNG CANCER the vast majority of patients still had intrathoracic disease after completion
of chemotherapy. After on the positive effects of PCI which not only reduced
Primo Lara
the risk of symptomatic brain metastases (40 versus 15%) but also improved
Internal Medicine/Hematology-Oncology, University of California Davis
overall survival (1 year: 27 versus 13% (P= 0,003)) [5], the next logical step was
Comprehensive Cancer Center, Sacramento/CA/United States of America
to investigate the use of thoracic radiotherapy in ES-SCLC as well. Evidence
Small cell lung cancer, which accounts for 10-15% of all lung cancers, is a for a possible role of thoracic radiotherapy (TRT) in ES-SCLC also comes from
biologically and clinically virulent malignancy that has a propensity to the results of a trial published by Jeremic et al. in 1999 [6] in which patients
disseminate systemically and therefore is often initially diagnosed at an with ES-SCLC and good prognosis with a complete response outside the
advanced incurable stage. Although typically associated with heavy tobacco thorax were randomized between TRT plus PCI during chemotherapy versus
use, there have been recent clinical observations of histologic evolution chemotherapy and PCI only. Overall survival was 17 months for the patients
from adenocarcinoma to a SCLC phenotype, particularly in tumors harboring who received thoracic radiotherapy versus 11 months for those who did not.
activating mutations in the epidermal growth factor receptor (EGFR) gene In the CREST trial, patients with ES-SCLC and any response after 4-6 cycles
that had been treated with EGFR inhibitors. Due to its high proliferative of platinum based chemotherapy were randomized between PCI plus TRT
rate, SCLC is known to be highly responsive – at least initially - to cytotoxic (30Gy/10 fractions) or PCI only. Overall survival at one year, the primary
chemotherapy. Tumor response rates of 50-70% following platinum-based endpoint of the study, was not statistically significant between the groups
chemotherapy are usually expected. Intracranial metastases, a common (p=0.066) but with longer follow up the survival curves diverged and at 2
feature of ES-SCLC, have been also shown to respond at a similar rate years, survival was 13% in patients who received TRT versus 3% in the controls
to cytotoxic therapy as that of metastases to other visceral organs. The (p=0,004). There was also significant difference in progression free survival.
standard frontline chemotherapy for ES-SCLC, unchanged for the past three In an additional analysis of patients with and without residual intrathoracic
decades, has been platinum (either cisplatin or carboplatin) plus etoposide. disease, which was one of the stratification factors of the study, it was
No other regimen has convincingly been demonstrated to be superior to demonstrated that there was no significant benefit of TRT in patients with
platinum-etoposide in the frontline setting. Neither dose intensification a CR in the thorax. However, in patients with residual intrathoracic disease
approaches nor the incorporation of other cytotoxic agents into the platinum after chemotherapy, TRT led to a significant improvement in overall survival
backbone have yielded any palpable or tangible survival benefits. In recent [7]. In patients who received thoracic radiotherapy the risk of intrathoracic
years, only prophylactic cranial irradiation and (in highly selected patients) recurrence was reduced from 80% to 44%. In patients who received thoracic
consolidative thoracic irradiation have been shown to marginally improve radiotherapy the most recurrences occurred outside the brain and the
survival outcomes. Furthermore, despite the high initial response rates thorax and at a later stage. The next logical step after demonstration of a
to chemotherapy, drug resistance and subsequent tumor progression are beneficial effect of PCI and TRT would be the use of higher doses for TRT
universal events. Following failure of frontline platinum-based therapy, and possibly also treatment of extrathoracic metastatic sites. This topic
therapeutic options are limited and generally are of very modest clinical was addressed in the NRG-RTOG0937 study and was presented at ASTRO
benefit. Current investigations into optimizing cytotoxic therapy include 2015 [8]. patients with ES-SCLC and a CR or PR after chemotherapy and
the development of novel cytotoxics (e.g., alisertib), sequential/combination 1-4 metastatic lesions were randomized between PCI or PCI plus TRT plus
strategies that involve novel “targeted” therapies and immunotherapeutics radiotherapy of metastatic sites. The study which accrued very slowly was
such as checkpoint inhibitors, or conjugating a cytotoxic payload onto a closed early due to observed toxicities. The study did not show a survival
monoclonal antibody directed against an antigen expressed on SCLC, among difference between the two groups, but included only 86 patients over a five
others. A critical appraisal of the current status and future directions of years period and had imbalance groups with worse prognostic factors in the
cytotoxic therapy in ES-SCLC will be presented. experimental arm. There were many, partly unrelated, Grade 4-5 toxicities
in the experimental arm. To define which patients are most likely to benefit
Keywords: sclc, small cell, neuroendodrine from a more aggressive approach we have performed an additional analysis
for patients from the top accruing centers from the CREST trial. An evaluation The role of surgical treatment in the management of patients with small-
of 260 patients showed significantly better outcome in patients with 0 to cell lung cancer (SCLC) remains controversial. Although in the past, two
2 metastases versus and without liver metastases [10]. These patients are randomized studies have failed to show any survival benefit by adding
believed to be best candidates for future studies.References: surgery to chemotherapy, different retrospective and prospective reports
including the recently published studies using the database of Cancer
1. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing Institute Surveillance Epidemiology and End Results (SEER), showed, that
of thoracic radiation therapy in combined modality therapy for limited-stage surgery offers a reasonable overall survival in a subset of patients with SCLC
small-cell lung cancer. J Clin Oncol 2004. 22, 4837-45. stage I and II disease. Two important recommendations have been introduced
2. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily regarding the histology of SCLC as a high grade aggressive neuroendocrine
thoracic radiotherapy in limited small-cell lung cancer treated concurrently tumor and the use of TNM classification in staging of SCLC and in clinical
with cisplatin and etoposide. N Engl J Med. 1999 340, 265-71. trials. Patient’s selection is important including extensive radiologic staging
3. Faivre-Finn C, Snee M, Ashcroft L. CONVERT: An international randomised and biopsy of the mediastinal nodes. The use of PET scanning is likely to
trial of concurrent chemo-radiotherapy (cCTRT) comparing twice-daily (BD) improve the accuracy of staging. Surgery can be performed with a curative
and once-daily (OD) radiotherapy schedules in patients with limited stage intent in patients with SCLC and stage I or II disease or significant nodal
small cell lung cancer (LS-SCLC) and good performance status (PS). ASCO response after chemotherapy. Weksler has used the SEER database and
Meeting abstracts J Clin Oncol 2016, 8504. analyzed the outcomes of 3566 patients with SCLC stage I and II from 1988
4. Slotman BJ, Senan S; Radiotherapy in small-cell lung cancer: Lessons learned to 2007. The surgical treatment was performed in 895 patients (25.1%); the
and future directions. Int J Radiat Oncol Biol Phys 2011, 79, 998-1003. median survival was 34 months in the surgical group versus 16 months in
5. Slotman BJ, Faivre-Finn C, Kramer G. Prophylactic cranial irradiation in the nonsurgical group. In a similar report by Yu and colleagues, 21 the 5-year
extensive small-cell lung cancer. N Engl J Med 2007, 357, 664-72. overall survival was 21.1%, but it was 50.3% for those patients who received
6. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the a resection (45.7% after pneumonectomy and 33.7% after sublobar one).
combined- modality treatment of patients with extensive disease small-cell This analysis confirmed the acceptable survival rates in a subset of patients
lung cancer; A randomized study. J Clin Oncol 1999,17, 2092-9. with stage I SCLC. By primary surgery or after induction chemotherapy
7. Slotman BJ, van Tinteren H, Praag JO, et al., Use of thoracic radiotherapy for complete tumor resection and systematic mediastinal lymphadenectomy
extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. should be undertaken. Adjuvant chemotherapy is recommended also for
Lancet 2015, 385, 239-44. stage I patients; prophylactic cranial irradiation prolongs survival in those
8. Slotman BJ, van Tinteren H. Which patients with extensive stage small-cell patients who achieve a complete or partial response to initial treatment.
lung cancer should and should not receive thoracic radiotherapy? Transl Lung Until now, the standard systemic treatment of patients with LD-SCLC
Cancer Res. 2015, 4, 292-4. remains the combination of platinum and etoposide. The following groups of
9. Gore EM, Hu C, Sun A, et al. NRG Oncology/RTOG 0937: Randomized phase patients could potentially benefit from surgical resection: a. Patients with
II study comparing prophylactic cranial irradiation (PCI) alone to PCI and small lesion unexpectedly identified as SCLC at the time of thoracotomy.
consolidative extra-cranial irradiation for extensive disease small cell lung Complete resection and systematic lymph node dissection should be
cancer (ED-SCLC). Proc ASTRO, Int J Radiat Oncol Biol Phys 2016, 94, 5. undertaken. Chemotherapy is recommended postoperatively and PCI should
be considered. b. For stage I and II disease after chemotherapy and tumor
Keywords: SCLC, thoracic radiotherapy, Radiotherapy
response, surgery can improve local control and increase cure rates and long
term survival. Complete resection and mediastinal lymph node resection
should be performed. If possible, rather than pneumonectomy sleeve
ED14: SMALL CELL LUNG CANCER lobectomy should be preferred. c. In patients with mixed histology initial
WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45 treatment should be chemotherapy to control the small cell component
and after that surgery to control the non-small cell part of the tumor. d. For
patients with initial failure to chemotherapy or patients with localized late
ED14.03 UPDATE ON PROPHYLACTIC CRANIAL IRRADIATION IN
relapse after treatment for pure small cell tumors salvage operations may be
SCLC considered on individual basis. e. In patients with second primary small cell
Takashi Seto or non-small cell lung cancer who achieved cure from primary SCLC, surgery
Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka/Japan should be considered in the course of an multidisciplinary approach f. Patients
with synchronous ispilateral or bilateral small and non small cell tumors could
Background: A previous study has shown that prophylactic cranial irradiation be potential candidates for surgery in a diagnostic or therapeutic intention g.
(PCI) reduced the risk of brain metastases (BM) and prolonged the overall In selected patients with IIIA N2 disease and complete histological regression
survival (OS) of patients (pts) with extended disease small cell lung cancer of tumor tissue in the mediastinal lymph nodes after induction chemotherapy
(ED-SCLC). However Japanese trial to reconfirm these results was stopped at or chemoradiortherapy, surgery can improve local control and survival. Taking
first interim analysis (n=163 pts) because of futurity. According to this study into account the TNM use in SCLC and the encouraging SEER results for
protocol, final follow up was done. Materials and methods: From March 2009 patients submitted to surgery, a reconsideration of the role of surgery seems
pts with ED-SCLC who had any response to first-line chemotherapy (platinum to be mandatory. Finally, to improve current management strategies for SCLC,
agent plus irinotecan or etoposide) were randomized to either PCI (25Gy/10 surgeons should participate in the evaluation of SCLC patients together with
fractions) or observation (Obs) alone. The patients were required to prove the oncologists and radiotherapists and common guidelines for indications and
absence of BM by MRI prior to enrollment. The primary endpoint was OS and a therapy concepts should be adopted. Interdisciplinary approaches should be
planned sample size of 330 was determined to detect the hazard ratio (HR) of employed in the context of controlled clinical trials.
0.75 at a significance level of 0.05 and a power of 80%. Secondary endpoints
included time to BM (evaluated every 3 months by imaging), progression-free Fox W, Scadding JG. Medical Research Council comparative trial of surgery and
survival (PFS), and adverse effects (AEs) and mini mental status examination radiotherapy for primary treatment of small-celled or oat-celled carcinoma of
(MMSE). Results: In Apr 2014, follow up analysis was conducted for the the bronchus. Ten-year follow-up. Lancet 1973;2(7820):63-65
survival data of 224 all enrolled pts. One hundred fourth-five deaths were
observed. The median OS was 11.6 and 14.1 months for PCI (n=112) and Obs Lad T, Piantadosi S, Thomas P, et al. A prospective randomized trial to
(n=111), respectively (HR=1.28, 95%CI= 0.95-1.72; stratified log-rank test, determine the benefit of surgical resection of residual disease following
P=0.107). PCI significantly reduced the risk of BM as compared to Obs (33.6% response of small cell lung cancer to combination chemotherapy. Chest
vs 59.7% at 12 months; Gray’s test, P<0.001), whereas PFS was comparable 1994;106:320-323
between the two arms (median, 2.3 vs. 2.4 months; HR=0.98, 95%CI=0.75-
Waddell TK, Shepherd FA. Should aggressive surgery ever be part of the
1.28). No significant difference in AEs greater than Grade 2 was observed
management of small cell lung cancer? Thorac Surg Clin 2004;14:271-281
between the two arms. At the MMSE there was no statistical difference
between two arms, however in pts age 70 and older pts in PCI tended to be Eberhardt W, Stamatis G. Stuschke M, et al. Prognostically orientated
worse over time. Conclusion: PCI after response to chemotherapy could not multimodality treatment including surgery for selected patients of small-cell
show the OS impact in pts with ED-SCLC even in this follow up data. lung cancer patients stage Ib to IIIB: long-term results ofc a phase II trial. Br J
Cancer 1999;81:1206-12
Keywords: phase III, overall survival, SCLC, PCI
Shepherd FA, Crowley J, Van Houte P, Postmus PE, Carney D, Chansky K,
Shaokh Z, Goldstraw P. International Association for the Study of Lung
Cancer International Staging Committee and Participating Institutions. The
ED14: SMALL CELL LUNG CANCER
WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45 International Association for the Study of Lung Cancer lung cancer staging
project: proposals regarding the clinical staging of small cell lung cancer in the
forthcoming (seventh) edition of the tumor, node, metastasis classification
ED14.04 IS THERE A ROLE FOR SURGERY IN SCLC? for lung cancer. J Thorac Oncol 2007;2:1067-77
Georgios Stamatis
Thoracic Surgery, Ruhrlandklinik/University Essen, Essen/Germany Valliéres E, Shepherd FA, Crowley J, Van Houte P, Postmus PE, Carney D,
Chansky K, Shaokh Z, Goldstraw P. International Association for the Study of

Lung Cancer International Staging Committee and Participating Institutions. response rate of 13% (7/80) with nivolumab 3 mg/kg and 31% (14/45) in a
The IASLC Lung Cancer Staging Project: proposals regarding the relevance of cohort of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg. The activity of
TNM in the pathological staging of small cell lung cancer in the forthcoming nivolumab alone or combined with ipilimumab was seen regardless of PD-L1
(seventh) edition of the TNM classification for lung cancer. J Thorac Oncol expression and not related to platinum sensitivity or line of therapy. The
2009;4:1049-59 responses were durable with one-year overall survival of 27% for nivolumab
alone and 48% for the combination arm. These results have led to two phase
Yu JB, Decker RH, Detterbeck FC, et al. Surveillance Epidemiology and End III studies among patients with SCLC evaluating nivolumab, nivolumab/
Results Evaluation on the Role of Surgery for Stage I Small Cell Lung Cancer. J ipilimumab versus placebo in the maintenance setting after first-line therapy
Thorac Oncol 2010; 5:215–9. and nivolumab versus placebo in the second-line setting. As part of a phase IB
multi-cohort study (KEYNOTE-028), pembrolizumab was evaluated among
Weksler B, Nason KS, Shende M, et al. Surgical resection should be considered
patients with relapsed SCLC with PD-L1 positive tumors.(9) Of the 135 SCLC
for stage I and II small cell carcinoma of the lung. Ann Thorac Surg 2012;
patients screened, 37 (27%) had PD-L1 positive tumors. The response rate was
94:889–93.
29% in 24 evaluable patients. The median duration of response was 29 weeks
Stamatis G. Neuroendocrine tumors of the lung: the role of surgery in small and durable responses were observed. There is an ongoing phase II study of
cell lung cancer Thorac Surg Clin. 2014 Aug; 24(3):313-26. this agent as maintenance therapy after the completion of standard first-line
therapy in extensive stage disease. A phase I trial is evaluating pembrolizumab
Keywords: SCLC Surgery Results Prognosis with conconcurrent chemoradiation. Adverse events associated with
checkpoint inhibitors is greater with CTLA-4 combined with the PD-1 antibody
combination but were generally manageable. The proportion discontinuing
therapy for toxicity was usually less than 10%. The literature contains
ED14: SMALL CELL LUNG CANCER
anecdotes of autoimmune syndromes such as limbic encephalitis.(8) Immune
para-neoplastic syndromes are expected in a small proportion of patients
with SCLC and an increase in their occurrence with immunotherapy requires
ED14.05 IMMUNOTHERAPY OF SMALL CELL LUNG CANCER close monitoring. However, this concern is currently insufficient to impede
Nevin Murray further trials with these promising agents. Conclusion Over the past 20 years,
Medical Oncology, British Columbia Cancer Agency, Vancouver/BC/Canada almost all phase III trials of systemic therapy for SCLC have failed to improve
outcome and advances have been restricted to improved application of
Immunotherapy of Small Cell Lung Cancer Nevin Murray MD, British Columbia radiotherapy. Like squamous carcinomas, the SCLC molecular battlefield is
Cancer Agency, Vancouver, Canada The general principles of cytotoxic complex and bleak with little opportunity of even temporary respite by
chemotherapy for advanced SCLC and NSCLC have many similarities and have identification of mutually exclusive oncogenic drivers that can be treated for
advanced minimally over the past two decades.(1) The success of cancer patient benefit. Ironically, this hyper-mutated genome and greater neo-
genomics research in changing the care of patients with NSCLC with a driver antigen expression may enhance the probability of success with
mutation suitable for targeted treatment has been a powerful incentive to immunotherapy. One senses that the likelihood is high for approval of
discover such molecular targets in SCLC. Although comparative genomic antibody-drug conjugates and immune checkpoint inhibitors for SCLC after
profiling shows some similarities between SCLC and NSCLC, for SCLC, the the current roster of clinical trials are reported.References 1. Murray N, Lam S.
abnormalities identified to date are mainly tumor suppressor genes.(2) These Contrasting Management of Small Cell Lung Cancer and Non-Small Cell Lung
loss-of-function alterations do not provide the clear opportunity for rapid Cancer: Emerging Data for Low-Dose Computed Tomography Screening. J
clinical translation offered by an activating mutation in a known receptor Thorac Oncol. 2016 Feb;11(2):139-41. 2. Pietanza MC, Ladanyi M. Bringing the
tyrosine kinase. A considerable number of targeted agents have already been genomic landscape of small-cell lung cancer into focus. Nat Genet. 2012
tried in SCLC clinical trials without notable success.(3) In contrast, there is a Oct;44(10):1074-5. 3. Murray N, Noonan K. Can we expect progress of targeted
growing body of evidence for immunotherapy as a promising new treatment therapy of small cell lung cancer? In: Dingemans A, Reck M, Westeel V, editors.
for both SCLC and NSCLC. Immunotherapy investigated for SCLC includes Lung cancer. Sheffield: European Respiratory Society; 2015. p. 234. 4. Rudin
interferon, vaccines, antibody-drug conjugates and immune checkpoint CM, Pietanza MC, Bauer TM, Spigel DR, Ready N, Morgensztern D, et al. Safety
inhibitors. Interferon and vaccines have been studied in phase II and III trials and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like
without sufficient activity to change practice. Although preliminary, the data protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or
emerging from trials of antibody-drug conjugates and immune checkpoint refractory small cell lung cancer (SCLC). ASCO Meeting Abstracts. 2016 June
inhibitors has generated more excitement and are the focus for this abstract. 21;34(18_suppl):LBA8505. 5. Starodub A, Camidge DR, Scheff RJ, Thomas SS,
Antibody-Drug Conjugates The components of an antibody-drug conjugate Guarino MJ, Masters GA, et al. Trop-2 as a therapeutic target for the
include an antibody directed at a defined antigen on cancer cells, a linker, and antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132), in
a cytotoxic agent. This package represents an effective mechanism of patients (pts) with previously treated metastatic small-cell lung cancer
targeted drug delivery potentially resulting in decreased toxicity and an (mSCLC). ASCO Meeting Abstracts. 2016 May 31;34(15_suppl):8559. 6. Reck M,
improved therapeutic index. Rovalpituzumab teserine targets the Notch Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in
pathway with a monoclonal antibody portion directed against the cell surface combination with paclitaxel and carboplatin as first-line therapy in
available Notch ligand delta-like protein 3 (DLL3), which is over-expressed in extensive-disease-small-cell lung cancer: results from a randomized,
SCLC tumor-initiating cells but not in normal tissue. Rudin et al.(4) have double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. 7.
reported a phase I study including 74 patients with previously treated SCLC. Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, et al. Phase III
The confirmed response rate in 56 evaluable patients was 16%, but in 26 that Randomized Trial of Ipilimumab Plus Etoposide and Platinum Versus Placebo
showed high DLL3 expression, the response rate was 31%. Response rate was Plus Etoposide and Platinum in Extensive-Stage Small-Cell Lung Cancer. J Clin
13% in second-line and 25% in the third-line setting with some durable Oncol. 2016 Jul 25. 8. Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M,
responses observed. A phase II trial for third-line treatment of patients with Eder JP, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent
DLL3 expressing tumors has begun and if positive will be the first approved small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2
agent in this setting. Sacituzumab govitecan is another antibody-drug trial. Lancet Oncol. 2016 Jul;17(7):883-95. 9. Ott PA, Callahan MK, Odunsi K,
conjugate of a topoisomerase I inhibitor linked to an antibody to the Trop-2 Park AJ, Pan LS, Venhaus RR, et al. A phase I study to evaluate the safety and
epithelial antigen.(5) In a phase I/II clinical trial enrolling 33 evaluable SCLC tolerability of MEDI4736, an anti- programmed cell death-ligand-1 (PD-L1)
patients with a median of 2.5 previous chemotherapies, the response rate was antibody, in combination with tremelimumab in patients with advanced solid
24% and the median overall survival was 8.1 months. Dose limiting tumors. ASCO Meeting Abstracts. 2015 May 18;33(15_suppl):TPS3099.
neutropenia was 34% and grade 3+ diarrhea was seen in 9%. Immune
Checkpoint Inhibitors Since immune checkpoint blockade is more active in
hyper-mutated tumors, SCLC should be a good candidate disease for this
treatment because of a strong association with tobacco carcinogenesis and a
high frequency of somatic mutations.(2) The most advanced trial evidence is
available for a cytotoxic T-cell antibody (CTLA4) and data for two programmed SESSION ED15: THYMIC MALIGNANCIES:
death (PD-1) immune checkpoint inhibitors is emerging. After a randomized
phase II trial of ipilimumab and phased chemotherapy showed a modest
UPDATE ON TREATMENT
improvement in progression-free survival as first-line treatment of advanced WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:50
SCLC,(6) a large phase III placebo controlled trial was performed in which 1,132
previously untreated patients were randomly assigned to receive either
etoposide and platinum for four cycles alone or together with the CTLA-4 ED15.02 CHEMOTHERAPY AND TARGETED THERAPIES OF THYMIC
antibody ipilimumab.(7) The trial was negative with similar response rates MALIGNANCIES
and no difference in the primary end point of overall survival (hazard ratio Nicolas Girard, Claire Merveilleux Du Vignaux
0.94; 95% CI 0.81-1.09). Immune checkpoint blockade with PD-1 or dual CTLA-4
Hospices Civils de Lyon, Lyon/France
and PD-1 inhibition may be a more effective strategy. In a large phase I/II trial
including 180 previously treated SCLC patients, Antonia et al.(8) reported a Thymic malignancies represent a heterogeneous group of rare thoracic
cancers. The histopathological classification distinguishes thymomas from Everolimus may then represent an option for refractory tumors. Several trials
thymic carcinomas. Thymomas are further subdivided into different types assessing the efficacy of PD-1 checkpoint inhibitors are currently ongoing.
(so-called A, AB, B1, B2, and B3) based upon the atypia of tumor cells, the A phase II study of pembrolizumab, a fully humanized IgG4 Ab that targets
relative proportion of the associated non-tumoral lymphocytic component, the PD-1 receptor, was recently reported; the study has accrued 30 patients.
and resemblance to the normal thymic architecture. Thymic carcinomas are Four serious autoimmune disorders developed. Out of 30 patients evaluable
similar to their extra-thymic counterpart, the most frequent subtype being for response so far the response rate is 24%. The off-label use of checkpoint
squamous cell carcinoma. The management of thymic epithelial tumours inhibitors is currently not recommended. Overall, a dramatic improvement in
is a paradigm of multidisciplinary collaboration. The treatment strategy is our knowledge of the management of thymic tumors has occurred in the last
primarily based on the resectability of the tumour. If complete resection few years. This improvement has primarily resulted from an increased interest
is deemed not to be achievable upfront based on imaging studies, what in these rare tumors at some dedicated centers, and from the development
is the case in Masaoka-Koga stage III/IVA tumors (classified as stage IIIA/ of international efforts that succeed in putting together large-volume, top-
IIIB/IVA in the 2015 IASLC-ITMIG TNM proposed system), after a biopsy quality centers all over the world, for databases, translational research, and
is performed, primary/induction chemotherapy is administered, part of clinical trials.
curative-intent sequential strategy integrating subsequent surgery or
radiotherapy. Cases not eligible for local treatment receive definitive Keywords: Thymoma, Thymic carcinoma
chemotherapy. Primary/induction chemotherapy is then standardin non-
resectable advanced thymic epithelial tumors. Cisplatin-based combination
regimens should be administered; combinations of cisplatin, adriamycin,
ED15: THYMIC MALIGNANCIES: UPDATE ON TREATMENT
and cyclophosphamide, and cisplatin and etoposide are the most usually WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:50
used. Primary chemoradiotherapy with platin and etoposide is an option,
especially for thymic carcinomas. Usually 2-4 cycles are administered before
imaging is performed to reassess resectability of the tumor. Surgery should be ED15.03 SURGERY OF THYMIC MALIGNANCIES
offered to patients for whom complete resection is thought to be ultimately Meinoshin Okumura
achievable; extended resection may be required. Hyperthermic intrapleural General Thoracic Surgery, Osaka Univeristy Graduate School of Medicine, Suita/
chemotherapy, as well as extra-pleural pneumonectomy may be discussed Japan
in case of stage IVA tumor. Postoperative radiotherapy is usually delivered.
When the patient is not deemed to be a surgical candidate - either because Thymic epithelial tumors
R0 resection is not thought to be achievable, or because of poor performance
Thymic epithelial tumors are the most common malignancy among
status or co-existent medical condition, definitive radiotherapy is
mediastinal tumors according to Japanese thoracic surgery survey (1). Surgical
recommended part of a sequential chemoradiotherapy strategy. Combination
resection is generally the treatment of choice for thymic epithelial tumors.
with chemotherapy (including cisplatin, etoposide chemotherapy and a total
Thymic epithelial tumors are classified into thymoma, thymic carcinoma
dose of radiation of 60 Gy) may be considered as well. Chemotherapy should
(TC), and thymic neuroendocrine carcinoma (TNEC). Retrospective surgical
be offered as the single modality treatment in advanced, non-resectable,
database of Japanese Association for Research of the Thymus (JART) revealed
non-irradiable or metastatic (stage IVB) thymic epithelial tumor to improve
that recurrence free 10-year survival after macroscopic complete resection
tumor-related symptoms the aim is to improve tumor-related symptoms
was 88% in thymoma, 51% in TC, and 11% in TNEC. Thymomas are further
through obtention of tumor response, while prolonged survival is uncertain.
classified mainly into 5 pathological subtypes, WHO type A, AB, B1, B2 and B3.
Cisplatin-based combination regimen should be administered. No randomized
Pathological subtype of thymoma has been shown to reflect the oncological
studies have been conducted, and it is unclear which regimens are best; multi-
behaviors, and post-operative recurrence rate increases in this order. JART
agent combination regimens and anthracycline-based regimens appear to
database study revealed that nearly 3 quarters of thymoma surgical cases
have improved response rates compared to others, especially the etoposide,
have Masaoka stage I or II disease. Pleural dissemination is often encountered
ifosfamide and cisplatin combination. Combinations of cisplatin, adriamycin,
either before or after resection in thymoma while hematogenous or lymphatic
and cyclophosphamide is preferred. Combination of carboplatin and paclitaxel
spread seldom occurs. On the other hand, TC is often associated with
is an option for thymic carcinoma. Surgery or radiotherapy is possible in rare
metastasis to distant organs as well as nodal involvement in the mediastinum
and selected cases with unknown survival benefit. Recurrences of thymic
and cervical region. Approximately 3 quarters of surgically treated TC have
epithelial tumors should be managed according to the same strategy as newly
Masaoka Stage III or IV disease in surgical cases. While most thymomas
diagnosed tumors. Complete resection of recurrent lesions represents a
are treated by surgical resection, a considerable portion of TC are judged
major predictor of favorable outcome, and surgery is then recommended in
unresectable at initial presentation. TNEC often has nodal involvement. Initial
case of resectable lesion. In non-resectable recurrences, several consecutive
resection is indicated when clinical diagnosis is a thymic epithelial tumor
lines of chemotherapy may be administered when the patient presents with
with Masaoka stage I or II. The standard procedure is extended thymectomy
tumor progression. The re-administration of a previously effective regimen
through median sternotomy even for tumors with Masaoka stage I or II
has to be considered, especially in case of previous response, late occurring
disease because of the possibility of post-thymectomy myasthenia gravis,
recurrence, and for anthracyclins, a patient in a good medical condition
intrathymic metastasis and multiple foci of tumor. JART database study,
and not having received cumulative doses precluding the safe delivery of
however, revealed that recurrence rate in thymoma with T1N0M0 by UICC was
at least 3 additional cycles. Preferred regimens for second-line treatment
not significantly different between two procedures, thymothymomectomy
include carboplatin plus paclitaxel, and platin plus etoposide; capecitabine
(1.4%) and thymomectomy (2.8%) (p = 0.192) (2). Furtheremore, systematic
plus gemcitabine is an option. These regimens were evaluated in dedicated
dissection of mediastinal lymph nodes is not supposed essential in thymoma
phase II trials. Options for subsequent lines include pemetrexed, oral
because incidence of nodal involvement is negligible. Advancement in video-
etoposide. In patients with octreoscan-positive thymoma, not eligible to
assisted thoracic surgery (VATS) has prompted endoscopic operation also
receive additional chemotherapy, octreotide alone or with prednisone may
for thymoma, and currently, partial resection of the thymus by VATS seems
represent a valuable option. The use of targeted agents may be done in an
accepted for less-invasive thymoma when myasthenia gravis is not associated,
off-label setting in advanced thymic malignancies. While KIT is overexpressed
but careful observation by annual examination by CT scan is recommended
in 80% of thymic carcinomas, KIT gene mutations are found only in 9% of
after partial thymectomy. Highly invasive thymomas should be treated by
cases, consisting of mutations observed in other malignancies (V560del,
preoperative induction chemotherapy to reduce the tumor size. Pathological
L576P) or mutations unique to thymic carcinomas (H697Y, D820E). Responses
diagnosis by biopsy is required before chemotherapy to differentiate between
and possibly prolonged survival was reported with the use KIT inhibitors
invasive thymoma and TC. Resection of the pericardium, lung, great vessels,
- imatinib, sunitinib, or sorafenib - , mostly in single-case observations.
and thoracic wall is sometimes required. JART database study revealed
Non-pretreated reported KIT mutants are not uniformly sensitive to imatinib,
that invasion of the thoracic wall was the independent factor of recurrence
based on the clinical and/or the preclinical evidence in thymic carcinoma
after complete resection. (3) Even subtotal resection sometimes results in
and/or other KIT-mutant malignancies. KIT sequencing (exons 9-17) is an
long-term survival. If complete resection is not achieved, radiotherapy is
option for refractory thymic carcinomas in the setting of possible access
supposed to control the remaining tumor. Surgery for thymoma with pleural
to off-label use of such inhibitors. KIT inhibitors also potently inhibiting
or intrapericardial dissemination can be indicated. JART database study
other kinases, including Vascular Endothelial Growth Factor Receptors and
revealed that the number of the disseminated lesions is a prognostic factor
Platelet-Derived Growth Factor Receptors activated in thymic malignancies.
and that patients with less than 10 lesions had better survival. (4) Operative
A phase II trial recently demonstrated the efficacy of sunitinib in terms of
procedure varies from partial pleurectomy to extrapleural pneumonectomy
response and disease control rate in thymic epithelial tumors, including
with resection of the primary lesion. The recommended procedure depends
thymic carcinomas (ORR 26%; DCR: 91%) and, to a lesser extent, thymomas
on the spread of disseminations. Although intrapericardial implantation is
(ORR:6%; DCR:81%). Sunitinib may then represent an option as second-line
commonly thought to be hard to resect, resection can be achieved in some
treatment for thymic carcinomas, independantly from KIT status. There
cases because thymomas usually do not invade into the heart muscle severely.
is no clinical data reporting on antitumor efficacy of other antiangiogenic
Preoperative chemotherapy is supposed to enable complete resection of
drugs. mTOR is emerging as a potential target in thymic epithelial tumors,
intrapericardial implantations through reduction of the tumor volume. Most
following tumor responses observed in phase I trials. Everolimus (10 mg daily)
of the hematogenous metastases of thymoma occur in the lung probably
was evaluated in thymic epithelial tumors in a recently reported phase II
because the neoplastic cells can directly enter the blood stream through
trial reporting on a 22% response rate, as well as a 93% disease control rate.
thymic veins. Surgical treatment for thymomas with lung metastasis is

feasible, but indication of surgery for thymoma with extrathoracic distant RT is an excellent treatment option for patients with unresectable thymic
metastasis should be determined carefully. Recurrence often occurs on the malignancies. While most thymic tumors are resectable, a subset of patients
pleural surface followed by the lung metastasis. Surgical resection of the is technically or medically inoperable, due to invasion of critical structures or
recurrent lesions in the intrathoracic cavity is generally thought to contribute comorbidities. In general, thymic malignancies are radiosensitive, allowing
to survival. (5) Preoperative induction therapy is almost mandatory in highly for long-term local control rates. Palliative RT should be considered even in
invasive TC and poorly-differentiated NEC. Concurrent chemoradiotherapy is the recurrent or metastatic setting. Image-guided hypofractioned ablative RT
effective in reducing the tumor size. Resection and reconstruction of even the may be used for oligometastatic disease as an alternative to surgical resection
ascending aorta under cardiopulmonary bypass can be attempted. Systematic and has been shown to be a highly effective treatment modality with >90%
mediastinal and cervical lymph node dissection is recommended because of long-term local control rates and minimal morbidity. Conventional palliative
high incidence of nodal involvement. RT is an important modality to improve quality of life by alleviating pain,
treating SVC syndrome, airway compression and other symptoms. Modern
Malignant germ cell tumors (GCT) radiation therapy techniques such as 3D conformal radiation therapy or
intensity-modulated radiation therapy should be used to minimize morbidity
Malignant GCT is a highly aggressive neoplasm arising in young males.
from treatment. Proton therapy may have advantages in certain clinical
Chemotherapy is recommended without pathological diagnosis when serum
scenarios and is currently under investigation.
tumor marker is extraordinarily elevated. In case of non-seminomatous
GCT, complete resection of the tumor after normalization of tumor marker Keywords: ADJUVANT, radiation therapy, Thymic malignancies
value by chemotherapy should be achieved, or otherwise, tumor recurrence
is highly possible. Resection and reconstruction of the great vessels under
cardiopulmonary bypass is often necessary.
Liposarcoma
Mediatinal liposarcoma is a rare neoplasms and sometimes appears as a

huge tumor. This neoplasm is supposed to be resistant to chemotherapy, and
complete surgical resection is required. Local recurrence occurs frequently
because obtaining safe surgical margin is difficult. Radiotherapy could be a
treatment of choice for recurrent tumors.
Lymphoid malignancies
Role of surgery is limited. Surgical biopsy is sometimes required when ML is

suspected by imaging and high value of serum sIL-2 receptor. When tumor
remains after chemotherapy, surgical resection is sometimes indicated.
Low-grade malignancy including MALT and Castleman’s disease can be
exceptionally treated by initial surgery.
References
Committee for Scientific Affairs, The Japanese Association for Thoracic

Surgery. Thoracic and cardiovascular surgery in Japan during 2013: Annual
report by The Japanese Association for Thoracic Surgery. Gen Thorac
Cardiovasc Surg. 2015 ;63:670-701.
Nakagawa K, et al. Is thymomectomy alone Appropriate for stage I (T1N0M0)

thymoma? Results of a propensity-score analysis. Ann Thorac Surg.
2016;101:520-6.
Yamada Y, et al. Surgical outcomes of patients with stage III thymoma in the
Japanese nation-wide database. Ann Thorac Surg 2015;100:961–7.
Okuda K, et al. Thymoma Patients With Pleural Dissemination: Nationwide

Retrospective Study of 136 Cases in Japan. Ann Thorac Surg 2014;97:1743–9.
Mizuno T, et al. Surgical management of recurrent thymic epithelial tumors. A

retrospective analysis based on the Japanese nationwide database. J Thorac
Oncol. 2015;10:199–205.
Keywords: Thymic neuroendocrine carcinoma, Thymoma, Malignant germ cell

tumor, Thymic carcinoma
ED15: THYMIC MALIGNANCIES: UPDATE ON TREATMENT

ED15.04 RADIATION OF THYMIC MALIGNANCIES

Andreas Rimner
Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York/NY/United
States of America
Radiation therapy (RT) plays an important role in the multimodality

management of thymic malignancies. It can be employed in the neoadjuvant,
adjuvant, definitive or palliative setting. Adjuvant RT is the most extensively
studied setting for RT in thymic malignancies. After complete resection
there is likely no role for adjuvant RT for patients with stage I thymomas, a
possible role for patients with stage II thymomas, and likely a survival benefit
in patients with stage III and IV thymomas. Several recent large database
and population-based studies have detected a survival benefit for advanced
thymomas, while the results for stage II thymomas have been mixed. For
thymic carcinomas the impact of adjuvant RT appears more significant.
Several large database and population-based studies have consistently
reported a survival benefit with adjuvant RT for thymic carcinoma across
various disease stages. For incompletely resected thymic tumors there is
a stronger rationale for adjuvant RT based on emerging data and general
oncologic principles. Neoadjuvant RT has been mostly explored in thymic
carcinoma and demonstrated high response and operability rates. Definitive
the mediastinum in lung cancer. J Clin Oncol 2008;26(20):3346-3350. (6)

SCIENTIFIC SESSIONS Szlubowski A, Zielinski M, Soja J, Filarecka A, Orzechowski S, Pankowski J,
Obrochta A, Jakubiak M, Wegrzyn J, Cmiel A. Accurate and safe mediastinal
SESSION SC01: STAGING BEFORE AND AFTER INDUCTION restaging by combined endobronchial and endoscopic ultrasound-guided
needle aspiration performed by single ultrasound bronchoscope. Eur J
THERAPY FOR N2 DISEASE Cardiothor Surg 2014;46:262-266. (7)Collaud S, Lardinois D, Tischler V, Steinert
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 H, Stahel R, Weder W. Significance of a new fluorodeoxyglucose-positive
lesion on restaging positron emission tomography/computed tomography
after induction therapy for non-small-cell lung cancer. Eur J Cardiothorac Surg
SC01.01 THE IMPORTANCE OF MEDIASTINAL DOWN-STAGING 2012;41:612-616. (8)H. Decaluwé, P. De Leyn, J. Vansteenkiste, C. Dooms, D.
DURING INDUCTION THERAPY OF N2 DISEASE Van Raemdonck, P. Nafteux, W. Coosemans, T. Lerut. Surgical multimodality
Paul De Leyn1, Herbert Decaluwe1, Christophe Dooms2, Johan Vansteenkiste3 treatment for baseline resectable stage IIIA-N2 non-small cell lung cancer.
1 Degree of mediastinal lymph node involvement and impact on survival. Eur
Thoracic Surgery, University Hospital Leuven, Leuven/Belgium, 2Respiratory
Oncology, University Hospital KU Leuven, Leuven/Belgium, 3Respiratory Oncology
J Cardiothoracic Surg 2009 ;36 :433-9. (9)Dooms C, Verbeken E, Stroobants
Unit (Pneumology), University Hospital KU Leuven, Leuven/Belgium S, Nackaerts K, De Leyn P, Vansteenkiste J. Prognostic stratification of
stage IIIA-N2 non-small-cell lung cancer after induction chemotherapy: a
Patients with preoperative pathological proven N2 disease have a dismal model based on the combination of morphometric-pathologic response in
prognosis after surgery. Neoadjuvant chemotherapy or chemoradiotherapy mediastinal nodes and primary tumor response on serial 18-fluoro-2-deoxy-
is a therapeutic option that is used in patients with baseline resectable stage glucose positron emission tomography. J Clin Oncol 2008;26(7):1128-1134.
IIIA-N2 non-small cell lung cancer. Mediastinal downstaging is an important
prognostic factor for long term survival. Different restaging techniques are Keywords: Mediastinal restaging, NSCLC, induction therapy
available. The mediastinum can be restaged by CT scan, remediastinoscopy,
VATS, PET-CT and EBUS-EUS fine needle aspiration. In primary staging, CT
scan has proved to have a low accuracy. It is not surprising that the accuracy
SC01: STAGING BEFORE AND AFTER INDUCTION THERAPY FOR N2 DISEASE
of CT scan in restaging the mediastinum is also low. In a Spanish study of MONDAY, DECEMBER 5, 2016 - 11:00-12:30
24 patients who underwent neoadjuvant chemotherapy for N2 non-small
cell lung cancer, staging was performed by CT scan and remediastinoscopy
(1). CT scan had a sensitivity of 41%, a specificity of 75% and an accuracy of SC01.02 PET-CT FOR RESPONSE ASSESSMENT DURING INDUCTION
58%. In a prospective study of 93 patients who were restaged by integrated THERAPY OF N2 NSCLC
PET-CT after induction chemoradiotherapy, repeat PET-CT was found to Christoph Pöttgen, Martin Stuschke
be more accurate than CT alone for pathological stages. However, there West German Cancer Center, University of Duisburg-Essen, Essen/Germany
were 20 false negative and 25 % false positive cases. So, in case of suspicion
of residual mediastinal disease, nodal biopsies are still required (2). We Approximately 30% of patients with non-small cell lung cancer (NSCLC) are
evaluated in a prospective single center study repeat mediastinoscopy found to have locally advanced stage III tumours at initial diagnosis. For
and PET-CT after induction chemotherapy for N2 disease. PET-CT had a these patients the curative therapeutic options include definitive high-dose
sensitivity of 77% and a specificity of 88% (3). Repeat mediastinoscopy, radiotherapy with concurrent chemotherapy or, alternatively, induction
technically much more difficult than the first procedure, offers the advantage treatment followed by surgery. Preoperative chemotherapy or combined
of providing histological evidence of response after induction therapy. radiochemotherapy protocols followed by resection result in cure rates
Although some centers obtain good results (4), most surgeons will accept of 25-35 percent at 3 years for locally advanced NSCLC. However, surgical
that remediastinoscopy is technically difficult and often incomplete. We resection in patients with stage IIIa N2 remains an issue of controversy
performed a prospective study to evaluate the accuracy of remediastinoscopy depending on the extent of lymph node involvement. Neoadjuvant
and PET-CT in restaging the mediastinum after mediastinoscopy proven chemo- or radiochemotherapy is being used to reduce disease burden in
N2 disease (3). The first mediastinoscopy was thoroughly performed with the mediastinum before surgery since patients who are downstaged via
a mean lymph node level of 3.6 per patient biopsied. In our experience, neoadjuvant therapy and then undergo resection experience a significantly
remediastinoscopy was technically feasible, but inaccurate due to severe longer 5-year survival of 40% to 50% than those who are found to have
adhesions and fibrosis. The sensitivity to detect residual mediastinal residual N2 disease at the time of surgery. Thus, identification of patients
lymph nodes was only 28,6% with an accuracy of 58,3%. Minimally invasive who are N2 negative after completion of their neoadjuvant therapy is a
endoscopic technique EUS and EBUS also obtain histological diagnosis. Their critical component for patient selection for thoracotomy. However, clinical
accuracy is very good in baseline mediastinal staging. In the study Herth et al restaging in these patients often is challenging. Endoscopic ultrasound
(5) EBUS-FNA was performed for restaging after induction chemotherapy or guided biopsies (EUS/EBUS-FNA) have increasingly become available and
chemoradiotherapy for N2 disease in 124 patients. The sensitivity was 76% are currently preferred procedures for staging and restaging before surgery
but the negative predictive value was as low as 20%. The largest series in the due to their high diagnostic accuracy.(1) Serial PET-CT imaging captures
literature is reported by Szlubowski (6). They combined EBUS-EUS FNA for anatomical changes and additionally offers semiquantitative information
restaging N2 disease in 106 patients. Sensitivity was 67% with a negative about morphometric and metabolic tissue changes during induction
predictive value of 73%. Some recent smaller studies showed better results treatment. Issues of PET-CT performance and quality assurance concerning
for EBUS-EUS to prove persistent nodal disease. Most of the new lesions standardization have been clarified during recent years and the validity
that appear after induction chemotherapy on PET-CT are not malignant (7). of repeated measurements has been approved.(2) Successful induction
We know that some patients with minimal persistent N2 disease (mainly treatment regimes have been frequently found to reduce 18F-FDG uptake and
single level) can have a good prognosis after surgical resection (8). In a study thus PET-CT allows to assess the therapeutic response. Reduction in FDG-
published by Dooms et al (9) patients with less than 10% viable tumor cells in uptake of mediastinal lymph nodes after induction therapy has been shown
mediastinal lymph node sampled at mediastinoscopy and s with more than to correlate well with histopathologic response (3), while postinduction
60% decrease of SUVmax of primary tumor had a five year survival of over 60%. PET avidity taken alone was not consistently found to be associated with
Therefore, we believe that a new staging algorithm could be used to select pathological N2 involvement (4). In the direct comparison of EUS-FNA with
patients for radical therapy after induction chemotherapy for N2 disease. PET-CT for restaging after induction chemoradiotherapy, concordance
At baseline staging, pathological N2 disease should be proved by EBUS-EUS between findings of restaging EUS-FNA and metabolic response of lymph
fine needle aspiration. PET-CT should be done to exclude distant metastasis node metastases was observed in 63% patients treated within a prospective
and to evaluate SUVmax of the primary tumor. At restaging, mediastinoscopy study but the diagnostic accuracy of PET-CT was limited.(5) Nevertheless,
with nodal dissection should be performed. Also repeat PET-CT should be serial FDG-uptake measurements seem to provide prognostic information
done. In patients with major pathological response in lymph nodes and a during induction therapy. Data collected in prospective trials suggest that
major SUV drop of the primary tumor, surgery can be performed with good a decrease in SUVmax between 45% to 60% optimally separates between
outcome.References (1)Mateu-Navarro M, Rami-Porta R, Bastus-Oiulats R, responders and non-responders (6-9). In a recent large retrospective analysis,
Cirera-Noqueras L, Gonzalez-Pont G. Remediastinoscopy after induction a decrease in SUVmax greater than 60% in the involved mediastinal nodes was
chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2000;70:391-5. the best predictor of overall survival, better than changes seen in the primary
(2)Cerfolio R, Bryant A, Ojha B. Restaging patients with N2 (stage IIIa) non- tumour site. (10) An analysis of a randomized trial in potentially resectable
small cell lung cancer after neoadjuvant chemoradiotherapy: a prospective stage III NSCLC of induction treatment (including a hyperfractionated
study. J Thorac Cardiovasc Surg 2006;131(6):1229-1235. (3)De Leyn P, Stoobants accelerated radiotherapy phase) and definitive radiochemotherapy compared
S, Vansteenkiste J, Dewever W, Lerut A. Prospective study of accuracy of with induction treatment followed by surgery confirmed that as early as
redo videomediastinoscopy and PET-CT in detecting residual mediastinal after two cycles of cisplatin-based induction chemotherapy percentage of
disease after induction chemotherapy for NSCLC. Lung Cancer 2005;49 Suppl SUVmax remaining represents a significant prognostic parameter.(9) PET-
2 : S3. (4)Rami-Porta R, Call S. Invasive staging of mediastinal lymph nodes: response was of higher importance than all other clinical factors. Cut-off
mediastinoscopy and remediastinoscopy. Thorac Surg Clin 2012: 22:177-89. levels between 0.45 and 0.55 were predictive for freedom from extracerebral
(5)Herth F, Annema J, Eberhardt R, Yasufuku K, Ernst A, Krasnik M, Rintoul R. progression in all randomized patients. No important differences in the
Endobronchial ultrasound with transbronchial needle aspiration for restaging predictive value were observed comparing resection versus definitive
radiochemotherapy. PET-response was closely related to extracerebral

distant metastases but not to local recurrences, independent of treatment. therapy, only TEMLA has been validated on two retrospective studies
One might conclude that less PET-responsive tumors are successfully conducted in the same institution. In the first series with 63 patients, the
controlled by intensified hyperfractionated accelerated radiochemotherapy diagnosis of N2-3 disease before induction treatment was confirmed with
or neoadjuvant radiochemotherapy and resection at loco-regional sites invasive techniques in 27 patients (20 with endosonography and 7 with
so that the highest risk of relapse remains at extracerebral distant sites. mediastinoscopy), and with CT in 36. Sensitivity, specificity and accuracy of
Therefore, a selection or intensification of the local therapy according restaging TEMLA were 95.5%, 100% and 98.3%, respectively [9]. In the second
to SUV-decrease is not warranted by these data. Functional imaging has series with 176 patients treated with chemo- or chemotherapy, the restaging
not yet been fully established for treatment guidance but prospective values of endobronchial endosonography (EBUS) and/or esophageal
evaluation is underway. In the group of poor-responding patients, treatment ultrasonograpy (EUS) (88 patients) were compared with those of TEMLA (78
intensification by independent systemic options such as targeted therapy or patients). There was a significant difference between EBUS/EUS and TEMLA
immunomodulating therapy may become emerging new treatment options for sensitivity (64.3% and 100%; p < 0.01) and NPV (82.1% and 100%; p < 0.01) in
within clinical trials.References: 1) De Leyn EJCTS 2014, 2) Young, EJC 1999, favor of TEMLA [10]. Regarding their use for primary staging, VAMLA and
3) Pöttgen CCR 2006, 4) Ripley JTCS 2016, 5) Stigt, Lung Cancer 2009, 6) TEMLA represent a new paradigm. Firstly, transcervical lymphadenectomies
Hoekstra, JCO 2005, 7) Eschmann, Lung Cancer 2007, 8) Dooms, JCO 2008, 9) could also be considered part of the induction treatment because the
Pöttgen, JCO 2016, 10) Barnett ATS 2016 mediastinum is staged and downstaged by these operations. Secondly, due to
the fact that nodal restaging is unnecessary, new parameters should be used
Keywords: PET-CT; N2; induction, restaging to select patients for lung resection after induction such as the stability of
the primary tumor and the absence of extrathoracic disease based on the
results of postinduction CT or PET. Finally, intraoperative pathologic study of
the remaining lymph nodes should confirm the absence of nodal involvement
before proceeding with lung resection, especially if pneumonectomy is
SC01: STAGING BEFORE AND AFTER INDUCTION THERAPY FOR N2 DISEASE
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 required. Conclusions In multimodality treatments for patients with stage
IIIA(N2) tumors, pathologic restaging after induction therapy is essential to
decide on subsequent treatment. ReMS is a useful procedure regardless of the
SC01.04 THE ROLE OF MEDIASTINOSCOPY IN INDUCTION THERAPY induction treatment used or the intensity of the first mediastinoscopy. The
OF N2 NCSLC role of transcervical lymphadenectomies in staging and restaging should be
Sergi Call implemented in clinical practice and validated in future clinical trials.
Department of Thoracic Surgery, Hospital Universitari Mútuaterrassa, Terrassa/ References 1. De Waele M, Serra-Mitjans M, Hendriks J, et al. Accuracy and
Spain survival of repeat mediastinoscopy after induction therapy for non-small cell
lung cancer in a combined series of 104 patients. Eur J Cardiothorac Surg
Rationale for restaging after induction therapy Persistent mediastinal nodal 2008;33:824-8. 2. Van Meerbeeck JP, Kramer GW, Van Schil PE, et al.
involvement after induction therapy is an independent prognostic factor Randomized controlled trial of resection versus radiotherapy after induction
associated with poor prognosis [1]. Based on the results of two phase III chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst
clinical trials on multimodality treatment for pathologically proven N2 2007;99:442-50. 3. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus
non-small cell lung cancer (NSCLC) [2,3], patients with persistent mediastinal chemotherapy with or without surgical resection for stage III non- small-cell
involvement do not benefit from surgical resection in terms of survival. The lung cancer: a phase III randomised controlled trial. Lancet 2009;374:379-86.
assessment of an objective response after induction therapy continues to be a 4. De Leyn P, Dooms C, Kuzdzal J, et al. Revised ESTS guidelines for
diagnostic challenge. For this reason, the use of ‘mediastinal downstaging’ as preoperative mediastinal lymph node staging for non-small-cell lung cancer.
a criterium to select patients for surgery requires a reliable restaging method Eur J Cardiothorac Surg 2014;45:787–98. 5. Lardinois D, Schallberger A,
to predict pathologic stage before lung resection. Algorithm for mediastinal Betticher D, et al. Postinduction video-mediastinoscopy is as accurate and
restaging The European Society of Thoracic Surgeons guidelines for safe as video-mediastinoscopy in patients without pretreatment for
preoperative lymph node staging for NSCLC recommend histological potentially operable non-small cell lung cancer. Ann Thorac Surg 2003;75:1102–
confirmation of objective response after induction therapy. This confirmation 6. 6. Call S, Rami-Porta R, Obiols C, et al. Repeat mediastinoscopy in all its
can be done with ultrasound-guided endoscopic techniques. However, the use indications: experience with 96 patients and 101 procedures. Eur J
of an invasive surgical technique is still recommended when the results of Cardiothorac Surg 2011; 39:1022-7. 7. Stamatis G, Fechner S, Hillejan L, et al.
endoscopic procedures are negative [4]. The role of mediastinoscopy Repeat mediastinoscopy as a restaging procedure. Pneumologie 2005;59:862-
Mediastinoscopy in restaging can be performed in the following situations: 1) 6. 8. Marra A, Hillejan L, Fechner S, et al. Remediastinoscopy in restaging of
after induction therapy with no pretherapeutic invasive diagnosis; 2) after lung cancer after induction therapy. J Thorac Cardiovasc Surg 2008;135:843-
induction therapy with mediastinal histological confirmation by endoscopic 9. 9. Zieliński M, Hauer L, Hauer J, et al. Non-small-cell lung cancer restaging
techniques; 3) after induction therapy preceded by staging mediastinoscopy. with transcervical extended mediastinal lymphadenectomy. Eur J
In this case, mediastinoscopy is a reoperation: a remediastinoscopy. The use Cardiothorac Surg 2010;37:776–80. 10. Zielinski M, Szlubowski A, Kołodziej M,
of first mediastinoscopy for restaging is addressed in a small series [5]. In this et al. Comparison of endobronchial ultrasound and/or endoesophageal
article, a negative predictive value (NPV) of 90% with a prevalence of ypN2 of ultrasound with transcervical extended mediastinal lymphadenectomy for
46% were reported. Theoretically, this approach could be a good strategy to staging and restaging of non-small-cell lung cancer. J Thorac Oncol 2013;8:630-
perform an easier and safe mediastinoscopy due to the absence of adhesions 6. Table 1. Staging values of the largest published series of
in the mediastinum. Remediastinoscopy (reMS) is a technique that does not remediastinoscopies for restaging after induction therapy.
differ much from a conventional mediastinoscopy. However, reMS is
technically more demanding because of peritracheal adhesions, resulting in a
Author Year N S NPV DA
lower accuracy in comparison with the first procedure. The main goal of this
procedure is to take new biopsies of those nodes that had been positive at Stamatis et al. [7] 2005 160 0.74 0.86 0.92
first mediastinoscopy. Moreover, if it is technically feasible, other nodal
De Waele et al. [1] 2008 104 0.71 0.73 0.84
stations should be reached to rule out subclinical progression of the disease.
Although reMS is not a common procedure, several authors have reported its Marra et al. [6] 2008 104 0.61 0.85 0.88
feasibility and consistent results (see table 1). In addition, its results do not
Call et al. [8] 2011 84 0.74 0.79 0.87
seem to depend on the type of the induction therapy (chemotherapy or
chemoradiation) or on the level of thoroughness of the initial
mediastinoscopy [6]. Morbidity rate ranges from 0% to 4%, and complications Abbreviations: N: number of patients; S: Sensitivity; NPV: Negative predictive
are not specific of reMS because they can also occur at first mediastinoscopy value; DA: Diagnostic accuracy
[1,6-8]. Regarding mortality, only one death has been reported. Based on the Keywords: restaging, Mediastinoscopy, induction therapy
four largest published series, this intraoperative death represents a mortality
rate of 0.2% [1,6-8]. The role of transcervical lymphadenectomies During the
last decade, two new surgical staging procedures were developed:
videoassisted mediastinoscopic lymphadenectomy (VAMLA) and SC01: STAGING BEFORE AND AFTER INDUCTION THERAPY FOR N2 DISEASE
transcervical extended mediastinal lymphadenectomy (TEMLA). The main MONDAY, DECEMBER 5, 2016 - 11:00-12:30
difference between these procedures is that VAMLA is an endoscopic
technique performed through a videomediastinoscope, and TEMLA is an open SC01.05 VIDEO-THORACOSCOPY FOR STAGING OF N2 NSCLC
procedure assisted by a videomediastinoscope or a videothoracoscope,
DURING INDUCTION THERAPY
depending on the nodal station dissected. Both techniques imply the removal
of all the lymph nodes of the explored nodal stations, allowing the Thomas D’Amico
identification of minimal nodal disease that is not identified on computed Surgery, Duke Cancer Institute, Durham/NC/United States of America
tomography (CT) or positron emission tomography (PET). Therefore, after a
The optimal strategy for patients with stage III non-small cell lung cancer
properly performed transcervical lymphadenectomy, the restaging of the
(NSCLC) is not well-established and significant variation in practice exists
mediastinum is unnecessary because there is no material left for a new
across the United States and Europe. In the U.S., the majority of National
biopsy. Focusing on the use of these procedures for restaging after induction
Comprehensive Cancer Network (NCCN) member institutions consider appearance is generally conserved. This implies that most metastases look
surgery to be indicated in stage IIIA patients with involvement of a single alike and in most instances also have a similar morphologic appearance as the
N2 lymph node station smaller than 3 cm who have undergone induction primary tumor. However, dedifferentiation occasionally occurs in metastases.
chemotherapy. However, there is no agreement among institutions regarding Thus it is reasonable to conclude that lesions of different histological types,
treatment for other manifestations of stage IIIA-N2 involvement (e.g., e.g. squamous cell and adenocarcinoma, are two separate primary cancers.
multi-station or bulky disease) and both NCCN and European Society of Recently, it was suggested that differences in a comprehensive histologic
Medical Oncology (ESMO) guidelines recommend that the role of surgery be assessment may provide an argument for separate primary cancers. However,
discussed in a multidisciplinary tumor board setting. The use of induction resection specimen analysis is required for this assessment, making this
chemotherapy vs induction chemoradiotherapy is currently of great interest approach only useful in about 15-20% of the cases. Moreover, an evidence
worldwide, and the use of the latter is still common despite the results of based data set supporting comprehensive histologic assessment is currently
numerous clinical trials and meta-analysis. The lack of consensus regarding lacking. Reproducibility has to be taken into account.6 In contrast to different
treatment strategies for stage III NSCLC is in part due to the relatively low morphological types, in case of two tumors with similar morphology a
number of randomized studies available to guide decision-making, as well conclusion for same lineage (primary tumor- metastases relation) or different
as institutional biases despite evidence. One important issue is the role and lineage (two primary tumors) is not easy to reach. The reason for this is that
methods of restaging after induction therapy for patients with potentially within an individual the genetic predisposition and etiologic factors are the
resectable Stage IIIA (N2) disease. While all would agree that pathologic same and may lead to separate tumors with the same morphology, which
confirmation of N2 disease prior to induction chemotherapy is mandatory, may still represent two lineages (thus two primary tumors) or alternatively,
using EBUS or mediastinoscopy, not all surgeons believe that restaging after the same morphology in metastatic setting is one lineage. In case of multiple
induction therapy to confirm response to chemotherapy is necessary, despite adenocarcinoma in-situ lesions, they are assumed to be separate primaries.
evidence that the overall and cancer-specific survival of non-responders In summary , in comparing two tumors differences in morphologic types
is quite low. There are 2 dominant strategies for staging and restaging is conclusive for second primary tumors, but demonstration of the same
patients with N2 disease: EBUS prior to induction therapy and restaging morphology is not sufficient for lineage analysis. DNA changes Demonstration
with videomediastinoscopy or mediastinoscopy prior to induction therapy of specific driver mutations by widely available PCR sequencing techniques
and restaging with thoracoscopy or repeat mediastinoscopy. There may be may have use in establishing lineage.7In case of different driver mutations
a role for each strategy depending on individual patient characteristics. between two tumors, this obviously provides a strong argument for two
Advantages of thoracoscopic restaging after induction therapy include the primary (lung) cancers. However the frequency of discordant driver mutations
ability to resect all ipsilateral nodes to most accurately assess response and is not so high. Noteworthy is that the demonstration of different passenger
the resection of nodal tissue at thoracoscopy is the first step in thoracoscopic mutations does not have any use for lineage determination. In case of equal
resection and thus greatly facilitates the procedure. The role of thoracoscopic driver mutations a conclusion about lineage is not easy to reach.8,9Not only
restaging after induction therapy will be reviewed, and the technical aspects because the genetic predisposition and etiologic factors are the same,
for successful restaging and thoracoscopic lobectomy after induction therapy but also because in certain genes hotspot mutations occur. Thus simple
are demonstrated in videos.References 1. Martins RG, D’Amico TA, Loo BW, Jr., demonstration of the same mutation does not provide definite evidence
et al. The management of patients with stage IIIA non-small cell lung cancer for lineage analysis. On this matter more research is needed with posterior
with N2 mediastinal node involvement. Journal of the National Comprehensive probability analysis involving a relevant number of similar mutations. A
Cancer Network : JNCCN. 2012;10(5):599-613. 2. Vansteenkiste J, De Ruysscher, detailed genetic assessment such as in comparative genomic hybridisation
D, Eberhardt WEE, Lim E, Senan S, Felip E, Peters s. Early-Stage and Locally (CGH) may have greater discriminative power but has been used in only
Advanced (non-metastatic) Non-Small-Cell Lung Cancer: ESMO Clinical a few small studies.10In array CGH the number of data points is orders of
Practice Guidelines. Annals of Oncology. 2013;24((suppl 6)):vi 89-98. 3. magnitude greater than in mutation analysis. Array CGH encompasses the
Ettinger DS, Wood DE, Akerley W, et al. Non-small cell lung cancer, version predisposition and etiologic factor related copy number variations (CNV) as
6.2015. Journal of the National Comprehensive Cancer Network : JNCCN. well as lineage specific CNV. In this sense comparison of exact breakpoints
2015;13(5):515-524. 4. Weeks JC, Uno H, Taback N, et al. Interinstitutional in gene rearrangements is useful. Although the data are limited as the
variation in management decisions for treatment of 4 common types of assessment was in the past complex, nowadays arrayCGH in the form of
cancer: A multi-institutional cohort study. Annals of internal medicine. shallow sequencing can reliable be performed on small biopsies as well. To
2014;161(1):20-30. 5. Pless M, Stupp R, Ris HB, et al. Induction chemoradiation which extend NGS with a large mutation panel may be useful remains to be
in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet. seen. In summary , different driver mutations is conclusive for second primary
2015;386(9998):1049-1056. 6. Katakami N, Tada H, Mitsudomi T, et al. A tumors, but demonstration of the same driver mutation is not sufficient for
phase 3 study of induction treatment with concurrent chemoradiotherapy lineage analysis. Clinical context Adding clinical context provides interesting
versus chemotherapy before surgery in patients with pathologically arguments. 1) Imaging may show multiple ground glass opacities (mGGO)
confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903). Cancer. and lack of enlarged lymph nodes. Although the morphology may be similar
2012;118(24):6126-6135. 7. Girard N, Mornex F, Douillard JY, et al. Is neoadjuvant (lepidic pattern with AIS, MIA, Invasive adenocarcinoma) the mGGO lesions
chemoradiotherapy a feasible strategy for stage IIIA-N2 non-small cell lung are considered to be separate primaries. In case of part solid component
cancer? Mature results of the randomized IFCT-0101 phase II trial. Lung the morphological equivalent is usually infarction (=benign) or invasive
Cancer. 2010;69(1):86-93. 8 Jaklitsch MT, Gu L, Harpole DH, D’Amico TA, et al. cancer. 2) Imaging may show multiple consolidations (pneumonic type) with
Prospective phase II trial of pre-resection thoracoscopic restaging following mostly the morphological correlate of invasive mucinous adenocarcinoma.
neoadjuvant therapy for IIIA(N2) non-small cell lung cancer: Results of CALGB 3) Abundance of nodular lesions, provides an argument for metastases
39803. J Thorac Cardiovasc Surg 2013;146: 9-16 9. Yang CF, Gulack BC, Gu L, et (although rare exceptions exist, e.g. DIPNECH, Carney’s triad), while lack of
al. Adding radiation to induction chemotherapy does not improve survival nodal or systemic metastases provides an argument of two primary lung
of patients with operable clinical N2 non-small cell lung cancer. The Journal cancers. 4) Clinical follow-up is in hindsight only partly useful: lack of nodal or
of thoracic and cardiovascular surgery. 2015;150(6):1484-1492; discussion systemic metastases provides an argument of two primary lung cancers, while
1492-1483. 10. Shah AA, Berry MF, Tzao C, et al. Induction chemoradiation is presence of local and/or distant metastases may be due to one of the two or
not superior to induction chemotherapy alone in stage IIIA lung cancer. Ann both lung cancers. Conclusion If morphological and/or DNA analysis provides
Thorac Surg. 2012;93(6):1807-1812. differences between two tumors it is relatively easy to establish that these
pulmonary foci of cancer are separate primary tumors. Many commonly used
Keywords: lung cancer surgery, minimally invasive surgery, stage IIIA characteristics are associated with a substantial rate of misclassification.
Careful review by a multidisciplinary tumor board, considering all available
information, is recommended.References 1. Detterbeck, F. C. et al. The IASLC
Lung Cancer Staging Project: Summary of Proposals for Revisions of the
Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement
SESSION SC02: MULTIFOCAL LUNG CANCER in the Forthcoming Eighth Edition of the TNM Classification. J. Thorac. Oncol.
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 11, 639–50 (2016). 2. Detterbeck, F. C. et al. The IASLC Lung Cancer Staging
Project: Background Data and Proposals for the Classification of Lung
Cancer with Separate Tumor Nodules in the Forthcoming Eighth Edition of
SC02.01 MULTIPLE PRIMARY LUNG CANCERS VERSUS LUNG the TNM Classification for Lung Cancer. J. Thorac. Oncol. 11, 681–92 (2016). 3.
Detterbeck, F. C. et al. The IASLC Lung Cancer Staging Project: Background
METASTASES: PATHOLOGICAL DIFFERENTIAL DIAGNOSIS
Data and Proposals for the Application of TNM Staging Rules to Lung Cancer
Erik Thunnissen Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a
VU University Medical Center, Amsterdam/Netherlands Pneumonic-Type of Involvement in the Forthcoming Eighth. J. Thorac. Oncol.
11, 666–680 (2016). 4. Kozower, B. D., Larner, J. M., Detterbeck, F. C. & Jones,
Introduction The pathological differential diagnosis of in a patient with
D. R. Special treatment issues in non-small cell lung cancer: Diagnosis and
synchronous multiple tumors has a similar thought process for classic
management of lung cancer, 3rd ed: American College of Chest Physicians
morphology as for DNA analysis. Metachronous multiple lung cancers are not
evidence-based clinical practice guidelines. Chest 143, e369S–99S (2013). 5.
discussed here, as the provided title implies a clinical situation at moment in
Detterbeck, F. C. et al. The IASLC Lung Cancer Staging Project: Background
time. In the end of the text the usefulness of clinical context is mentioned.1–5
Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers
Morphology In the setting of obvious metastatic dissemination, histologic

from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming The outcome of patients who had surgery for multiple lung cancers is
Eighth Edition of the TNM Classification for Lung Cancer. J. Thorac. Oncol. 11, generally quite good and not statistically different than the outcome for
651–65 (2016). 6. Thunnissen, E. et al. Reproducibility of histopathological a solitary lung cancer. The patients in these series were highly selected.
subtypes and invasion in pulmonary adenocarcinoma. An international In most cases the pathology of these lesions is a mix between invasive
interobserver study. Mod. Pathol. 25, 1574–83 (2012). 7. Vignot, S. et al. adenocarcinoma (various subtypes), minimally invasive adenocarcinoma and
Next-generation sequencing reveals high concordance of recurrent somatic adenocarcinoma in-situ. Whether mutations are identified is variable and
alterations between primary tumor and metastases from patients with does not seem to influence prognosis.
non-small-cell lung cancer. J. Clin. Oncol. 31, 2167–72 (2013). 8. Arai, J. et al.
Clinical and molecular analysis of synchronous double lung cancers. Lung Use of adjuvant therapy depends on the completeness of resection, the
Cancer 77, 281–7 (2012). 9. de Bruin, E. C. et al. Spatial and temporal diversity nodal status and the molecular analysis of the resected tumors. In general,
in genomic instability processes defines lung cancer evolution. Science (80-. assuming no nodal involvement and complete resection of the lesions
). 346, 251–256 (2014). 10. Macintyre, G., Ylstra, B. & Brenton, J. D. Sequencing removed, no adjuvant therapy is recommended. In all cases close follow-up is
Structural Variants in Cancer for Precision Therapeutics. Trends Genet. 32, mandatory with visits and frequent ct scans (2-3/yr for 2 years then 1-2/year
530–42 (2016). for 3 years then 1/yr for life). Graph of Survival for patients treated by surgical
resection for synchronous primary lung cancers.
Keywords: multiple lung cancer, Pathology, Genomics
Figure taken from: Finley et al. Journal of Thoracic Oncology. 2010. (ref 2)
SC02: MULTIFOCAL LUNG CANCER

MONDAY, DECEMBER 5, 2016 - 11:00-12:30
SC02.02 SURGICAL CHOICES FOR PATIENTS WITH MULTIFOCAL

LUNG CANCER
Scott Swanson
Thoracic Surgery, Brigham and Women’s Hospital, Boston/United States of America
The Surgical Choices for Patients with Multifocal Lung Cancers Surgery for
patients with multiple lung lesions is a growing domain. CT scans are obtained
frequently and have high resolution such that any lesion in the lung that is 2
millimeters or larger can be identified. Also, it appears that multifocal lung References:
lesions are more common now. At the same time, surgical technique and
technology (minimally invasive) have evolved so identifying and resecting Shimada et al. Survival of a surgical series of lung cancer patients with
small lesions is straightforward and associated with very little morbidity and synchronousmultiple ground-glass opacities, and the management of the
pain. In most cases there is one lesion (primary lesion) that is more concerning residual lesions. Lung Cancer 2015
and others that are smaller, less solid or relatively unchanged over time.
Finley et al. Predictors of outcomes after surgical treatment of synchronous
Often a diagnosis of all of the lesions is not known at the time of surgical
primary lung cancers. Journal of Thoracic Oncology. 2010.
intervention and in many cases no diagnosis is known ahead of time. Thus,
the surgeon must integrate many factors when operating on multifocal lung Bonanno et al. Morphological and genetic heterogeneity in multifocal lung
findings. adenocarcinoma: The case of a never-smoker woman. Lung Cancer 2016.
What are risk factors that the patient will have lung cancer, what are the Fonseca A and Detterbeck FC. How many names for a rose: Inconsistent
patient’s co-morbidities and underlying lung function? When is it important classification of multiple foci of lung cancer due to ambiguous rules. Lung
to establish a pre-operative diagnosis? How important is it to resect all of Cancer 2014.
the pulmonary lesions seen on CT scan? Will other therapy be needed? In
general, our approach is to obtain a pre-operative diagnosis when possible Yasuda M et al. How should synchronous multiple primary adenocarcinomas
if the surgery will be particularly challenging based on the location and of the lung be resected? Annals of Thoracic Surgery 2014.
number of the lesions and/or if the patient has very compromised lung
function. The most important point is to anatomically resect the primary Wolf AS et al. Lobectomy versus sublobar resection for small (2 cm or less)
lesion; that nodule which is largest, most solid and/or growing the fastest. non-small cell lung cancers. Annals of Thoracic Surgery 2011.
If the lesion is 2 centimeters or smaller and located within a segment that
Mohiuddin K et al. Relationship between margin distance and local recurrence
is straightforward to resect (superior segment lower lobe, lingula or upper
among patients undergoing wedge resection for small (<2 cm) non-small cell
division of the left upper lobe, posterior segment of the right upper lobe,
lung cancer. Journal of Thoracic and Cardiovascular Surgery. 2014.
medial basilar segment of the lower lobe or composite basilar segments of
lower lobe) then a segmentectomy is the procedure of choice. This will provide Nakata M et al. Surgical treatments for multiple primary adenocarcinoma of
an excellent oncologic outcome and more readily permit other pulmonary the lung. Annals of Thoracic Surgery. 2004.
resection than if a lobectomy or greater had been carried out. In all cases a
lymph node dissection should be performed and in the case of a sublobar Battafarano RJ et al. Surgical resection of multifocal non-small cell lung cancer
resection it is important to assess, by frozen section, the intersegmental is associated with prolonged survival. Annals of Thoracic Surgery. 2002.
node or nodes between the area being removed and the part of the lobe being
left (sump), to be sure no disease remains related to this primary lesion. If Gu B et al. A dominant adenocarcinoma with multifocal ground glass lesions
the sump node is positive then a lobectomy should be strongly considered. does not behave as advanced disease. Annals of Thoracic Surgery. 2013.
If the lesion is greater than 2 centimeters and for those deep seated more
central lesions, a lobectomy is the best operation. If the lesion is about one
centimeter and subpleural then a wide wedge resection can be considered
though this is an unusual situation for the primary lesion. For the other SC02: MULTIFOCAL LUNG CANCER
lesions (non-primary), if they are ipsilateral and easy to identify and resect MONDAY, DECEMBER 5, 2016 - 11:00-12:30
then they should be removed at the time of the surgery for the primary lesion.
If it is possible to resect these lesions with a segment (preferable) or wide
wedge this is best. If the non-primary lesions are pure ground glass, relatively SC02.03 SURGERY FOR GROUND GLASS OPACITY: SUBLOBAR
small (i.e. less than 2-3 centimeters) and stable then it is reasonable to leave RESECTION?
them in place for close follow-up. Once the permanent pathology including Shun-Ichi Watanabe
molecular analysis is done and the patient has recovered then surgery for Thoracic Surgery, National Cancer Center Hospital, Tokyo/Japan
the contralateral lesions is considered. Factors that are important in this are
residual pulmonary function (repeat pft’s after the first operation), size (both History of standard surgical procedure for lung cancer: In 1933, Graham
baseline and recent growth) and density of the contralateral lesions. Also, reported the first successful pneumonectomy for a lung cancer patient,
pathology of the resected tumors and whether they represented separate who survived for 18 years after surgery. In 1951, Cahan suggested that
primary tumors or possibly were metastatic tumors, although even with pneumonectomy with regional lymph node dissection should be a routine
molecular analysis this can be difficult to ascertain, is important in planning. procedure for lung cancer in 1951. Then in 1960, Cahan reported the first 48
Surgery on the contralateral lesions should be as lung-sparing as possible with cases that successfully underwent lobectomy with regional lymph node
segmentectomy being the procedure of choice when possible followed by dissection, which was called “radical lobectomy.” Since then, this procedure
wide-wedge resections or lobectomy if dictated by size and location. was universally accepted and has remained a standard surgery for lung cancer.
As for sublobar resection, segmentectomy was initially used for the resection
of localized bronchiectasis as reported by Churchill and Belsey (1939). In 1973, SESSION SC03: ADVANCES IN RADIATION ONCOLOGY
Jensik reported their 15-year successful experience of segmentectomy for
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
lung cancer patients. However, the use of sublobar resection as definitive
management of NSCLC has been a controversial issue. Lung Cancer Study
Group (LCSG) (1995) conducted the only randomized trial comparing sublobar
resection with lobectomy for stage IA NSCLC patients. They observed a 75% SC03.01 ADVANCES IN STEREOTACTIC BODY RADIOTHERAPY
increase in recurrence and a 50% increase in cancer death in the patients Matthias Guckenberger
undergoing sublobar resection, compared to those in the patients undergoing Radio-Oncology (Klinik Für Radio-Onkologie), University Hospital Zurich
lobectomy. This is the reason why lobectomy has remained a standard lung (Universitätsspital Zürich), Zurich/Switzerland
cancer surgery for a half century since Cahn’s successful report in 1960.
Advances in Stereotactic Body Radiotherapy Matthias Guckenberger,
However, recently, we encounter many patients with the subsolid nodule,and
Switzerland Stereotactic Body Radiotherapy (SBRT) has become the
a certain percentage of those patients are multifocal lesion. The significance
guideline-recommended treatment of choice for patients with early stage
and role of sublobar resection for subsolid tumor have become importanat so
NSCLC, who are medically inoperable because of their comorbidities. This
far. Controversies in sublobar resection for patients with small-sized NSCLC:
reflects that SBRT has transformed from an emerging technology practiced
Sublobar resection is a lung parenchyma-preserving surgery with limited
only by few and highly experienced centres to a mature treatment practice
nodal dissection. However, even small-sized lung cancer less than 2 cm in
broadly in the radiation oncology community setting. Nevertheless, the
size shows hilar and mediastinal nodal disease with an incidence of more
methodology of SBRT has continuously evolved covering all aspects of
than 20%. Although positron emission tomography (PET) is considered to
patient selection, practice of SBRT planning and delivery and follow-up
be the most sensitive and accurate investigation for screening of lymph
assessment. Patient selection: In many centres, SBRT has been introduced
node involvement, with a sensitivity of 79 to 85% and specificity of 90 to
as a replacement for conventionally fractionated radiotherapy in patients
91% in a meta-analysis, the assessment of nodal status by PET is not reliable
considered fit enough for a six weeks long radical treatment but unfit for
in patients with microscopic nodal metastasis. Riquet (1989) reported that
surgical resection. Recent data have demonstrated that SBRT is also well
lung cancer metastasizes so easily to the mediastinum that selection of the
tolerated in very old (> 80 years) patients and patients suffering from
patients for limited surgery should be discussed carefully. Furthermore,
severe comorbidities 1. Simultaneously, the patient characteristics of
lung cancer has a phenomenon termed “skip metastasis” consisting of N2
age, performance status and patients comorbidities are not suitable to
disease without N1 involvement with the incidence of 20-38% in N2 patients.
accurately predict a high risk of early non-cancer death such that these
Therefore, lobectomy with hilar and mediastinal lymph node dissection is
patients could be offered best supportive care and they would not benefit
considered to be a basic standard procedure for lung cancer. Differences
from SBRT as a curative treatment approach 2. However, several studies
in survival between sublobar resection and lobectomy: However, with the
have identified interstitial lung disease as a highly significant factor for
recent development of the CT scanner, the number of very early-stage lung
severe post-SBRT radiation induced pneumonitis; these patients should be
cancer showing ground-grass opacity (GGO) on CT is rising as well, and a
treated only with caution 3. On the other end of the patient spectrum, there
new therapeutic strategy for nodal dissection has been required. Proposals
is an increasing amount of data comparing SBRT with surgical resection,
of sublobar resection for small-size lung cancer less than 2 cm have been
lobectomy and sublobar resection: despite a growing evidence suggests
undertaken in some previous reports. Many retrospective studies of sublobar
equivalent outcome, lobectomy remains the standard of care for properly
resection have already been undertaken for stage IA NSCLC patients.
selected patients 4,5. SBRT planning and delivery: Multiple advanced
Regarding surgery for compromised stage IA patients, Hoffmann (1980),
radiotherapy treatment planning and treatment delivery technologies as
Landreneau (1997) and Campione (2004) showed no significant survival
well as dedicated SBRT delivery machines have been developed and have
difference between sublobar resection and lobectomy group. Okada (2001)
become clinically available within the last years. Despite simulations studies
and Koike (2003) conducted the comparative study between intentional
showed a benefit for most these technologies, it remains unclear whether
sublobar resection and standard lobectomy in patients with tumors 20mm or
small improvements in accuracy and dosimetry will translate into a clinically
less in diameter. They showed no significant difference in survival between
meaningful improvements of patient outcome. The upcoming ESTRO
two groups and suggested that sublobar resection was acceptable operation
ACROP practice guideline has therefore only identified few technologies
for small-sized lung cancer. Nakamura (2005) reported the results of meta-
as mandatory components of up-to-date SBRT practice (e.g. type B dose
analysis of 14 comparative studies showing survival difference between
calculation algorithm, image guidance, 4D motion compensation strategy).
lobectomy and sublobar resection. He showed survival after lobectomy was
SBRT dose and fractionation has been one of the most controversially
slightly better at 1, 3, and 5 years, but the differences were not significant.
discussed topics in lung SBRT and patterns-of-practice analyses reported a
Therefore, lobectomy with mediastinal dissection could be an excessive
large variability between institutions. Comparison of different fractionation
resection for selected patients with early lesion. Lobectomy, however, still
schedules requires radiobiological modelling and several recent studies
remains to be a standard procedure for most patients with lung cancer, simply
suggested that the traditional linear-quadratic model (LQ-model) describes
because there has been no universally accepted guidelines for conducting
the observed outcome with sufficient accuracy 6. Consequently, biological
sublobar resection in the clinical settings. We should wait the final results of
effective doses (BED) or 2-Gy equivalent doses are used by most studies
clinical trials shown in the following chapter. Clinical trials regarding sublobar
for dose-effect modelling. Several studies consistently showed that a
resection vs. lobectomy and future perspective: Japan Clinical Oncology Group
threshold dose of minimum 100Gy BED (alpha/beta ratio 10Gy) is required
(JCOG) has conducted a cohort study (JCOG0201) evaluating correlation
for a local tumor control probability of >90%. Furthermore, not only the
between radiological and pathological findings in stage I adenocarcinomas.
minimum dose at the PTV edge but also the maximum dose within the GTV
With pathologic non-invasive adenocarcinoma defined as those with no
was shown as important predictor for local tumor control supporting the
lymph node metastasis or vessel invasion, radiological non-invasive lung
traditional SBRT concept of inhomogeneous dose distributions within the
adenocarcinoma was defined as those with a consolidated maximum tumour
PTV. After central tumor location has been called a no-fly-zone for SBRT
diameter to tumour diameter ratio (C/T ratio) of less than 0.5. Currently, a
based on studies with “excessive” toxicity of very high dose SBRT, recent
prospective, randomized, multiinstitutional phase III trial for small-sized
retrospective and prospective data suggest that lower total doses combined
(<=2 cm) lung cancer patients is being conducted by Cancer and Leukemia
with more fractionated SBRT protocols improve the therapeutic ratio.
Group B (CALGB140503) to determine the effectiveness of an intentional
Nevertheless, our understanding of the radiation tolerance of critical central
sublobar resection for small-sized peripheral tumors. Similar phase III study
structures is still insufficient and further research is necessary. Follow-up:
is also being conducted by JCOG (JCOG0802). JCOG has already accumulated
The development of radiation induced fibrosis in the high dose region is well
planned number of patients and now following the patients. JCOG is also
documented following SBRT. Only recently, algorithms for differentiation
conducting other two prospective multiinstitutional phase II trials regarding
between local tumor recurrence and fibrosis have been developed and
the sublobar resection for GGO-dominant type tumors. One is JCOG0802,
validated 7,8: CT features of bulging margin and cranio-caudal growth appear
wide wedge resection or segmentectomy for non-solid GGO lesion less than
to best differentiate between fibrosis and tumor recurrence. More advanced
2cm, and the other is JCOG1211, segmentectomy for part-solid GGO lesion with
studies evaluate the value of mathematical image analysis methods,
less than 50% solid part inside and 2.1-3.0 cm in tumor diameter. Since the
radiomics, but such studies strongly require external validation. 1. Takeda A,
clear evidence regarding the survival benefit of sublobar resection for lung
Sanuki N, Eriguchi T, et al: Stereotactic ablative body radiation therapy for
cancer patient is lacking so far, lobectomy should be an appropriate therapy
octogenarians with non-small cell lung cancer. Int J Radiat Oncol Biol Phys
for medically operable lung cancer patient at the moment. Abovementioned
86:257-63, 2013 2. Klement RJ, Belderbos J, Grills I, et al: Prediction of Early
randomized trials will clearly define the role of sublobar resection in patients
Death in Patients with Early-Stage NSCLC-Can We Select Patients without a
with stage I patients. As the number of early-stage peripheral lung cancers is
Potential Benefit of SBRT as a Curative Treatment Approach? J Thorac Oncol,
increasing, and a certain number of patients are with multifocal small lesion,
2016 3. Ueki N, Matsuo Y, Togashi Y, et al: Impact of pretreatment interstitial
the surgical procedure for lung cancer should be tailored to each case by
lung disease on radiation pneumonitis and survival after stereotactic body
considering CT findings.
radiation therapy for lung cancer. J Thorac Oncol 10:116-25, 2015 4. Chang JY,
Keywords: lobectomy, sublobar resection, segmentectomy, ground-grass Senan S, Paul MA, et al: Stereotactic ablative radiotherapy versus lobectomy
opacity for operable stage I non-small-cell lung cancer: a pooled analysis of two
randomised trials. Lancet Oncol 16:630-7, 2015 5. Nagata Y, Hiraoka M, Shibata
T, et al: Prospective Trial of Stereotactic Body Radiation Therapy for Both
Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical

Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys 93:989-96, 2015 stage IB than in stage IA because distant metastatic recurrences are common.
6. Guckenberger M, Klement RJ, Allgauer M, et al: Applicability of the linear- A combination of CIRT with systemic therapy is therefore essential to improve
quadratic formalism for modeling local tumor control probability in high survival. CIRT demonstrates a better dose distribution than both SBRT and
dose per fraction stereotactic body radiotherapy for early stage non-small proton therapy in most cases of early-stage lung cancer. Therefore, CIRT may
cell lung cancer. Radiother Oncol 109:13-20, 2013 7. Huang K, Dahele M, Senan be safer for patients with adverse conditions such as large tumors, central
S, et al: Radiographic changes after lung stereotactic ablative radiotherapy tumors, and poor pulmonary function. Multi-institutional retrospective study
(SABR) - Can we distinguish recurrence from fibrosis? A systematic review of CIRT for stage I NSCLC was completed and will be presented at ASTRO 2016
of the literature. Radiother Oncol 102:335-42, 2012 8. Peulen H, Mantel by the Japan Carbon-ion Radiation Oncology Study Group (J-CROS). Carbon-
F, Guckenberger M, et al: Validation of High-Risk Computed Tomography ion therapy of locally advanced non-small cell lung cancer There was only one
Features for Detection of Local Recurrence After Stereotactic Body Radiation report about CIRT for locally advanced NSCLC. A prospective nonrandomized
Therapy for Early-Stage Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol phase I/II study of CIRT in a favorable subset of locally advanced NSCLC
Phys 96:134-41, 2016 was reported from NIRS (9). They showed that short-course carbon-ion
monotherapy (72GyE/16Fr) was associated with manageable toxicity and
Keywords: stereotactic body radiotherapy, non-small cell lung cancer, early encouraging local control rates. Among them, cT3-4N0M0 patients were good
stage candidates for CIRT. There is otherwise a lack of evidence currently for CIRT
for locally advanced NSCLC, and more study is needed. Moreover, concurrent
systemic therapy is essential to improve survival for locally advanced NSCLC.
Future directions We organized a multi-institutional study group of carbon-
ion radiation oncology in Japan (J-CROS). This group is currently conducting
SC03: ADVANCES IN RADIATION ONCOLOGY
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 trials on several tumor sites which are thought to be most attractive for
CIRT, including NSCLC, head and neck disease, locally advanced unresectable
pancreatic cancer, hepatocellular carcinoma, locally recurrent rectal cancer,
SC03.02 PROTON THERAPY OF LUNG CANCER and others. The outcomes of CIRT for stage I NSCLC at all Japanese carbon
Jeffrey Bradley centers were pooled and retrospectively analyzed. Consequently, CIRT may be
Radiation Oncology, Washington University School of Medicine, St. Louis/United considered a low-risk and effective treatment option for patients with stage I
States of America NSCLC. J-CROS has now begun a confirmatory multi-institutional prospective
study to confirm these results.References: 1. Kamada T, Tsujii H, Blakely EA,
This session will focus on the use of proton beam radiation therapy for et al. Carbon ion radiotherapy in Japan: an assessment of 20 years of clinical
lung cancer. We will review the basic physics of proton beam therapy, why experience. Lancet Oncol 2015; 16: e93-100.
protons are different from photon-based radiation therapy, and the potential
advantages of using proton beam therapy to treat lung cancer. We will review 2. Sawabata N, Miyaoka E, Asamura H, et al. Japanese lung cancer registry
the current data about the use of protons, both published and unpublished, study of 11,663 surgical cases in 2004: demographic and prognosis changes
and provide updates about ongoing clinical trials testing proton therapy in over decade. J Thorac Oncol 2011; 6: 1229-35.
lung cancer patients.
3. Miyamoto T, Yamamoto N, Nishimura H, et al. Carbon ionradiotherapy for
Keywords: protons, radiation therapy, lung cancer, clinical trials stage I non-small cell lung cancer. Radiother Oncol 2003; 66: 127-140.
4. Miyamoto T, Baba M, Yamamoto N, et al. Curative treatment of Stage I

non-small-cell lung cancer with carbon ion beams using a hypofractionated
regimen. Int J Radiation Oncol Biol Phys 2007; 67: 750-758.
SC03: ADVANCES IN RADIATION ONCOLOGY
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 5. Miyamoto T, Baba M, Sugane T, et al. Carbon ion radiotherapy for stage I
non-small cell lung cancer using a regimen of four fractions during 1 week. J
Thorac Oncol 2007; 10: 916-926.
SC03.03 CARBON-ION THERAPY OF LUNG CANCER
Yuko Nakayama 6. Sugane T, Baba M, Imai R, et al. Carbon ion radiotherapy for elderly patients
Department of Radiation Oncology, Kanagawa Cancer Center, Yokohama/Japan 80 years and older with stage I non-small cell lung cancer. Lung Cancer 2009;
64: 45-50.
Introduction Approximately 65 particle therapy facilities are in operation
worldwide. Among them, only 10 have carbon-ion therapy (CIRT) facilities (5 in 7. Takahashi W, Nakajima M, Yamamoto N, et al. Carbon ion radiotherapy in a
Japan, 2 in Germany, 2 in China, and 1 in Italy), and the remainder have proton hypofractionation regimen for stage I non-small-cell lung cancer. J Radiat Res
therapy facilities. More than 137,000 patients were treated with particle 2014; 55(suppl 1): i26–i27.
therapy worldwide from 1954 to 2014, including 15,000 in 2014, 86% of which
8. Karube M, Yamamoto N, Nakajima M, et al. Single-fraction carbon-ion
were treated with protons and 14% with carbon ions and other particles.
radiation therapy for patients 80 years of age and older with stage I non-small
(from the Particle Therapy Co-Operative Group: http://www.ptcog.ch/). The
cell lung cancer. Int J Radiation Oncol Biol Phys 2016; 95: 542-548.
National Institute of Radiological Sciences (NIRS) Chiba, Japan, has been
treating cancer with high-energy carbon ions since 1994. Most of the patients 9. Takahashi W, Nakajima M, Yamamoto N, and et al. A prospective
who have been cured of cancer worldwide with carbon ions were treated nonrandomized phase I/II study of carbon ion radiotherapy in a favorable
at NIRS (1). From NIRS’s data, the efficacy of CIRT for non-small cell lung subset of locally advanced non-small cell lung cancer (NSCLC). Cancer 2015;
cancer (NSCLC) has been suggested. Here those results are reviewed, and the 121: 1321-7.
issue of this modern technology is discussed. Characteristics of carbon-ion
therapy CIRT has better dose distribution to tumor tissue, while minimizing 5-yr
surrounding normal tissue dose, compared with photon radiotherapy. Total dose 5-yr 5-yr Toxicity
Mean T1: F/U cause-
Moreover, carbon ions have potential advantages over protons. They provide Ref. Pts. (GyRBE) local overall
age T2 (months) specific
a better physical dose distribution due to lessened lateral scattering. Further, / fractions control survival grade 3 <
survival
their higher relative biological effectiveness and lower oxygen enhancement
59.4-
ratio are desirable features for targeting radioresistant, hypoxic tumors. 41: lung
3) 81 72 95.4/ 52.6 76% 60% 42%
The difference between densely ionizing nuclei and sparsely ionising x-rays 41 3.7%
9-18
and protons offers further potential radiobiological advantages, such as
reduced repair capacity, decreased cell-cycle dependence, and possibly 30: skin
4) 50 74.1 72/ 9 59.2 94.7% 75.7% 50.0%
stronger immunological responses. Carbon-ion therapy of early non-small 21 2%
cell lung cancer Surgical resection with lobectomy has been the standard 42: 52.8-
5) 79 74.8 38.6 90% 68% 45% 0%
treatment of choice for early-stage NSCLC. In a 2004 study of a Japanese lung 37 60/ 4
cancer registry comprising 11,663 surgical cases, overall survival (OS) rates 12: 52.8-72/
at 5 years for stages IA and IB disease are 82.0% and 66.8%, respectively 6) 28 82 NA 95.8% NA 30.7% 0%
17 4-9
(2). Radiotherapy is an option for patients who are not eligible for surgery
91:
or refuse it. Recently, hypofractionated radiotherapy is regarded as an 7) 151 73.9 36-50/ 1 45.6 79.2% NA 55.1% 0%
60
alternative to surgery for localized NSCLC, using x-ray stereotactic body
radiotherapy (SBRT) or particle therapy using protons or carbon-ions. With 39:
8) 70 83 28-50/ 1 42.7 85.8% 64.9% 39.7% 0%
regard to CIRT, for peripheral stage I NSCLC, the number of fractions was 31
reduced in different trials from 18 to 9, then 4, and finally to a single fraction
Keywords: carbon-ion therapy, non-small cell lung cancer, J-CROS
at NIRS (Table 1). The results with CIRT in stage IA NSCLC are similar to the best
SBRT results reported worldwide. For stage IB disease, CIRT results appear
superior to those reported for photon SBRT in terms of local control and lung
toxicity. Despite high local control, disease-specific survival is much lower in
SESSION SC04: EGFR TYROSINE KINASE INHIBITORS:A using other mechanisms. Heterogeneities in terms of resistant mechanisms
within a single patient become evident when specific therapeutic pressure
MODEL FOR SUCCESSFUL DRUG DEVELOPMENT
persists. Therefore, we also need to have armamentarium that utilizes
MONDAY, DECEMBER 5, 2016 other mechanisms to cure lung cancer. Recent advances of immunotherapy
targeting immune checkpoints appear attractive in this respect. These
SC04: EGFR TYROSINE KINASE INHIBITORS: A MODEL FOR SUCCESSFUL DRUG
DEVELOPMENT mechanism-driven therapeutic approaches will convert this fatal disease into
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 a more chronic disorder, and eventually into a curable disease with the least
patient burden.
SC04.02 MANAGEMENT OF RESISTANCE TO EGFR TYROSINE Keywords: Adenocarcinoma, EGFR, Resistance, T790M
KINASE INHIBITORS
Tetsuya Mitsudomi
Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama/Japan
SC04: EGFR TYROSINE KINASE INHIBITORS: A MODEL FOR SUCCESSFUL DRUG
DEVELOPMENT
Discovery of activating mutations of the EGFR gene in adenocarcinoma of MONDAY, DECEMBER 5, 2016 - 11:00-12:30
the lung in 2004 opened the door to a new era for personalized therapy in
thoracic oncology. Lung cancers with EGFR mutation are highly sensitive to
EGFR-tyrosine kinase inhibitors (TKI) such as gefitinib, erlotinib, or afatinib, SC04.03 SEQUENCING OF EGFR TYROSINE KINASE INHIBITORS
resulting in significantly prolonged progression free survival compared with Keunchil Park
those treated with platinum doublet chemotherapy. However, acquired Div of HEM/ONC, Samsung Med Ctr, Sungkyunkwan Univ School of Med, Seoul/
resistance inevitably develops usually after a median of 10~12 months. The Korea, Republic of
mechanisms for this resistance have been extensively studied and can be
classified into 1) target gene alteration, 2) activation of bypass / accessory Treatment of EGFR-mutant (EGFRm) lung cancer with specific EGFR TKIs,
pathway, and 3) histologic transformation (Fig.). such as gefitinib, erlotinib or afatinib, has opened the door to the precision
medicine in the management of advanced non-small cell lung cancer with
remarkable tumour shrinkage and improvement in progression-free survival
(PFS) and quality of life compared to standard chemotherapy. Despite such
a remarkable initial clinical response with EGFR TKIs in patients with EGFR+
NSCLC, however, the disease eventually comes back with the emergence of
acquired resistance and median PFS is ~ 1 year. The most common mechanism
of resistance is acquisition of the T790M gatekeeper mutation and the
3rd-generation EGFR TKIs irreversibly inhi bit mutant EGFR, esp. T790M,
with sparing wild-type(WT) EGFR. There are several EGFR mutant specific
inhibitors (EMSIs) under development including AZD9291, CO-1686, BI1482694
/HM61713, ASP8273, etc.
All these 3rd-generation EGFR TKIs have shown a promising early clinical
efficacy in T790M(+) EGFRm NSCLC patients with ORR of ca. 60% and PFS
of 9.6 – 10.3 months and appear to be well tolerated. Based upon these
encouraging early results many confirmatory phase 3 trials(e.g., NCT02151981,
NCT02322281) comparing to the standard chemotherapy in the 2nd-line
setting are underway.
It is very tempting that one might like to move the 3rd-generation EGFR TKI
to 1st-line setting. The development of the 3rd-generation agents as the first-
line therapy for patients with EGFRm disease has already started. Recently
AZD9291 demonstrated an encouraging clinical activity and a manageable
The most common (50~60%) mechanism for acquired resistance to the tolerability profile in 1st-line: confirmed objective response rate of 77%
EGFR-TKI is a missense mutation at codon 790 of the EGFR gene resulting in (95% CI 64, 87) and mPFS of 19.3 months (investigator-assessed). Currently
substitution of threonine to methionine (T790M). This amino acid change it is being compared with the 1st/2nd-generation EGFR TKI in the 1st-line
reduces affinity between EGFR kinase and EGFR-TKI compared with that setting. The Phase III FLAURA study (NCT02296125), comparing AZD9291 80
between EGFR-kinase and ATP, leading to reactivation of down-stream mg once daily versus current standard of care EGFR-TKIs for treatment-naïve
pathways. L747S, D761Y, and T854A are also known as secondary mutations patients, is enrolling. Though the preliminary result in the 1L setting is quite
that cause acquired resistance, but they are very rare. In these cases, cancer provocative, extreme caution needs to be exerted since the currently available
cells are still addicted to or dependent on EGFR pathway. Amplification of data are not mature enough to determine which agent is the best in its class
the MET gene which codes for a receptor of hepatocyte growth factor (HGF) and only from a small subset of patients.
was the first that was identified as a bypass track resistance mechanism
Though it is hoped that the T790M-mediated resistance can be delayed or
against EGFR-TKI. Following this report, aberrant activation of other receptor
prevented by using the EMSIs in the TKI-naïve setting, it is also possible that
tyrosine kinases such as HER2, HER3, AXL, IGF1R, have been reported. It is
other less well known escape mechanisms might emerge. Given that EMSI
also shown that some ligands for the receptor tyrosine kinases such as HGF,
works well after failing 1st/2nd-generation EGFR TKI I believe it seems to be
FGF or IGF cause acquired resistance to EGFR-TKIs. Similarly, alteration of
a more reasonable approach to investigate if EMSI in the TKI-naïve setting
downstream molecule cause resistance. These molecules include BRAF,
is more effective than 1st/2nd-generation EGFR TKI followed by EMSI when
PTEN, JAK2, CRKL, DAPK, NF-kB, or PUMA. The third mechanism of acquired
failing 1st/2nd-generation EGFR TKI with acquired resistance.
resistance is histologic transformation that includes small cell lung cancer
transformation and epithelial-mesenchymal transition EMT). Exact One of the biggest questions to emerge in the era of next-generation
mechanisms of these histologic changes are not fully understood. However, inhibitors that have activity against the basic driver oncogene is whether
AXL, Notch-1, TGFb pathway activation as well as down regulation of MED12 it makes sense to use this approach before the development of acquired
((Mediator Complex Subunit 12) have been proposed as mechanisms of EMT. resistance to prevent it from occurring in the first place. Can its use in the 1st-
Then, How are we able to cope with these resistance? For T790M gatekeeper line(TKI-naïve) setting prevent the development of acquired resistance and
mutations, the third generation EGFR inhibitors that selectively inhibit lead to a longterm control of the disease?
EGFR-T790M while sparing the wild-type EGFR are active. One of these
drugs, osimertinib is already approved and gives a response rate of ~60% Considering the well-known genomic heterogeneity with its possible
and progression free survival of ~11 months. Therefore, identification of association with resistance to EGFR TKIs we need better understanding of the
T790M at the time of disease progression by rebiopsy is important. We biology and resistance mechanisms to this class of new generation EGFR TKIs
have recently found that three other secondary EGFR mutations implicated in order to develop better strategies for subsequent therapies to overcome
in acquired resistance are also sensitive to osimertinib. Tumor resistance the resistance including how to best sequence the available EGFR TKIs in the
caused by activation of accessory pathways can be theoretically coped with clinic as well as combination therapies.
by combination of the inhibitor of EGFR and involved molecules. However,
because of rarity of each mechanism, there is no clear evidence whether It is fair to say that during the past few years we’ve clearly made another
these combination therapies will actually improve patient outcome In other progress in the management of NSCLC patients with EGFRm, including those
cases, cytotoxic chemotherapy is still an important strategy. According to who failed previous EGFR TKIs. However, the currently available data are
the IMPRESS study, median progression free survival for patients without not mature enough to determine which agent is the best in its class, with
T790M who received cisplatin plus pemetrexed was 5.4 months. Eeven with the notable differences primarily related to toxicity and we’re not there yet
these strategies, cancer cells are smart enough to escape from the therapy and still lots of unanswered questions remain and further researches are
warranted.

by a second assay in tumor-derived DNA. Apart from inflating spending on

molecular diagnostics, this may result in further treatment delays, which is
hard to bear for patients in particular in the first-line setting. While these
obstacles may be soon overcome by technological advances and evolving
data from validation studies, “liquid biopsies” focusing on DNA and/or RNA
will always miss out on the histopathological information that can be derived
from a biopsy of a tumor or metastasis. In the era of immunomodulatory
antibody therapy information of tumor-infiltrating immune and stromal
cells as well as expression of biomarkers by specific cell populations or with
spatial variation become increasingly important. Until this information
cannot be reproducibly derived by novel assay technologies the detection
of genomic biomarkers in blood-derived DNA will become a highly valuable,
additive modality for specific scenarios of primary diagnosis and treatment
monitoring.References:
1 N Engl J Med. 2008 Jul 24;359(4):366-77.
2 Clin Cancer Res. 2009 Apr 15;15(8):2630-6.
3 PLoS One. 2014 Jan 21;9(1):e85350.
4 Lung Cancer. 2015 Dec;90(3):509-15.
References 5 Nat Med. 2015 Jun;21(6):560-2.
1. DR Camidge, et al. Acquired resistance to TKIs in solid tumours: learning 6 Clin Cancer Res. 2016 Mar 1;22(5):1103-10.
from lung cancer. Nat Rev Clin Oncol 2014;11: 473–481
7 J Clin Oncol. 2016 Jun 27. pii: JCO667162.
2. SS Ramalingam, et al. The Next Generation of Epidermal Growth Factor
Receptor Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer. Cancer Keywords: EGFR, biomarker, Genomics, Resistance
2015;121:E1-E6
3. GR Oxnard et al. Acquired EGFR C797S mutation mediates resistance to

AZD9291 in non–small cell lung cancer harboring EGFR T790M. Nature Med
2015;21:560-564 SESSION SC05: NOVEL DRUGS IN THORACIC CANCERS
4. LV Sequist et al. Heterogeneity Underlies the Emergence of EGFR T790 MONDAY, DECEMBER 5, 2016 - 11:00-12:30
Wild-Type Clones Following Treatment of T790M-Positive Cancers with a
Third-Generation EGFR Inhibitor . Cancer Discov 2015;5(7): 713–22
SC05.02 NOVEL CYTOTOXIC DRUGS IN LUNG CANCER
5. CM Lovly et al. Shades of T790M: Intratumor Heterogeneity in EGFR Jean-Charles Soria
-Mutant Lung Cancer. Cancer Discov 2015;5(7): 694–6.
Drug Development Department, Gustave Roussy, Villejuif/France
6. S Ramalingam, et al. ELCC 2016; Abstract LBA1_PR
Even in the era of precision medicine and immunotherapy, cytotoxic
Keywords: EGFR TKI, Resistance, Sequence chemotherapies remain an essential component of lung cancer treatment,
both in resectable disease as well as in advanced/metastatic lung cancer.
We have chosen to focus on 2 new cytotoxic compounds, which are likely to
emerge as new players in the field of lung cancer management. One (named
SC04: EGFR TYROSINE KINASE INHIBITORS: A MODEL FOR SUCCESSFUL DRUG PM1183) has activity in small-cell lung cancer (SCLC), the other TAS-114 has
DEVELOPMENT
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
activity in non-small cell lung cancer (NSCLC). PM1183 is a DNA-binding
chemotherapy with a new mechanism of action. PM1183 acts as an inhibitor
of transcription. Binding of PM1183 to CG-rich motifs, triggers sequential
SC04.04 LIQUID BIOPSIES FOR DYNAMIC MONITORING OF EGFR phosphorylation of Pol II and stalling of elongating Pol II. This leads to
MUTATIONS IN LUNG CANCER recruitment of the ubiquitin-proteasome machinery, RNA Pol II degradation,
Martin Schuler and recruitment of XPF, generation of DNA breaks and induction of apoptosis.
PM1183 has been tested in a phase IB trial in combination with doxorubicine.
West German Cancer Center, University Hospital Essen, Essen/Germany
In the dose-finding part: recommended dose (RD) was defined at PM1183 4.0
Somatic mutations clustering in exons 18 to 21 of the EGFR gene characterize mg flat dose (FD) or 2.0 mg/m2 + DOX 50 mg/m2 both on day (D)1 every three
distinct lung cancer biologies. Patients with metastatic EGFR-mutated weeks (q3w). Myelosuppression was dose-limiting (DLT). Compelling activity
lung cancer are exquisitely sensitive to targeted agents inhibiting the EGFR was observed during escalation phase. It was especially remarkable as 2nd line
tyrosine kinase, which have demonstrated superior progress-free survival in SCLC patients: 5 of 7 evaluable pts (71%) had objective partial response (PR)
and, in some instances, overall survival when compared to platinum-based as per RECIST v.1.1. In an expansion cohort of 20 patients, PM1183 and DOX
chemotherapy in first-line treatment. Several studies have shown that EGFR showed outstanding clinical activity: 67% response rate, including 10% of CRs,
mutations can be detected by highly sensitive assay technology in free DNA as 2nd line treatment in SCLC patients. A randomized phase III trial testing
circulating in the blood from patients with EGFR-mutated lung cancers PM1183 + DOX is planned and will compare this combination with topotecan
1,2,3. Circulating EGFR-mutated DNA may drop below the level of detection or CAV. TAS-114 is a first-in-class oral deoxyuridine triphosphatase (dUTPase)
in patients responding to EGFR-TKI, and persistence or reoccurrence of inhibitor that acts as a modulator of the pyrimidine nucleotide metabolic
circulating EGFR-mutated DNA may associate with primary and acquired pathway by blocking the conversion of 2’deoxyuridine-5’-triphosphate
resistance 1,3. In addition, clonal evolution of EGFR-mutated lung cancers (dUTP; FdUTP) into 2’-deoxyuridine-5’-monophophate (dUMP; FdUMP)
under EGFR-TKI therapy can be mirrored by the detection of gatekeeper through reversible inhibition of dUTPase (gatekeeper protein), resulting in
mutations, such as EGFR T790M or the EGFR C797S, in circulating DNA 4,5. the enhanced incorporation of both uracil and fluorouracil into DNA. The
Hence, mutation analysis in circulating free DNA has been suggested as a activity of TAS-114, administered in combination with thymidine synthase (TS)
clinically more feasible and less invasive method for detection of predictive inhibitors, 5-FU, S-1 or capecitabine, has been studied pre-clinically in various
genomic biomarkers and treatment monitoring in advanced lung cancer. The cancer cell lines and animal models. TAS-114 selectively inhibited dUTPase and
development of more sensitive technologies and bioinformatic algorithms showed a higher affinity than the substrates of dUTPase, dUTP and FdUTP,
enables the study of comprehensive genomic biomarker panels in blood- inhibition constant values of TAS-114 were 0.13 μM and 0.10 μM, respectively.
derived DNA, which cover a broader spectrum of actionable mutations in The antitumor effect of TAS-114 combined with S-1 as compared to that of S-1
treatment-naïve patients and those with acquired TKI resistance. Currently, alone was investigated in vivo using a xenograft mouse model with NCI-H2228
there are still several limitations to overcome. First, the predictive value of (human NSCLC). Both regimens were administered orally (TAS-114: 600 mg/
a mutation detected in blood-derived DNA cannot be simply extrapolated kg/day and S-1: 8.3 mg/kg/day vs S-1: 8.3 mg/kg/day through day 1 to 28) and
from validation studies conducted with tumor-derived DNA. In consequence, resulted in relative tumor volumes of 1.61% vs 3.04%, p<0.01, inhibition rates
prospective clinical validation of blood-based biomarkers is mandatory. of 52.7% vs 10.8%, and body weight changes of 6.8% vs 3.3%, respectively. A
Secondly, most studies comparing EGFR mutation detection in tumor and phase 1 clinical study of TAS-114 and S-1 combination treatment is currently
“liquid” biopsies side-by-side reveal inferior sensitivity of blood-based assays. ongoing to investigate the safety and to determine the maximum-tolerated
Also, there is a considerable degree of discordance between such assays 4,6,7. dose (MTD) and recommended dose (RD) in patients (pts) with advanced
Thus, “negative” findings in circulating tumor DNA have to be confirmed refractory solid tumors. TAS-114 and S-1 are administrated orally twice a day
for 14 days followed by 7 days resting period for a 21-days cycle at the starting and manageable safety profile in patients with BRAF V600E mutations [9,
dosage of 5 mg/m² with the fixed dosage of 25 mg/m², respectively. To date, 10]. In 57 previously treated metastatic NSCLC patients with BRAF-V600E
a total of 96 pts were enrolled with 37 pts in the dose escalation and 59 pts in mutations, 63.2% patients (36/57) achieved an overall response [9]. Other
the MTD expansion stages. TAS-114 and S-1 were escalated up to 240 mg/m² novel molecular targets maybe serving as oncogenic drivers including
and 36 mg/m², respectively, with 2 DLTs observed at the highest dose level (1 mutations in HER2 (neratinib and pyrotinib) and PI3KCA (BKM120 and
patient with G3 rash and 1 patient with G2 rash/G2 HFS), therefore TAS-114 at GDC0941), ROS1 (entrectinib, foretinib and lorlatinib), RET (XL184) and NTRK
240 mg/m² and S-1 at 30 mg/m² was determined to be the MTD and RD. The (entrectinib) rearrangements and FGFR1 gene amplification (AZD4547,
most common treatment related adverse events were anemia and rash. There Lenvatinib and FP-1039) are being evaluated either in preclinical settings or
were 4 confirmed partial responses observed in 2 non-small cell lung (NSCLC) early-stage clinical trials. Reference: 1. Mok TS, Wu YL, Thongprasert S, Yang
pts, 1 pancreas pt and 1 colorectal cancer patient to date. Amongst 6 evaluable CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary
NSCLC pts to date, there was an overall response rate of 33% (2/6) with 2 adenocarcinoma. N Engl J Med 2009;361: 947-957. 2. Solomon BJ, Mok T,
confirmed PR and a disease control rate of 100% (6/6). Pharmacodynamics Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. First-line crizotinib versus
analysis performed on patient tumor specimens treated at MTD indicated chemotherapy in ALK-positive lung cancer. N Engl J Med 2014;371: 2167-2177.
TAS-114 target engagement by reductions in the amount of intra-tumoral 3. Sequist LV, Soria JC, Goldman JW, Wakelee HA, Gadgeel SM, Varga A, et al.
dUMP, a “surrogate” metabolite indicative of dUTPase inhibition, following Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med 2015;372:
TAS-114/S-1 combination as compared to S-1 alone administration. When TAS- 1700-1709. 4. Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam
114 is administered in combination with S-1, an additional cytocidal antitumor SS, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N
effect to TTP depletion by TS inhibition is expected as TAS-114 inhibits a Engl J Med 2015;372: 1689-1699. 5. Jia Y, Yun CH, Park E, Ercan D, Manuia M,
gatekeeper protein, thereby allowing increased DNA incorporation of both Juarez J, et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance with
uracil and 5-FU resulting in DNA damage. mutant-selective allosteric inhibitors. Nature 2016;534: 129-132. 6. Ou SH, Ahn
JS, De Petris L, Govindan R, Yang JC, Hughes B, et al. Alectinib in Crizotinib-
Keywords: new cytotoxics, small-cell lung cancer, non-small cell lung cancer Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global
Study. J Clin Oncol 2016;34: 661-668. 7. Shaw AT, Kim DW, Mehra R, Tan DS,
Felip E, Chow LQ, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer.
N Engl J Med 2014;370: 1189-1197. 8. Paik PK, Drilon A, Fan PD, Yu H, Rekhtman
SC05: NOVEL DRUGS IN THORACIC CANCERS
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 N, Ginsberg MS, et al. Response to MET inhibitors in patients with stage IV
lung adenocarcinomas harboring MET mutations causing exon 14 skipping.
Cancer Discov 2015;5: 842-849. 9. Planchard D, Besse B, Groen HJ, Souquet PJ,
SC05.03 NOVEL TYROSINE KINASE INHIBITORS IN LUNG CANCER Quoix E, Baik CS, et al. Dabrafenib plus trametinib in patients with previously
Caicun Zhou treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-
Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai/ label, multicentre phase 2 trial. Lancet Oncol 2016;17: 984-993. 10. Planchard
China D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, et al. Dabrafenib in patients
with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm,
The invited talk will firstly talk about the recent advances in novel TKIs multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17: 642-650.
overcoming resistance during EGFR-TKI and ALK-TKI treatment. Afterwards,
several novel TKIs with CNS penetration that may substantially change Keywords: EGFR; ALK; targeted therapy; lung cancer
the prognosis and treatment strategy of patients with brain metastases
will be discussed. Finally, we will take an overview about targeted therapy
against rare and novel, potentially druggable oncogenic drivers either in
preclinical settings or early-stage clinical trials. As we know, the presence SC05: NOVEL DRUGS IN THORACIC CANCERS
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
of EGFR activating mutations and ALK chromosomic rearrangements
with corresponding tyrosine kinase inhibitors (TKIs) has revolutionized
the treatment strategies of patients with non-small cell lung cancer SC05.04 LUNG CANCER VACCINES: AN UPDATE
(NSCLC) [1, 2]. Although tremendously initial response and manageable Elisabeth Quoix
toxicity profiles, however, acquired resistance inevitably develops after Pneumology, Hôpitaux Universitaires de Strasbourg Nouvel Hôpital Civil,
approximately 1 year treatment with EGFR-TKIs (erlotinib and gefitinib) Strasbourg/France
and ALK inhibitor (crizotinib). Encouragingly, third-generation EGFR-TKIs
including AZD9291, CO1686 and HM61713 have showed striking efficacy Treatment of small-cell lung cancer (SCLC) has not been modified since
overcoming acquired resisitance driven by T790M secondary mutations [3, decades : and consists in a chemotherapy (CT) with platin+etoposide+/-
4]. In patients who get acquired resistance to first-generation EGFR-TKIs concurrent radiotherapy (RT) and prophylactic cranial irradiation in case of a
with T790M mutations, the objective response rate (ORR) of AZD9291 was (near)complete response to therapy. Non-small cell lung cancer (NSCLC)
61% and median progression-free survival (PFS) was 9.7 months [4]. Other represents 85% of all lung cancers and around 50% are metastatic at
novel third-generation EGFR-TKIs such as ASP8274, EGF816, PF-06747775 presentation. Systemic treatment (platin-based doublets) has been
and avitinib are also being investigated in early-stage clinical trials and the implemented for stage IV NSCLC but also for locally advanced and early stages
survival and safety data will be released in the near future. Another promising as a (neo)adjuvant therapy to surgery or RT. By the end of the XXth century, a
novel EGFR-TKI, namely AZD3759 has showed promising response in patients plateau has been reached with CT in stage IV disease with similar results
with brain metastases and leptomeningeal disease, a major case leading to whatever the drug used in conjunction with platin-salt. Since the beginning of
treatment failure. In BLOOM study, 11 out of 21 patients with measurable the XXIst century there have been tremendous innovations in the systemic
brain metastases and heavily pre-treated progressed both extracranially treatment of NSCLC. First, adjunction of bevacizumab to CT for stage IV
and intracranially had tumor shrinkage in the brain at dose ≥50mg BID. non-squamous cell carcinoma and the use of maintenance therapy have led to
Recently, EAI045, an EGFR allosteric inhibitor, in combination with cetuxmab an improvement in median survival time (MST) exceeding now one year.
exhibit antitumor activity in mouse models of lung cancer driven by L858R/ Second, targeted therapies proved to be of major interest for patients with
T790M/C797S, a common resistant mechanism of AZD9291 [5]. Meanwhile, EGFR activating mutations leading to a MST>2 years. Other targets of interest
second-generation ALK inhibitors (ceritinib, alectinib and brigatinib) have have been found such as ALK and ROS1 translocations, V600EBRAF mutations
entered clinical applications for NSCLC patients with ALK rearrangements leading to prolonged survival with appropriate treatments. Third,
after failure of crizotinib and third-generation ALK inhibitors (lorlatinib immunotherapy represents now an exciting approach especially for those
and ASP3026) are also being evaluated in clinical trials overcoming known patients without targetable mutations/translocations. Lung cancer has long
ALK resistant mutations[6, 7]. In patients who progress on crizotinib, the been considered as a poor candidate for immunotherapy because of low
ORR and PFS of brigatinib at 180mg was 54% and 12.9 months. Lorlatinib, a content of tumor-infiltrating lymphocytes (TIL) compared to other tumors.
third-generation ALK inhibitor, also demonstrated robust clinical activity in On the other hand, in case of the presence of TIL the prognosis is better (1).
ALK-rearrangement patients with NSCLC. The ORR was 57% in patients who The fact that incidence of lung cancer is especially high in patients who were
received 1 prior ALK-TKI and 42% in patients who received ≥2 prior ALK-TKIs. transplanted (2)or in patients with HIV infection (3)is against the assumption
On the other hand, with the development of high-throughput sequencing, of lung cancer being non immunogenic. There are two types of
called next-generation sequencing (NGS) and genomic technologies, more immunotherapy : the immune checkpoint blockers which aim at enhancing a
novel molecular targets such as MET 14 exon skipping splicing mutations[8] T-cell response directed against tumoral cells and abrogate the immune
have been identified as potential therapeutic targets and simultaneously tolerance and the therapeutic vaccines designed to induce or amplify an
analyzing hundreds of molecular alterations have turned out reality with immune response directed against tumor-associated antigens (TAA). The
limited tumor tissues. In the recent years, the emergence of numbers of immune checkpoint blockers in current development are anti CTLA4
oncogenic drivers other than EGFR mutations and ALK rearrangements has monoclonal antibodies (ipilimumab), first used in the treatment of melanoma
divided NSCLC into multiple distinct subtypes amenable to corresponding and now investigated in NSCLC and SCLC, anti PD1 (nivolumab,
targeted therapy, including ROS1 rearrangement, RET arrangement, BRAF- pembrolizumab) or anti PDL1 (avelumab, atezolizumab). All these molecules
V600E mutations, HER2 mutations and MET 14 exon skipping mutations are now either at an advanced stage of development or already authorized (4).
et al. For instance, dabrafenib either as monotherapy or in combination Therapeutic vaccines have already a long story beginning with Coley toxins at
with MEK inhibitor (trametinib) has displayed promising antitumor activity the end of the nineteenth century (5). The Coley’s toxins, (cultures of

streptococci) were infused in patients with bone and soft tissue sarcomas and study some efficacy has been observed in subgroups of NSCLC patients but
some impressive regressions were observed. The hypothesis was that the mostly in post hoc analyses. All vaccine studies have shown that there is no
immune reaction provoked by the infusion of the “toxins” present in the safety problems. The fact that nowadays, considerable interest has been
infectious material was able to destroy the tumoral cells. However, due to the developed toward checkpoint inhibitors, probably explains the disaffection
reluctance of doctors to administer dangerous bacterial culture and the toward vaccines. Hopefully it will be only transient and the already long story
appearance of novel treatments of cancer (CT and RT), the Coley’s toxin of therapeutic vaccines will continue.
approach has been abandoned although numerous articles were devoted to
this subject (6). Non specific vaccines using for example BCG to stimulate Product Trials conducted Author (ref)
innate immunity have been disappointing as well in SCLC (7-8)and NSCLC (9). Phase IIB maintenance study
Specific immunotherapy aims at the stimulation of adaptive immunity Tecemotide
in stage III/IV NSCLC Phase III Butts(10) Butts(11)
against the vaccine components and thus induces or amplifies an immune (Stimuvax*)
Merck Serono maintenance therapy after CT-RT in Mitchell(12) Wu(13)
response against TAA. These vaccines are either peptides (Tecemotide, non resectable stage III disease
MAGE-A3), cellular vaccines (Belagenpumatucel) or vaccines using viral vector
Adjuvant treatment after surgery
(TG4010). Tecemotide and TG4010 are a MUC1 antigen-specific cancer Vansteenkiste(14)
MAGE A3 GSK Phase II randomized study Phase III
immunotherapy. MUC1 is expressed at the apical surface of mucin-secreting Vansteenkiste(15)
study (Magrit trial)
normal epithelial cells of various tissues and can be overexpressed and
Belagenpuma-
aberrantly glycosylated in some tumors and thus is an attractive target for Phase III study as maintenance in
tucel Lucanix* Giaccone(16)
immunotherapy. Tecemotide is a liposomal vaccine. In a randomized phase II stage IV disease after 1st line CT
NovaRx
trial (10), 171 NSCLC patients who were not progressing after induction CT or
In combination with first line CT
CT-RT received subcutaneous tecemotide plus best supportive care (BSC) or
TG4010 in stage IV disease NSCLC Phase II Ramlau(17)
BSC alone as maintenance therapy . Median survival time (MST) was longer in
Transgene study Phase IIB randomized study Quoix(18) Quoix(19)
patients receiving tecemotide (17.2 vs. 13.0 months) but this did not reach
Phase IIB/III randomized study
statistical significance. As in a post hoc analysis the benefit appeared to be
more important for patients with stage IIIB disease, it was decided to perform Table 1 Phase II and III vaccine studies in NSCLCReferences 1. Kawai O, et
a phase III study in locally advanced NSCLC (11,12)comparing in non- al. Predominant infiltration of macrophages and CD8(+) T Cells in cancer
progressing patients after CT with platin-based doublet and RT, tecemotide nests is a significant predictor of survival in stage IV nonsmall cell lung
versus placebo. MST was 25.8 months with tecemotide versus 22.4 months cancer. Cancer 2008;113:1387–95. 2. Engels EA, et al. Spectrum of cancer risk
with placebo (HR 0.89, 95%CI 0.77-1.03, p=0.111). In the concurrent CT-RT among US solid organ transplant recipients. JAMA 2011;306:1891–901. 3.
subgroup, there was a significant survival benefit in favor of tecemotide Hleyhel M, et al. Risk of non-AIDS-defining cancers among HIV-1-infected
whereas in the sequential CT-RT subgroup, survival did not differ between the individuals in France between 1997 and 2009: results from a French cohort.
two arms. A similar study (13)was initiated in Asian people. This trial was AIDS 2014;28:2109–18. 4. El-Osta H,et al. Immune checkpoint inhibitors:
prematurely terminated as the sponsor decided to discontinue program with the new frontier in non-small-cell lung cancer treatment. OncoTargets
tecemotide in NSCLC MAGE-A3 is an antigen expressed in 76% of melanoma Ther. 2016;9:5101–16. 5. Coley WB. The Treatment of Inoperable Sarcoma by
and in 35% of NSCLC. It is absent from normal tissues except for testis and Bacterial Toxins (the Mixed Toxins of the Streptococcus erysipelas and the
placenta. This vaccine, has been investigated in early stage of NSCLC as an Bacillus prodigiosus). Proc R Soc Med. 1910;3(Surg Sect):1–48. 6. Zacharski
adjuvant treatment. A randomized phase II study(14)compared the MAGE-3A LR, Sukhatme VP. Coley’s toxin revisited: immunotherapy or plasminogen
vaccine to a placebo in 182 patients operated of a stage IB or II NSCLC with activator therapy of cancer? J Thromb Haemost 2005;3:424–7. 7. Maurer
their tumor expressing MAGE-A3 antigen. The randomization was on a 2 :1 LH, et al. Combined modality therapy with radiotherapy, chemotherapy,
basis. The main objective was to compare the Disease Free Interval (DFI) and immunotherapy in limited small-cell carcinoma of the lung: a Phase III
defined as the time from resection to the date of recurrence (any type) or cancer and Leukemia Group B Study. J Clin Oncol 1985;3:969–76. 8. Giaccone
second primary lung neoplasm. Although there was a trend toward a G, et al. Phase III study of adjuvant vaccination with Bec2/bacille Calmette-
numerically longer DFI in the MAGE-A3 vaccine group, the main objective was Guerin in responding patients with limited-disease small-cell lung cancer.
not met. Nevertheless, even if these trends were by far not significant, the J Clin Oncol 2005;23:6854–64. 9. Robinson E, et al. Combined-modality
results appear promising to the sponsors and a phase III trial was launched treatment of inoperable lung cancer (i.v. immunotherapy, chemotherapy, and
(MAGRIT trial) with the same scheme(15). Unfortunately, the biggest trial ever radiotherapy). Cancer Treat Rep. 1985;69:251–8. 10. Butts C, et al. Randomized
performed with the inclusion of 2312 NSCLC patients is negative regarding as phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell
well the primary objective: disease-free survival (DFS) but also the secondary lung cancer. J Clin Oncol 2005;23:6674–81. 11. Butts C, et al. Tecemotide
objective, DFS in the group of patients not receiving adjuvant chemotherapy (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-
or other subgroups. Belagenpumatucel-L is a vaccine comprising 4 tranforming cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet
growth factor-β2-antisense gene-modified irradiated allogeneic NSCLC cell Oncol. 2014;15:59–68. 12. Mitchell P, et al. Tecemotide in unresectable stage
lines. A randomized phase III trial (16)comparing this vaccine to a placebo was III non-small-cell lung cancer in the phase III START study: updated overall
performed after platinum-based CT for stage III/IV disease in non progressing survival and biomarker analyses. Ann Oncol 2015;26:1134–42. 13. Wu Y-L, et
patients. This trial was negative with no difference in overall survival and in al. INSPIRE: A phase III study of the BLP25 liposome vaccine in Asian patients
PFS. However, in a prespecified multivariate analysis, there was an improved with unresectable stage III non-small cell lung cancer. BMC Cancer. 2011;11:430.
survival for patients who were randomized within 12 weeks after CT and for 14. Vansteenkiste J, et al. Adjuvant MAGE-A3 immunotherapy in resected
patients who received prior radiation therapy. TG4010 is a suspension of a non-small-cell lung cancer: phase II randomized study results. J Clin Oncol
recombinant modified vaccinia virus strain Ankara coding for the MUC1 TAA 2013;31:2396–403. 15. Vansteenkiste JF, et al. Efficacy of the MAGE-A3 cancer
and IL2. Feasibility of either upfront combination of TG4010 with cisplatine- immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-
vinorelbine or TG4010 alone until progression has been demonstrated in a positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind,
phase II study(17). Sixty-five patients were randomized. Response rate was 30 placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:822–35. 16. Giaccone
% in the combined upfront schedule, MST was 12.7 months and one-year G, et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell
survival rate 53%. Taking into account these results, a phase II randomized vaccine, as maintenance therapy for non-small cell lung cancer. Eur J Cancer
study (18)comparing CT with cisplatin and gemcitabine to the same CT + 2015;51:2321–9. 17. Ramlau R, et al. A phase II study of Tg4010 (Mva-Muc1-Il2)
TG4010 was performed. One hundred and forty eight patients with stage IIIB in association with chemotherapy in patients with stage III/IV Non-small cell
or IV disease were included. The primary endpoint was 6-month PFS with the lung cancer. J Thorac Oncol 2008;3:735–44. 18. Quoix E, et al. Therapeutic
hypothesis that it will be at least 40% in the combined arm. This objective was vaccination with TG4010 and first-line chemotherapy in advanced non-small-
met with a 6-months PFS of 43% compared to 35.1% in the CT alone arm. There cell lung cancer: a controlled phase 2B trial. Lancet Oncol. 2011;12:1125–33.
was a non significant trend toward a higher response rate and a longer time to 19. Quoix E, et al. TG4010 immunotherapy and first-line chemotherapy for
progression in the combined arm. An exploratory analysis of the subgroups advanced non-small-cell lung cancer (TIME): results from the phase 2b part
defined by the level of activated NK cells (CD16+CD56+CD69+lymphocytes or of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet
TrPAL) shows that a better outcome was observed for those patients with Oncol. 2016;17:212–23.
normal level of TrPAL and that the vaccine might be deleterious for those with
high level of TrPAL. A phase IIB was then performed to confirm the role of the Keywords: lung cancer, Checkpoint blockers, Vaccine
level of TrPAL(19). 222 patients were randomly allocated to CT+TG4010 or
CT+placebo. Median PFS was 5.9 months in the TG4010 group versus 5.1
months in the placebo group (HR 0.74, 95%CI 0.55-0.98, p= 0.019). In patients
with TrPAL values less or equal ULN, the HR for PFS was 0.75 (95%CI 0.51-1.03)
with a posterior probability of HR being <1 of 98.4% and thus the primary SESSION SC06: NOVEL THERAPIES IN MALIGNANT
endpoint was met. In patients with high level of TrPAL, there was no PLEURAL MESOTHELIOMA AND THYMIC MALIGNANCIES
deleterious effect but no benefit as the HR for PFS was 0.77 (95%CI 0.42-1.40).
As a conclusion, all studies with vaccines have been quite disappointing. To
MONDAY, DECEMBER 5, 2016 - 14:30-15:45
the best of my knowledge, the only vaccine still under investigation remains
TG4010, but..phase III trial is not implemented at this time. In each vaccine
SC06.03 INTRAOPERATIVE THERAPIES IN MALIGNANT PLEURAL
MESOTHELIOMA histological subtype), but the progression free survival was only 9.6 months
Isabelle Opitz [13]. Intracavitary gene therapy (iGT) Gene therapy is based upon transfer of
genetic material, including complementary DNA, full-lengths genes, small
Division of Thoracic Surgery, University Hospital Zurich, Zurich/Switzerland
interfering RNA or oligonucleotids into cells for therapeutic purposes. For
The rational of localized / intracavitary treatment is to eliminate microscopic sufficient gene delivery, adenovirus is the most widely used in clinical trials
residual disease (MRD) after macroscopic complete resection (MCR) for among a variety of viral and non-viral vectors. In addition to delivering
mesothelioma patients. The advantage of the treatment is that local effects cytokine expressing vectors or re-directed T cells (see iIT part), several
can be enhanced whereas systemic side effects of the therapeutic agents different cancer gene therapy approaches are currently used including the so
applied might be reduced. Several approaches have been investigated called suicide gene therapy wherein a neoplasm is transduced with a cDNA
over the past decades in preclinical and clinical trials, such as intracavitary encoding for an enzyme rendering tumor cells sensitive to a benign agent by
chemotherapy (iCTX), immunotherapy (iIT), photodynamic therapy (PDT) converting the product to a toxic metabolite. The Herpes Simplex Virus 1-
and gene therapy (iGT). Intracavitary chemotherapy (iCTX) iCTX has thymidine kinase (HSVtk) gene encodes for an enzyme that converts
been studied after mesothelioma resection, not only after extrapleural ganciclovir, an antiviral drug, to its cytotoxic metabolite. Intrapleural
pneumonectomy (EPP) but also after (extended) pleurectomy/decortication adenovirus HSVtk/ganciclovir administration was safe in MPM and two
((e)P/D). The main therapeutic agent used is cisplatin. In some trials patients survived >6.5 years. Nevertheless, due to the fact that transgenes
hyperthermia was additionally added with the aims to enhance the HSVtk were only detected at the surface of tumor tissues, the authors
penetration of cisplatin into tissues and maximize its cytotoxicity in tumor suggested that the treatment efficacy may be a result of antitumor immune
cells [1]. Hyperthermic intrapleural perfusion had a maximum tolerated response stimulation [14]. MPM tumor genome is characterized by frequent
dose of 225-250 mg Cisplatin/m2 BSA [2]. The morbidity ranges from 13 to mutations in tumor suppressor genes such NF2, BAP1 or p53, thus the delivery
85% and the mortality from 0 to 29% [2, 3]. Some complications are related of tumor suppressor gene expressing vectors into tumor cells can serve as an
to renal toxicity which was the dose limiting adverse event [2]. Median attractive treatment approach. The delivery of adenovirus expressing p53 has
survival time reaches up to 35.3 months in low-risk MPM patients receiving been tested in clinical trials for lung cancer but did not show better clinical
hyperthermic intraplueral cisplatin chemotherapy following MCR [4]. This benefit over chemotherapy [15]. This may be due to limited transfection
treatment is only considered for well-designed clinical trials. In vivo preclinical efficiency of the vector and the stimulation of neutralizing antibody,
model using intrapleural administration of cisplatin-mixed loaded to a fibrin therefore an improvement of transfection is still needed for the further
carrier improved the local drug concentration and prolonged the exposure development of gene therapy.References: 1. Sugarbaker, P.H., et al., Update on
of tissue to high cisplatin concentration [5]. Our phase I dose escalation chemotherapeutic agents utilized for perioperative intraperitoneal
trial (INFLuenCe – Meso; see figure) has proven the safety of this treatment chemotherapy. Oncologist, 2005. 10(2): p. 112-22. 2. Richards, W.G., et al.,
approach (manuscript in preparation). This treatment regimen is now being Phase I to II Study of Pleurectomy/Decortication and Intraoperative
tested in a phase II trial (NCT01644994). Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma. J Clin Oncol,
2006. 24(10): p. 1561-1567. 3. de Bree, E., et al., Cytoreductive surgery and
intraoperative hyperthermic intrathoracic chemotherapy in patients with
malignant pleural mesothelioma or pleural metastases of thymoma. Chest,
2002. 121(2): p. 480-7. 4. Sugarbaker, D.J., et al., Hyperthermic intraoperative
pleural cisplatin chemotherapy extends interval to recurrence and survival
among low-risk patients with malignant pleural mesothelioma undergoing
surgical macroscopic complete resection. J Thorac Cardiovasc Surg, 2013.
145(4): p. 955-63. 5. Lardinois, D., et al., Intrapleural topical application of
cisplatin with the surgical carrier Vivostat increases the local drug
concentration in an immune-competent rat model with malignant
pleuromesothelioma. J Thorac Cardiovasc Surg, 2006. 131(3): p. 697-703. 6.
Tada, Y., et al., An intrapleural administration of zoledronic acid for inoperable
In addition to chemotherapy, other substances have also been tested for malignant mesothelioma patients: a phase I clinical study protocol.
intracavitary treatment. Recently, Tada, et. al. reported study plan for a phase Springerplus, 2016. 5: p. 195. 7. Astoul, P., et al., Intrapleural recombinant IL-2 in
I trial for intrapleural treatment with zoledronic acid, a third generation of passive immunotherapy for malignant pleural effusion. Chest, 1993. 103(1): p.
bisphosphonates, in inoperable MPM, after having successfully proven the 209-13. 8. Antoniou, K.M., E. Ferdoutsis, and D. Bouros, Interferons and their
efficacy of zoledronic in a pre-clinical model [6]. Intracavitary application in the diseases of the lung. Chest, 2003. 123(1): p. 209-16. 9.
immunotherapy (iIT) MPM is not a classical “immunogenic” tumor. Sterman, D.H., et al., A phase I clinical trial of single-dose intrapleural IFN-beta
Intrapleural instillation of cytokines such as interleukin (IL)-2, interferon gene transfer for malignant pleural mesothelioma and metastatic pleural
(IFN)-α and IFN-γ provided a good control of malignant pleural effusion (MPE) effusions: high rate of antitumor immune responses. Clin Cancer Res, 2007.
and MPM with minimal toxicity [7, 8]. To prolong and increase local exposure 13(15 Pt 1): p. 4456-66. 10. Sterman, D.H., et al., A phase I trial of repeated
of IFNs, recent studies implemented immuno-gene therapy approach using intrapleural adenoviral-mediated interferon-beta gene transfer for
adenoviral vector expressing human IFNs. Four out of 10 patients with MPM mesothelioma and metastatic pleural effusions. Mol Ther, 2010. 18(4): p.
and metastatic pleural effusions showed stable disease following a single 852-60. 11. Sterman, D.H., et al., Pilot and Feasibility Trial Evaluating
dose of intrapleural adenoviral vector expressing IFN-β [9]. Nevertheless due Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery
to rapid production of neutralizing antibody against adenovirus, no of Adenovirus-IFNalpha Combined with Chemotherapy. Clin Cancer Res, 2016.
improvement of gene transfer efficacy was achieved after the second dose 22(15): p. 3791-800. 12. Simone, C.B., 2nd and K.A. Cengel, Photodynamic
[10]. The same research group conducted a clinical trial assessing the safety of therapy for lung cancer and malignant pleural mesothelioma. Semin Oncol,
adenoviral-mediated IFN-α2b in combination with chemotherapy. Recent 2014. 41(6): p. 820-30. 13. Friedberg, J.S., et al., Radical pleurectomy and
data from this trial showed that the treatment is well tolerated and 25% of intraoperative photodynamic therapy for malignant pleural mesothelioma.
patients had partial response [11]. An intrapleural treament with re-directed T Ann Thorac Surg, 2012. 93(5): p. 1658-65; discussion 1665-7. 14. Sterman, D.H.,
cells genetically engineered to express chimeric antigen receptor (CAR) that et al., Long-term Follow-up of Patients with Malignant Pleural Mesothelioma
specifically recognizes tumor antigens is an attractive therapeutic option. A Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir
clinical phase I trial for intrapleural administration of fibroblast activation Suicide Gene Therapy. Clin Cancer Res, 2005. 11(20): p. 7444-7453. 15. Schuler,
protein (FAP)-specific re-directed T cells is currently being conducted M., et al., Adenovirus-mediated wild-type p53 gene transfer in patients
(NCT01722149). Photodynamic therapy (PDT) PDT is a light based cancer receiving chemotherapy for advanced non-small-cell lung cancer: results of a
therapy. Most modern PDT applications involve three key components: a multicenter phase II study. J Clin Oncol, 2001. 19(6): p. 1750-8.
photosensitizer, a light source and tissue oxygen. The photosensitizing agent
accumulates in tumor cells and is activated by light of a specific wavelength to Keywords: malignant pleural mesothelioma, intracavitary chemotherapy,
produce reactive singlet oxygen that mediates cellular toxicity. The tumor Intracavitary Immunotherapy, photodynamic therapy
cells are killed through both apoptosis and necrosis and by damaging tumor
vasculature. It may also induce inflammatory reaction capable of stimulating
a tumor directed host immune response. The advantages of this treatment are
that its efficacy is not influenced by chemo- or radio-resistance of tumor cells, SC06: NOVEL THERAPIES IN MALIGNANT PLEURAL MESOTHELIOMA AND THYMIC
MALIGNANCIES
that it can be repeated at the same site without compromising its efficacy and MONDAY, DECEMBER 5, 2016 - 14:30-15:45
that it does not compromise the ability to administer other treatment
modalities in patients with recurrent or residual disease. PDT should be
combined with macroscopic complete resection due to limited depth of SC06.04 IMMUNOTHERAPY OF MALIGNANT PLEURAL
penetration. Localized inflammation and fluid accumulation after treatment MESOTHELIOMA AND THYMIC MALIGNANCIES: THE END OF THE
can modestly extend hospital stay. PDT appears promising and may improve BEGINNING?
local control and potentially prolong survival in properly selected patients Jan Van Meerbeeck
who are able to undergo MCR, with clinical outcomes appearing best when Thoracic Oncology, Antwerp University Hospital, Edegem/Belgium
PDT is combined with lung-sparing definitive surgery [12]. Friedberg reported
a median survival of 31.7 months (41.2 months in patients with epithelioid The significant improvement in outcome observed with immune checkpoint

inhibitors in advanced melanoma and NSCLC have triggered their use in chemotherapy will be randomized between standard follow up and a
mesothelioma and thymic tumours. Both tumours are characterized by maintenance treatment consisting of 5 injections of DC’s, pulsed with an
an unmet need to improve their prognosis and an immunosuppressive allogeneic lysate obtained from 5 well-characterized clinical grade human
environment induced by (i) the (over-)expression of checkpoint receptors, malignant mesothelioma cell lines. Cell-based immunotherapy carries high
responsible for controlling and inactivating the immune system in order expectations but remains cumbersome and labour-intensive. Anti-CTL-A4
to avoid autoimmunity and prevent collateral tissue damage- and (ii) by antibody-based immunotherapy in mesothelioma has so far failed to deliver
a silencing of the antigen presenting function of dendritic cells by tumor- the expected improvement in outcome. Whether this also applies to anti-
derived soluble factors, leading to a defective induction of cytotoxic T– PD-(L)1 monoclonal antibodies remains to be seen from ongoing and future
lymphocytes response [1]. The new paradigm consists of reactivating these trials. A low mutational burden and the limited formation of neo-epitopes
silenced immune responses by either monoclonal antibodies or cell-based under chemotherapy, -both considered important predictive factors for
therapies. CTLA-4 is responsible for modulating central T-cell activation in the immune checkpoint therapy- are the challenges for this approach. As in other
lymph nodes. Under physiological conditions, the immune inhibitory effect tumour types, studying a combination of different checkpoint inhibitors
of CTLA-4 is involved in provoking an effective immune response without either with or without chemotherapy or with anti-angiogenic agents is of
causing excessive damage to the normal surrounding tissue. However, interest [9]. In thymic tumours, the presence or risk of developing immune-
tumor cells can stimulate abnormal expression of CTLA-4 by secreting mediated paraneoplastic syndromes is of particular concern. This could be
TGF-beta, that induces CTLA-4 overexpression, resulting in a state of T-cell an argument to prioritize checkpoint inhibitors in thymic carcinomas[10].
dysfunction whereby T-cells fail to proliferate and are no longer able to References 1: Marcq E et al. Targeting immune checkpoints: new opportunity
exert their effector functions. Tremelimumab and ipilimumab are selective for mesothelioma treatment? Cancer Treatm Rev 2015; 41(10):914 2:Kindler
monoclonal antibodies against CTL-A4 and block its binding to CD80 and CD HL et al. Tremelimumab as second- or third-line treatment of unresectable
86, thereby enhancing T cell activity and anti tumor immunity. There are no malignant mesothelioma (MM): Results from the global, double-blind,
known predictive factors for anti-CTL-A4 therapy in mesothelioma. After 2 placebo-controlled DETERMINE study. J Clin Oncol 2016; 34 (suppl): abstr
phase 2 trials at different dose levels –which were negative for their primary 8502 3: Katsuya Y et al. Immunohistochemical status of PD-L1 in thymoma
endpoint, but nevertheless considered promising- DETERMINE compared and thymic carcinoma. Lung Cancer. 2015;88(2):154 4: Alley EW et al. Single-
tremelimumab to placebo as second line treatment in MPM [2]. No difference Agent Pembrolizumab for Patients with Malignant Pleural Mesothelioma.
in outcome was reported, but an increased class specific toxicity in the J Thorac Oncol 2015; 10(9) supplement 2: abstr O11.03 5: Quispel-Janssen J et
patients treated with tremelimumab. The PD-1-PD-L1 axis is responsible for al. NIVOLUMAB IN MALIGNANT PLEURAL MESOTHELIOMA (NIVOMES): AN
controlling peripheral T-cell activation at the tumor site. Overexpression of INTERIM ANALYSIS. Proc IMiG 13, Birmingham 2016; abstr MS 04.07 6: Hassan
PD-L1 is thought to induce immune tolerance. In MPM, PD-L1 expression by R et al. Avelumab in patients with advanced unresectable mesothelioma
immunohistochemistry was reported in 20-70% of formalin-fixed paraffin from the JAVELIN solid tumor phase Ib trial: safety, clinical activity and PD-L1
embedded mesothelioma, in 70% of thymic carcinomas and in 23% of expression. J Clin Oncol 2016; 34(suppl): abstr 8503 7: Berneman ZN et al.
thymomas [1,3]. In mesothelioma, PD-L1 expression overexpression is more Dendritic cell vaccination in malignant pleural mesothelioma: A phase I/II
common in non-epitheloid histology, is associated with a significantly worse study. J Clin Oncol 2014; 32:5s: abstr 7583 8: Zauderer MG et al. Randomized
survival. PD-L1 expression is furthermore considered a –weak- predictive phase II study of adjuvant WT1 vaccine (SLS-001) for malignant pleural
factor for the activity of immune checkpoint inhibitors in NSCLC, besides mesothelioma after multimodality therapy. J Clin Oncol 2016; 34 (suppl): abstr
mutagenic load and the formation of neo-epitopes. Several anti PD-(L)1 8519 9: Anonymous. Nivolumab Monotherapy or Nivolumab Plus Ipilimumab,
antibodies are registered and/or in development for use in other tumour for Unresectable Malignant Pleural Mesothelioma (MPM) Patients (MAPS2).
types. Promising phase 2 trial results in mostly pretreated mesothelioma Available at: https://clinicaltrials.gov/ct2/show/NCT02716272 10: Anonymous.
patients are summarized in the table [4-6]. Expression level of PD-L1 did not MK-3475 in Patients With Thymic Carcinoma. Available at: https://
correlate with response in either trial. clinicaltrials.gov/ct2/show/NCT02364076
Keywords: thymic tumours, Mesothelioma, Immunotherapy, check point

Checkpoint inhibitors in mesothelioma
inhibitors
Sub- ORR/
Trial Drug Phase Line N PFS
type DCR (%)
DETERMINE Tremeli- Ep:
3 2/3 382 4.5/31.7 2.8 m
(2) mumab 83%
KEYNOTE Pembro-
2 2 25
all
28/76
49.4% SESSION SC07: NEW CHALLENGES FOR LUNG CANCER:
28 (4) lizumab PDL1+ @ 6m WATERPIPES AND E-CIGARETTES
NIVOMES Nivo- MONDAY, DECEMBER 5, 2016 - 16:00-17:30
2 NR 18 NR 27/49 NR
(5) lumab
Avelu- Ep:
JAVELIN (6) 1b 2-5 53 9.4/56.6 17.1 w
mab 83% SC07.03 CONNECTIONS OF NICOTINE TO CANCER AND ITS
Dendritic cells (DC), obtained by leukapheresis, can be loaded with synthetic INFLUENCE ON CANCER TREATMENT
peptides coding for parts of tumor-associated antigens, a lysate of tumor Sergei Grando
material of the patient itself (autologous dendritic cell-therapy) or with other University of California, Irvine/CA/United States of America
sources of tumor-specific antigens (allogeneic dendritic cell-therapy). Wilms’
tumor 1 (WT1) is an ideal candidate for a tumor selective cancer vaccine in There is a growing evidence of direct contributions of nicotine to cancer onset
cancers expressing WT1, such as MPM. Two vaccines have investigated this and growth. The list of cancers reportedly connected to nicotine is expanding
approach. Vaccination with autologous DC’s, electroporated with mRNA and presently includes small-cell and non-small-cell lung carcinomas, as well
encoding the WT1 antigen was evaluated in 10 patients with mesothelioma as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical,
not progressing after platinum/ pemetrexed-based chemotherapy [7]. urinary bladder and kidney cancers. The mutagenic and tumour-promoting
Biweekly intradermal vaccinations were administered for an intended activities of nicotine may result from its ability to damage the genome,
period of 6 months, followed by monthly or bimonthly injections. DC disrupt cellular metabolic processes, and facilitate growth and spreading of
vaccination was well-tolerated: no systemic toxicity was recorded; local transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are
reactions at the injections sites occurred in all patients, but were mild and activated by nicotine, can activate several signaling pathways that can have
self-limiting. At a median follow-up of 22.7 months, 6 patients are alive, 4 tumorigenic effects, and these receptors might be able to be targeted for
have died and 1 year survival rate is 90% from start of treatment, suggesting cancer therapy or prevention. There is also growing evidence that the unique
that adjuvant DC-based immunotherapy provides a clinical benefit. In a genetic makeup of an individual, such as polymorphisms in genes encoding
pilot trial in pretreated MPM, the multivalent native and synthetic WT1 nAChR subunits, might influence the susceptibility of that individual to
peptide vaccine Galinpepimut-S was well-tolerated and CD4/8 immune the pathobiological effects of nicotine. The emerging knowledge about the
responses were generated. After completing multimodality therapy, carcinogenic mechanisms of nicotine action should be considered during the
40 mesothelioma patients were randomized to receive maintenance evaluation of regulations on nicotine product manufacturing, distribution
Montanide and GM-CSF with or without Galinpepimut-S [8]. There were no and marketing.
serious treatment related adverse events. Based on a pre-specified futility
Keywords: Cancer, Nicotinic acetylcholine receptor, nicotine
analysis, accrual was stopped. Median PFS from randomization was 11.4
months in the experimental arm vs. 5.7 months in the control arm (HR
0.69). Similarly, median overall survival (OS) from randomization was 21.4
months in the Galinpepimut-S arm vs. 16.6 months in the control arm (HR
0.52). In the subgroup with R0 resection, median OS was 39.3 months in
the Galinpepimut-S and 24.8 in the control arm (p = 0.04). A confirmatory SESSION SC08: IASLC-ESTS JOINT SYMPOSIUM:
adequately powered randomized adjuvant study is awaited. In the European THE BORDERLINE PATIENT
DENIM trial, patients not progressing after 1st line platinum-pemetrexed MONDAY, DECEMBER 5, 2016 - 16:00-17:30
been recommended as the approach of choice for stage I lung cancer patients.
SC08.01 IMPACT AND MANAGEMENT OF CO-MORBIDITIES Several studies showed that this approach is associated with lower incidence
Alessandro Brunelli of complications, shorter hospital stay and in some cases lower mortality
St. James’ University Hospital, Leeds/United Kingdom
rates compared to thoracotomy. The benefits of VATS are particularly evident
in patients with poor pulmonary function. Large series found that the
Introduction: Due to general ageing population, many patients with lung difference in pulmonary complication rates after lobectomy by VATS versus
cancer are elderly and with frequent underlying co-morbidities. The most thoracotomy was present only in patients with a FEV1<60%. Burt and coll.8
frequent co-morbidities associated with lung cancer are cardiac (i.e. coronary found that patients with ppoFEV1<40% or ppoDLCO<40% and submitted to
artery disease) and pulmonary diseases (i.e. COPD). Cardiac co-morbidity: VATS lobectomy had a markedly reduced incidence of mortality compared to
Coronary artery disease (CAD) is present in approximately 10-15% of lung those operated on through thoracotomy (ppoFEV1<40%: 0.7% vs. 4.8%,
resection candidates. The risk of major adverse cardiac events (MACE) and p=0.003; ppoDLCO<40%: 2% vs. 5.2%, p=0.003). Recent evidences have shown
cardiac mortality is 4-fold higher in patients with previous history of CAD1 and that anatomic segmentectomies provide equivalent oncologic results
patients with a previous coronary stent procedure within 1 year from lung compared to lobectomy for tumours smaller than 2 cm, whilst preserving
resection had MACE and mortality rates of 9.3% and 7.7% after surgery, much more respiratory function and being associated with lower incidence of
respectively2. Cardiac evaluation is therefore particularly important in this postoperative complications9,10. This extent of resection appears therefore
population to optimize their treatment and reduce surgical risk. A specific ideal for patients with a limited baseline pulmonary function.
cardiac risk score was recently developed and is named Thoracic RCRI SelectedReferences: 1. Brunelli A, et al. Recalibration of the revised cardiac
(ThRCRI). Patients in the highest class of risk had a incidence of MACE of 23% risk index in lung resection candidates. Ann Thorac Surg. 2010;90(1):199-203.
versus only 1.5% in those in the lowest class of risk1. These findings were 2. Fernandez FG, et al. Incremental risk of prior coronary arterial stents for
subsequently validated by a number of independent studies. Detailed pulmonary resection. Ann Thorac Surg. 2013 Apr;95(4):1212-8 3. Fleisher LA, et
evaluation for coronary heart disease is not recommended in patients who al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and
have an acceptable exercise tolerance and with low cardiac risk score. For care for noncardiac surgery: a report of the American College of Cardiology/
patients whose exercise capacity is limited, those with a ThRCRI > 1.5 or those American Heart Association Task Force on Practice Guidelines (Writing
with known or newly suspected cardiac condition, non-invasive cardiac Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular
evaluation is recommended as per AHA/ACC guidelines3 to identify patients Evaluation for Noncardiac Surgery): developed in collaboration with the
needing more invasive interventions. Appropriately aggressive cardiac American Society of Echocardiography, American Society of Nuclear
interventions should be instituted prior to surgery only in patients who would Cardiology, Heart Rhythm Society, Society of Cardiovascular
need them irrespective of the planned surgery. However, prophylactic Anesthesiologists, Society for Cardiovascular Angiography and Interventions,
coronary revascularization prior to surgery in patients who otherwise do not Society for Vascular Medicine and Biology, and Society for Vascular Surgery.
need such a procedure does not appear to reduce perioperative risk4. Circulation 2007: 116(17): 418-499. 4. McFalls EO, et al. Coronary-artery
Pulmonary co-morbidity: Approximately 20-25% of patients with early stage revascularization before elective major vascular surgery. N Eng J Med 2004;
lung cancer have a concomitant moderate to severe COPD (FEV1<80% and 351(27): 2795-2804 5. Brunelli A, et al. ERS/ESTS clinical guidelines on fitness
FEV1/FVC ratio < 70%). Many studies have shown the association between for radical therapy in lung cancer patients (surgery and chemo-radiotherapy).
FEV1 or predicted postoperative FEV1 (ppoFEV1), and surgical risk. In Eur Respir J 2009; 34:17-41. 6. Brunelli A, et al. Physiologic Evaluation of the
particular the risk of pulmonary morbidity and mortality has been shown to Patient With Lung Cancer Being Considered for Resectional Surgery:
increase when FEV1 is below 50-60% or ppoFEV1< 30-40%. However, recent Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest
evidence has shown that even patients with moderate to severe COPD and Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013 May;143(5
lung cancer can undergo safely to lung resection. In these patients, the Suppl):e166S-90S 7. Brunelli A, et al. Peak Oxygen Consumption During
resection of the most affected parenchyma containing the tumor may Cardiopulmonary Exercise Test Improves Risk Stratification in Candidates to
determine a minimal loss or even an improvement in respiratory mechanics Major Lung Resection. Chest 2009; 135:1260-1267. 8. Burt BM, et al.
and elastic recoil, similar to what happens in typical end-staged emphysema Thoracoscopic lobectomy is associated with acceptable morbidity and
patients candidates to lung volume reduction surgery. Nearly one third of mortality in patients with predicted postoperative forced expiratory volume
COPD patients may actually improve their FEV1 3 months after pulmonary in 1 second or diffusing capacity for carbon monoxide less than 40% of normal.
lobectomy for cancer. Therefore, although a reduced FEV1 or ppoFEV1 is J Thorac Cardiovasc Surg. 2014 Jul;148(1):19-28 9. Okada M, et al. Radical
associated with increased morbidity and mortality, most recent guidelines sublobar resection for small-sized non-small cell lung cancer: a multicenter
recommended against using this parameter alone to exclude patients from study. J Thorac Cardiovasc Surg. 2006 Oct;132(4):769-75 10. Yano M, et al.
surgery even in case of very low values5,6. Patients with idiopathic pulmonary Survival of 1737 lobectomy-tolerable patients who underwent limited
fibrosis (IPF) and lung cancer are a more challenging population to manage. resection for cStage IA non-small-cell lung cancer. Eur J Cardiothorac Surg.
Surgical treatment of these patients is high risk for postoperative acute 2015 Jan;47(1):135-42
exacerbations of IPF, which is associated with 80-100% mortality rate. The
postoperative mortality rate of these patients has been reported to range Keywords: coronary artery disease, copd, Comorbidity, lung cancer surgery
between 7 and 18%. Moreover, long-term prognosis of IPF itself affects long
term survival following surgery for cancer. Additional fitness tests Carbon
monoxide lung diffusion capacity (DLCO) appears to be a more sensitive IASLC-ESTS JOINT SYMPOSIUM: THE BORDERLINE PATIENT
indicator of poor pulmonary function and more reliably associated with MONDAY, DECEMBER 5, 2016 - 16:00-17:30
postoperative respiratory complications and mortality. Until recently, DLCO
measurement has been mainly reserved to patients with abnormal FEV1.
However, recent studies have shown that FEV1 and DLCO are poorly correlated SC08.04 SABR VERSUS SURGERY
and that more than 40% of patients with normal FEV1 (>80%) may have Norihiko Ikeda, Tatsuo Ohira, Naohiro Kajiwara
reduced DLCO. A low DLCO or ppoDLCO is a reliable predictor of Department of Surgery, Tokyo Medical University, Tokyo/Japan
cardiopulmonary morbidity and mortality not only in patients with COPD but
also in those with normal respiratory function. This is the rationale behind the In recent years, the number of early stage lung cancers has enormously
most recent recommendations to measure DLCO systematically in all lung increased and this tendency is more prominent in octogenarians. Both
resection candidates. Cardiopulmonary exercise test: Cardiopulmonary curability and non-inavasiveness should be required for such situation.
exercise test is the gold standard in preoperative evaluation of lung resection Surgery is the standard treatment for early stage lung cancer and VATS
candidates. In addition to the most frequently used parameter, VO2max, it lobectomy or sublobar resection have been routinely performed for selected
provides several other direct and derived measures that permit, in case of a patients to maintain performance status1). Especially, the indication of
limited aerobic reserve, to precisely identify possible deficits in the oxygen sublobar resection is considered to be related to the aggressive nature of
transport system. Several series have shown that a VO2max>20 mL/kg/min is tumors, thus several studies by HRCT findings and PET-CT were performed
safe for every extent of resection, whilst values < 10 mL/kg/min are associated to predict the invasive nature as well as clinical stage. In JCOG 0201, 545
with a high risk of potoperative mortality. We recently found that VO2max<12 case who received lobectomy and mediastinal lymph node dissection due
mL/kg/min was associated with 13% in-hospital mortality rate following open to stage I NSCLC were enrolled prospectively. Pathological non-invasive
major anatomic lung resections7. A parameter, which has gained recent cancer (both vascular and lymphatic invasion negative) was evaluated by
interest in our specialty is the minute ventilation to carbon dioxide output the consolidation/tumor ratio on preoperative HRCT. Adenocarcinoma <2.0
(VE/VCO2) slope, also named as ventilatory efficiency slope. VE/VCO2 slope cm with <0.25 consolidation to the maximum tumor diameter (35 patients,
can be increased due to either pulmonary or cardiac diseases. Several studies 12.1%) revealed pathological non-invasiveness in 98.7% (95% CI: 93.2–100.0%),
have shown that a value greater than 35 is associated with increased and this criterion could be used for radiological early lung cancer2). The
respiratory complications and mortality after lung resection. We found that prognostic study of cases enrolled in JCOG0201 revealed that 5 year OS and
the mortality rate of patients with VE/VCO2>35 was 7% versus only 0.6% of RFS survivals of the entire patients were 90.6% and 84.7%, respectively. The
those with lower values. The association between this parameter and 5-year OS of radiologic early and invasive adenocarcinomas were 97.1% and
respiratory complications remained the same for patients with and without 92.4%, respectively (p=0.259). If the consolidation/tumor ratio lower than 0.5
COPD and for those with VO2max greater or lower than 15 mL/kg/min. VATS in cT1a-b was used as a cutoff, the 5-year OS of radiologic early (121 patients,
and sublobar resections: Videoassisted thoracoscopic surgery (VATS) has 22.2%) was 96.7% and invasive adenocarcinomas, 88.9% (p<0.01)3). Based
on the criteria of radiologic early cancer obtained by JCOG0201, randomised

phase 3 trial to evaluate non-inferiority in OS of segmentectomy compared not be pursued. Currently, up to 90% of LMIC inhabitants lack sufficient
to lobectomy (JCOG0802)4). The maxSUV of the primary tumor on PET/CT radiotherapy access and about 30 countries in Africa do not have a single
could be used as a prognostic marker of early stage lung cancer. Analyses of treatment machine. It is estimated that by 2020, >9000 treatment machines,
610 resected stage IA adecocarcinoma showed that maxSUV and GGO ratio >10,000 radiation oncologists, and thousands of physicists and therapists
cutoffs to predict recurrence were 2.9 and 25%, respectively. They were also are needed to treat patients in LMICs per evidence-based radiotherapy
related to nodal metastasis, histological tumor invasiveness and recurrence. recommendations [2]. Recently, a group of experts with the Lancet Oncology
The 5-year RFS of cases with maxSUV <2.9 (n=456) was 95%, while cases Commission [3] reviewed the current radiotherapy capacity in LMICs and
with maxSUV>2.9 (n=154), 72% (p<0.001)5). Surgical management of early estimated the 20-year burden of cancer requiring radiotherapy and the
stage lung cancer should be selected by based on the tumor size, GGO ratio needed investments to bring radiotherapy capacity in these countries
and maxSUV to predict the biological malignancy of each case. Streotactic to the needed levels. The published report provides compelling evidence
ablative radiotherapy (SABR) has attained importance for efficacy and safety that investment in radiotherapy not only will save millions of lives but will
for the treatment of early cancers located in the peripheral lung. There are also bring significant economic benefits. The initial capital costs of scaling
two representative randomised phase 3 trial (STARS and ROSEL) to compare up radiotherapy may appear prohibitive, but these figures are based on
SABR and surgery. Eligible patients of these studies were T1-2a (<4cm) N0M0 estimations and projections that promise to deliver radiotherapy that is
and a total of 58 cases were registered (31 received SABR and 27, surgery). safe, timely, effective, efficient, equitable and patient centered. By aiming at
The combined analysis of these two studies revealed that 3 year OS in SABR quality care delivery, we can guarantee the highest returns on investments
(95%) was superior to that of surgery (79%) (p=0.037) and RFS at 3 years was not only in oncologic outcomes but also in curbing loss in health-related
similar; 86% in SBRT and 80% in surgery (p=0.54). Only 10% of cases in SBRT productivity and life years. We hereby discuss few strategies to directly or
group suffered grade 3 toxicity but 44% of surgery group developed grade indirectly reduce the capital or operating costs of such an expansion: - Trans-
3 and 4 toxicities. The pooled analysis of the two studies showed SBRT had national, public and private partnerships: International organizations (such
similar treatment efficacy to that of surgery in spite of the small sample as the WHO, IAEA, etc) in collaboration with interested academic consultants
size6). Japan Clinical Oncology Group evaluated the efficacy and safety of and national governments should plan the required radiotherapy centers
SBRT for operable/inoperable T1N0M0 patients (JCOG 0403). A total of 164 based on individualized national cancer priorities in the setting of a wide
patients (100 inoperable and 64 inoperable) were treated by 48 Gy. The 3 cancer care policy. This will require however a significant buy-in from national
year OS was 59.9% in inoperable patients and 76.5% in operable patients7). governments which are expected to establish effective social security
Investigations into the effectiveness of SABR for operable patients as well as systems with universal health coverage, create reliable cancer registries,
the optimal indication, dose and fraction should be clarified by prospective implement effective cancer preventative and early diagnosis programs and
manner. SABR has become a radical treatment for inoperable stage I lung finally promote outreach health literacy programs in real-world settings. Once
cancer. In addition, if operable cases treated by SABR in JCOG0403 show international investments are coupled to national needs/efforts, minimal
favorable outcome, further comparable trial of SABR versus less invasive wasting of resources and maximal return on investment will be attained. -
surgery should be warranted.References 1) Committee for Scientific Affairs Centralization and pooling of resources regionally and internationally: This
The Japanese Association for Thoracic Surgery, Thoracic and cardiovascular is a crucial step to at least jump start radiotherapy programs especially in the
surgery in Japan during 2013 : Annual report by the Japanese Association for very low income countries where efforts are generally starting from nothing
Thoracic Surgery. Gen Thorac Cardiovasc Surg.2015;63:670-701. 2) Suzuki K, or close to nothing at best. High quality radiotherapy/simulation units
Koike T, Asakawa T, et al.: A prospective radiological study of thin-section donated by and refurbished in developed countries can provide a starting
computed tomography to predict pathological noninvasiveness in peripheral point around which other resources can be pooled. Regional centers can
clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol create circles of remote dosimetry/physics support and chart rounds via video
2011;6:751-756 3) Asamura H, Hishida T, Suzuki K, et al. Radiographically conferencing to promote continued education and high quality treatment
determined noninvasive adenocarcinoma of the lung: Survival outcomes of plans. These regional networks can be also connected to international
Japan Clinical Oncology Group 0201 J Thorac Cardiovasc Surg 2013;146:24- cancer centers of excellence for further support and collaboration. Tax
30 4) Nakamura K, Saji H, Nakajima R, et.al. A Phase III Randomized Trial of breaks could be offered to academic institutions or manufacturers in rich
Lobectomy Versus Limited Resection for Small-sized Peripheral Non-small countries to participate in this process. - Investing in technology/science
Cell Lung Cancer (JCOG0802/WJOG4607L) Jpn J Clin Oncol 2010;40:271–274 5) adapted to local needs in developing countries: Even if the capital is
Uehara H, Tsutani Y, Okumura S, et al. Prognostic Role of Positron Emission available, current manufacturing capabilities will not be able to build the
Tomographyand High-Resolution Computed Tomography in Clinical Stage required number of machines by 2020 as required. There is thus an immense
IA Lung Adenocarcinoma Ann Thorac Surg 2013;96:1958–1965 6) Chang JY, need for innovative low cost, high quality radiotherapy units. Research and
Senan S, Paul MA et al. Stereotactic ablative radiotherapy versus lobectomy development departments should be offered incentives to create these tools.
for operable stage I non-small-cell lung cancer: A pooled analysis of two Optimizing the use of radiation techniques and per-unit activity to adapt to
randomized trials. Lancet Oncol 2015;16:630–637. 7) Nagata Y, Hiraoka M, the treatment demands in developing countries will also improve benefit to
Shibata T, et al. Prospective trial of stereotactic body radiation therapy cost ratio. - Hypofractionation: The number of “radiation fractions per year”
for both operable and inoperable T1N0M0 non-small cell lung cancer: Japan is used as a surrogate for radiotherapy demand. Hypofractionation, thus, is a
Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys major strategy to optimize radiotherapy utilization and decrease operating
2015;93;989-996. costs without compromising outcomes in many cancer sites. For example, in
the case of 1000 early breast [4] and 1000 early prostate cancer [5] patients
Keywords: early lung cancer, segmentectomy, SABR requiring radiotherapy per year, using evidence-based hypofractionated
treatments, not necessarily the extremely hypofractionated high-tech
stereotactic radiation, would decrease the number of needed treatment
machines from 10 to 6 and the number of therapists from 25 to 14. It will also
decrease the duration of treatment per patient and thus allow more patients
SESSION SC09: RADIOTHERAPY FOR A GLOBAL CANCER to be treated daily. Despite these benefits, hypofractionation remains widely
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 underutilized even in developed countries [6].
SC09.02 THE QUEST FOR HIGH QUALITY AFFORDABLE

RADIOTHERAPY IN DEVELOPING COUNTRIES
Osama Mohamad1, Hak Choy 2
1
Radiation Oncology, Univeristy of Texas Southwestern, Dallas/TX/United States
of America, 2Radiation Oncology, UT Southwestern Medical Center, Dallas/United
States of America
In 2030, 60% of all new cancer diagnoses (15/25 million cases) and 80% of
cancer related deaths (10/13 million deaths) will occur in low and middle
income countries (LMICs) [1]. This explosion in cancer incidence is attributed
to prolonged life expectancy in steadily growing populations with high
levels of modifiable risk factors such as tobacco/alcohol and unhealthy
diets. Despite the significant health burden, LMICs spend less than 10% - Investing in building local skills: Skilled radiation oncologists, therapists
of the global cancer budget. Cancer therapies are exponentially sprouting and physicists are very expensive commodities. While initial external support
in rich countries but LMICs are not proportionally benefitting from this is crucial, new radiation centers need to eventually become self-sufficient and
growth. Corruption, lack of infrastructure, poverty, and absence of national sustainable. Establishing local training programs should be a national priority
cancer policies/goals have hindered the development of quality cancer care in developing countries to decrease the cost of external training and limit
programs. Radiotherapy has particularly suffered because of the perceived brain drain. There is no magic wand to decrease the initial cost of investing in
assumption that establishing quality radiotherapy centers in LMICs is building radiotherapy capabilities but through careful planning and strong
unaffordable, non-sustainable and therefore unattainable and should collaborations, millions of lives can be saved. Cost is crucial but we should not
lose compass of our goal: delivering quality radiotherapy treatments to cure, For example, the ratio in Beijing, Tianjin, Shanghai, and Shandong
improve the quality of life and alleviate pain in of millions of patients with municipalities/province, where are considered regions of better economic
cancer who are desperately in need. development, is 3.07, 3.28, 2.19, and 2.28, respectively. Meanwhile, rural and/
or less populous regions such as Tibet are often under 1.00. In conclusion, it is
Keywords: affordability radiotherapy LMIC developing still obvious that cancer patients have limited access to radiotherapy facilities
as well as qualified radiation oncologist, though remarkably robust
development in all facets of radiation oncology over the last 30 years in
mainland China. Clearly, much more effort should be made in regards to access
SC09: RADIOTHERAPY FOR A GLOBAL CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 to radiation oncology facilities and their service for cancer patients.
SC09.04 RADIOTHERAPY IN CHINA

Luhua Wang 1, Jiade Lu2, Jinyi Lang 3
1
Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences,
Beijing/China, 2 Shanghai Proton and Heavy Ion Center, Shanghai/China, 3Sichuan
Cancer Hospital, Chengdu/China
Cancer incidence and mortality have been increasing in mainland China,

making cancer the leading cause of death since 2010 and a major public health
problem in the country. Much of the rising burden is attributable to
population growth and ageing and to socio-demographic changes. According
to the National Central Cancer Registry of China (NCCR), an estimated
4292,000 new cancer cases and 2814,000 cancer deaths would occur in
mainland China in 2015, with lung, stomach, esophageal, liver and colorectal
cancer being the most five common incident cancers and the leading cause of
cancer death, for which radiotherapy always plays an important role in the
comprehensive therapy. The earliest record of radiation therapy for cancer in
China dates back to the early 1930s. The establishment of the Sino-Belgian Figure 1. The growth radiation therapy equipment in China from 1986 to 2015
Radium Institute in 1931 signified the initiation of modern radiation oncology based on the2015 CSTRO report by Lang et al.
in China. However, the development of cancer treatment has been hampered
by several major wars and political turmoil in the following decades until the
late 1970s and early 1980s: the era of national economical reform in mainland
China. It was at this point when the academic and research bodies started to
focus on the availability of radiation oncology service and their access by
cancer patients. In the next over 30 years, China has undergone a period of
incredible economic growth and radiation oncology, has clearly improved in
terms of equipment and its utilization, although the shortage of facilities and
workforce remain to be improved. The Chinese Society of Radiation Oncology
(CSTRO) started its survey of the personnel and equipment in radiation
oncology in mainland China since 1986. The updated survey results of 2015
were recently compiled and analyzed. Comparison of these crucial data clearly
demonstrates the increase in the number of the facilities as well as advances
in the quality of service (Figures 1 and 2). Based on the report of the third
survey (of 1997) (first English-vision survey published in the International
Journal of Radiation Oncology * Biology * Physics), there were 453 radiation
oncology centers equipped with 286 linear accelerators, 381 cobalt units, 179
deep X-ray machines, and 302 brachytherapy units. These facilities were
staffed with 3,440 physicians, 423 physicists, and 2,245 radiation therapists.
Figure 2. The changes in the configuration of radiotherapy team in China
It is important to note that less than 1,200 physicians were trained at major
from 1986 to 2015 based on the 2015 CSTRO report by Lang et al.References
cancer centers within the radiation oncology specialty. The rest were of other
1. Gu XZH, Feng NY, Yu Y, et al. Investigation report on the composition of
specialties (e.g., surgeons) and received only several months of “practical
equipment and technical level of radiation therapy team in China. Radiat
training” (i.e., mentorship by experienced radiation oncologist with
Oncol China. 1989, 3(1): 41-43. [Published in Chinese] 2. Yin WB, Chen B,
customized lectures) in a few major cancer centers mostly in major cities such
Gu XZH, et al. General survey of radiation oncology in China. Chin J Radiat
as Beijing, Shanghai, and Guangzhou, rather than formal residency training in
Oncol, 1995, 4(4):271-275. [Published in Chinese] 3. Yin WB, Tian FH, Gu XZH.
radiation oncology. The ratio of medical physicists to radiation oncology
Radiation Oncology in China: the third survey of personnel and equipment
centers was less than 1 as well. (Figure 1) The two decades after 1997 signifies a
in radiation oncology. Int J Radiat Oncol Biol Phys, 1999, 44(2):239-241. 4.
rapid advance in the quality of radiation therapy facilities as well. The number
Yin WB, Tian FH. Survey report on national radiation therapy personnel and
of linear accelerators exhibited a nearly 6-fold increase in these 20 years, and
equipment in 2001. Chin J Radial Oncol, 2002, 11(3): 145-147. [Published in
more facilities are now equipped with computerized treatment planning
Chinese] 5. Chinese Society of Radiation Oncology (Yin WB, Yu Y, Chen B, et
systems (increased from 177 to 1,921) as well. On the other hand, the
All). Fifth nationwide survey on radiation oncology of China in 2006. Chin
registered radiation oncology centers were established in most of the major
J Radial Oncol, 2007, 16(1): 1-5. [Published in Chinese] 6. Chinese Society of
cities, increased to 1,431 (a 210% increase from the 1997 survey), which makes
Radiation Oncology (Yin WB, Chen B, Zhang CL, et al). The sixth nationwide
radiotherapy much more easily accessed by cancer patients. The number of
survey on radiation oncology of continent prefecture of China in 2011. Chin
radiation oncologists increased to 15841 (a 360% increase). Besides, medical
J Radiat Oncol, 2011, 20(6): 453-457. [Published in Chinese] 7. Yin WB, Chen
physics, a crucial specialty for the quality and safety of the clinical application
B, Tian FH, et al. The growth of radiation oncology in mainland China during
of radiotherapy, has substantially improved. The number of trained medical
the last 10 years. Int J Radiat Oncol Biol Phys, 2008, 70(3): 795-798. 8. Chen
physicists has undergone a nearly 7-fold increase to 3,294 in total. (Figure 2)
W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin.
At the same time period for accelerated development regarding radiation
2016, 66(2):115-132.
therapy capacity, the population and cancer incidence of mainland China had
also increased, which resulted in the radiotherapy remained much Keywords: radiation therapy, equipment, Mainland China
insufficient. According to the recently cancer statistics in mainland China, the
cancer incidence was 4.29 million in 2015. Given that approximately 50%
require RT as part of definitive treatment, around 2.15 million Chinese cancer
patients need RT annually. This number is most likely higher, since it does not
include recurrent and palliative indications (estimates put this number into
the 65-75% range for all malignancies), and cover all the area in mainland
SESSION SC10: SQUAMOUS CELL NSCLC
China. In fact, the numbers of annual new radiotherapy consultation and daily MONDAY, DECEMBER 5, 2016 - 16:00-17:30
treatment was 919,339 and 76,612 in 2015. Therefore, only 50% patients who
would need radiotherapy received radiotherapy in Mainland China in 2015. The
current status is caused by two main reasons. First, the ratio of tele-therapy SC10.03 ANTI-EGFR MONOCLONAL ANTIBODIES IN SQUAMOUS
facility (linear accelerator and Co60 combined) per million was 1.49 in 2015, CELL NSCLC
which are quite low compared to 8.2 in the United States, 7.5 in France, 3.4 in Robert Pirker
the United Kingdom, and 2-3 recommended by the World Health Organization.
Department of Medicine I, Medical University of Vienna, Vienna/Austria
Second, the distribution of radiotherapeutic resources is uneven by region.

Patients with advanced squamous NSCLC receive first-line chemotherapy SC10: SQUAMOUS CELL NSCLC
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
with a platin-based doublet. Combining first-line chemotherapy with
EGFR-directed monoclonal antibodies has been studied as a strategy to
improve outcome of these patients. Anti-EGFR monoclonal antibodies inhibit SC10.04 SECOND-LINE THERAPY AND BEYOND IN SQUAMOUS CELL
EGFR-mediated signal transduction and may also act via immunological NSCLC
mechanisms. Several monoclonal antibodies have been studied within
Tiziana Vavala1, Silvia Novello2
clinical trials and data from phase III trials are available for cetuximab and
1
necitumumab (for review see ref. 1). Two randomized phase III trials compared Department of Oncology, A.S.L. Cn1, Cuneo/Italy, 2Department of Oncology,
University of Turin, Orbassano/Italy
chemotherapy plus cetuximab with chemotherapy alone in patients with
advanced NSCLC (2, 3). The FLEX trial demonstrated improved overall survival Lung cancer is the leading cause of cancer-related mortality worldwide with
for cetuximab added to chemotherapy in patients with advanced NSCLC and 1.59 million deaths in 2012 and, with an estimated 1.8 million new lung cancer
enriched for EGFR expression in their tumors (2). The hazard ratio was 0.87 cases, it accounts for about 13% of total cancer diagnoses[1]. Non-small cell
(p=0.044), median survival times were 11.3 months and 10.1 months, and 1-year lung cancer (NSCLC) represents around 85% of all lung cancers with the
survival rates were 47% and 42%, respectively. For patients with squamous majority of patients in advanced stages of the disease when diagnosed.
cell carcinomas (n=347), the hazard ratio was 0.80 and median survival times Squamous cell carcinoma (SqCC) is the second most common histology in
were 10.2 months and 8.9 months, respectively. The BMS 099 trial failed to NSCLC accounting for 20-30% of cases[2]. Compared to the most frequent
show an improvement in progression-free survival for cetuximab added to advanced lung adenocarcinoma, for which targeted therapies are available in
carboplatin plus paclitaxel in unselected patients with advanced NSCLC case of presence of actionable mutations, treatment options for advanced
(3). A meta-analysis based on individual patient data from four randomized lung SqCC have not changed with the same vividness in the last decade. But,
trials demonstrated a survival benefit for chemotherapy plus cetuximab to date, we can definitely say that also for these patients, the research has
compared to chemotherapy alone (4). The hazard ratio was 0.88 (95% CI 0.79- made progresses and new therapeutic scenarios are now open. Docetaxel and
0.97; p=0.009). The benefit was greater in patients with squamous NSCLC erlotinib were the only standard second-line treatment options for lung SqCC
in whom a hazard ratio of 0.77 (95% CI 0.64-0.93) was seen. Necitumumab until, in December, 2014, the US Food and Drug Administration (FDA)
has also been studied in combination with first-line chemotherapy in two approved ramucirumab (an anti-VEGFR-2 antibody) in combination with
phase III trials (5, 6). The SQUIRE trial assessed cisplatin plus gemcitabine docetaxel, for the treatment of metastatic NSCLC patients who progressed
with or without necitumumab in 1,093 patients with advanced squamous during or after a platinum-based chemotherapy. In March 2015 nivolumab (an
NSCLC (5). Necitumumab was intravenously administered at a dose of 800 immune-checkpoint-inhibitor) was approved, for treatment of patients with
mg on days 1 and 8 of every 21 days and was planned to be continued after metastatic SqCC, who progressed during or after a platinum-based
the end of chemotherapy until disease progression or intolerable toxicity. chemotherapy and pembrolizumab (another immune-checkpoint-inhibitor)
Necitumumab improved the outcome of chemotherapy. The hazard ratio was approved in October, in the same setting of patients but whose tumors
was 0.84 (95% CI 0.74-0.96; p=0.012). Median survival times were 11.5 months expressed PD-L1 (evaluated with the approved specific companion diagnostic,
and 9.9 months, and 1-year survival rates were 47.7% and 42.8% for the the PD-L1 IHC-22C3 pharmDx test). Finally, in April 2016, afatinib (an EGFR
chemotherapy-plus-necitumab arm and chemotherapy arm, respectively. tyrosine-kinase inhibitor) was approved for treatment of patients with
Progression-free survival and response rates were also improved with the metastatic SqCC progressing after a platinum-based chemotherapy[3],[4],[5],[6].
combined treatment. Grade ≥3 adverse events more frequently seen with It has been suggested that SqCC patients treated with docetaxel had a poorer
chemotherapy plus necitumumab compared to chemotherapy were skin survival compared to non-SqCC patients hypothesizing that docetaxel may be
rash and hypomagnesemia. Based on these results, necitumumab has been less effective in squamous compared with non-squamous lung cancer[7]. This
approved as first-line therapy of squamous NSCLC in combination with was also evidenced in the phase III study (REVEL), in which squamous and
gemcitabine and cisplatin. In contrast to the SQUIRE trial, the INSPIRE non-squamous NSCLC patients were treated with docetaxel with or without
trial was prematurely stopped after enrolment of 634 patients because an ramucirumab: an OS benefit was seen with ramucirumab-docetaxel in the
interim analysis showed increased thrombo-embolic events and a lack of whole population (10.5 vs 9.1 months, HR 0.86, 95% CI 0.75–0.98, p = 0.023). In
survival benefit for the combined treatment (6). Research has also focussed those patients who presented squamous cell histology (25%) the OS benefit,
on the characterization of predictive biomarkers. Immunohistochemical when treated with ramucirumab-docetaxel, was 9.5 months (4.4–17.6) vs 8.2
EGFR protein expression and EGFR FISH positivity were of particular months (3.6–14.9, HR: 0.88, 95% CI 0.69–1.13) in placebo-docetaxel subgroup,
interest. In the FLEX trial, immunohistochemical EGFR expression of tumor while in those with non-squamous disease a better OS was described (11.1
cells was prospectively assessed by means of the DAKO pharmDxTM kit (7). months, Interquartile Range, IQR 5.3–24.3) in the ramucirumab-docetaxel
Membrane staining intensity was divided into no staining, weak staining (1+), group, vs 9.7 months (4.4–19.6) in the control group (HR 0.83, 95% CI
intermediate staining (2+), and strong staining (3+). The fractions of cells at 0.71–0.97), however it needs to be noted that subgroup analyses in this study
the various staining intensities were determined. An immunohistochemistry were not pre-planned4. In LUX-Lung 8, a phase III study of second-line afatinib
score (IHC) based on both intensity and frequency of staining was then used vs erlotinib, which enrolled squamous patients only, OS was 7.9 vs 6.8 months
for further analysis on the association between EGFR expression levels and (HR 0.81, 95% CI 0.69–0.95, p = 0.007), in the afatinib subgroup vs erlotinib
clinical outcome. Patients were divided into those with high (IHC score ≥200) one7. Survival benefits highlighted in these studies when compared to older
and those with low (IHC score <200) EGFR expression. High EGFR expression studies with docetaxel, while statistically significant, evidenced modest
was seen in 31% of the patients. Among patients with high EGFR expression, developments in the treatment of advanced-stage SqCC, as a consequence,
patients treated with chemotherapy plus cetuximab had prolonged survival novel therapeutic approaches have been considered and well accepted in the
compared to those treated with chemotherapy alone. The hazard ratio was oncology community as well as largely awaited. Research on tumor
0.73 (95% CI 0.58–0.93; p=0.011), median survival times were 12.0 and 9.6 immunosurveillance led to the development of PD-1 immune-checkpoint-
months, and 1-year survival rates were 50% versus 37%. Among patients inhibitors, such as nivolumab and pembrolizumab, and the PD-L1 inhibitors
with low EGFR expression, survival times were not different between the atezolizumab (MPDL3280A), durvalumab (MEDI4736) and avelumab
two treatment arms. The treatment interaction between EGFR expression (MSB0010718C)[8]. Nivolumab produced response rates equal to 15 to 17%
levels and treatment effect was statistically significant (p=0.04). The survival with a median OS of 8.2 to 9.2 months, in phase I and II trials, among
benefit achieved by the addition of cetuximab to chemotherapy in patients previously treated patients with advanced SqCC5. Then in the phase III
with high EGFR expression was seen across most subgroups including all CheckMate 017, Nivolumab induced a median OS of 9.2 months (95% CI,
major histological subgroups. Among patients with squamous NSCLC and 7.3-13.3) vs 6 months (95% CI, 5.1-7.3) with docetaxel. The results in the
high EGFR expression, the hazard ratio was 0.62 (0.43-0.88) in favour of docetaxel group were worst than expected. The risk of death was 41% lower
cetuximab plus chemotherapy compared to chemotherapy alone. The survival with nivolumab than with docetaxel (HR, 0.59; 95% CI, 0.44-0.79; p < 0.001)5.
benefit by the addition of cetuximab to chemotherapy in patients with high PD-L1 expression is largely debated and its specific influence in the squamous
EGFR expression was achieved without an increase in toxicity. In summary, population still needs further elucidations, since a total of 83% of the
patient selection based on EGFR expression levels resulted in a clinically patients who underwent randomization (225 of 272 patients) in this trial had
meaningful improvement in the risk benefit assessment of platinum-based quantifiable PD-L1 expression and PD-L1 was assessed on archival tumor
first-line chemotherapy plus cetuximab in patients with advanced NSCLC tissue, which may not have reflected its real status at the time of treatment5.
(7). The SWOG S0819 biomarker validation study indicated that EGFR FISH SqCC is considered the tumor with the second highest amount of molecular
positivity predicted benefit from cetuximab, particularly in patients with aberrations, (eg, FGFR1 amplification, PIK3K3 abnormalities, DDR2
squamous NSCLC (8). Similarly, the benefits from necitumumab appeared mutations), providing a plausible explanation about heterogeneity of
to be greater in patients with EGFR FISH positivity or high EGFR expression treatment responses and efficacy results in the second-line setting[9].
(5, 9-10).References 1. Pirker R et al. Curr Opin Oncol 2015, 27, 87-93 2. Pirker However, despite the identification of those specific molecular alterations,
R et al. Lancet 2009, 373, 1525-31 3. Lynch TJ et al. J Clin Oncol 2010, 28, 911-7 progress in targeting oncogenic drivers in SqCC still runs behind
4. Pujol JL et al. Lung Cancer 2014, 83, 211-8 5. Thatcher N et al. Lancet Oncol adenocarcinoma. There is a need to develop predictive and specific molecular
2015, 16, 763-74 6. Paz-Ares L et al. Lancet Oncol 2015, 16, 328-37 7. Pirker R et biomarkers, that might identify subgroups of patients with lung SqCC that
al. Lancet Oncol 2012, 13, 33-42 8. Herbst R et al. J Thorac Oncol 2015, 10, S795 are most likely to benefit from targeted treatments or immunotherapic
9. Hirsch F et al. J Thorac Oncol 2015, 10, S797 10. Paz-Ares L et al. Ann Oncol approaches. In this context Pilotto et al. elaborated a project with the aim to
2016, 27, 1573-9 evaluate the molecular profile of resected SqCC in order to identify those
immunologic pathways and molecular aberrations potentially able to
Keywords: Cetuximab, Necitumumab, biomarker, squamous NSCLC
estimate the probability of disease recurrence (prognostic factors) and to treatment of ROS1-positive NSCLC by the FDA since March 2016 and by the
characterize novel biomarkers, whose targeting with specific drugs could EMA since August 2016. Treatment of ROS1-positive NSCLC with crizotinib
potentially limit the oncogenic potential and change the natural history of thus has become standard first-line treatment in the leading international
this disease (predictive factors). Preliminary results of this study were guidelines. Current challenges for the further development and improvement
consistent with literature data: several molecular alterations might be of targeted treatment of ROS1-positive patients are (I) implementation
identified [PIK3CA, MET, FGFR3, DDR2, FRS2, CDKN2A, SMAD4, PD-L1] and of ROS1 diagnostics in routine molecular diagnostics and (II) development
some of them might impact on the biological behavior of SqCC contributing in of next-generation ROS1 inhibitors overcoming crizotinib resistance. The
the determination of patients prognosis[10]. These data will be further increasing number of actionable mutations in NSCLC including ROS1 requires
presented at WCLC this year. In conclusion, as more treatment options turn implementation of molecular multiplex testing, since sequentially conducted
out to be available for patients, it will become essential to tailor those choices single gene assays are no more feasible given the usually limited biopsy tissue
on patient’s unique molecular characteristics and his own needs, identifying specimens. However, conventional NGS technology is restricted to point
the best sequence of treatments, especially in the era of rising healthcare mutations and does not cover copy number variations (CNV) and gene fusions.
costs and longer lifespan of advanced lung cancer patients.References [1] Thus, new NGS technologies have to be integrated in routine diagnostics like
WHO Statistics. http://www.who.int/mediacentre/factsheets/fs297/en/ hybrid capture-based NGS, which does not require DNA amplification by PCR
[Accessed on 21 August , 2016]. [2] Travis WD. Pathology of lung cancer. Clin and thus allows to detect reliably CNV and gene fusions. While increasing
Chest Med 2011; 32: 669–92. [3] Garon EB et al. Ramucirumab plus docetaxel knowledge of the molecular mechanisms underlying TKI resistance has led
versus placebo plus docetaxel for second-line treatment of stage IV to the development of a series of highly potent next-generation inhibitors in
non-small-cell lung cancer after disease progression on platinum-based ALK-positive NSCLC now, resistance of ROS1-positive patients to crizotinib
therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. is incompletely understood. In preclinical studies as well as in biopsy tissue,
Lancet 2014; 384: 665–73. [4] Brahmer J et al. Nivolumab versus docetaxel in somatic mutations in the ROS1 kinase domain associated with acquired
advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; crizotinib resistance have been described (7). In functional studies these
373(2):123-35. [5] FDA approves Keytruda for advanced non-small cell lung mutations were associated with different degrees of resistance. Alternatively,
cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ bypass activation of oncogenic signal transduction pathways has been
ucm465444.htm [Accessed on 21 August , 2016]. [6] Soria JC et al. Afatinib described as mechanism underlying resistance. For instance, a cKIT activating
versus erlotinib as second-line treatment of patients with advanced mutation and EGFR pathway activation have been reported in single cases
squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised (8). In vitro, the multikinase inhibitors cabozantinib, foretinib and lorlatinib
controlled phase 3 trial Lancet Oncol 2015; 16: 897–907. [7] LE Ang Y et al. have been shown to overcome crizotinib reistance triggered by secondary
Profile of nivolumab in the treatment of metastatic squamous non-small-cell mutations in ROS1. Response to cabozantinib has also been described in a
lung cancer. OncoTargets and Therapy 2016:9 3187–3195. [8] Melosky B et al. ROS1-positive patient with a mutation confering resistance to crizotinib
Pointed Progress in Second-Line Advanced Non–Small-Cell Lung Cancer: The (10) and was also observed in a phase I trial of lorlatinib in the same clinical
Rapidly Evolving Field of Checkpoint Inhibition. J Clin Oncol 2016;34:1676- setting. In summary, ROS1 positivity characterizes a subgroup of patients
1688. [9] The Cancer Genome Atlas Research Network. Comprehensive with a major benefit from treatment with crizotinib. Consequently, crizotinib
genomic characterization of squamous cell lung cancers. Nature 2012; has become the current standard of care for these patients. ROS1 status thus
489(7417): 519–525. [10] S. Pilotto et al. Analyzing prognostic outliers to should be available before decision on first-line treatment. Acquired resitance
unravel biologically and clinically relevant molecular and immunologic to crizotinib may be caused by mutations in the ROS1 kinase domain or by
pathways: a model from resected squamous cell lung carcinoma (R-SQCLC). activation of bypass pathways. The multikinase inhibitor cabozantinib and
Poster presented at 58 Annual Meeting of the Italian Cancer Society helded in the next-generation ALK/ROS1 inhibitor lorlatinib have shown promising
Verona on 5-8 September 2016. efficacy in early clinical evaluation. (1) Rikova K et al. Global survey of
phosphotyrosine sgnaling identifies oncogenic kinases in lung cancer. Cell
Keywords: lung cancer, squamous carcinoma, second line treatment 2007, 14; 131(6):1190-203. (2) Bergethon K et al. ROS1 rearrangements define
a unique molecular class of lung cancers. J Clin Oncol 2012, 30(8):863-70. (3)
Scheffler M et al. ROS1 rearrangements in lung adenocarcinoma: prgnostic
impact, therapeutic options and genetic variability. Oncotarget 2015,
6(12):10577-84. (4) Shaw A et al. Crizotinib in ROS1-rearranged non-small
SESSION SC11: ALK, ROS1 AND RARE MUTATIONS IN NSCLC cell lung cancer. NEJM 2014, 371(21): 1963-71. (5) Mazieres J et al. Crizotinib
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 therapy for advanced lung adenocarcinoma and a ROS1 rearrangement:
results from the EUROS1 cohort. J Clin Oncol 2015, 33(8):867-76. (6) Michels
e al. EUCROSS: a prospective European phase II trial to evaluate efficacy
SC11.03 ROS1 AS A THERAPEUTIC TARGET IN ADVANCED NSCLC and safety of crizotinib in advanced adenocarcinoma of the lung harboring
ROS1 translocations. WCLC 2016 (oral presentation). (7) Awas MM et al.
Jürgen Wolf Acquired resistance to crizotinib from a mutation in CD74-ROS1. NEJM 2013,
Center for Integrated Oncology, University Hospital of Cologne, Cologne/Germany 368(25):2395-401. (8) Dzadziuszko R et al. Activating KIT mutation induces
crizotinib resistance in ROS1-positive lung cancer. J Thorac Oncol 2016,
In non-small cell lung cancer (NSCLC) chromosomal rearrangements
11(8):1273-81. (9) Davies KD et al. Resistance to ROS1 inhibition mediated
involving the gene encoding for the receptor tyrosine kinase ROS1 have been
by EGFR pathway activation in non-small cell lung cancer. PLoS One 2013,
first described in 2007 (1). These aberrations have been shown to trigger
13 (8):e82236. (10) Drilon et al. A novel crizotinib-resistant solvent-front
constitutive kinase activity and activation of downstream pathways like
mutation responsive to cabozantinib therapy in a patient with ROS1-
the MAPK pathway. ROS1 rearrangements can be found in about 2% of
rearranged lung cancer. Clin Cancer Res 2016, 22 (10):2351-8.
lung adenocarcinoma and are associated with female gender and never-
smoking status (2). Different fusion partners have been described. In routine
diagnostics ROS1 fusion genes can be reliably detected by fluorescence
in situ hybridization (FISH; e.g. dual color break apart FISH), RT-PCR or SC11: ALK, ROS1 AND RARE MUTATIONS IN NSCLC
next-generation sequencing (NGS). ROS1 fusions occur mutually exclusive MONDAY, DECEMBER 5, 2016 - 16:00-17:30
of aberrations in EGFR, ALK and KRAS. However, using NGS, co-occuring
mutations, preferentially in TP53, but also in other genes involved in
SC11.04 RARE MUTATIONS IN LUNG CANCER
oncogenic pathways, can be found in about 50% of these patients (3). ROS1
fusions also seem to be of prognostic relevance, since remarkable long survival Oliver Gautschi
times have been described in patients treated with chemotherapy only (3). Medical Oncology, Lucerne Cantonal Hospital, Luzern/Switzerland
The ALK/MET/ROS1 inhibitor crizotinib has been evaluated in a US-American
“Lung adenocarcinoma” is a genetically heterogenous disease entity,
cohort of 50 ROS1 positive patients with advanced, mostly pretreated lung
characterized by a wide spectrum of different mutations. Some of these
adenocarcinoma and showed impressive activity (4). The overall response
mutations lead to constitutive activation of receptor tyrosine kinases,
rate (ORR) was 72% (95% CI 58 to 84) with 3 complete responses. Median
which can be inhibited by small molecules (tyrosine kinase inhibitors,
progression free survival (PFS) was 19.2 months (95% CI 14.4 to not reached).
TKIs). EGFR mutations (2004) and ALK rearrangement (2007) were among
Treatment was well tolerated and the side effect profile resembled that
the first actionable driver mutations identified in lung adenocarcinomas.
observed in the treatment of ALK positive lung cancer with crizotinib. A
Today, several drugs are approved for the treatment of advanced lung
similiar ORR of 80% was reported in a retrospectively analyzed European
adenocarcinomas with EGFR mutations or ALK/ROS1 rearrangement.
cohort (5). However, PFS was only 9.1 months in these patients. The EUCROSS
Combined, these molecular subgroups make up at least 20% of all lung
trial, a collaborative study of the German Lung Cancer Group Cologne and the
adenocarcinomas or more, depending on the poplulation. Further actionable
Spanish Lung Cancer Group, is a prospective European phase II trial which
driver mutations include the genes BRAF, HER2, MET, and RET. These genes
recruited 34 ROS1 positive patients between June 2014 and September 2015.
are less frequently mutated than EGFR/ALK, nevertheless, rare drivers are
ROS1 fusion genes were diagnosed using dual color break apart FISH and the
clinically relevant because of the availability of targeted therapies approved
results were confirmed by next-generation sequencing. With an ORR of 69%
for other indications in oncology (ALK-lung, HER2-breast, RET-thyroid, and
(95% CI, 49.1 to 84.3) similar efficacy has been reported (6). Based on its high
BRAF-melanoma). The discussant will summarize current knowledge about
activity and favorable toxicity profile, crizotinib is now approved for the

rare driver mutations, with a strong clinical focus. HER2 insertion 20, present function test and/or quantitative thoracic CT imaging can benefit a sub-
in about 1% of lung adenocarcinomas, was initially proposed by Cappuzzo et population who would otherwise not meet the current criteria for lung cancer
al as a potential indication for trastuzumab-based therapy [1]. Prospective screening with CT or reduce the frequency and duration of follow-up CTs in
trials with HER2 targeting drugs are currently ongoing. BRAF V600E, present a population based lung cancer screening program require further study.
in about 3% of lung adenocarcinomas, was associated with high activity of References 1. Skillrud DM, Offord KP, Miller RD. Higher risk of lung cancer in
combined therapy with dabrafenib and trametinib in a prospective phase II chronic obstructive pulmonary disease. A prospective, matched, controlled
trial by Planchard et al [2]. Crizotinib, recently approved by the FDA for the study. Ann Intern Med 1986;105:503-7. 2. Turner MC, Chen Y, Krewski D, Calle
treatment of ROS1-NSCLC, is also active in tumors harboring MET exon 14 EE, Thun MJ. Chronic obstructive pulmonary disease is associated with lung
mutations as demonstrated by Drilon et al [3]. Cabozantinib and vandetanib cancer mortality in a prospective study of never smokers. Am J Respir Crit
are active in tumors with RET rearrangement as shown by three recent phase Care Med. 2007 Aug 1;176(3):285-90. 3. Vestbo J, Hurd SS, Agustí AG, Jones
II trials [4-6]. Entrectinib showed preliminary activity in tumors harboring TRK PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura
rearrangement in an early basket Trial [7]. These results will be discussed in M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis,
detail, together with the results of international registries (EUHER2, EURAF, management, and prevention of chronic obstructive pulmonary disease:
EUROS1 and GLORY [8]). Moreover, current treatment recommendations for GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-
patients with advanced lung adenocarcinomas and rare driver mutations will 65. 4. de-Torres JP, Marin JM, Casanova C, et al. Identification of COPD patients
be summarized.References 1. Cappuzzo et al. N Engl J Med. 2006;354(24):2619- at high risk of lung cancer mortality using the COPD-LUCSS_DLCO. Chest
21. 2. Planchard et al. Lancet Oncol. 2016;17(7):984-93. 3. Drilon et al. J Clin 2016; 149:936-42. 5. Lynch DA, Austin JH, Hogg JC, Grenier PA, Kauczor HU,
Oncol 34, 2016 (suppl; abstr 108) 4. Drilon et al. Cancer Discov. 2013;3(6):630-5. Bankier AA, Barr RG, Colby TV, Galvin JR, Gevenois PA, Coxson HO, Hoffman
5. Seto et al. J Clin Oncol 2016;34(suppl; abstr 9012) 6. Lee et al. J Clin Oncol EA, Newell JD Jr, Pistolesi M, Silverman EK, Crapo JD. CT-Definable Subtypes
2016;34(suppl; abstr 9013) 7. Drilon et al. AACR 2016 (abstract CT007) 8. of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner
Gautschi et al. WCLC 2016 (abstract 4325) Society. Radiology. 2015 Oct;277(1):192-205. 6. COPDGene CT Workshop
Group, Barr RG, Berkowitz EA, Bigazzi F, Bode F, Bon J, et al. A combined
Keywords: NSCLC, Driver Mutations, Targeted Therapies pulmonary-radiology workshop for visual evaluation of COPD: study design,
chest CT findings and concordance with quantitative evaluation. COPD.
2012 Apr;9(2):151-9. doi: 10.3109/15412555.2012.654923. 7. Tammemagi MC,
Katki HA, Hocking WG, Church T, Caporaso N, Kvale P, et al. Selection criteria
for lung-cancer screening. N Engl J Med 2013;368:728-36. 8. Tammemagi M,
SESSION SC13: INTERACTION OF COPD AND LUNG CANCER Lam S, McWilliams A, Sin D. Incremental value of pulmonary function and
– CONSEQUENCES FOR EARLY DIAGNOSIS AND MANAGE- sputum DNA image cytometry in lung cancer risk prediction. Cancer Prev Res
MENT (Phila). 2011 Apr;4(4):552-61. 9. Schwartz AG, Lusk CM, Wenzlaff AS, Watza D,
Pandolfi S, et al. Risk of Lung Cancer Associated with COPD Phenotype Based
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 on Quantitative Image Analysis. Cancer Epidemiol Biomarkers Prev. 2016 Sep;
25(9):1341-7. 10. US Preventive Services Task Force (USPSTF). Screening for
chronic obstructive pulmonary disease. US Preventive Services Task Force
SC13.02 INCREASED RISK FOR LUNG CANCER IN COPD recommendation statement. JAMA April 5, 2016; 315(13):1372-1377. Supported
Stephen Lam by the Terry Fox Research Institute.
Integrative Oncology, British Columbia Cancer Agency, Vancouver/BC/Canada
Keywords: risk assessment, screening
Globally, chronic obstructive pulmonary disease (COPD) and lung cancer
are among the top 5 causes of death. The two diseases share common risk
factors such as tobacco smoking, outdoor and household air pollution.
SC13: INTERACTION OF COPD AND LUNG CANCER – CONSEQUENCES FOR EARLY
COPD is associated with a two to four fold increased risk for lung cancer DIAGNOSIS AND MANAGEMENT
independent of smoking.1,2 COPD can be defined by symptoms, lung function TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
criteria (forced expiratory volume in one second (FEV 1) <80% predicted for
age, gender and height, FEV 1/ forced vital capacity (FVC) <0.7, or diffusing
SC13.03 LIMITATION BY COPD FOR DIAGNOSTIC PROCEDURES
capacity <80%.3,4 COPD has also been defined by computed tomography
(CT) changes such as pulmonary emphysema by visual examination or by Gyula Ostoros 1, János Varga2, Anna Kerpel-Fronius3
1
quantitative measurement (percent voxels < -950 HU based on a threshold of Viii. Tudobelosztaly, Orszagos Koranyi Tbc Es Pulmonologiai Intezet, Budapest/
4.8%) or air trapping from comparison between inspiratory and expiratory Hungary, 2Oktpi, Budapest/Hungary, 3Radiology, National Koranyi Institute for
CT scans.5,6 In the PLCOm2012 risk prediction model7, self-reported COPD was Pulmonology, Budapest/Hungary
significantly associated with lung cancer risk (OR 1.45, 95% CI: 1.25-1.67). The
Limitation by COPD for Diagnostic Procedures Ostoros, Gy. Varga, J. and
area under the ROC curve (AUC) was 0.559. The AUC of the prediction model
Kerpel-Fronius A. National “Korányi” Institute for Pulmonology Hungary,
with and without a history of COPD was 0.800 and 0.799 respectively (M.
Budapest Lung cancer and COPD are smoking dependent diseases. Smoking
Tammemagi, personal communication). A study in British Columbia examined
cessation is crucial before and during the diagnostic procedures because of
the incremental value of pulmonary function test in 2,596 ever smokers above
the consequences of smoking (e.g. sputum retention, mucociliary dysfunction
40 years of age who had smoked ≥20 pack-years. One hundred and thirty-nine
and potential other more serious complications after the procedures).
participants developed lung cancer after a median follow-up of 7.7 years.8.
Severe obstructive or restrictive pulmonary disorders limit the diagnostic
Lower FEV 1% increased the lung cancer risk for both men and women, but did
possibilities in patients with malignant pulmonary diseases. The screening
so more strongly for men than in women (interaction P <0.001). FEV 1% was
of lung cancer with low-dose CT has become the gold standard in the past
found to substantially improve lung cancer prediction in a risk prediction
decade. The two imaging-based phenotypes of COPD can be well distinguished
model that included age, sex, education level, body mass index, family history
by this technique. CT screening can also help to identify non-diagnosed
of lung cancer and smoking. In this study, although CT detected emphysema
emphysema patients and may lead to early treatment of the disease. It has
was significantly associated with lung cancer in unadjusted analysis (OR 2.22,
been showed that non-smoker emphysema patients have a similar risk of lung
95% CI: 1.17 – 3.78; P=0.012), in the fully adjusted model, neither emphysema
cancer as smokers with emphysema. Thus, patients with emphysema may
nor a history of chronic bronchitis, which were significant in other studies,
be an eligible subgroup for a more intensive lung cancer screening program.
approached significance. A recent case-control study showed that only air
However, once a suspicious lesion is found severe COPD, it can limit the
trapping on quantitative CT imaging and FEV1/FVC <0.7 were independent
choices available for differential diagnosis seriously - CT guided lung biopsies
predictors of lung cancer risk in a multivariable model.9 Thirty-five percent
in COPD patients carry a higher risk of haemorrhage and pneumothorax.
of lung cancer cases and 55% of the controls had no evidence of COPD on
Patients with severe COPD and respiratory failure with decreased oxygen
spirometry or air trapping on quantitative CT. Forty-nine percent of lung
saturation limit the indication of diagnostic bronchoscopic procedures as
cancer patients had FEV1/FVC >0.7. In the Pan-Canadian lung screening
well. The examination of exhaled breath condensate (EBC) is a non invasive
study of 2,537 ever smokers between the age of 50 to 75 with a 6 year lung
process. There are efforts to discriminate lung cancer and COPD with EBC.
cancer risk of ≥2% using a prototype PLCO prediction model, 50.6% of the
Lung tumours have influence on lung function. Besides the severity of COPD,
participants had FEV 1/FVC <0.7 and 42.8% had FEV 1<80%. Among those
the result of the lung function test (LFT) depends on the size and position of
who were found to have lung cancer, 63% had FEV 1/FVC <0.7 and 54.5% had
the pulmonary tumour as well. In the case of a big central tumour or a huge
FEV 1<80%. In those without lung cancer, the corresponding figures were
amount of pleural fluid, the LFT will show rather restrictive than obstructive
49.5% and 42% respectively. While COPD detected by pulmonary function
character. A small peripheral malignancy will not change the shape and
test(s) and/or thoracic CT identify smokers at higher risk of lung cancer, a
volume of the LFT. If the tumour is in the trachea or compresses it’s wall,
strategy to focus CT screening using these criteria may miss a significant
the inspiratory phase of the flow-volume chart could be flat. Sometimes the
proportion of lung cancers. Quantitative CT imaging of air trapping requires
lung tumours could lead a misdiagnosis of COPD. A centrally located small
an inspiratory and expiratory CT with added cost and radiation exposure. The
tumor which is not visible on the chest X-ray but compresses the trachea
US Preventive Services Task Force recommended against screening for COPD
or any of the pulmonary vessels can cause breathlessness, fatigue and
in asymptomatic adults.10 Whether identification of COPD by pulmonary
decreased oxygen saturation. A mediastinal conglomerate of lymph nodes
can cause similar symptoms. Low physical activity, obesity, smoking and COPD, newly developed devices appear to show promising outcome. Both
comorbidities are significant negative factors for risk stratification before stereotactic body radiotherapy (SBRT) and ion beam radiotherapy have
any pulmonary diagnostic procedure as well. Pulmonary rehabilitation such a nice radiation dose distribution that high doses of irradiation are
can improve functional reserves if functional capacity is at borderline. possible with low impact to normal tissues. Some reports suggest that
Pulmonary rehabilitation has positive effect on cardiovascular function, patients’ outcomes by these treatment modalities may be not worse or
metabolism, muscle-function and lung mechanics. As for lung function sometimes better than surgical treatment (5). In addition, smoking cessation
parameters, we need to focus on forced expiratory volume in one second is, of course, important issue as a pre- and postoperative management.
(FEV 1) and diffusion capacity (DLCO). We can follow the common agreement Since lung cancer patients with COPD are increasing over all area in the
of minimum criteria of the European Society of Chest Surgeon and European world, appropriate treatment should be chosen with the utmost care and
Respiratory Society for risk stratification before a diagnostic pleuroscopy. attention. In addition, it is an urgent issue to establish more effective
Based on this protocol, FEV1 and DLCO need to be >35%pred. In the case of and safe treatment modalities to these patients.References 1) Young RP,
35%pred< FEV 1 and DLCO<75%pred, we need to consider VO2/kg during a Hopkins RJ, Christmas T, et al. COPD prevalence is increased in lung cancer,
cardiopulmonary exercise test. If VO2 is <10 ml/kg/min, the patient need a independent of age, sex and smoking history. Eur Respir J. 2009;34(2):380-
pulmonary rehabilitation program to improve functional reserves. Regarding 6. 2) Kiri VA, Soriano J, Visick G, Fabbri L. Recent trends in lung cancer and
lung function, we need to focus on lung mechanics and lung kinematics as its association with COPD: an analysis using the UK GP Research Database.
well. Lung mechanics can be monitored by resting functional reserve capacity Prim Care Respir J. 2010;19(1):57-61. 3) De Sanctis A, Taillade L, Vignot S, et
(FRC) and residual volume (RV). Lung kinematics can be monitored by chest al. Pulmonary toxicity related to systemic treatment of nonsmall cell lung
expansion. Improved resting or dynamic hyperinflation and lung kinematics of cancer. Cancer. 2011;117(14):3069-80. 4) Rabe KF, Hurd S, Anzueto A, Barnes
the patients with chest physiotherapy and complex pulmonary rehabilitation PJ, et al. Global strategy for the diagnosis, management, and prevention of
is also suggested. As a general effect of rehabilitation, training programs can chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir
improve the cardiovascular response, oxygen uptake and the metabolism. Crit Care Med. 2007;176(6):532-55. 5) Chehade S and Palma DA. Stereotactic
We may also focus on physical activity, which is a general prognostics marker. radiotherapy for early lung cancer: Evidence-based approach and future
Physical activity can be monitored by pedometer. Obesity can influence directions. Rep Pract Oncol Radiother. 2015;20(6):403-10.
the complications of the surgical procedure and it has some effect on lung
mechanics as well. If we have time, in case of an obese patient we may also Keywords: bronchodilator, stereotactic body radiotherapy, Surgery, lung
consider improving their body composition before the invasive procedure. To function
sum up, comorbidities have to be considered before an invasive diagnostic
procedure of lung cancer. Patients with impaired pulmonary hemodynamics,
ischemic heart disease, diabetes or obesity have to be carefully evaluated. de
Torres JP. Casanova C. et al. : Exploring the impact of screening with low-dose
CT on lung cancer mortality in mild to moderate COPD patients: A pilot study.
Respiratory Medicine, 107, 5, 702-707. 2013. Wiener RS. Schwarcz LM. et al.
SESSION SC14: IMMUNOTHERAPY OF NSCLC
Population-Based Risk of Complications Following Transthoracic Needle Lung TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
Biopsy of a Pulmonary Nodule. Annals of Internal Medicine, 155, 3, 137-144.
2011. GOLD-www.goldcopd.org Brunelli, A. Charloux, A. et al : ERS/ESTS
clinical guidelines on fitness for radical therapy in lung cancer patients Eur. SC14.01 IMMUNOTHERAPY IN THE FIRST-LINE SETTING OF
Resp. J., 34, 1, 2009. ADVANCED NSCLC
Roy Herbst
Keywords: diagnosis, copd, lung cancer
Medical Oncology, Yale School of Medicine, Yale Cancer Center, and Smilow Cancer
Hospital, New Haven/CT/United States of America
SC13: INTERACTION OF COPD AND LUNG CANCER – CONSEQUENCES FOR EARLY Lung cancer remains the leading cause of cancer-related deaths worldwide.
DIAGNOSIS AND MANAGEMENT Advances in screening, surgery and treatment have helped to improve the
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 median survival for patients with lung cancer over the past decade, however,
the five-year survival rate remains less than 20%. The majority of patients are
SC13.04 LIMITATIONS BY COPD FOR TREATMENT diagnosed with advanced stage disease, who are treated with platinum-based
chemotherapy, followed by targeted, combination, or immunotherapies.
Yoichi Nakanishi Given the response rates seen with the use of immunotherapy in the second-
Research Institute for Diseases of the Chest, Kyushu University, Fukuoka/Japan line setting, it was appropriate to begin to explore if these agents could be
given to patients earlier in their treatment. Immunotherapies have been
The most common cause of death among patients with COPD is lung cancer as
found to be better tolerated than chemotherapy and have the potential
well as respiratory failure, and COPD often co-exists with lung cancer with a
for long-term survival, thus could benefit patients as first-line therapy, as
range of 40 to 70% (1). While lung cancer survival is generally very low, survival
some patients will never go on to receive second-line treatment. Two agents,
is even lower among patients with COPD, i.e. in one study, it is reported that
nivolumab and pembrolizumab, both monoclonal antibodies targeting
26% of lung cancer patients without COPD were still alive 3 years after their
programmed cell death protein 1 (PD-1), are approved for use in patients with
diagnosis compared to 15% of lung cancer patients with COPD (2). One of the
non-small cell lung cancer (NSCLC) who have received prior chemotherapy.
reasons why prognoses of lung cancer patients with COPD are worse is that
The KEYNOTE-024 randomized phase III trial of pembrolizumab vs. standard
treatment options are limited due to affected lung function. For surgical
of care (platinum-based chemotherapy), demonstrated superior progression-
treatment for lung cancer patients with COPD, post-operative residual lung
free survival (PFS) and overall survival (OS) for first-line treatment in patients
function should be maintained within a certain level. Therefore, patients
with tumors expressing high levels of programmed cell death ligand 1 (PD-L1)
with severely reduced lung function may be rejected for surgical treatment,
(tumor proportion score ≥50%). The CheckMate-026 randomized, phase III
or at least they may not able to receive standard surgical procedures. For
study of nivolumab vs. standard of care in treatment-naïve patients with
patients rejected for surgery because of poor lung function, radiotherapy is
tumors expressing ≥5% PD-L1 did not meet the primary endpoint of PFS. For
an alternative treatment option. However, radiotherapy itself affects lung
this presentation, the use of predictive markers in the front-line setting will
function because of post treatment radiation pneumonia. For drug therapy,
be discussed and implications for combination therapy will be reviewed.
drug-induced lung toxicities are emerging issues, especially due to the use of
EGF receptor tyrosine kinase inhibitors, ALK inhibitors or immune check point Keywords: NSCLC, PD-L1, Immunotherapy
inhibitors (3). In cases whose lung function is severely affected, drug-induced
lung toxicities may be lethal, and special attention should be payed to such
patients. Therefore, to overcome these limitations of treatment is an urgent
issue in the daily practice. For surgical treatment, assessment of preoperative SC14: IMMUNOTHERAPY OF NSCLC
lung function is essential to judge its indication. Both predicted post-
operative lung function and DLco values are mainly used as parameters for the
indication of surgical treatment. Therefore, optimization of these functions SC14.04 THE CD47 MACROPHAGE CHECKPOINT AS A NEW
by medical therapy, pulmonary rehabilitation and smoking cessation may IMMUNOTHERAPY TARGET
extend the opportunities of surgical treatment, resulting in better patients’
Branimir I. Sikic 1, Sukhmani K. Padda1, Sumit A. Shah1, A. Dimitros
outcomes. Regarding with medical therapy, the Global Initiative for Chronic
Colevas1,Sujata Narayanan1, George A. Fisher 1, Dana Supan 1, Heather A.
Obstructive Lung Disease (GOLD) (4) and American Thoracic Society and
Wakelee1, Rhonda Aoki1, Mark D. Pegram1, Victor M. Villalobos1,2, Jie Liu3,4,
the European Respiratory Society guidelines for COPD management point
Chris Takimoto4, Mark P. Chao3-5, Jens P. Volkmer3,4, Ravindra Majeti 3-5, Irving
out the usefulness of bronchodilators as well as inhaled corticosteroids. In
L. Weissman3,4
addition, pulmonary rehabilitations would be recommended for pre-operative
1
lung cancer patients with poor lung function because of its safety, although Department of Medicine, Division of Oncology, Stanford University School
of Medicine, Stanford/CA/USA 2 Department of Medicine, Division of Medical
there are no data clearly showing the efficacy of pulmonary rehabilitations
Oncology, University of Colorado Cancer Center, Aurora, CO/USA 3Institute for Stem
on patients’ outcome. For radiotherapy for lung cancer patients with

Cell Biology and Regenerative Medicine, Stanford University School of Medicine,

Stanford/CA/USA 4Forty Seven, Inc., Palo Alto/CA/USA 5Department of Medicine,
Division of Hematology, Stanford University School of Medicine, Stanford/CA/USA
Background: Hu5F9-G4 is a humanized monoclonal antibody that targets

CD47, blocking its anti-phagocytic “don’t eat me” signal through macrophage
receptor SIRPα, leading to tumor phagocytosis. CD47 is overexpressed on
human cancers and also on red blood cells (RBCs). In primate toxicology
studies, Hu5F9-G4 caused a transient anemia that was improved with a
single lower Priming Dose allowing higher Maintenance Doses. Materials and
Methods: Relapsed/refractory solid tumors and lymphomas were included.
This dose escalation study included: Part A, to determine the Priming Dose
and Part B, to determine the Maintenance Dose. The maximum tolerated
dose (MTD) in part A was used for the single Priming Dose in part B (Hu5F9-G4
dosed weekly). The primary objective is to determine safety and secondary
objectives are to determine PK and PD. Preliminary data reported from data
cutoff of July 22, 2016. Results: 25 patients have enrolled. Part A included
0.1 (N=1), 0.3 (N=2), 1 (N=6), and 3 (N=2) mg/kg. There were 2 dose-limiting
toxicities (DLTs) in Part A at the 3 mg/kg dose: grade (G) 3 abdominal pain
and G3 hemagglutination (H) (protocol-specific scale of G1 H on peripheral SESSION SC15: CLINICAL TRIALS: HOW TO SET PRIORITIES?
blood smear (PBS) and G2 headache). 1 mg/kg was selected as the Priming TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
Dose, with no >G2 anemia. Pharmacodynamic studies show almost 100%
RBC receptor occupancy at the Priming Dose. Treatment-related adverse
event (TRAE) in Part A included: anemia (3 G1, 3 G2), hyperbilirubinemia (3 SC15.01 THE AMERICAN PERSPECTIVE
G1, 2 G2; unconjugated), headache (6 G1, 1 G2), H on PBS (8 G1), and nausea
(3 G1). Part B included 3 (N = 4), 10 (N = 3), and 20 mg/kg (N=6, ongoing). Suresh Ramalingam
There have been no DLTs in 3 patients on 10 mg/kg, and one DLT (headache Hematology & Medical Oncology, Winship Cancer Institute of Emory University,
Atlanta/United States of America
with hemagglutination) in 6 patients at the 20 mg/kg maintenance dose
(ongoing). Most toxicities were was associated with the initial single Priming The treatment of lung cancer has changed dramatically in the past few years.
Dose and were completely reversible. TRAE in Part B at 3 mg/kg included: From a time when treatment decisions were made without regard to histology
anemia (2 G1, 2 G2), hyperbilirubinemia (1 G1, 1 G3), headache (3 G1), H on or genotype, an era of personalized therapy, at least for a subset of patients
PBS (1 G1), retinal toxicity (G2 protocol-specific scale, asymptomatic). TRAE with lung cancer, is a reality. The treatment of EGFR mutation-positive
at 10 mg/kg included: anemia (3 G1), headache (2 G1), and nausea (1 G1). patients with EGFR inhibitors has resulted in significant improvements in
Two patients with adenoid cystic carcinoma in Part A had stable disease outcomes over standard chemotherapy. Similarly, for patients with ALK- and
for 16 and 8 months. In Part B, 2 of 3 patients have had prolonged stable ROS1-positive non-small cell lung cancer (NSCLC), targeted therapies have
disease at 10 mg/kg for 8+ months (follicular thyroid cancer) and 7+ months proven to be superior. However, for patients with KRAS mutations, which
(myoepithelioma of the head and neck). Evaluation of subjects in the 20 mg/ are seen in approximately 25-30% of lung adenocarcinomas, there is no
kg cohort is ongoing. Conclusions: Hu5F9-G4 is well tolerated at 10 mg/kg effective targeted therapy option. For nearly 70% of patients with NSCLC,
weekly, with 1 mg/kg Priming Dose. Part B with a Maintenance Dose of 20 systemic chemotherapy remains the standard approach. The emergence of
mg/kg is ongoing. Acknowledgements: Stanford Clinical and Translational immune-checkpoint inhibitors has resulted in considerable change in the
Research Unit; California Institute for Regenerative Medicine; Forty Seven, treatment algorithm for advanced NSCLC. These agents are now preferred
Inc. Trial Registration: NCT02216409 1. Willingham SB, et al. The CD47-signal salvage therapy after progression following platinum-based chemotherapy.
regulatory protein alpha (SIRPa) interaction is a therapeutic target for As immunotherapy moves to the first-line therapy setting for advanced
human solid tumors. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6662-7. 2. NSCLC, it is anticipated that at least 25-30% of the patients without a driver
Liu J t al. Pre-Clinical Development of a Humanized Anti-CD47 Antibody with mutation will be treated with immune-checkpoint inhibitors. All of these
Anti-Cancer Therapeutic Potential. PLoS One. 2015 Sep 21;10(9):e0137345. exciting developments call for careful evaluation of ongoing and planned
References: clinical trials, so that appropriate new priorities are established. The newly
1. Willingham SB, et al. The CD47-signal regulatory protein alpha (SIRPa) established NCI National Clinical Trials Network (NCTN) includes all the
interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci adult cancer cooperative groups (ALLIANCE, ECOG-ACRIN, SWOG, & NRG
U S A. 2012 Apr 24;109(17):6662-7. Oncology) is actively engaged in conducting the new generation of clinical
trials for lung cancer. Despite, the success with targeted agents in advanced
2. Liu J t al. Pre-Clinical Development of a Humanized Anti-CD47 Antibody with stage NSCLC, patients do not achieve a cure. Using these agents in early stage
Anti-Cancer Therapeutic Potential. PLoS One. 2015 Sep 21;10(9):e0137345. NSCLC provides the best chance for a cure. The ALCHEMIST study has been
launched by the NCTN to evaluate personalized adjuvant therapy for early
Figure: CD47 is a myeloid-specific immune checkpoint. stage NSCLC. In this study, patients with early-stage lung cancer (stages IB,
II and IIIA) are treated with systemic chemotherapy after surgical resection,
as per standard of care. Subsequently, their tumor is subjected to molecular
testing. Patients with ALK-positive disease are randomized to treatment
with crizotinib or placebo. Patients with EGFR mutations are randomized
to erlotinib or placebo. Patients who are negative for EGFR and ALK, are
randomized to nivolumab or observation. These studies will evaluate the
effect of the personalized adjuvant therapy on overall survival and disease-
free survival. Another ongoing effort is to understand the therapeutic
value of targeted strategies in patients with advanced stage squamous
cell lung cancer. The lung-MAP study enrolls patients with advanced stage
squamous NSCLC. Following next-gen sequencing, patients with selected
targets are treated with an appropriate targeted agent. The study includes
a phase 2 component, which can be rapidly adapted to phase 3 if a agent
demonstrates the pre-defined level of efficacy. This trial is also designed to
accelerate the development of treatments leading to full approval by the
FDA by shortening timelines. These individualized treatment approaches
based on genotype are likely to answer important questions in a definitive
manner. As immunotherapy becomes integrated in the standard treatment
paradigms, considerable changes are also warranted for patients without
driver mutations. For a subset of patients, as immunotherapy becomes
the first line treatment in the advanced stage disease setting, the role of
platinum-based chemotherapy in the second line needs to be investigated.
It is also important to evaluate the need for continued immunotherapy after
disease progression when patients are switched to chemotherapy. Another
key question relates to the duration of therapy for patients receiving immune
checkpoint inhibitors. Appropriately designed trials to understand the
optimum duration of therapy will optimize benefits, reduce toxicity, and
decrease cost. Combination strategies using immune checkpoint inhibitors
with chemotherapy and other targeted agents is also an important area of scan and contrast-enhanced brain imaging (CT or MRI). Routine blood work
priority. The role of biomarkers to select therapy is another critical research and pulmonary function testing are standard as well. However, there are
priority. We should also make efforts to improve the percentage of patients two additional radiographic studies which are necessary for each superior
enrolled to clinical trials. A major reason for this is the stringent eligibility sulcus tumors: (1) MRI scan of the brachial plexus; (2) MRI scan of the cervical
criteria that excludes a significant proportion of patients in order to select and thoracic spine. The rationale for imaging of the brachial plexus is not to
the ‘fittest’ candidates for clinical trials. While this is certainly appropriate confirm that the plexus is invaded (which is evident based on the presenting
in early phase drug development, if patients enrolled in clinical trials do not symptoms and a physical examination), but rather to assess the degree of its
represent the ‘real-world’ patient population, the applicability of the results vertical involvement, since only the lowest trunks of the brachial plexus can
are limited. The next wave of clinical trials should also take into consideration be safely resected without fear of causing paralysis of the upper extremity.
the impact of new treatments on the overall cost of care and the clinical The MRI of the vertebral column serves a double purpose: (1) to assess the
significance of improvements in efficacy. The national Cooperative groups in degree (if any) of vertebral involvement and resulting resectability; (2) to
the United States are committed to a collaborative approach to address key image the proximity of the tumor to the spinal cord, which is crucial for
research questions and improve outcomes for lung cancer. radiation planning. SSTs can cause thecal sac or spinal cord compression by
extending into the spinal canal through neural foramina, without apparent
Keywords: NSCLC, Adjuvant therapy, ALCHEMIST, immunotherapy spine invasion, hence the need for the MRI, which provides a superior image
quality than a chest CT scan. The overall treatment strategy depends on the
nodal status (“N” stage). For those patients without nodal involvement (“N0”)
or with involvement only of the ipsilateral hilar lymph nodes (“N1”), a common
SC15: CLINICAL TRIALS: HOW TO SET PRIORITIES?
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 approach is to use concurrent induction chemo-radiotherapy, followed by the
surgical resection. If obvious mediastinal nodal involvement is seen (“N2 or
N3”), the recommendation is for definitive concurrent chemo-radiotherapy
SC15.04 THE JAPANESE PERSPECTIVE without subsequent surgery. Therefore, invasive staging of the mediastinum,
Yuichiro Ohe either with mediastinoscopy or with EBUS, is mandatory, since it may result in
Thoracic Oncology, National Cancer Center Hospital, Tokyo/Japan avoiding surgery as part of management. General thoracic radiation therapy
(RT) principles apply to the SSTs, such as: (1) use of the CT simulation for
In Japan, several cooperative study groups, such as Japan Clinical Oncology tumor and normal tissue imaging; (2) use of 6-10 MV photon energies (unless
Group (JCOG), West Japan Oncology Group (WJOG), North East Japan Study protons are applied); (3) careful definition of the GTV, Gross Tumor Volume, to
Group (NEJ), Thoracic Oncology Research Group (TORG), Tokyo Cooperative include the visible tumor on lung windows and the abnormal lymph nodes on
Cooperative Oncology Group (TCOG), Oncology Group in Kyushu (LOGiK), soft tissue windows; (4) adequate margins for the CTV, Clinical Target Volume,
Okayama Lung Cancer Study Group (OLCSG) and so on are conducting and the PTV, Planning Target Volume. In particular, a tendency to have very
investigator initiated cooperative clinical studies for lung cancer. Phase 3 tight margins around the tumor which is in close proximity to the spinal cord
studies are mainly conducted by JCOG, WJOG and NEJ. JCOG and WJOG are should be avoided at all cost, since this may result in a marginal tumor failure.
conducting intergroup phase 3 studies for lung cancer. More recently, multi- In comparison to lung cancers in other locations, local tumor progression of
group phase 3 studies are also started. JCOG is a multicenter clinical study a SST can have devastating clinical consequences, resulting in unmanageable
group for cancer treatment fully funded by the national research grants in pain, limb paralysis and a low quality of life. The commonly used total RT
Japan. The goal of the JCOG is to establish effective standard treatments for doses are: 45-60 Gy in trimodality therapy (chemo-RT, then surgery) or 60-70
various types of malignant tumors by conducting nationwide multicenter Gy in bimodality therapy (chemo-RT) in 2 Gy daily fractions. The dose-
clinical trials, and to improve the quality and outcome of the management of limiting normal structures are usually the spinal cord and brachial plexus.
cancer patients. JCOG consists of 16 subgroups and JCOG Lung Cancer Study The maximum allowed dose to the spinal cord may need to be higher (54-55
Group (JCOG-LCSG) consists of 44 institutions, was established in 1982. JCOG Gy) in SSTs than in other lung cancers (50 Gy) in order not to compromise
also have JCOG Lung Cancer Surgical Study Group (JCOG-LCSSG) established the minimum dose prescribed to the PTV by attempting to “spare” spinal
in 1986. cord. In patients presenting with severe pain, a simple field arrangement
(such as anterior and posterior opposed fields) treating the tumor with wide
Only JCOG is supported by no industries but National Cancer Center and
margins is a good initial option allowing for a quick start, followed by a more
grants of Japan Agency for Medical Research and Development (AMED). Thus,
advanced planning technique, such as 3-dimensional RT, intensity modulated
JCOG studies are conducting completely independent from pharmaceutical
RT (IMRT) or VMAT. The tolerance of brachial plexus was classically described
companies. Other groups are supported by mainly pharmaceutical companies
as a maximum dose of 65 Gy, with recent publications suggesting that higher
and grants of AMED. JCOG-LCSG has been conducting many randomized
doses, up to 78 Gy result in 12% risk of Grade>3 radiation-related brachial
trials for small cell lung cancer and elderly non-small cell lung cancer. In case
plexopathy, and that brachial plexopathy is more common as a result of tumor
of JCOG-LCSG, protocol concepts are discussing in the group meeting held
progression than radiation damage. The most quoted prospective clinical trial
every 3 months. The protocol concept agreed in the group meeting will discuss
reporting on treatment outcomes of SSTs is a landmark Phase II SWOG 9416
in JCOG Protocol Review Committee and finally approved by JCOG Steering
study, in which 95/110 enrolled patients without disease progression (86%)
Committee. Kawano Y, Okamoto I, Fukuda H, et al. Current status and future
received thoracic RT to 45 Gy in 1.8 Gy fractions with concurrent cisplatin
perspectives of cooperative study groups for lung cancer in Japan. Respir
and etoposide chemotherapy, followed by surgery and further adjuvant
Investig 52: 339-347, 2014.
chemotherapy. Eligible patients were those with T3-T4 primary tumors and N0
Keywords: Japan Clinical Oncology Group, West Japan Oncology Group, or N1 nodal status. The resection rate was 80% and 75% achieved a complete
Investigator initiated multicenter clinical study (R0) resection. The pathologic response rate (no tumor in the specimen or
microscopic residual) was 56%; the overall 5 yr survival rate was 44% for all
patients and 54% for those with a complete tumor resection. Since then,
recognition in the surgical community that operating after RT doses higher
than 45 Gy is safe, led to a more common use of the full RT dose, i.e. 60 Gy. If
the patient initially planned for trimodality therapy is no longer a surgical
SESSION SC16: SUPERIOR SULCUS TUMORS candidate or refuses surgery, thoracic RT should continue to definitive
TUESDAY, DECEMBER 6, 2016 - 14:30-15:45 dose without interruption. Therefore, it is crucial to perform re-imaging for
response assessment in the last week of chemo-RT (if doses of <60 Gy are
used) rather than schedule those several weeks later.References:
SC16.03 RADIOTHERAPY FOR SULCUS SUPERIOR TUMORS
Rusch, V.W., Giroux, D.J., Kraut et al. Induction chemoradiation and surgical
Maria Werner-Wasik
resection for non-small cell lung carcinomas of the superior sulcus (initial
Radiation Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University,
results of Southwest Oncology Group trial 9416 (Intergroup trial 0160)) . J
Philadelphia/PA/United States of America
Thorac Cardiovasc Surg 121: 472–483, 2001.
Superior sulcus tumors (SST) are unique among lung cancer in that they
Kwong KF, Edelman MJ, Suntharalingam M et al. High-dose radiotherapy in
have a tendency for the invasion into the chest wall and a spread superiorly
trimodality treatment of Pancoast tumors results in high pathologic complete
outside the lungs, namely into the brachial plexus and the sympathetic
response rates and excellent long-term survival. J Thoracic Cardiovasc Surg,
chain, therefore causing a well-defined constellation of symptoms and
129:1250-57, 2005.
signs, such as chest wall/arm/shoulder pain, Horner’s syndrome, spinal cord
compression, upper extremity edema etc. A primary surgical resection is rarely Eblan MJ, Corradetti MN, Lukens JN et al. Brachial plexopathy in apical non-
performed, and bi- or trimodality therapies are most often implemented, small cell lung cancer treated with definitive radiation: dosimetric analysis
depending on tumor stage. A comprehensive evaluation of the tumor extent and clinical implications. Int J Radiat Oncol Biol Phys.85:175-81, 2013.
is mandatory before any intervention is undertaken. Following tumor biopsy
to establish a diagnosis of non-small cell lung cancer, standard lung cancer Keywords: superior sulcus tumor, Pancoast tumor, radiation therapy, Surgery
staging studies need to be obtained, such as the chest and upper abdomen
computerized tomography (CT) scan with intravenous contrast, a PET CT

SC16: SUPERIOR SULCUS TUMORS for 1st line chemotherapy (CT). ORR was 20-25% for platinum-duplets,
1-year survival – 27,5-37,5 month. The 1-year survival showed best results
in absolute figures with paclitaxel and platinum compounds in SCC and
SC16.04 INDIVIDUALIZED EXTENDED LUNG CANCER SURGERY: THE gemcitabine and platinum compounds in non-SCC, but the value was not
CHINESE EXPERIENCE statistically significant neither for 1-year nor for median survival. For SCLC
new combination with irinotecan and platinum compound showed ORR –
Qinghua Zhou
55,1% and stabilization of disease in 24,3% of pts. Conclusions: Nowadays the
Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai/ treatment approaches to lung cancer in Russia depends from morphological
China
type of tumors, IGC results and needs further investigations. Keywords:
Backgroud: Lung cancer is the leading cause of cancer deaths in the world. NSCLC, NET, Squamous cell carcinoma, Adenocarcinoma, lung cancer
For patients with advanced non-small cell lung cancer (NSCLC), survival
prognosis is very poor with chemotherapy and radiotherapy. However, the
possibility of occult metastases may lead to discrepancy between clinical SC17: LUNG CANCER: A GLOBAL CANCER WITH DIFFERENT REGIONAL CHALLENGES
and pathologic staging and underestimation of the disease severity, and TUESDAY, DECEMBER 6, 2016 - 14:30-15:45
how to individualized choose the appropriate patients with locally advanced
non-small cell lung cancer for surgery is controversies. In this study, we
presented here the Chinese experience: individual precision surgery for locally SC17.02 LUNG CANCER IN CHINA: CHALLENGES AND PERSPECTIVES
advanced non-small cell lung cancer based on molecular staging. Methods: Li Zhang
We developed several molecular biomarkers and molecular models from Medical Oncoloyg Dept., Sun Yat-Sen University Cancer Center, Guangzhou/China
Circulation Tumor Cell (CTC ) detection, mi-RNA chip, Gene Chip from 1990.
We used these Molecular biomarkers and molecular models for molecular Lung cancer is still the leading cause of cancer death in China. The estimated
staging, molecular typing, choosing indication of operation and neoadjuvant new lung cancer cases and deaths were 733,300 and 610,200 in 2015,
chemotherapy, predicting postoperative recurrence and prognosis of locally respectively. Non-small cell lung cancer (NSCLC) remains the predominant
advanced non-small cell lung cancer. Results: We developed two molecular form of the disease in China, with majority of patients being diagnosed at
staging model for individualized surgical treatment for locally advanced advanced stages. Thus this presentation will focus on advanced stage NSCLC.
non-small cell lung cancer involving heart, great vessels or both. 3308 patients Current treatment strategy The current treatment algorithm for wild-type
with locally advanced non-small cell lung cancer were underwent completely non-squamous and squamous NSCLC were shown in Figure 1 and 2,
resection of the cancer in the three medical center. The 1-, 3-, 5- and 10 year respectively.
survival rate were 74.5%,62.3%,31.5% and 22.9%, respectively. We used our
molecular staging model for neoadjuvant chemotherapy for 665 patients
with locally advanced lung cancer. The 1-, 3-, 5- and 10-year survival rate were
79.35%, 51.46%, 27.39% and 20.34% of the patients, respectively. We used our
molecular model to divide N2 lung cancer into invasive N2 and Non-invasive
N2 group. We used our molecular models adenocarcinoma and squamous
carcinoma to divide T4 lung cancer into high recurrence and low recurrence
groups, and help postoperative adjuvant therapy. Conclusion: Our molecular
staging and typing models can help us carry out individual precision surgery,
predicting prognosis and cancer recurrence of the cancer for locally advancer
no-small cell lung cancer. Keywords: non-small cell lung cancer, individual
precision surgery, Molecular staging, molecular typing
SESSION SC17: LUNG CANCER: A GLOBAL CANCER WITH

DIFFERENT REGIONAL CHALLENGES Figure 1. Treatment algorithm for non-squamous NSCLC (wild-type)
SC17.01 LUNG CANCER IN RUSSIA: CHALLENGES AND

PERSPECTIVES
Vera Gorbunova
Russian Oncological Research Center, Institution of Russian Academy of Medical
Science, Moscow/Russian Federation
Background: Cancer is set to become a major cause of morbidity and

mortality in coming decade in every region of the world. Methods: The
mortality, morbidity and treatment variants in Russia were evaluated.
Results: The incidence of lung cancer morbidity in Russia in 2014 numbered
57 685, mortality – 49 730. Standardized index incidence rate demonstrates
improvement of men since year 2009. It was 55,0 on 100 000 population in
2009; 49,15 in 2013 and 49,0 in 2014. It means a 10,9% decrease since 2009 to
2014. It takes stable first place in men.
In women the same years showed different values: 7,0; 7,17; 7,3 at 2009, 2013
Figure 2. Treatment algorithm for advanced squamous NSCLC
and 2014 years respectively, that means + 4,3%. It takes 10-12 places of all
malignant diseases among women. Among men lung cancer is on the first For patients with activating EGFR mutations, EGFR-TKIs therapy will
place (26,6%) in mortality rates. A non-interventional, prospective cohort be used as front-line therapy. Commercial available EGFR-TKIs in China
study included 838 patients, average age 58,7; male – 78,4%; female – 21,6%, include Gefitinib, Erlotinib and Icotinib. For patients harbouring an ALK
smokers – 26,5%; ex-smokers – 24,1%, current smokers – 49,4%. Disease stages rearrangement, crizotinib will also be considered as first-line treatment.
at diagnosis were: stage I-II – 36,8%; stage III – 37,8%; stage IV – 25,4%. It was When failed from EGFR-TKIs or ALK-Inhibitor therapy, patients will be
squamous-cell carcinoma – 54,3%; adenocarcinoma – 31%; BAR – 6,4%; LCC – treated according to clinical model of disease progression. For patients
2,9%, adenosquamous carcinoma – 2,3%, other – 3,1%. with asymptomatic progression, continuing EGFR-TKIs or ALK-Inhibitor
is recommended. For patients with local progression, EGFR-TKIs or ALK-
Proportion of EGFR positive tumors constitutes 10,1% (85/838) pts. Surgery
Inhibitor will also be continued with additional local therapy such as whole
was performed for 393 pts (46,9%). Radiotherapy was administered to 145
brain radiation. However, for patients with aggressive progression, EGFR-TKIs
pts (17,8%). 370 pts (44,2%) underwent first-line CT and 96 (11,8%) – second-
or ALK-Inhibitor will be substituted by chemotherapy. Unfortunately, it is
line. The treatment depends on the morphology type of the tumor. We
difficult to overcome drug resistance according to molecular mechanism
consider four main types NSCLC (AdenoCa and SCC), LCLC and NETs. NETs
because novel agents such as Osimertinib and Alectinib haven’t been
group included typical and atypical carcinoids, LCNEC, SCLC. We participated
approved by Chinese FDA. Challenge and perspective 1. Genetic alterations
in 53 different multicenter international trials in lung cancer, including 930
assays Genetic alterations are frequent in Chinese NSCLC patients.
patients. Outside of these protocols we analyzed 567 pts with advanced
According to PIONEER study (NCT01185314), which is a prospective molecular
NSCLC: 255 pts with squamous cell cancer (SCC) and 250 pts with non-SCC
epidemiology study in newly diagnosed advanced lung adenocarcinoma, series of 1009 patients presenting to our institute from 1977-86 had shown
the EGFR active mutation rate is 50.2% in Chinese patient population. The squamous histology to the commonest (34.3%) followed by adenocarcinoma
incidence of EGFR mutations in patients who never smoked can be as high (25.9%) and small cell lung cancer (SCLC; 20.3%). Subsequent analysis of 250
as 59.6%. ALK rearrangement is also common in this patient population. In a patients presenting to us three decades later (2007-09), we found that the
large cross-sectional study enrolled 1160 NSCLC patients, the incidence of ALK histological pattern was largely unchanged with squamous still being the
rearrangements is 8.1%. Noteworthy, 44% of patients younger than 30 years commonest (34.8%) followed by adenocarcinoma (26.0%) and SCLC (18.4%).
old harbor ALK rearrangements. However, genetic alterations test rate used The male-female ratio as well as the current/ex-smoker to never-smoker ratio
to be low in China. According to a large national survey, the EGFR mutation was also similar between the two cohorts. A possible reason for the lack of
test rate was only 9.6% in 2011. However, as the turnover time shortens, the change in demographic profile of lung cancer was thought to be related to
testing fee decreases, and ctDNA testing becomes available, the EGFR/ALK the fact that ‘bidi’ and NOT cigarette is the most common form of tobacco
assays have turned into routine practice in China. Moreover, NGS platforms smoking in India. The ratio of bidi to cigarette smoking in India ranges from
detecting panels of mutations are commonly used in some leading centers 2.5:1 to 7.0:1 in different parts of India and unlike cigarette making, there
now. 2. Novel agent availability There is severe delay in the approval for novel has been no change in the process of bidi manufacturing which is primarily
agents by Chinese FDA. For instance, Bevacizumab was approved by FDA for a cottage industry. The other important aspect related to its association
treatment of NSCLC in 2006, while it was approved by Chinese FDA 9 years of quantified tobacco smoke exposure. The smoking index (SI; number of
later. To improve availability of novel agents, Chinese oncologists are active in combined bidis and cigarettes smoked per day multiplied by number of years
participation in international multi-center clinical trials. In addition, more and smoked) has been developed for this purpose. Patients can be categorized
more innovative drugs have been developed by domestic pharma industry and as either never-smokers (SI=0), light to moderate smokers (SI=1-300) and
entered clinical trials (Table 1). Moreover, Chinese FDA makes new policies to heavy smokers (SI≥301). In a cohort of 520 non-small cell lung cancer (NSCLC)
encourage innovative drugs and accelerating new drug application. patients, we observed that age, gender, histological type and stage differed
significantly between the three groups. Never-smokers had significantly
Agent ID Classification Indication Phase more females (52%), were younger (mean age 54.5 years), lesser squamous
histology (28%), more advanced stage (IIIB/IV; 92%), more metastatic
Mutation disease (67.4%) and more extra-thoracic metastases (42%) while group of
Avitinib selected EGFR- EGFR T790M Mutation Phase I heavy smokers had more males (98%), were older (mean age 61.2 years), more
TKI squamous histology (58%), lesser advanced stage (81%), lesser metastatic
Nonsquamous NSCLC disease (39%) and lesser extra-thoracic metastases (17%). We have identified
Apatinib VEGFR-TKI Phase III another risk factor in women to be the exposure to Biomass fuel. Majority
in 3L
of patients (approximately 83% of NSCLC histology at our centre) present
Nonsquamous NSCLC with advanced stage(IIIB/IV) at the time of diagnosis and are managed
Famitinib VEGFR-TKI Phase III
in 3L non-surgically. Misdiagnosis as tuberculosis and empirical treatment with
Theliatinib EGFR inhibitor EGFR amplification Phase I anti-tubercular drugs prior to referral to higher centre is one of the important
causes for delayed diagnosis of this disease in India. Developing and under-
Volitinib c-MET inhibitor c-MET amplification Phase I developing countries are often constrained with regards to availability of
SHR-1210 PD-1 antibody NSCLC in 2/3L Phase I health care and other resources necessary for appropriate management of
the health related requirements of their population and this holds true for
Table 1. Innovative drugs from China in clinical trials 3. Lung cancer prevention lung cancer as well. Some of the challenges in resource constrained settings
The incidence rate of lung cancer remains high in China between 2000 and include: · Large population with high population density · Illiteracy and poor
2011. Factors that have contributed to this issue include tobacco smoking health awareness · Sub-optimal economic and infrastructure inputs for health
and air pollution. 50% adult Chinese men were current smokers in 2010. In care · Suboptimal ratios of doctor and nurses for population · Overburdened
addition, smoking rates in adolescents and young adults are still rising in hospitals and health care facilities · Huge burden of TB that hinders
China. To reduce tobacco use in China, the government enact a strict smoking differentiation by the primary physician with lung cancer Important issues in
control law in Beijing in June 2015. However, the air pollution is still a severe resource constrained settings include choosing the platinum agent as well as
problem and needs to be improved urgently. 4. Economic burden There are the non-platinum agent. Decision on dose intensity may also be influenced by
several factors which have contributed to the heavy economic burden of lung similar factors (efficacy, tolerance, toxicity profile and packaging strengths of
cancer patients in China. First, the residents’ income is still low in China. In marketed drugs). A list of some of the important factors influencing decision
2015, per capita disposable income (one year) was only $3300. Second, the are shown below.
cost of anti-cancer drugs is very high (Crizotinib/cycle $8500, Gefitinib/cycle
$2200, Pemetrexed/cycle $3000, and Bevacizumab/cycle $4500). Moreover, Characteristic Relative importance
only 20% of whole medical expense can be covered by insurance, and majority
of targeted drugs can’t be covered. Disease related
Keywords: genetic alterations assays, lung cancer prevention, novel agents Age ++
availability, economic burden Gender +
Histology +++
SC17: LUNG CANCER: A GLOBAL CANCER WITH DIFFERENT REGIONAL CHALLENGES Molecular profile of tumor ++
Stage +
Performance Status +++
SC17.03 LUNG CANCER IN INDIA: CHALLENGES AND PERSPECTIVES
Digambar Behera Unrelated to disease
Pulmonary Medicine, Postgraduate Institute of Medical Education and Research Co-morbid illnesses +
(PGIMER), Chandigarh/India
Socio-economic background/financial
Lung cancer is the commonest type of cancer in males and the leading +++
constraints
cause of cancer death in both sexes world-wide. It is also the commonest
in men in India accounting for 11.3% of all new cancers and also is the most Medical reimbursement/insurance issues +++
common cause of cancer death (13.7%). In contrast to a decline trend in men Wishes of patient/family members ++
in developed countries with a plateau for females, in India, the incidence
continues to rise for both males and females. Data from the population based Frequency of hospital visits ++
cancer registries developed under the National Cancer Registry Program of Dr. D. Behera Senior Professor & Head, Dept. of Pulmonary Medicine,
the Indian Council for Medical Research(ICMR) indicates that there is wide Postgraduate Institute of Medical Education & Research, Chandigarh - 160012
geographical variability in the incidence of this disease in different parts (INDIA) Email: [email protected] SelectReferences and suggested reading
of the country. The highest age adjusted incidence rates of 45 per 100000 1. Behera D, Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci
population are seen in the North-East region of India and are similar to areas 2004; 46 : 269-81 2. Behera D. Managing lung cancer in developing countries:
reporting the highest incidence rates in some parts of the US and Europe. In difficulties and solutions. Indian J Chest Dis Allied Sci 2006; 48: 243-4 3. Jindal
other areas of India, especially the Western region, the age adjusted incidence SK, Behera D. Clinical spectrum of primary lung cancer: review of Chandigarh
rates are as low as 2 per 100000 population. The demographic profile experience of 10 years. Lung India 1990; 8: 94-98 4. Singh N, Aggarwal AN,
including age, gender, stage, histology and even the molecular epidemiology Gupta D, Behera D, Jindal SK. Unchanging clinico-epidemiological profile of
(prevalence of EGFR mutations and ALK rearrangements) varies considerably lung cancer in North India over three decades. Cancer Epidemiol 2010; 34:
in different parts of India. However, the overall incidence is much lower than 101-4. 5. Behera D, Balamugesh T. Indoor air pollution as a risk factor for lung
that compared to many western countries. The demographic profile of lung cancer in women. J Assoc Physicians India 2005; 53: 190-2. 6. Singh N, Aggarwal
cancer seen in India needs special mention. In the past, a single-centre large AN, Gupta D, Behera D, Jindal SK. Quantified smoking status and non-small

cell lung cancer stage at presentation: analysis of a North Indian cohort and a lower the cost of health care to encourage the patients to go for treatment
systematic review of literature. J Thorac Dis 2012; 4: 474-84. 7. Singh N, Behera and to get the proper care. There should be special dealing for the economic
D. Lung cancer epidemiology and clinical profile in North India: Similarities pressure and avoidance of financial toxicities for the patient. The last point
and differences with other geographical regions of India. Indian J Cancer 2013; that have to be ameliorated in Africa developing countries is research through
50: 291 8. Singh N, Aggarwal AN, Behera D. Management of advanced lung International collaboration as studying genetic polymorphism and relation to
cancer in resource constrained settings : a perspective from India. Expert smoking and changing patient concept about drugs received in clinical trials
Rev Anticancer Ther 2012: 12: 1479–95. 9. Maturu VN, Singh N, Bal A, Gupta N, that use new drugs, proper investigations and lower the cost of treatment and
Das A, Behera D. Relationship of epidermal growth factor receptor activating may get better outcome.References 1- Globocan 2012 (IARC): Estimated cancer
mutations with histologic subtyping according to International Association incidence, mortality and prevalence worldwide, section of cancer surveillance
for the Study of Lung Cancer/American Thoracic Society/European 2- Jemal A, Center MM, DeSantis C, Ward EM (2010) Global patterns of cancer
Respiratory Society 2011 adenocarcinoma classification and their impact on incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev
overall survival. Lung India 2016; 33: 257-66. 10. Bal A, Singh N, Agarwal P, Das 19: 1893-1907. 3- Sankaranarayanan R, Jayant K, Brenner H 2011: An overview
A, Behera D. ALK gene rearranged lung adenocarcinomas: molecular genetics of cancer survival in Africa, Asia, the Caribean and central America: the case
and morphology in cohort of patients from North India. APMIS 2016 Aug 8; for investment in cancer health services. IARC Sci Publ: 257-291. 4- Gaafar RM,
DOI: 10.1111/apm.12581 [Epub ahead of print] Eldin NH (2005) Epidemic of mesothelioma in Egypt. Lung Cancer 49: S17-S20.
5- Tao Z, Shi A, Lu C, Song T, Zhang Z, etal. 2014: Breast cancer : Epidemiology
Keywords: India, epidemiology, lung cancer, Management in Resource and Etiology. Cell Biochem Biophysi
Constraints
Keywords: Lung cancer, cancer control, obstacles and perspectives, smoking
SC17: LUNG CANCER: A GLOBAL CANCER WITH DIFFERENT REGIONAL CHALLENGES

SESSION SC18: PRECISION SCREENING FOR LUNG CANCER

SC17.05 LUNG CANCER IN AFRICA: CHALLENGES AND TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
PERSPECTIVES
Rabab Gaafar
Medical Oncology, National Cancer Institute, Cairo/Egypt SC18.01 FIELD CANCERIZATION IN THE AIRWAYS AND ITS
APPLICATION TO LUNG CANCER EARLY DETECTION
Lung cancer has been the most common cancer in the world for several
decades. The number of new cases estimated in 2012 is 1.8 million cases (12.9% Ignacio Wistuba
of the total), 58% of which occurred in the less developed regions. The disease Translational Molecular Pathology, The University of Texas MD Anderson Cancer
remains as the most common cancer in men worldwide (1.2 million, 16.7% of Center, Houston/United States of America
the total) with the highest estimated rates in Nothern America (33.8%) and
Molecular alterations that are characteristic of lung tumors have been
Northern Europe (23.7%), a relatively high rate in Eastern Asia (19.2) and
shown to be present in normal-appearing airway epithelium adjacent to
the lowest rates in Western and middle Africa (1.1 and 0.8 respectively). In
lung tumors suggestive of an airway field cancerization phenomenon (1, 2).
developing countries, lung cancer is the most common cancer among males
These field effects include altered gene expression, loss of heterozygosity
and the third most common cancer among females. Lung cancer is the most
(LOH), gene mutation and methylation and microsatellite instability (3-7).
common cause of death from cancer worldwide estimated to be responsible
Microarray studies have pointed to expression profiles that are dissimilar
for nearly one in 5 (1.59 million deaths, 19.4% of the total) (1). Temporal
between airways in smokers with and without lung cancer (8, 9). It has been
analyses reveal that significant reductions in lung cancer mortality have been
recently demonstrated gene expression profiles that are shared between
observed in developed countries due to increased awareness of the harmful
normal-appearing airway cells and nearby NSCLCs and that can distinguish
effects of smoking , asbestos and other factors The role of early detection is
airways of smokers with lung cancer from those without the malignancy (8).
also evident. (2). In contrast, lung cancer incidence and mortality rates have
Studies from several groups suggest that the field cancerization provides
increased in some low and medium resourced countries (3). The regional
biological insights into non-small cell lung carcinoma (NSCLC) ad small cell
differences are mainly due to increased tobacco smoking in the developing
lung carcinoma (SCLC) pathogenesis and clinical opportunities for lung
countries , smoking waterpipe, cannabis or even passive and secondary smoke
cancer detection (6, 8). It is important to note that smoking perpetuates
and in the mean time there is lack of proper tobacco control. There are also
inflammation throughout the exposed airway epithelium (10). This effect
occupational risk factors such as asbestos exposure, dust, fumes, nickel
is pronounced in patients with Chronic Obstructive Pulmonary Disease
,silica and insecticides and up till now there are areas that have not banned
(COPD) (10). Notably, among smokers, even after smoking cessation, airway
asbestos or succeeded to control occupational and environmental exposure
inflammation persists while the risk of lung cancer continues to increase
and incidence of mesothelioma is increasing. (4) Many studies have shown
(10). It is not known which tumor promoting profiles in the airway field
that cases have genetic susceptibility to develop lung cancer specially in
cancerization may drive lung cancer development in COPD patients. Using
North Africa. Another important factor specially the Middle East North Africa
microarray profiling, studies have pointed to expression profiles that are
is the increase in the elderly population that may be attributed to better
dissimilar between airways in smokers with lung cancer and airways in
infection control and improvement of general health care . As life expectancy
smokers without cancer (11-13). Importantly, these gene-expression changes
continues to increase throughout the African continent, the burden of
within the “field of injury” have been leveraged for development and
cancer is likely to increase. Given that an estimated 32,640 new lung cancer
validation of a clinically-relevant biomarker that can improve the diagnostic
cases will be seen in Africa in 2015 ( 5) .We have to remember also that cancer
performance of bronchoscopy for detection of lung cancer (predominantly
diagnosis rate in Africa is relatively low and patients present usually in an
NSCLC) among smokers with suspect disease (8, 12). In addition, gene
advanced stage so underreporting may be another factor . Accordingly, it is
expression array analysis pointed to airway field expression profiles that
essential to know the magnitude of lung cancer in different regions in Africa
are spatially and temporally modulated in early stage patients following
by having cancer registry for the countries . So, obstacles to the global fight
surgery and that may be associated with disease relapse (13). Further, we
against lung cancer include lack of registry in some parts of Africa, low public
have recently demonstrated that there is significant enrichment in gene
awareness of lung cancer and absence of screening for the high risk cases
expression profiles measured in both small (adjacent to tumor) and large
, overburdened treatment centers and insufficient financial support. The
(mainstem bronchus) airway compartments of the airway field of injury,
ways to combat all these obstacles start by setting strategies for prevention
suggesting that gene-expression changes in the large airway can serve as
and earlier detection in the low income countries. Public health awareness
a surrogate for the molecular changes occurring in the airway epithelium
of the risk factors that cause lung cancer and the importance of avoiding /
adjacent to the tumor (9). Taken together, studies from our group and others
stopping smoking and banning asbestos should be clear and this is the role of
suggest that, by sampling “normal” and relatively accessible tissue (e.g.,
public health authorities, medical journals and public media. The war against
bronchial airway), the airway field of injury provides biological insights into
tobacco companies should start and everyone should understand the danger
the earliest phases in the development of lung malignancy and potential
of smoking. This is done also by cooperation of scientific organizations of
valuable clinical opportunities such as early detection (1, 2). Identifying
governmental and non governmental organizations. Also, we should reduce
molecular aberrations that precede cellular morphological changes will
air pollution and regulate the occupational exposure of the employees to
provide biological insights into why some smokers develop lung cancer and,
avoid the appearance of lung cancer and mesothelioma. As for early detection
thus, clinical opportunities for improved lung cancer detection.References:
, screening can help in high risk patients and many authorities and NGOs
1. Kadara H, Wistuba, II. Field cancerization in non-small cell lung cancer:
can help to catch the early cases. In the mean time there should be ways to
implications in disease pathogenesis. Proceedings of the American Thoracic
access modern imaging techniques to detect the cancer and use the minimal
Society. 2012;9(2):38-42. 2. Steiling K, Ryan J, Brody JS, Spira A. The field of
requirements for diagnosis and care . Accordingly it is essential to set the
tissue injury in the lung and airway. Cancer Prev Res. 2008;1(6):396-403. 3.
treatment guidance protocols to facilitate the management of the patients
Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson
and to educate and train the doctors that should acquire degree granting
E, Baylin SB, Herman JG. Aberrant methylation of p16(INK4a) is an early
programs and get certificates in the oncological field. It is mandatory to to
event in lung cancer and a potential biomarker for early diagnosis. Proc
Natl Acad Sci U S A. 1998;95(20):11891-6. 4. Mao L, Lee JS, Kurie JM, Fan YH, measurable disease and before a chest CT has been done. Consideration
Lippman SM, Lee JJ, Ro JY, Broxson A, Yu R, Morice RC, Kemp BL, Khuri FR, of the use of such biomarkers should trigger a discussion with the patient
Walsh GL, Hittelman WN, Hong WK. Clonal genetic alterations in the lungs of before ordering it to address the intent of the test and the implications of
current and former smokers. J Natl Cancer Inst. 1997;89(12):857-62. 5. Tang X, the possible results. Many biomarkers have been developed over the years
Shigematsu H, Bekele BN, Roth JA, Minna JD, Hong WK, Gazdar AF, Wistuba, to predict tumor development. Let us consider the characteristics of such
II. EGFR tyrosine kinase domain mutations are detected in histologically a biomarker to assess the risk of lung cancer. For screening purposes, given
normal respiratory epithelium in lung cancer patients. Cancer research. the low prevalence of disease, a strong negative predictive value (NPV) of a
2005;65(17):7568-72. 6. Wistuba, II, Behrens C, Milchgrub S, Bryant D, Hung test is a very attractive feature. High specificity on the other hand is always
J, Minna JD, Gazdar AF. Sequential molecular abnormalities are involved in desirable so we do not overcall cancers (false positive). Should such a test
the multistage development of squamous cell lung carcinoma. Oncogene. be positive, it would push individuals into a higher risk group to consider
1999;18(3):643-50. 7. Wistuba, II, Lam S, Behrens C, Virmani AK, Fong KM, appropriate surveillance. The biomarker could measure a genetic risk (e.g.
LeRiche J, Samet JM, Srivastava S, Minna JD, Gazdar AF. Molecular damage in altered metabolism of carcinogens, DNA repair machinery abnormalities,
the bronchial epithelium of current and former smokers. J Natl Cancer Inst. predisposition to inflammation, or germline mutations) or the influence
1997;89(18):1366-73. 8. Spira A, Beane JE, Shah V, Steiling K, Liu G, Schembri of the environment on tumor development (exposure to carcinogens or
F, Gilman S, Dumas YM, Calner P, Sebastiani P, Sridhar S, Beamis J, Lamb surrogates of risk such as epigenetic changes in the airway epithelium or
C, Anderson T, Gerry N, Keane J, Lenburg ME, Brody JS. Airway epithelial the prevalence of preinvasive lesions). There has been recent interest in
gene expression in the diagnostic evaluation of smokers with suspect lung the potential for genetic variants to give insight into the pathogenesis of
cancer. Nat Med. 2007;13(3):361-6. 9. Kadara H, Fujimoto J, Yoo SY, Maki Y, lung cancer. These variants indicate that there is great heterogeneity in
Gower AC, Kabbout M, Garcia MM, Chow CW, Chu Z, Mendoza G, Shen L, mechanisms of disease development that is modulated by inherited genetic
Kalhor N, Hong WK, Moran C, Wang J, Spira A, Coombes KR, Wistuba, II. variation. With these come the opportunity to improve models predicting
Transcriptomic architecture of the adjacent airway field cancerization in non- lung cancer risk. A larger question of timeliness of biomarker use in clinical
small cell lung cancer. J Natl Cancer Inst. 2014;106(3):dju004. 10. Punturieri practice will be discussed during the presentation. What are the risk and
A, Szabo E, Croxton TL, Shapiro SD, Dubinett SM. Lung cancer and chronic benefits of precision screening? Are current risk prediction models safe to
obstructive pulmonary disease: needs and opportunities for integrated use or robust to guarantee an advantage over current standard of care?
research. J Natl Cancer Inst. 2009;101(8):554-9. 11. Gustafson AM, Soldi R, There is a clear need to evaluate the benefit of risk assessment biomarkers
Anderlind C, Scholand MB, Qian J, Zhang X, Cooper K, Walker D, McWilliams with repeated measures over time. The assumption is that as risk increases,
A, Liu G, Szabo E, Brody J, Massion PP, Lenburg ME, Lam S, Bild AH, Spira molecular moieties should be more readily available (e.g. in the circulation)
A. Airway PI3K pathway activation is an early and reversible event in lung over time. This may be true for tumor specific antigens and ctDNA, but
cancer development. Sci Transl Med.2(26):26ra5. 12. Silvestri GA, Vachani would not apply to genetic risk. Statistical models could test the ability of
A, Whitney D, Elashoff M, Porta Smith K, Ferguson JS, Parsons E, Mitra N, different biomarkers to complement each other in a single population, in
Brody J, Lenburg ME, Spira A, Team AS. A Bronchial Genomic Classifier for the order to eventually determine those that could be tested prospectively.
Diagnostic Evaluation of Lung Cancer. N Engl J Med. 2015;373(3):243-51. 13. Given biomarkers’ non-specificity and commonality in predicting diseases,
Kadara H, Shen L, Fujimoto J, Saintigny P, Chow CW, Lang W, Chu Z, Garcia modeling multiple markers of the same clinical diagnostic criteria can be used
M, Kabbout M, Fan YH, Behrens C, Liu DA, Mao L, Lee JJ, Gold KA, Wang J, to develop more accurate individual and cumulative risk estimates for specific
Coombes KR, Kim ES, Hong WK, Wistuba, II. Characterizing the molecular diseases. We should therefore consider a joint effects approach to determine
spatial and temporal field of injury in early-stage smoker non-small cell individual biomarker associations as well as to ascertain the impact of
lung cancer patients after definitive surgery by expression profiling. Cancer simultaneous increases in multiple biomarker concentrations on the diagnosis
prevention research. 2013;6(1):8-17. of lung cancer. Biomarkers of risk would ideally be tested prospectively in
a randomized clinical trial. However, given the relatively low prevalence of
Keywords: Early Detection, field of canerization, field of injury this disease, the number needed to screen may be prohibitive; therefore the
development of registries is most appropriate. Registries are longitudinal
cohort prospective studies where a biomarker is introduced but does not
force providers to change their management. The lead time to diagnosis may
SC18: PRECISION SCREENING FOR LUNG CANCER
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 be sufficient to cause a stage shift and therefore improve outcome. Finally, it
is through better understanding of the biology of cancer development and of
preinvasive lesions that we will shed further light into the field of biomarker
SC18.02 INTEGRATING LUNG CANCER BIOMARKERS INTO FUTURE research.
SCREENING PROGRAMS
Pierre Massion
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt-Ingram Cancer
SC18: PRECISION SCREENING FOR LUNG CANCER
Center, Nashville/TN/United States of America TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
Low-dose computed tomography for high-risk individuals has for the first time
demonstrated unequivocally that early detection save lives. The currently SC18.05 UK LUNG SCREENING TRIAL COST EFFECTIVENESS AND
accepted screening strategy comes at the cost of a high rate of false positive CURRENT PLANNING STATUS OF INTERNATIONAL LUNG CANCER
findings while still missing a large percentage of the cases. Therefore, there is SCREENING PROGRAMS
increasing interest in developing strategies to better estimate the risk of an
individual to develop lung cancer, to increase the sensitivity of the screening John Field
process, to reduce screening costs and to reduce the numbers of individuals Department of Molecular and Clinical Cancer Medicine, The University of Liverpool,
Liverpool/United Kingdom
harmed by screening and follow-up interventions. New molecular biomarkers
candidates show promise to improve lung cancer outcomes. This review The pilot UKLS lung cancer RCT screening trial recruited 4,000 individuals [1],
discusses the current state of biomarker research in lung cancer screening using the LLPv2 risk model (5% risk over 5 years) [2]. The lessons learnt from
with the primary focus on risk assessment. The rationale for developing the UKLS CT pilot screening trial are:
biomarkers for the early detection of lung cancer is very strong and well
established. It stems from the fact that, at the population level, the earlier we UKLS – A Population based trial – all IMD’s (socioeconomic groups) included
detect the disease, the better the outcome and the lower the health care cost. [1].
The impetus for biomarker development has grown stronger since the NLST
trial demonstrated that early detection via chest CT screening reduced the Risk Stratification (LLPv2 5 % risk over 5 years) [2]
relative risk for lung cancer death in the high risk individuals. Low dose chest
Volumetric assessment of CT detected nodules [3].
CT in this group alone may save up to 12,000 lives a year, but it represents
only about 8 % of individuals dying of this disease every year. Thus, much is Care Pathway – Management pathway implemented [3].
to be done to capture these lung cancers that escape chest CT screening as
currently recommended despite its high sensitivity and specificity. The reason Early Stage Disease (Stage 1 68%: Stage I&II 86%) [4]
for limited detection relates to how many at-risk individuals are studied with
CT and to how we best define this risk. Detection and careful management High Proportion suitable for Surgery (83%) [4]
of indeterminate pulmonary nodules are integral parts of this effort. Lung
1.7% lung cancers identified at baseline scan [1]
cancer screening using chest CT also raises many questions, some of which
could be addressed with well poised biomarkers. For example, who is at Benign Resection rate – 10.3% (NLST 27%)[1]
utmost risk for lung cancer? How do we expand the screening criteria from the
NLST without causing more harm than good? Once the CT screening studies Psychological impact – transient not significant [5, 6]
are done, how do we approach a non-invasive diagnosis of lung cancer? How
do we prevent the overdiagnosis bias? Here we focus on biomarkers that Cost effectiveness modelling within NICE parameters [1]
could be used in a risk assessment evaluation for screening programs. We will
The cost effectiveness of the UKLS trial has been modelled and compared
discuss current molecular biomarkers of risk assessment in those without

with that of the US National Lung Screening Trial (NLST), which has published sheath (EBUS-GS) 1, 2 The GS-covered probe is advanced to the PPL, then
an estimate of $81,000 per quality-adjusted life-year (QALY) as its mean after confirmation by EBUS that the lesion has been reached, the probe is
incremental cost-effectiveness ratio (ICER) [7]. All UKLS cost estimates were removed before inserting the brush and biopsy forceps through the GS that
based on 2011-12 NHS tariffs (Costs provided in $: £1=$1.5 on 30-11-15). Owing is held in place in the lesion. This technique enables cytology and biopsy to
to the brief duration of the trial, observations relevant to economic be performed several times with minimal risk of bleeding. 4) Insertion of the
evaluation were limited to cost-incurring events associated with screening bronchoscope (saline immersion technique) After observing the bronchial
and the initial management of screen-detected cancers. Expected outcomes lumen, the bronchoscope should be advanced while visualizing the branches
of the cancers detected were simulated on the basis of both life tables and to the bronchus near the peripheral lesion. Upon reaching a position where
published survival data from other studies. The costs incurred from UKLS are further advancement is not possible, flushing of 1-ml saline (total 5-10 ml)
those of baseline and repeat screens ($424,072), diagnostic workup ($113,478), several times is performed through the working channel of the bronchoscope;
and treatment ($449,243), which totaled $1,036794 (95% CI, $719,332 to this is done to fill the bronchus, remove any sputum, and visualize the lumen.
$1,350,766). Recruitment costs ($15) per person for invitation and selection) The GS-covered probe is then inserted from the working channel into the
were modelled from the UK colorectal screening programme and we assumed bronchus. In cases of ground glass nodule (GGN), we do not perform the saline
a participation rate of 30% of those invited. The gross current costs of the immersion technique. Because the saline immersion technique will occur
programme amounted to $1,133,217 (CI $817,887 to $1,450,610). Summary of EBUS images of hyperechoic points which resemble EBUS image of GGN. 5)
findings: The ICER of screen-detection compared with symptomatic detection EBUS visualization The operator advances the US probe from the working
was estimated at $9495 per life-year gained. Using data from previous studies, channel of the 4-mm bronchoscope towards the periphery and stops when
we associated quality of life weights with the estimated survival gains, some resistance is felt. The duration of X-ray fluoroscopy should be limited
enabling us to report outcomes as QALYs. On this basis, the ICER equaled as much as possible; also, an iris of the fluoroscopy machine should be used
$12,709 per QALY gained (CI $ 8280 to $18966). The difference in cost for fluoroscopy. Scanning while pulling back the probe from the distal site to
effectiveness between NLST and UKLS as suggested by the estimated ICERs is the proximal site reduces strain on the probe and provides clear EBUS images.
more apparent than real. Most of the discrepancy can be explained by We have reported that EBUS imaging of PPLs can be used to diagnose and
differences between settings in (i) local unit costs, (ii) intensity of resource assess the degree of differentiation between benign and malignant lesions3.
use, (iii) number of screening rounds and (iv) disease prevalence in the target PPLs are classified as type I if the internal echoes are homogeneous, type
population. Thus, UKLS selected high-risk subjects only whereas NLST III if the internal echoes are heterogeneous, and type II if there are mainly
screened a general population, yet the latter reported an ICER as low as hyperechoic lines and dots near the probe. About 92% of type I lesions were
$32,000 for its highest-risk quintile. Expected QALY gains from screen- benign, whereas 99% of type II and type III lesions were malignant. The
detection were similar in both trials. positional relationship between the probe and a PPL is classified as “within”
(probe placement within a lesion), when the 360° area around the probe is
entirely surrounded by the lesion; and “adjacent to” (probe is in contact with
a lesion) when a lesion is depicted, but the 360° area around the probe is not
entirely surrounded by the lesion. Higher diagnostic yields have also been
reported for lesions with a positive bronchus sign on computed tomography.
Minezawa et al.4 reported that the CT bronchus sign was a significant
predictive factor for successful bronchoscopic diagnosis in the multivariate
analysis. We believe that bronchoscopists should trace the accurate bronchus
leading to the PPL on CT axial images. When the lesion located in the middle
lobe, the lingular segment, or bilateral lower lobes, we inverse CT axial images
right to left, or left to right for watching the bronchus from the cranial site.
When the lesion located in the right upper lobe, we rotate CT axial images
counterclockwise 90 degrees. When the lesion located in the left superior
segment, we rotate CT axial images clockwise 90 degrees. While tracing the
bronchus on CT images, we could draw the illustration of the bronchus leading
to PPLs. We usually use virtual bronchoscopic navigation (VBN) and compare
the hand-written illustration of the bronchus leading to PPLs. Asano et al.5
reported that the diagnostic yield by EBUS-GS and VBN was between 63.3
and 84.4% in reports on VBN for PPLs searched in PubMed as of November
2013. When the ultrasonic probe advanced to the different bronchus a little
far from the target lesion, EBUS image is invisible. In this case, we should
Keywords: CT-Screening, cost-effectiveness, CT-implementation change the direction of the tip of the bronchoscope using the up and down
lever of the bronchoscope under fluoroscopy. We select the direction of the
tip of the bronchoscope for facing the target lesion, and pull back and push
the probe/GS for trying to insert the target lesion. When the ultrasonic probe
advanced to the bronchus adjacent to the target lesion, EBUS image is called
SESSION SC19: INTERVENTIONAL PULMONOLOGY IN DIAG- as “adjacent to”. In this case, we could change the direction of the tip of the
NOSIS AND TREATMENT OF THORACIC MALIGNANCIES bronchoscope using the up and down lever of the bronchoscope under the
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 EBUS image. We use the up or down lever of the bronchoscope for changing
the position of the probe and GS (probe/GS) to be close to the target lesion
on EBUS image. Then we keep the same angle of the tip of the bronchoscope,
and pull back and push the probe/GS for trying to insert the target lesion. 6)
SC19.01 DIAGNOSIS OF LUNG CANCER: MULTIMODAL DEVICES FOR
Cytology and tissue biopsy from the guide sheath The GS tip is placed within
PERIPHERAL PULMONARY LESIONS or adjacent to the PPL before passing the brush and biopsy forceps through
Noriaki Kurimoto the GS.
Kanagawa Prefecture/Japan
References
When bronchoscopy is performed for peripheral pulmonary lesions
(PPLs), a radial ultrasonic probe can be inserted from the working channel Kurimoto N, Fielding D, Musani A. Endobronchial Ultrasonography. 2011, Willy
of the bronchoscope to reach the PPL1. We began using this technique Blackwell
of endobronchial ultrasonography (EBUS) in 1994. EBUS using a guide Kurimoto N, Miyazawa T, Okimasa S, Maeda A, Oiwa H, Miyazu Y, Murayama
sheath (GS) also began in 19962. We would like to explain the technique M. Endobronchial ultrasonography using a guide sheath increases the ability
and advantages of diagnosing PPLs using EBUS, GS, Navigation, and etc. to diagnose peripheral pulmonary lesions endoscopically. CHEST 2004; 126:
1) Radial ultrasonic miniature-probe A radial probe emits US while being 959-65.
rotated 360°; the reflected US waveform is rendered as an image. The radial
probe scans from the bronchial lumen to provide a short-axis image of the Kurimoto N, Murayama M, Yoshioka S, Nishisaka T. Analysis of the
bronchial and para-bronchial tissue. 2) Analyzing the internal structure of internal structure of peripheral pulmonary lesions using endobronchial
peripheral pulmonary lesions with a radial mini-probe EBUS imaging before ultrasonography. CHEST 2002; 122: 1887-94
surgery has been compared with histopathologic findings of surgically
resected tissue to determine the internal structures of PPLs that can be Minezawa T, Okamura T, Yatsuya H, et al. Bronchus sign on thin-section
depicted by EBUS3. PPLs can be classified as heterogeneous or homogeneous computed tomography is a powerful predictive factor for successful
based on irregularities in brightness within lesions seen on EBUS. Internal transbronchial biopsy using endobronchial ultrasound with a guide sheath for
structures within peripheral lesions that can be identified by EBUS include small peripheral lung lesions: a retrospective observational study. BMC Med
patent blood vessels, patent bronchi, hemorrhage, calcification, dilated Imaging. 2015 21; 15:21
bronchi, necrosis, and small amounts of air in alveoli. 3) EBUS using a guide
Asano F, Eberhardt R, Herth F. Virtual Bronchoscopic Navigation for
Peripheral Pulmonary Lesions. Respiration 2014; 88: 430-440 new cases of lung cancer (117,920 in men and 106,470 in women) About 158,080
deaths from lung cancer (85,920 in men and 72,160 in women) Lung cancer
Keywords: bronchoscopy, peripheral pulmonary lesion, guide sheath, EBUS is by far the leading cause of cancer death among both men and women;
about 1 out of 4 cancer deaths are from lung cancer. Each year, more people
die of lung cancer than of colon, breast, and prostate cancers combined. One
third of the new lung cancer cases are candidates for surgery, and about half
SC19: INTERVENTIONAL PULMONOLOGY IN DIAGNOSIS AND TREATMENT OF THORACIC
MALIGNANCIES of the rest develops some kind of major airways involvement. This can be
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 endobronchial tumor, extrinsic compression or combined. Besides lung cancer,
metastases from other types of tumors are also candidates for intrabronchial
treatments. There are different methods available for treating endobronchial
SC19.02 INVASIVE STAGING OF LUNG CANCER: EBUS, EUS AND
malignancies, in most of the cases the combination of two or more procedure
BEYOND needed to reach optimal result. To reestablish the airway patency improves
Kazuhiro Yasufuku quality of life, and provides sufficient time to apply different lung cancer
Division of Thoracic Surgery, Toronto General Hospital, Univeristy of Toronto, treatment, chemo, radio and immunotherapy Methods available include
Toronto/ON/Canada mechanical debulking, use of different types of laser, electrocautery,
cryotherapy, intraluminal brachytherapy, argon-plasma coagulation, and
Despite the advances in surgical treatment and multimodality treatment,
microvawe instruments. Different types of silicon and self expandable
lung cancer is still the leading cause of death from malignant disease
metallic stents are useful for keeping the airways open after successful
worldwide. Accurate staging is important not only to determine the prognosis
reopening. Balloon dilatation may help to insert stent to the compressed
but also to decide the most suitable treatment plan. During the staging
airways. The use of locally installed substances like chemo, different
process of non-small cell lung cancer (NSCLC), mediastinal lymph node
angiogenesis inhibitors are in the focus again. With the use of endobronchial
staging is one of the most important factors that affect the patient outcome.
ultrasound the needle can easily be inserted into the peripheral or central
Non-invasive staging such as computed tomography (CT) and positron
tumor, and lymphnodes. Most of the procedures are done under general
emission tomography (PET) indicate size and metabolic activity, respectively.
anesthesia, with the use of rigid bronchoscope. Ideally the bronchoscopist can
However imaging alone is inaccurate and therefore tissue sampling is the
choose from the different methods available, using the best appropriate one
preferred and most reliable. Surgical staging by mediastinoscopy has been
in the given situation. Sufficient training is necessary before starting each
the gold standard for mediastinal lymph node staging but requires general
new method. Simulation, low fidelity models are available to learn without
anesthesia and complications cannot be ignored. Endoscopic ultrasound
having the unnecessary risk in a real case. One has to be prepared for treating
techniques provide a minimally invasive alternative for surgical staging.
different complications, such as heavy bleeding from the tumor, or bleeding
The current available endoscopic ultrasound techniques for mediastinal
caused by the procedure itself. Well trained personnel is a must to start with
staging include transesophageal endoscopic ultrasound guided fine needle
these kind of procedures. Anesthesiologist, assistants trained in endoscopic
aspiration (EUS-FNA) and endobronchial ultrasound guided transbronchial
procedures are essential before starting the procedure.
needle aspiration (EBUS-TBNA). Both procedures can be performed in an
outpatient setting under local anesthesia. EUS-FNA is a sensitive and safe Keywords: lung cancer, bronchoscopy, palliation
method of evaluating the inferior mediastinal nodes (stations 7, 8, and 9)
and some parts of the anterior mediastinal nodes if the lymph nodes are
accessible from the esophagus. However, in spite of the strength of EUS-FNA
for evaluating the inferior mediastinal nodes, its ability to evaluate lesions
anterior to the trachea is limited. On the other hand, EBUS-TBNA has reach SESSION SC20: SMALL IS BEAUTIFUL: IMPACT OF SUR-
to the paratracheal and subcarinal (stations 2R, 2L, 4R, 4L, 7), as well as the
N1 lymph nodes (stations 10, 11, 12). In experienced hands, EBUS can be used
GICAL APPROACH
through the esophagus for a EUS-like approach to the inferior mediastinal TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
lymph nodes. Thus, EUS-FNA and EBUS-TBNA are complementary methods
for lymph node staging in lung cancer and most of the mediastinum and
the hilum can be evaluated with these endoscopic procedures. Aortic nodes SC20.01 MUSCLE-SPARING THORACOTOMY: CAN IT STILL BE
(stations 5 and 6) are exceptions and must be evaluated by surgical methods CONSIDERED A STANDARD?
(anterior mediastinotomy, VATS, thoracotomy). Based on the current Clemens Aigner
evidence, EBUS-TBNA and EUS-FNA presents a minimally invasive endoscopic
Thoracic Surgery, Ruhrlandklinik - University Clinic Essen, Essen/Germany
procedure as an alternative to mediastinoscopy for mediastinal staging of
NSCLC with discrete N2 or N3 lymph node enlargement, provided negative Muscle sparing thoracotomy has been a standard approach in thoracic surgery
results are confirmed by surgical staging. EBUS-TBNA can access all lymph for a long time. Minimal invasive approaches have gained a widespread
nodes accessible by mediastinoscopy as well as hilar (N1) lymph nodes. acceptance recently and were included in the treatment guidelines for early
EUS-FNA has access to the inferior mediastinal lymph nodes not accessible stage NSCLC by several societies. Prospective randomized trials comparing
by mediastinoscopy. EBUS-TBNA and/or EUS-FNA have in fact replaced minimal invasive approaches versus muscle sparing thoracotomy in stage
mediastinoscopy in many patients with diffuse mediastinal adenopathy, I NSCLC have already been performed more than twenty years ago and
where a simple tissue diagnosis is required to determine treatment. When demonstrated equal morbidity and mortality. Nevertheless it took until 2013
combined the techniques offer safe and accurate assessment of mediastinum, that the American College of Chest Physician guidelines recommended a VATS
with accuracy surpassing that of the pervious gold standard – cervical approach for clinical stage I NSCLC over a thoracotomy in experienced centers
mediastinoscopy. EBUS-TBNA and/or EUS-FNA can also be repeated with ease (1). No recommendation is made for more advanced stages. When analyzing
and have been used for mediastinal restaging in patients who underwent national registry data still a high percentage of procedures in performed in
neoadjuvant therapy in preparation for definitive surgical intervention. an open way. This means that in current practice thoracotomy is still used as
Ultrasound image analysis of lymph nodes may assist bronchoscopists a standard approach by many surgeons. Minimal invasive approaches – both
during EBUS-TBNA or EUS-FNA. Standard sonographic classification of lymph videothoracoscopic and robotic – are not different operations but different
nodes can help characterize mediastinal and hilar lymph nodes as benign or approaches towards performing an operation. It has been proven in several
malignant, which may guide the decision on which lymph nodes to sample. studies that in early stage lung cancer minimal invasive approaches in its
Newer imaging technology such as elastography can potentially enhance US various form lead at least to equivalent or even better oncologic outcome
guided image analysis of the lymph nodes. compared to an open approach. Nevertheless in more advanced stages this
proof is lacking. Experienced centers reported individual series of minimal
invasive approaches towards advanced procedures such as sleeve resection,
pneumonectomy, chest wall resection and Pancoast tumor resection. While
SC19: INTERVENTIONAL PULMONOLOGY IN DIAGNOSIS AND TREATMENT OF THORACIC
MALIGNANCIES this is technically feasible no data on long-term outcome of larger patient
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 cohorts are available and an open approach is considered standard in these
cases. Thus for tumors with invasion of hilar structures or sleeve resection
a muscle sparing thoracotomy currently remains a standard approach.
SC19.04 ENDOBRONCHIAL PALLIATION IN THORACIC
Perceived advantages of minimal invasive approaches – VATS as well as RATS
MALIGNANCIES – include less pain, fewer complications, shorter length of stay, faster return
Zsolt Pápai-Székely to normal activity and higher rate of adjuvant chemotherapy compliance.
Pulmonology and Thoracic Oncology, Szent György University Teaching Hospital of There are a few single center studies challenging these assumptions (2,3) as
Fejér County, Székesfehérvár/Hungary well as a recent analysis of Danish national data (4), however the majority
of studies are in favor of minimal invasive approaches. In summary muscle
Lung cancer is the second most common cancer in both men and women In
sparing thoracotomy remains a standard approach for advanced stage
men prostate cancer, while in women breast cancer is more common. About
tumors, whereas early stage lung cancer should be treated minimally invasive
14% of all new cancers are lung cancers. The American Cancer Society’s
in experienced centers.References 1) Detterbeck FC1, Lewis SZ, Diekemper
estimates for lung cancer in the United States for 2016 are: About 224,390
R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and

management of lung cancer, 3rd ed: American College of Chest Physicians VATS technique: a single centre experience. J Thorac Dis 2016;8 (suppl 3):235-
evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):7S- 241
37S. 2) Rizk NP, Ghanie A, Hsu M, Bains MS, Downey RJ, Sarkaria IS, Finley
DJ, Adusumilli PS, Huang J, Sima CS, Burkhalter JE, Park BJ, Rusch VW. A Keywords: VATS, advanced cases, future
prospective trial comparing pain and quality of life measures after anatomic
lung resection using thoracoscopy or thoracotomy. Ann Thorac Surg. 2014
Oct;98(4):1160-6. 3) Kuritzky AM, Aswad BI, Jones RN, Ng T. Lobectomy by
SC20: SMALL IS BEAUTIFUL: IMPACT OF SURGICAL APPROACH
Video-Assisted Thoracic Surgery vs Muscle-Sparing Thoracotomy for Stage TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
I Lung Cancer: A Critical Evaluation of Short- and Long-Term Outcomes. J Am
Coll Surg. 2015 Jun;220(6):1044-53 4) Licht PB, Schytte T, Jakobsen E. Adjuvant
chemotherapy compliance is not superior after thoracoscopic lobectomy. Ann SC20.04 UNIPORTAL VATS
Thorac Surg. 2014 Aug;98(2):411-5 Diego Gonzalez Rivas
Thoracic Surgery and Lung Transplantation, CoruÑa University Hospital, CoruÑa/
Spain
SC20: SMALL IS BEAUTIFUL: IMPACT OF SURGICAL APPROACH Introduction Uniportal video-assisted thoracic surgery (VATS) has been
established as an alternative surgical approach for the treatment of most
intrathoracic conditions. The potential benefits of a better view, anatomic
SC20.02 WHAT HAVE WE ACHIEVED? SHOULD IT BE PERFORMED instrumentation, better cosmesis and potential less postoperative pain
FOR STAGES HIGHER THAN STAGE I DISEASE? and paraesthesia have led this approach to become of increasing interest
worldwide. Performing surgery through a single incision approach represents
Tomasz Grodzki an evolution of VATS to a less invasive approach. The early period of uniportal
Pomeranian Medical University, Department of Thoracic Surgery and VATS development was focused on minor procedures until the second phase
Transplantation, Szczecin/Poland
uniportal VATS started in 2010 with the development of the technique
Since the introduction of the videothoracoscopic anatomical lung resections for major pulmonary resections. The creation of specific uniportal VATS
in the early 90-ties both indications and contraidications for this type of programs in high volume centers like the Shanghai pulmonary hospital
approach have changed dramatically (1,2). There is common agreement that (the biggest thoracic program in the world with more than 8000 major
the oncological principles during surgery for lung cancer have to be the same resections per year) has contributed to spread out the technique to a large
regardless the type of approach: standard, minimally invasive (MIS – VATS number of surgeons from all over the world in a short period of time. Surgical
multiportal or uniportal, intubated or non-intubated) or robotic. It regards technique Uniportal VATS represents a radical change in the approach to
predominantly requirements such like careful and atraumatic dissection, lung resection compared to the conventional three-port VATS. Since the
sufficient free-of-neoplasm margins and proper lymphadenectomy (standard placement of all the surgical instruments and the camera is done through
or extended). Keeping it in mind we have to admit that stage I NSCLC seems the same incision, Uniportal VATS can pose a challenge for both the surgeon
„ideal” indication for MIS, particularly for less experienced surgeons. This and the assistant. The surgeon and the assistant should be positioned in
type of surgery (MIS for stage I) is widely accepted and performed worldwide front of the patient in order to have the same thoracoscopic vision during
in thousands of cases. However, many experienced centers and surgeons all steps of the procedure and experience more coordinated movements.
have moved the borders forward treating more advanced cases by MIS with Even though the field of vision is only obtained through the anterior access
acceptable results regarding complications, mortlity, conversion rate or site, the combined movements of the thoracoscope along the incision will
quality of lymphadenectomy. Gonzalez-Rivas presented the series of 43 create different angles of vision (in this context, a 30 degree thoracoscope
advanced patients (tumors bigger > 5cm, T3 or T4, treated by neoadjuvant is recommended to achieve a panoramic view). The advantage of using the
chemo- or radiotherapy) who were treated by uniportal VATS with good thoracoscope in coordination with the instruments is that the vision is
results comparable with earlier stages (3). Authors stated that „Skilled VATS directed to the target tissue, bringing the instruments to address the target
surgeons can perform 90% or more of their lobctomies thoracoscopically, lesion from a direct, sagittal perspective. Instruments must preferably be
reserving thoracotomy only for huge tumors or complex bronchovascular long and curved to allow the insertion of 3 or 4 instruments simultaneously.
reconstructions”. Large multicenter series of more than 400 advanced cases Optimal exposure of the lung is vital in order to facilitate the dissection of the
treated by VATS approach compared with propensity score matched open structures and to avoid instrument interference. The rule of thumb is that
thoracotomy group with no differences in overall survival was published for any lobectomy, the Uniport is best sited between the mid- and anterior
by Cao et al. (4). According to the VATS Consensus Statement (among 50 axillary lines in the 5th intercostal space. This slightly anterior position takes
international experts to establish a standardized practice of VATS lobectomy advantage of the naturally wider intercostal spaces at the front of the human
after 20 years of clinical experience) eligibility for VATS lobectomy should body. If the wound is sited too high – in the 4th space for an upper lobectomy
include tumors <7cm and N0 or N1 status. Chest wall involvement was – the dissection of the hilar vessels may be easier, but the instruments enter
considered contraindication while centrality of tumour was considered a directly towards the hilum so that there is a smaller angle for the stapler to
relative contraindication when invading hilar structures (5). This important pass without impinging on the structures behind. If the wound is too low,
statement is widely accepted however some surgeons consider it too there may be a good angle for the stapler to pass, but the distance to the
restrictive regarding chest wall invasion. Currently there is a relatively small hilum becomes too great and the arc in which instruments can be placed
(but growing) group of thoracic surgeons who are performing double-sleeve towards the hilum becomes too narrow – leading to more chance of ‘fencing’
(pulmonary vessels and bronchi) and carinal resections by MIS – extremely between the instruments and camera. The incision itself is typically 3-4cm
complex procedures even in open surgery (6). It requires modern instruments, long, although longer incisions can be used (e.g. for an inexperienced surgeon,
sutures and definitely is not a procedure for beginners. Published series are large tumor, thicker chest wall, etc) without any obvious disadvantage to the
small and overall experience is limited but this initial efforts are good example patient. It is helpful to rotate the surgical table away from surgeons during
of the continuos drive of thoracic surgeons community to move indications the hilar dissection and division of structures, and towards the surgeons for
for MIS further and further. Advanced NSCLC cases started to be treated the lymph node dissection. For most of the surgical steps the thoracoscope
by MIS just few years ago and there are no prospective randomised studies is usually placed at the posterior part of the utility incision working with
available in medical literature therefore we cannot definitively compare and the instruments in the anterior part. For lower lobectomies the normal
assess the long term results but keeping in mind that the main oncological sequence of dissection is as follows: inferior pulmonary ligament, inferior
principles should be preserved and remain the same in every type of surgical pulmonary vein, pulmonary artery, bronchus and finally completion of the
approach we can expect comparable and similar results as it was reported in fissure. In case of upper lobectomies, the pulmonary artery is normally
currently published papers. We all know that generally speaking the future is divided first, followed by vein, bronchus and fissure. When the lobectomy
unpredictable but inevitable from the other side. Considering MIS in advanced is completed, the lobe is removed in a protective bag and a systematic lymph
NSCLC cases we can state with just minimal exagerration that the future is node dissection is accomplished. The intercostal spaces are infiltrated with
now. SelectedReferences: 1. Roviaro G, Varoli F, Vergani C et al.: Long term bupivacaine at the end of the surgery under thoracoscopic view. A single-chest
survival after videothoracoscopic lobectomy for stage I lung cancer. Chest tube is placed in the posterior part of the incision. We do not routinely employ
2004;126:725-732 2. Hanna JM, Berry MF, DÀmico TA: Contraindications epidural or paravertebral catheters. Future Recent industry improvements
of videoassisted thracoscopic surgical lobectomy and determinants of such as the specifically designed surgical instrumentation with double
conversion to open. J Thorac Dis 2013;5:182-189 3. Gonzalez-Rivas D, Fieira articulation, improvements in high definition video-camera systems, new
E, Delgado M et al.: Is uniportal thoracoscopic surgery a feasible approach energy devices and more narrower and angulated curved tip staplers have
for advanced stages of NSCLC? J Thorac Dis 2014;6:641-648 4. Cao C, Zhu ZH, made single-port VATS, for major lung resections, easier to adopt and
Yan TD et al.: Videoassisted thoracic surgery versus open thoracotomy for learn than conventional VATS. The demonstrated benefits of geometrical
NSCLC: a propensity score analysis based on a multi-institutional registry. characteristics of the technique enables expert surgeons to perform
Eur J Cardiothorac Surg 2013;44:849-54 5. Yan TD, Cao C, DÀmico TA et al.: complex cases and reconstructive techniques, such as broncho-vascular
Videoassisted thoracoscopic surgery lobectomy at 20 years: a consensus procedures or even carinal resections. The future of the thoracic surgery is
statement. Eur J Cardiothorac Surg 2014;45:633-639 6. Lyscov A, Obukhova based on the evolution of minimally invasive procedures and innovations
T, Ryabova V et al.: Double-sleeve and carinal resections using the uniportal directed towards reducing even more the surgical and anaesthetic trauma.
We can expect more developments of subcostal or embryonic natural orifice
translumenal endoscopic surgery access, evolution in anaesthesia strategies, inhibitors (ICI) directed against the immunosuppressive molecules
and cross-discipline imaging-assisted lesion localization for single-port programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has
VATS procedures. Improvements in anaesthetic techniques such as non- been in clinical trials since 2009. At present, the anti-PD-1 antibodies
intubated or awake uniportal VATS,may further quicken postoperative nivolumab (a fully human IgG4 antibody) and pembrolizumab (an engineered
recovery allowing the tumor resection to be performed in an ambulatory humanized IgG4 antibody) have been approved for NSCLC by different
setting. Furthermore, the need to reduce the risk of intercostal nerve damage regulatory agencies worldwide. EMA approved nivolumab for advanced NSCLC
associated with the transthoracic incision has led to the recent development after prior chemotherapy, and pembrolizumab for advanced NSCLC in adults
of uniportal subxiphoid VATS technique for major pulmomary resections. We whose tumors express PD-L1 and who have received at least one prior
truly believe in the use of the uniportal approach, combined with yet-to-come chemotherapy regimen. At the time of writing of this contribution, there were
3D image systems (adapted on the screen, no glasses) and single port robotic no public randomized study data on the use of these agents in 1st line therapy,
technology and wireless cameras in awake patients. We understand that we will therefore concentrate on the relapse therapy setting. Despite the real
the future goes in the direction of digital technology which will facilitate the progress made by ICI therapy, we must realize that at present only about 20%
adoption of single-port technique worldwide in the next coming years. of the patients respond to single-agent ICI treatment, while 50% have early
progression (Checkmate 017 [3]; Checkmate 057 [4]). Moreover, the cost of
Keywords: Thoracoscopy, lung cancer surgery, uniportal VATS, lobectomy these drugs is considerable. Hence it is important to define optimal
candidates in clinical practice. Elements in this decision are a)
clinicopathological factors; b) possible predictive biomarkers; and c) the
availability of other treatment choices. As for (a) clinicopathological factors,
there is no evidence that age, gender or ethnicity determine activity of ICIs.
Smoking history, on the other hand, is strongly associated with better
SESSION SC21: PREDICTIVE BIOMARKERS FOR OUTCOME response rate to ICI therapy. Although EGFR oncogene pathway activation has
OF SYSTEMIC THERAPY IN NSCLC been linked to upregulation of PD-L1 in tumor cells, response rates to ICIs in
these patients are generally reported to be lower. In e.g. Checkmate 057, the
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 overall response rate was 19%. It was 22% in smokers vs. 9% in non-smokers,
18% in EGFR-wildtype vs. 11% in EGFR-mutant tumors. Further understanding
and refinement of the use of ICIs in tumor with an oncogene driver is needed.
SC21.04 PATIENT-DERIVED XENOGRAFTS FOR GUIDING THERAPY (b) A multitude of potential predictive biomarkers of response to PD-1/PD-L1
OF LUNG CANCER pathway inhibitors have been reported. In particular, PD-L1 expression
Byoung Chul Cho
Medical Oncology, Yonsei Cancer Center, Seoul/Korea, Republic of
Preclinical drug screening and biomarker discovery in the NCI-60 cancer cell
line panel as well as the xenograft developed by growing these cell lines
subcutaneously in immunodeficient mice have repeatedly failed to predict
clinical responses. In an attempt to circumvent the limited predictive values
of conventional preclinical models, there has been increasing attention in
the development and characterization of Patient-derived tumor xenograft
(PDX) models. The PDX models, which were created by direct implantation
of patient’s tumor in immunodeficient mice, have shown to reflect principal
histologic and genetic characteristics of original patient tumors and retain
tumor heterogeneity better than any other preclinical model. These models
have been shown to be predictive of clinical outcomes and are being used for
translational research, preclinical drug screening and biomarker identification
and validation. The PDX model may also be used in the application of ‘co-
clinical trial’ approach, in which it is developed from a patient enrolled in
a clinical trial and treated with the same experimental agents to emulate
clinical response. This strategy permits the assessment of drug response in tumor and/or immune cells, the presence of TILs (tumor-infiltrating
simultaneously in the patient and mouse model, providing an interesting lymphocytes, CD8+ T-cells in particular), and the overall mutational load in the
platform to investigate resistance mechanism, predictive biomarkers and tumor cells have been linked to activity of ICIs [5]. PD-L1 expression on tumor
novel combination strategies in a real-time manner. I will present the utility cells, determined by immunohistochemistry (IHC) staining is by far the one
of PDX models, which faithfully replicated the histologic, genomic and most close to clinical practice for selecting optimal candidates for
pharmacologic features observed in the original patients, and ‘co-clinical immunotherapy. This biomarker is quite distinct and less powerful than e.g.
trial’ that mirror a phase II trial of agents targeting fibroblast growth factor EGFR mutation as predictor of efficacy of EGFR TKIs. EGFR mutation is limited
receptor (FGFR) in non-small cell lung cancer. to the tumor, it is located in a distinct pathway, and is a yes/no phenomenon.
PD-L1 IHC, on the other hand, relates to the tumor and its micro-environment,
Keywords: Predictive biomarker, patient-derived tumor xenograft, co-clinical is only one of the many checkpoints in a complex interaction, and is a gradual
trial phenomenon. Nonetheless, as can be noted from the figure, in most datasets
of phase III studies – except Checkmate 017 – PD-L1 IHC predicts efficacy of ICI
therapy. We added the large phase I study Keynote 001 to the figure as a very
illustrative example: Over the categories of PD-L1 expression, response rate
increased from 8% in the lowest to 45% in the highest category [6]. In the
SESSION SC22: SELECTION AND MONITORING OF PATI- Keynote 010 phase III study, the hazard ratio of OS versus chemotherapy was
ENTS FOR IMMUNE CHECKPOINT INHIBITORS 0.76 in the low-, but 0.54 in the high-expression group [7]. In the Checkmate
057, the OS hazard ratio even was 1.00 in all patients with tumors having PD-L1
<10%. Thus, except for the Checkmate 017 dataset, PD-L1 IHC enriches the
response rate and differential OS benefit vs. chemotherapy, and can be used
to designate these expensive agents to the optimal candidates. (c) Docetaxel
SC22.01 HOW DO I DEFINE OPTIMAL CANDIDATES FOR single-agent chemotherapy was the comparator in the phase III studies on
IMMUNOTHERAPY IN MY PRACTICE? relapse therapy. In the meanwhile, progress has been made in conventional
Johan Vansteenkiste 1, Els Wauters2 relapse therapy as well. In the LUME-Lung 1 trial, the combination of docetaxel
1
Respiratory Oncology Unit (Resp. Medicine), University Hospital KU Leuven, and the triple angiogenesis inhibitor nintedanib resulted in a significantly
Leuven/Belgium, 2Respiratory Oncology (Resp Medicine), University Hospital KU better OS than docetaxel alone – with a difference in median OS of 2.3 months
Leuven, Leuven/Belgium – in patients with adenocarcinoma [8]. In the REVEL study, patients treated
with docetaxel plus ramucirumab, a VEGF receptor 2 inhibiting monoclonal
Over the recent decade, we witnessed important progress in the treatment of antibody, had significantly better OS than those treated with docetaxel alone
patients with advanced NSCLC in three domains. First, cytotoxic across all NSCLC histologies [9]. In conclusion, the choice of ICI therapy for
chemotherapy, where histology-directed chemotherapy with cisplatin- relapsing NSCLC needs to be considered in the available treatment options for
pemetrexed, followed by pemetrexed maintenance therapy in appropriate these patients, and this can be based on clinicopathological factors,
candidates, has resulted in a median overall survival (OS) of 16.9 months in predictive biomarkers, and comparison of efficacy of various treatments in
adenocarcinoma [1]. Second, the use of tyrosine kinase inhibitors (TKIs) in specific subgroups. While PD-L1 is not a biomarker with the strength such as
tumors driven by specific molecular pathways, such as EGFR, ALK and others, e.g. EGFR mutation, it helps to optimize the response rate and differential OS
has largely improved progression-free survival (PFS) compared to the one with benefit of ICI therapy vs. chemotherapy, and to and can be used to designate
chemotherapy in randomized studies, and had led to OS times of several years these expensive agents to the optimal candidates. See Figure below.
in many of these patients [2]. Third, immunotherapy with immune checkpoint

References 1. Paz-Ares LG, De Marinis F, Dediu M et al. PARAMOUNT: Final outpatient and primary care, but also inpatient care and particularly drug
overall survival results of the phase III study of maintenance pemetrexed expenditures. Cancer drug-related health care costs, thus differ between
versus placebo immediately after first-line treatment with pemetrexed plus less than € 10.- per person up to over € 50.- per person. This divergence has
cisplatin for advanced nonsquamous non-small cell lung cancer. J Clin Oncol been described previously and put into context with cancer outcomes (1)
2013; 31: 2895-2902. 2. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or as well as cancer-associated mortality (2). Therefore, the European Society
carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: for Medical Oncology decided to create a magnitude of clinical benefit
947-957. 3. Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus docetaxel scale (ESMO-MCBS) “in order to promote high quality, rational, responsible
in advanced squamous cell non-small cell lung cancer. N Engl J Med 2015; 373: and affordable cancer care wanting to highlight treatments which bring
123-135. 4. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel substantial improvements to the duration of survival and/or the quality of life
in advanced nonsquamous non-small cell lung cancer. N Engl J Med 2015; 373: of cancer patients” (3). It was intended that the scale was used for accelerated
1627-1639. 5. Rizvi NA, Hellmann MD, Snyder A et al. Mutational landscape reimbursement evaluation. Factors taken into account for the ESMO-MCBS
determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science were particularly overall survival and/or progression-free survival as assessed
2015; 348: 124-128. 6. Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for by hazard ratios, quality of life, toxicity of the compound in question and
the treatment of non-small cell lung cancer. N Engl J Med 2015; 372: 2018- the prognosis of the individual condition. Costs were not analysed in view of
2028. 7. Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel their significant heterogeneity across Europe. While generating two different
for previously treated, PD-L1-positive, advanced non-small cell lung cancer scales for the curative versus the non-curative setting, a couple of rules
(KEYNOTE-010): A randomised controlled trial. Lancet 2016; 387: 1540-1550. were followed regarding the performed analyses: the priority was a strong
8. Reck M, Kaiser R, Mellemgaard A et al. Docetaxel plus nintedanib versus level of evidence from large phase III studies with a careful analysis of each
docetaxel plus placebo in patients with previously treated non-small-cell control arm and the identification of endpoints. For the required HR, the
lung cancer (LUME-Lung 1): A phase 3, double-blind, randomised controlled lower limit of the 95% CI was used to take into account the variability of the
trial. Lancet Oncol 2014; 15: 143-155. 9. Garon EB, Ciuleanu TE, Arrieta O et al. estimate. Before being published, the scale and its outcomes were broadly
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line tested and evaluated in and by various institutions. The first full-length field
treatment of stage IV non-small-cell lung cancer after disease progression on testing (FT-MCBS) of the ESMO-MCBS was published recently (4) in which
platinum-based therapy (REVEL): a multicentre, double-blind, randomised the results of non-small cell lung cancer (NSCLC) corresponded well with the
phase 3 trial. Lancet 2014; 384: 665-673. original ESMO-MCBS. Regarding the use of the immune checkpoint inhibitor
Nivolumab, the FT-MCBS generated the highest grade (i.e. “5”) for squamous
Keywords: Real-world practice, Immunotherapy, PD-L1 NSCLC according to data generated within the Checkmate 017-Trial whereas a
grade “4” was given for non-squamous NSCLC, as assessed in the Checkmate
057-Trial. Thus, the immune checkpoint inhibitor Nivolumab has acquired
the highest or almost highest degree in the magnitude of clinical benefit, as
SC22: SELECTION AND MONITORING OF PATIENTS FOR IMMUNE CHECKPOINT
INHIBITORS assessed by the FT-MCBS scale. Soon after market introduction, concerns
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 about the financial toxic dose of immune checkpoint inhibitors emerged
leading to the rejection of NICE of Nivolumab in the second-line-treatment
of NSCLC, whereas – in contrast - the Scottish authorities decided to include
SC22.03 HOW DO I MONITOR FOR AND TREAT IMMUNE-RELATED
Nivolumab into their reimbursement strategies. Very recent analyses on this
EVENTS? very topic showed that Nivolumab was not cost effective versus Docetaxel in
Alexander Spira the second-line-treatment of NSCLC based upon data generated in Checkmate
Virginia Cancer Specialists Research Institute, Virginia Cancer Specialists, Fairfax/ 057-Trial. However, cost effectiveness could be very well reached by including
VA/United States of America and stratifying patients according to PD-L1 testing and the use of Nivolumab
in PD-L1 overexpressing tumors on one side or – in statistical models - by the
Immunotherapy (IT) has become one of the most potent new treatments
reduction of drug costs on the other. Either of these strategies would improve
for all cancers, particularly non small lung cancer. However, it has a unique
the cost effectiveness of Nivolumab (5, 6) Scientifically, however, the doubt
toxicity profile different than most therapies (chemotherapy; biologic;
remains to linger whether PD-L1 would be an optimal biomarker resulting in
targeted therapy) than most oncologists are familiar with, specifically
appropriate decision making for the choice of compound optimally suitable
immune related adverse events; irAE. These toxicities may be acute but also
for the treatment of NSCLC without unjustly excluding patients who might
can occur weeks and months after starting or even stopping therapy. Given
have benefitted due to other factors from treatment: Thus, it is well known
the prolonged duration that patients may be exposed to these drugs, they
that certain somatic mutations occur more frequently in very special tumors
become important to manage over a short and long period. Further, given
than in others (7). Along this line, the efficacy of Nivolumab correlated
the responses and the relative milder toxicity compared with traditional
with higher non-synonymous mutation burden in the Checkmate 063-Trial
chemotherapy agents, the older patient population may be exposed to these
population (8). Therefore, it seems correct to conclude that we still have a long
agents at a somewhat higher frequency. The use of immunomodulatory
way to go to fully understand biomarkers predictive for the outcome of an
drugs to counter irAE toxicity will be discussed as to how it affects efficacy of
optimal treatment of NSCLC with immune checkpoint inhibitors. Accordingly,
immunotherapy. This lecture will focus on:
appropriate analyses necessary for biomarker identification might translate
Timeframe and monitoring for immune related toxicity (with special attention into cost effectiveness. Such analyses might result in a primarily increased
paid towards pulmonary, gastrointestinal and endocrinopathies) using the diagnostic cost, but lead to an ameliorated patient selection and, thus,
appropriate immunosuppressive drugs ameliorated cost effectiveness in the appropriate use of immune checkpoint
inhibitor treatment in NSCLC. In the meantime, the scientific community
Management of toxicities related to IT remains fascinated by the insights and results which are generated by the use
of these compounds in a variety of diseases including NSCLC.References 1.
Decision making on re-exposure to drug after iRAE Jedrzejewski M. et al., The Oncologist 20: 28, 2015; 2. .Ades F. et al., Ann. Oncol.
24: 2897, 2013; 3. N.I. Cherny et al., Ann. Oncol. 26: 1547, 2015; 4. B. Kiesewetter
Patient education
et al., ESMO Open 1: e000066, 2016; 5. K. Matter-Walstra et al., J. Thoracic
Toxicities associated with combination IT drugs that may be used in the future Oncol., 2016, ePub.: http://dx.doi.org/10.1016/j.jtho.2016.05.032; 6. P.N. Aguiar
or on clinical trials et al., J. Clin. Oncol. 34, abstr. 9033, 2016; 7. L.B. Alexandrov et al., Nature. 22:
415, 2013; 8. N.A. Rizvi et al., Science 2015, ePub.: pii:aaa1348
Keywords: Immunotherapy, adverse events
Keywords: Immune Checkpoint Inhibitors, Cost-Effectiveness, Clinical
Benefit, ESMO
SC22: SELECTION AND MONITORING OF PATIENTS FOR IMMUNE CHECKPOINT

INHIBITORS
SC22.04 HOW CAN IMMUNOTHERAPY BE IMPLEMENTED IN A SESSION SC23: THE IMPORTANCE OF CO-OPERATIVE
COST-EFFECTIVE STRATEGY? GROUPS
Christoph Zielinski TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
Department of Medicine I and Comprehensive Cancer Center, Medical University
Vienna, Vienna/Austria
SC23.01 COOPERATIVE GROUPS IN LATIN AMERICA
When talking about immunotherapy and its cost-effectiveness, the
Clarissa Mathias
story of disharmony between the magnitude of clinical benefit and the
cost-effectiveness of certain drugs clearly emerges. I will try to illustrate Medical Oncology, NOB, Salvador/Brazil
this by the following arguments and data: The total health care costs of
More than 100 million people in Latin America will be > 60 years of age by
cancer per person varies widely within EU countries not only concerning
2020. Age, smoke exposure and infectious causes of cancer (HPV, Hepatitis B, research quality and protection of study subjects. Some decades ago, the
and H. pylori) will continue to drive the burden of cancer in the region. Cancer development of global clinical research could have been considered a dream;
mortality rates in Latin America are approximately twice those of the United it is now a pressing need that should be considered unavoidable in the
States (1). Until not so long ago, drug development and cancer clinical research future (2).References: 1 Goss, P; Lee, BL; Badovinac-Crnjevic, T et al. Planning
were conducted almost exclusively in wealthy developed regions of the world. Cancer Control in Latin America and the Caribbean. Lancet Oncol 2013; 14:
However, over the last 2 or 3 decades, clinical trials have been progressively 391–436 2 Barrios, C; Werutsky, G and Martinez-Mesa, J. The Global Conduct
incorporated in a challenging globalization process. As such, the conduct of of Cancer Clinical Trials: Challenges and Opportunities. ASCO Educational
trials in a global scale represents a major aspect to be taken into account when Book, e132- e139, 2015 3 Drain PK, Robine M, Holmes KK, et al. Trail watch:
analyzing the future development of the area. The globalization of clinical global migration of clinical trials. Nat Rev Drug Discov. 2014;13:166-167   4
trials, as well as multinational and multi-institutional research collaboration, Thiers FA, Sinskey AJ, Ernst R. Trends in the globalization of clinical trials.
represents a scenario that requires permanent and concentrated efforts Nature Reviews Drug Discovery. 2008;7:13-14. 5 www.clinicaltrials.gov 6 Kaitin
by all involved if we are to achieve the fundamental objective of generating KI. The Landscape for pharmaceutical innovation: drivers of  cost- effective
the appropriate answers to the health problems we face around the world clinical research. Pharm Outsourcing. 2010;2010:  3605. 7 Rolfo C, Caglevic
(2). Up to the 1980s, North American and European cooperative groups C, Bretel B et al. Cancer clinical research in Latin America: current situation
mostly sponsored by the National Cancer Institute (NCI) conducted most of and opportunities. Expert opinion from the first ESMO workshop on clinical
the pivotal practice changing trials. At that time, a progressive shift in the trials, Lima, 2015. ESMO Open 2016;1 8 Smith WT. FDA requires foreign clinical
funding of research toward pharmaceutical companies was seen. In parallel, studies be in accordance with  good clinical practices to better protect human
an increasing participation of research sites from countries outside North subjects. ABA Health  eSource. 2008; 5:1-3.  
America and Western Europe was identifıed and has since transformed the
development of new medications to what is now an increasingly globalized Keywords: Cooperative Groups, Latin America, research
process (2). The number of registered clinical trials has increased in all
geographic regions during this time period, with the average annual growth
greatest in the Asian (30%) and Latin American/ Caribbean (12%) regions (3).
SC23: THE IMPORTANCE OF CO-OPERATIVE GROUPS
Early trials seem to be conducted more frequently in North America (62%), TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
whereas confırmatory trials are more frequent in Eastern Europe, Latin
America, and Asia (4). Data from ClinicalTrials.gov shows that over 70% of the
registered cancer phase I trials are conducted in the United States, whereas SC23.03 HOW COULD HIGH-VOLUME CENTERS IN DEVELOPING
less than 1% are conducted in Latin America. In larger registered phase III COUNTRIES ACCESS COOPERATIVE GROUP TRIALS?
studies, 40% are conducted in the United States, 43% in Western Europe, Ugur Yılmaz
and 17% in Latin America (5). Involvement of investigators from developing Pulmonary Medicine, Izmir, Dr. Suat Seren Chest Disease and Surgery Training and
countries in the planning phases of the trial is essential as they may provide Research Hospital, Izmir/Turkey
valuable contribution while being exposed to an experience that will have
long lasting effects in the future development of regional studies. Other than Lung cancer has the second highest absolute incidence globally as well as
addressing a question that interests a pharmaceutical company, developing in developing countries and ranks fourth in developed countries. It is the
a reliable research infrastructure and local expertise allow researchers to most common cause of cancer death by absolute cases globally as well as in
expect the development of locally coordinated research addressing pertinent developing and developed regions. The economic burden of lung cancer care
regional health questions benefıting the local community. As quality is a is highest relative to other cancers in the European Union. Research is at the
fundamental principle in the conduct of clinical research, we need to address core of achieving improved outcomes from cancer, be it in defining country-
monitoring, auditing, and inspections as a basic element in the process of specific epidemiology of the disease, understanding the pathogenesis of
globalization. In recent years, a number of independent research groups have disease, identifying new targets for therapeutic agents, or directing policy to
been created in Latin America: achieve affordable and equitable outcomes. Cancer researchs are one of the
most globally active domains of science, with more than $14 billion per annum.
The Chilean Cooperative Group for Oncological Research (Grupo Oncológico A critical part of the health research portfolio is the testing of interventions
Cooperative Chileno de Investigación, or GOCCHI) is a nonprofit corporation through randomized controlled trials. Trials can range from highly controlled
registered in Chile since 1998. GOCCHI is conducting academic clinical trials in explanatory trials through to pragmatic trials of new health technologies
oncology based on the highest scientific, methodologic, and ethical standards and models of service delivery. Recruitment problems also have practical
(http://www.gocchi.org). and financial impacts, as they can delay completion of research or reduce its
timely impact on patient health and wellbeing. Achieving appropriate levels
The Peruvian Oncology Clinical Studies Group (Grupo de Estudios Clínicos of patient and professional participation has been a significant obstacle to
Oncológicos Peruano, or GECOPERU) was founded in March 2005 as a evidence-based practice. Published data show that the minority of trials
nonprofit academic and research organization. It has a central operating recruit successfully, either in terms of reaching their planned sample size, or
office and partnerships with several international groups (CIBOMA, IBCSG, delivering the planned sample in the expected recruitment window Despite
BIG, and others) (http://www.gecoperu.pe). all the diffuculties, clinical trials have become increasingly globalized due to
Founded in 2007, the Argentine Group for Clinical Research in Oncology the inclusion of more non-traditional locations, especially those in central and
(Grupo Argentino de Investigación Clínica en Oncología, or GAICO [is eastern Europe, Latin America, and Asia. The increased globalization of clinical
composed of 15 cooperating groups and includes various health professionals research has arisen for several reasons, but primarily due to the need for
from public and private institutions (www.gaico.org.ar). faster and more economically efficient studies. Moves towards standardizing
and harmonizing clinical research practices have facilitated the rise of
The Latin American Cooperative Oncology Group (LACOG) was founded in globalized clinical research. However, the expansion of multinational clinical
2008 by medical oncologists from several Latin American countries that research peaked in 2009, which could reflect that the large-scale expansion
has developed a network of investigators in oncology for epidemiologic and of multinational clinical research effort has reached its global capacity.
clinical studies in cancer. LACOG has 47 members in 39 sites from 10 countries When the distribution of multinational clinical trials is examined after being
in the region. Currently, the group has several ongoing studies. The Brazilian stratified according to the condition or disease, lung cancer is not among
Group of Thoracic Oncology (GBOT) is currently hosted at LACOG and is the five most frequently studied conditions apart from Asia. The results of a
involved in some research initiatives (www.lacog.org.br) (www.gbot.med.br). bibliometric analysis of global research on lung cancer between 2004-2013 in
the 24 leading countries in cancer research showed that despite a doubling
CLICaP (Latin American Consortium for Lung Cancer Research) This of the volume of lung cancer research worldwide between 2004 and 2013,
consortium was created in 2010 to develop collaborative studies on the it still only accounts for a small proportion of the overall oncology research
biology, diagnosis and treatment of lung cancer. CLICaP has published over 20 publication output (5.6%). In fact, the relative commitment (RC) to lung
studies involving participants from Mexico, Costa Rica, Panama, Venezuela, cancer research compared with that to total oncology research output has
Colombia, Ecuador, Peru, Chile, Argentina and Uruguay. Some of this work has fallen in most countries during this period, including in the 23 countries with
established genomic differences between populations for mutations in EGFR, exception of the China. Turkey, Poland, Canada, Greece, and the United States,
KRAS and ALK ROS1 following analysis of over 8500 samples (7). despite having the highest country-specific burden of lung cancer, have all
seen a decrease in their RC to lung cancer research. Research from Norway,
There are several challenges of research in South America including costs
Austria, Switzerland, Belgium, and Sweden had the highest proportion of
(6), regulatory issues and difficulty in recruitment but there also several
international contributors . By comparison, relative to their research output,
advantages of performing trials in developing countries such as availability
the East Asian countries (Taiwan, India, the Republic of Korea, and Japan)
of patients, lower costs and faster accrual. As an added and very important
and Turkey had the least amount of international collaboration. With regard
characteristic, patients enrolled in developing countries are more frequently
to multinational studies, only 1.2% of articles had collaborators from five or
treatment-naive and have less, or many times, no competing trials as
more countries and 0.3% from 10 or more countries. The aim of co-operative
alternative (8) As more trials are conducted in resource-limited settings,
groups in oncology is to perform multi-center clinical trials for cancer
good clinical practices and ethical assurances must be secured. Human
research. Research results are often conveyed to the worldwide medical
participation in clinical research is essential to advance medicine and public
community through scientific publications. In order to complete the trials
health, and expanding clinical trials mandates constant oversight to ensure
within the period specified, it is obvious the need of the qualified and high-

volume cancer centers. The barriers to participation of high-volume hospitals modalities. Take CTONG 0802 study (OPTIMAL) for example, the multicenter
in the cooperative group trials should be determined and eliminated. Since the open-label randomized phase II study compared erlotinib with combination
1970s, centers for thoracic diseases that emerged from former tuberculosis of gemcitabine and cisplatin in first-line treatment of patients with EGFR
hospitals, particularly in Europe, have focused on the diagnosis and treatment mutation-positive NSCLC1, Median progression-free survival was significantly
of patients with lung cancer. Traditionally, these centers were staffed by longer in erlotinib-treated patients than in those on chemotherapy (13.1
pulmonologists and thoracic surgeons, but now include an extended range of [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI
health care workers including the disciplines of radiation oncology, medical 0.10-0.26; p<0.0001). Chemotherapy was associated with more grade 3 or
oncology, palliative care and rehabilitation medicine. These high-volume 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72
centers treat all aspects of problems affecting patients with lung cancer. In patients and thrombocytopenia in 29 [40%] patients on chemotherapy vs
2010, the hospitals with a median 400 new patients per year were in Albania, no patients with either event on erlotinib), which suggested that erlotinib
Belarus, Bulgaria, the Czech Republic, Poland, Romania and Slovenia. The is important for first-line treatment of patients with advanced EGFR
hospitals with more than 1000 new patients with lung cancer per year were mutation-positive NSCLC. The results of CTONG0802 was orally presented
in Poland, Bulgaria, Croatia, Turkey. We have to foster the cooperative study on ESMO2010, WCLC 2011, discussed on ASCO 2011 and published on Lancet
groups in lung cancer to provide collaboration between study group and these Oncology. CTONG 0901 study compared erlotinib with gefitinib in patients
hospitals. High-volume hospitals should be identified and hospital-based with EGFR mutation positive stage IIIb/IV NSCLC and found no PFS or OS
representatives should be determined. Supreme organisations as European difference between these two regimens which offered solid evidence for
Thoracic Oncology Platform providing collaboration among study groups clinical choice2. CTONG also paid attention to first-line maintenance therapy,
and hospitals, should be able to invite the high-volume hospitals with site second-line treatment, Another well-known study of CTONG is FASTACT-II
evaluation. These high-volume centers have to review whether adequately (CTONG0902) proved that erlotinib maintenance therapy after first-line
equipped and set up or not for participation in research projects and clinical gemcitabine combined with cisplatin improves overall survival of stage IIIB/
trials.References 1- Gaga M. An Official American Thoracic Society/European IV NSCLC patients3. CTONG 0806 study suggested improvement in PFS and an
Respiratory Society Statement: The role of the pulmonologist in the diagnosis improved OS trend with pemetrexed compared with gefitinib as second-line
and management of lung cancer. Am J Respir Crit Care Med 2013; 188(4): 503-7. setting treatment of EGFR wild-type advanced non-squamous NSCLC 4. There
2- Blum T. G. The European initiative for quality management in lung cancer were also many studies focused on palliative treatment, brain metastasis
care. Eur Respir J. 2014; 43: 1254-77 3- Loddenkemper R, 100 years DGP-100 and peri-operative treatments and achieved meaningful results in these
years of pneumology in Germany. Pneumologie 2010; 64:7-17. 4- Richter TA. fields. Additionally, CTONG has initiated the very first real-world study in
Clinical research: A globalized network. PLoS ONE 2014; 9(12): 1-12 5- Aggarwal China targeting 1st line treatment pattern of advanced non-squamous NSCLC
A. The state of lung cancer research: A global analysis. J Thorac Oncol 2016; patients, the study concern difference between scientific achievements
11(7): 1040-50 and clinical practice in China and set a great beginning of caring for patients’
actual profits. The currently ongoing reform for new drug approval of CFDA
Keywords: clinical trial, lung cancer, study groups provides great chances for the development of clinical trials in China and
domestic drug innovation such as icotinib and apatinib. CTONG and other
study groups also face more opportunities. CTONG, as the successful example
of CSCO study groups, is expected to make more contributions to china lung
SC23: THE IMPORTANCE OF CO-OPERATIVE GROUPS
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 cancer treatment. Hopefully, CSCO achievements will finally benefit more
Chinese cancer patients and make more contribution to world cancer control.
Reference: 1. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy
SC23.04 COOPERATIVE GROUPS IN CHINA: THE CSCO EXPERIENCE as first-line treatment for patients with advanced EGFR mutation-positive
Qing Zhou non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-
Guangdong Lung Cancer Institute; Guangdong General Hospital (GGH)& label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735-742. 2.
Guangdong Academy of Medical Sciences, Guangzhou/China Yang JJ, Zhou Q, Yan HH, et al. A Randomized Controlled Trial of Erlotinib
versus Gefitinib in Advanced Non-Small-Cell Lung Cancer Harboring EGFR
In order to keep up with the rapid development of world cancer treatment Mutations (CTONG0901). J Thorac Oncol 2015;10(2), S321(ABSTRACT MINI
exploring, Chinese clinical oncology professionals, relevant enterprises and 16.03) 3. Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of
public institutions voluntarily constituted a non-profit professional academic chemotherapy and erlotinib for patients with advanced stage non-small-cell
group which is known as The Chinese Society of Clinical Oncology (CSCO) in lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol.
April 1997. The CSCO organization not only pay attention to international 2013 Jul;14(8):777-86. 4. Zhou Q, Cheng Y, Yang JJ, et al. Pemetrexed versus
collaboration such as establishing reciprocal memberships with American gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell
Society of Clinical Oncology (ASCO) , European Society for Medical Oncology lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter
(ESMO), Clinical Oncological Society of Australia (COSA) and participating randomized trial. Ann Oncol. 2014 ;25(12):2385-2391.
rotation of presidency organization of Asia Clinical Oncology Society (ACOS),
but also committed to Chinese Oncology development. The CSCO annual Keywords: Chinese Thoracic Oncology Group (CTONG), Cooperative Groups,
meeting delivered the latest advancements and research fruit from home and Chinese Society of Clinical Oncology (CSCO)
abroad which offered a great academic exchange platform for vast amount
of Chinese oncologists. CSCO also organize experts to make tumor diagnosis
and treatment standardized guideline. Up to date, CSCO has launched
dozens of guidelines regarding many major cancers in china, including non-
small cell lung cancer, colorectal cancer and hepatocellular carcinoma. The SESSION SC24: MANAGEMENT OF INDETERMINATE PUL-
newly made guideline about non-small cell lung cancer has fully considered
MONARY NODULES
Chinese special situation, not only disease characteristics, but also social
economic factors, which made a good example of better suiting Chinese WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
oncologists and patients. Other than this, CSCO developed multi-center
clinical researches which offered solid evidence for Chinese cancer patients
and made contribution to world cancer diagnosis and treatment. Most of SC24.01 RISK ASSESSMENT IN THE MANAGEMENT OF PULMONARY
clinical researches were carried out by Study Group majored in different NODULES
cancers, such as Chinese Thoracic Oncology Group (CTONG), Chinese Breast Satoshi Shiono 1, Naoki Yanagawa2
Cancer Study Group (CBCSG) and Chinese Gastrointestinal Oncology Group 1
Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata/Japan,
(CGOG). The CSCO also keeps an open mind and follows the trend of hot 2
Pathology, Yamagata Prefectural Central Hospital, Yamagata/Japan
spot, such as building expert committee on cancer biomarkers and precise
medicine, even making consensus on standard of driver gene mutation test, Background: Solitary pulmonary nodules are seen on approximately 0.1% of all
standard of operation procedure and so on. Of all the Study Groups in CSCO, chest X-ray films.1 High-resolution computed tomography (HRCT), which is
CTONG is the most active and fruitful committee. CTONG is also the most used in lung cancer screening programs, can detect pulmonary nodules that
active organization in lung cancer field in China. Through the great effort of are smaller than those detected by conventional radiography. The radiological
four top experts majored in lung cancer (Yi-Long Wu, Li Zhang, Shun Lu and diagnosis and treatment of these small pulmonary nodules are now the focus
Cai-Cun Zhou), CTONG was successfully established in 2007. With the goal of lung cancer research. The timely detection of lung cancers is essential for
of designing and developing multi-center clinical trials in the field of chest successful treatment. The guidelines and recommendations for the
tumor, especially for lung cancer, providing high level of evidence for clinical management of pulmonary nodules include follow up, nonsurgical biopsy, or
practice of thoracic tumor, promoting standardization, modernization and surgery; and are based on the size of the nodule, and ground glass opacity
internationalization of clinical and research work in thoracic tumor area and (GGO) ratio or size of the solid component.2-4 Diagnosis: The diagnosis of a
finally improving the level of diagnosis and treatment of chest tumor in China, pulmonary nodule is frequently problematic. The management of pulmonary
as well as international status, CTONG has actually made massive efforts and nodules is based on their characteristics. When a pulmonary nodule is
achieved great success. Up to date, CTONG has 31 members from 15 provinces monitored by CT, the important features include not only its size but also its
and municipality cities and has successfully performed 47 clinical trials in density. According to the guidelines of the American College of Chest
China. Half of these clinical trials established China lung cancer treatment Physicians, solid nodules measuring > 8 mm in diameter need further
examination.3 The Fleischner Society for Thoracic Imaging and Diagnosis uses Figure 2.
a cutoff diameter of 5 mm for decision making for subsolid nodules.2 It should
be kept in mind that solid nodules that are suspicious for lung cancer are
frequently invasive. A subsolid nodule can be classified as a pure ground glass
nodule (GGN) or part-solid nodule. Subsolid nodules grow slowly and may
develop a solid component. The HRCT findings of early lung adenocarcinomas
were significantly correlated with the histopathologic findings of the
resected specimens.5 In the evaluation of subsolid nodules, the features
indicating noninvasive lung adenocarcinoma include tumor disappearance
rate, diameter of consolidation, and GGO ratio.6 However, even HRCT cannot
accurately assess the areas of solid opacities or GGO, and results might vary
between investigators. In the upcoming 8th TNM classification, the Lung
Cancer Staging Project of the International Association for the Study of Lung
Cancer showed that the solid part of a nodule on HRCT represents the clinical
T factor, and that measurement of the solid part is essential for lung cancer
staging.5 Positron emission tomography (PET)-CT has a clearly established
References 1. Ost D, Fein AM, Feinsilver SH. The solitary pulmonary nodule.
role in lung cancer clinical practice. Based on the pretest probability, PET-CT
N Engl J Med 2003;348:2535-42. 2. Naidich D, Bankier AA, MacMahon H,
should be used for patients with a solid, indeterminate nodule > 8 mm in
Schaefer-Prokop CM, Pistolesi M, Goo JM, et al. Recommendations for the
size.3,4 For adenocarcinomas in situ (AIS) and minimally invasive
management of subsolid pulmonary nodules detected at CT: A statement
adenocarcinomas (MIA) of the lung that show solid opacities on HRCT, the
from the Fleischner Society. Radiology 2013;266:304-17. 3. Gould MK,
preoperative PET-CT and thin-section CT findings together can provide
Donington J, Lunch WR, Mazzone PJ, Midthun DE, Naidich DP, et al. Evaluation
information on the aggressiveness of the tumor. Our study group found that
of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and
these modalities used together could detect aggressive lung cancers in clinical
management of lung cancer 3rd ed: American College of Chest Physicians
stage IA (Fig. 1).7 However, since PET-CT can show false-negative results for
evidence-based clinical practice guidelines. Chest 2013;143:e93s-120s.
slow-growing and low-grade lung malignancies, we think that HRCT is the best
4. National Comprehensive Cancer Network. Guidelines for surveillance
modality for identifying indolent lung cancers. Transthoracic biopsy,
following therapy for non-small cell lung cancer Ver 4.2016. Available at: www.
bronchoscopy, or surgery is used for obtaining specimens for
nccn.com. 5. Travis WD, Asamura H, Bankier AA, Beaseley MB, Detterbeck
histopathological diagnosis. The definitive diagnosis of small pulmonary
F, Flieder DB, et al. The IASLC Lung Cancer Staging Project: Proposals for
nodules, especially GGO-dominant nodules, is challenging. The diagnostic
coding T categories for subsolid nodules and assessment of tumor size in
yields of percutaneous CT-guided fine needle aspiration biopsy for GGO-
part-solid tumors in the forthcoming eighth edition of the TNM classification
dominant and solid-dominant lesions were 51.2% and 75.6%, respectively (p =
of lung cancer. J Thorac Oncol 2016;11:1204-23. 6. Suzuki K, Koike T, Asakawa
0.018).9 The diagnostic yield of GGO-dominant lesions < 10 mm was 35.2%.
T, Kusumot M, Asamura H, Nagai K, et al. A prospective radiological study of
Since invasive biopsy is not without risk, a histopathological diagnosis should
thin-section computed tomography to predict pathological noninvasiveness
be limited to nonsurgical candidates. For cases with high likelihood of lung
in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J
cancer, a surgical biopsy followed by lung resection might be warranted.
Thorac Oncol 2011;6:751-6. 7. Shiono S, Yanagawa N, Abiko M, Sato T. Detection
Although surgery might be performed on patients with benign nodules, it
of non-aggressive stage IA lung cancer using chest computed tomography and
does provide the definitive diagnosis. If surgery is performed after careful
positron emission tomography/computed tomography. Interact Cardiovasc
preoperative assessment, the surgical mortality is very low, and the surgical
Thorac Surg. 2014;21:637-43. 8. Nakamura K, Saji H, Nakajima R, Okada
risk may be acceptable. Treatment: While lobectomy is the standard
M, Asamura H, Shibata T et al. A phase III randomized trial of lobectomy
procedure for lung cancers, sublobar resection, meaning segmentectomy or
versus limited resection for smallsized peripheral non-small cell lung cancer
wedge resection, might be justified for patients with noninvasive small lung
(JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271–4. 9. Shimizu K, Ikeda N,
cancers. However, to date, which procedure, sublobar resection or lobectomy,
Tsuboi M, Hirano T, Kato H. Percutaneous CT-guided fine needle aspiration for
provides a better outcome remains unclear in these cases, since prospective
lung cancer smaller than 2 cm and revealed by ground-glass opacity at CT. Lung
randomized control trials are ongoing (JCOG0802/WJOG4607L 8 and
Cancer 2006;51:173-9. 10. Shiono S, Yanagawa N. Spread through air spaces
CALGB140503). One of the concerns in sublobar resection is recurrence at the
is a predictive factor of recurrence and a prognostic factor in stage I lung
surgical margin (Fig. 2). Recurrence at the surgical margin might be accounted
adenocarcinoma. Interact Cardiovasc Thorac Surg. 2016 Jun 26. pii: ivw211.
for by tumor cells spreading via air spaces.10 Accurate intraoperative cytology
and adequate surgical margins have been reported to be important for Keywords: pulmonary nodules, computed tomography, sublobar resection,
preventing recurrence at the surgical margin. Another concern is lymph node lung cancer
metastasis. In a prospective radiological study for clinical stage IA lung cancer,
47 of 545 (8.6%) patients had lymph node metastasis.6 Sublobar resection,
especially wedge resection, dose not allow evaluation of lymph nodes for
metastatic disease. Conclusion: HRCT findings play an important role in SC24: MANAGEMENT OF INDETERMINATE PULMONARY NODULES
discriminating the biological behaviors of pulmonary nodules. The definitive
diagnosis by HRCT can be difficult, and the combination of HRCT and PET-CT
might be beneficial. Randomized control trials should clarify the role of SC24.02 RADIOLOGICAL TECHNIQUES FOR THE EVALUATION OF
sublobar resection in treating patients with noninvasive lung cancer. Figure 1. PULMONARY NODULES
Reginald Munden
Radiologic Sciences, Wake Forest Baptist Medical Center, Winston-Salem/NC/
United States of America
Radiologic Techniques for the Evaluation of Pulmonary Nodules The incidental

detection of pulmonary nodules has increased with improved CT technology
and thin section imaging techniques1,2. Adding to this increased detection of
nodules is the heightened interest in the purposeful search for nodules such
as in oncology patients and lung cancer screening programs. The management
of CT detected nodules is a subject of much debate and dependent upon the
clinical setting. For instance, in a lung cancer screening setting, there has
been a large volume of investigation of solid, semi-solid and ground glass
nodules that is the foundation of management recommendations such as
LungRads3. In patients with a known malignancy, there is minimal literature
on management recommendations and thus more influenced by pulmonary
metastatic potential of the malignancy and clinician experience4. Finally
incidentally detected nodule management is greatly influenced by cancer
risk factors and nodule texture; for these situations, the Fleischner criteria
have been the most widely used and accepted management guidelines5. The
radiologic evaluation of nodules most often utilizes conventional imaging
techniques of chest radiographs, computed tomography (CT), PET/CT.
Occasionally MRI and ultrasound may be employed. Most recent changes
involve risk stratification, computer software applications to enhance nodule
analysis such as nodule enhancement patterns, volumetric computations,
and texture analysis6-8. Future directions include incorporation of genomics
into imaging as well as radiomic analysis and machine learning9,10. This

presentation will review the highlights of the radiologic methods for (HR 0.68, 95% CI 0.50 – 0.93 p=0.015), with median OS increasing from 17.7 to
evaluating pulmonary nodules with a focus on current guidelines and future 24.3 months. Bevacizumab has also been evaluated in the second line setting
directions. Reference: 1. Frank L, Quint LE. Chest CT incidentalomas: thyroid in combination with erlotinib (in patients unselected for EGFR mutations),
lesions, enlarged mediastinal lymph nodes, and lung nodules. Cancer imaging : without significant impact on overall survival in the BeTa study5.
the official publication of the International Cancer Imaging Society 2012;12:41- Ramucirumab is a monoclonal antibody directed against the VEGFR2 receptor.
8. 2. Jacobs PC, Mali WP, Grobbee DE, van der Graaf Y. Prevalence of incidental It has been evaluated in a randomised trial in the second line setting. Patients
findings in computed tomographic screening of the chest: a systematic were randomised to receive treatment with docetaxel with or without
review. Journal of computer assisted tomography 2008;32:214-21. 3. Lung CT ramucirumab6. Treatment was continued till progression, with monotherapy
Screening Reporting and Data Systen (Lung-RADS). 2014. (Accessed March ramucirumab continued if toxicity developed to docetaxel (and vice versa).
27, 2015, at www.acr.org/Quality-Safety/Resources/LungRADS ) 4. Munden The primary endpoint of the study was overall survival, and the results
RF, Erasmus JJ, Wahba H, Fineberg NS. Follow-up of small (4 mm or less) indicated an improvement in overall survival for patients receiving
incidentally detected nodules by computed tomography in oncology patients: ramucirumab (HR 0.86, 95% CI 0.75 – 0.98; p=0.023), with median survival
a retrospective review. J Thorac Oncol 2010;5:1958-62. 5. McMahon PM, Meza increasing from 9.1 to 10.5 months. By contrast to the various studies of
R, Plevritis SK, et al. Comparing benefits from many possible computed bevacizumab, this study included patients with squamous cell cancer, as well
tomography lung cancer screening programs: extrapolating from the National as those with non-squamous tumours, with the magnitude of benefit being
Lung Screening Trial using comparative modeling. PloS one 2014;9:e99978. similar in both histologic types. Addition of ramucirumab resulted in an
6. McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of cancer in increase in toxicity, with more hypertension, bleeding, and febrile
pulmonary nodules detected on first screening CT. N Engl J Med 2013;369:910- neutropenia. However the rate of serious adverse events and of deaths due to
9. 7. Revel MP, Merlin A, Peyrard S, et al. Software volumetric evaluation adverse events were similar between the two study arms. The results of this
of doubling times for differentiating benign versus malignant pulmonary study led to the approval of ramucirumab for patients with previously treated
nodules. AJR Am J Roentgenol 2006;187:135-42. 8. Talwar A, Gleeson FV, in NSCLC in some parts of the world, including the USA and Europe. However,
Rahman NM, Pickup L, Gooding M, Kadir T. A Review Of The Use Of Computer subsequently, the results of trials of immune checkpoint inhibitors in the
Aided Texture Analysis For Pulmonary Nodules Classification. American same patient population has resulted in many of these patients not receiving
journal of respiratory and critical care medicine 2015;191. 9. El-Zein RA, Lopez docetaxel chemotherapy, making it difficult to assess the appropriate role for
MS, D’Amelio AM, Jr., et al. The cytokinesis-blocked micronucleus assay as this agent. The addition of a tyrosine kinase inhibitor to chemotherapy has
a strong predictor of lung cancer: extension of a lung cancer risk prediction been evaluated extensively in patients with advanced NSCLC in both the first
model. Cancer epidemiology, biomarkers & prevention : a publication of the and second line settings. The results of these trials have been disappointing,
American Association for Cancer Research, cosponsored by the American with none of them demonstrating an overall survival benefit. Many, however,
Society of Preventive Oncology 2014;23:2462-70. 10. Gillies RJ, Kinahan PE, did show some improvement in progression free survival. Only one of these
Hricak H. Radiomics: Images Are More than Pictures, They Are Data. Radiology agents, nintedanib, is approved (in Europe) for the treatment of patients with
2016;278:563-77. NSCLC. This is based on the results of the LUME-1 study, which compared
treatment with docetaxel alone with docetaxel plus nintedanib in patients
Keywords: Radiomics, Incidental, nodules, CT with previously treated NSCLC7. In this study, progression free survival (the
primary endpoint) was longer with the addition of nintedanib (3.4 vs. 2.7
months, HR 0.79, 95% CI 0.68 – 0.92; p=0.0019). Although there was no
SESSION SC26: ANGIOGENESIS INHIBITION: ADVANCES & difference in overall survival in the whole study population, in the predefined
subset of patients with adenocarcinoma and progression within 9 months of
PERSPECTIVES
initial therapy median overall survival increased from 7.9 to 10.9 months (HR
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 0.75, 95% CI 0.60 – 0.92; p=0.007). Similar, though less extreme results
occurred in all patients with adenocarcinoma. There was no effect on survival
of patients with squamous histology. The combination resulted in an increase
SC26.02 ANGIOGENESIS INHIBITION IN LUNG CANCER: RECENT in the rate of adverse events, predominantly diarrhoea, liver function
ADVANCES AND PERSPECTIVES abnormalities and vomiting. To date, no biomarker of angiogenesis that allows
Michael Boyer the selection of patients for treatment with has been identified. As a
Department of Medical Oncology, Chris O’Brien Lifehouse, Camperdown/NSW/ consequence, patient selection (for bevacizumab) is based on the avoidance
Australia of toxicity, by excluding groups of patients known to be at higher risk (e.g.
those with squamous cell histology, or a history of haemoptysis). Furthermore
Angiogenesis is an important process in the development and progression of the inability to identify those patients most likely to benefit, along with the
tumours. Across a range of tumour types markers of angiogenesis, such as relatively small improvements in survival means that from an economic
elevated VEGF levels or increased micro vessel density, have been shown to be viewpoint, the cost per life year gained is high. This has resulted in
associated with poorer patient outcomes. The recognition that VEGF antiangiogenics not being widely used in some countries.References 1.
mediated signalling is a key driver of angiogenesis within tumours led to the Paclitaxel Carboplatin alone or with bevacizumab for non-small-cell lung
development of a range of anti-angiogenic approaches targeting this cancer. Sandler et al. N Engl J Med 2006; 355: 2542 – 2550 2. Phase III trial of
biological process. These approaches have included monoclonal antibodies cisplatin plus gemcitabine with either placebo or bevacizumab as first-line
(bevacizumab, ramucirumab), decoy receptors (aflibercept), and receptor therapy for non-squamous non-small-cell lung caner: AVAiL. Reck et al. J Clin
tyrosine kinase inhibitors (nintedanib, sorafenib, sunitinib, motesanib, Oncol 2009; 27: 1227 – 1234 3.Systematic review and meta-analysis of
vandetanib, cediranib, pazopanib), all of which have been evaluated in lung randomised, phase II/III trials adding bevacizumab to platinum based
cancer. Despite this volume of clinical research, only three of these agents chemotherapy as first-line treatment in patients with advanced non-small cell
have been shown to produce benefit in patients with advanced non-small cell lung cancer. Soria et al. Ann Oncol 2013; 24: 20 – 30. 4. BEYOND: A randomized,
lung cancer (NSCLC): bevacizumab, ramucirumab and nintedanib. No double-blind, placebo-controlled, multicentre phase III study of first-line
antiangiogenic agent has to date been shown to be of benefit in small cell lung carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with
cancer. Bevacizumab, an anti-VEGF monoclonal antibody, was the first advanced or recurrent non-squamous non-cell lung cancer. Zhou et al. J Clin
antiangiogenic therapy to be evaluated in NSCLC. Early studies identified that Oncol 2015; 33: 2197 – 2204 5. Efficacy of bevacizumab plus erlotinib versus
patients with squamous cancers were at risk of increased toxicity due to erlotinib alone in advanced non-small-cell lung cancer after failure of standard
haemorrhage so randomised trials have been restricted to patients with first-line chemotherapy (BeTa): a double-blind placebo-controlled phase 3
non-squamous tumours. The ECOG 4599 randomized trial evaluated trial. Herbst et al. Lancet 2011; 377: 1846 – 1854 6. Ramucirumab plus docetaxel
treatment with carboplatin and paclitaxel with or without bevacizumab1. In versus placebo plus docetaxel for second-line treatment of stage IV
this study, as in most other studies of antiangiogenics, bevacizumab was non-small-cell lung cancer after disease progression on platinum-based
continued in a maintenance phase following the conclusion of chemotherapy. therapy (REVEL): a multicentre double-blind randomised phase 3 trial. Lancet
The study demonstrated an improvement in overall survival (HR 0.79, 95% CI 2014; 384: 665 – 673 7. Docetaxel plus nintedanib versus docetaxel plus
0.67 – 0.92 p = 0.003). A second phase 3 study, AVAiL, evaluated the addition of placebo in patients with previously treated non-small-cell lung cancer
two different doses of bevacizumab to the combination of gemcitabine and (LUME-1): a phase 3 double blind , randomised controlled trial. Reck et al.
cisplatin, in a double blind manner2. The study demonstrated an improvement Lancet Oncol 2014; 15: 143- 155
in progression free survival, but with no difference in overall survival. Based
on the results of these two trials, bevacizumab received approval in several Keywords: angiogenesis
jurisdictions, but there remained some doubts over the benefit to patients
given the lack of a confirmatory trial showing improved overall survival. A
recent meta-analysis3 incorporating these and other randomised studies has
SC26: ANGIOGENESIS INHIBITION: ADVANCES & PERSPECTIVES
shown that bevacizumab produces a modest, but statistically significant WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
improvement in overall survival (HR 0.90, 95% CI 0.81 – 0.99; p=0.03).
Subsequently, a further randomised trial, BEYOND4, has been published, with
bevacizumab added to the combination of carboplatin and paclitaxel in a SC26.03 PREDICTIVE BIOMARKERS FOR ANGIOGENESIS
purely Asian population. This trial showed an improvement in overall survival INHIBITORS: AN UPDATE
Martin Reck agents, resulting in significantly improved survival of patients with lung
Lungen Clinic Grosshansdorf, Großhansdorf/Germany cancer.2Parallel to the progress in lung cancer treatment, imaging techniques
aiming at improving diagnosis, staging, response evaluation, and detection of
The concept of tumor-induced neoangiogenesis has been shown to be a tumour recurrence have also considerably advanced in recent years.3However,
relevant factor for tumor proliferation and metastasis already a couple of standard morphologic computed tomography (CT) and magnetic resonance
years ago (1). Therefore interaction with proangiogenic pathways appears imaging (MRI) as well as fluor-18-fluorodeoxyglucose (18F-FDG) positron
to be a promising therapeutic target across several solide tumors. In eligible emission tomography CT (PET-CT) are still the currently most frequently
patients with advanced non-squamous NSCLC the addition of the anti utilized imaging modalities in clinical practice and most clinical trials.4,5Novel
vascular endothelial growth factor (anti VEGF) antibody bevacizumab state-of-the-art functional imaging techniques such as dual-energy CT
to platinum based chemotherapy has shown consistent improvement of (DECT), dynamic contrast enhanced CT (DCE-CT), diffusion weighted MRI
response, progression free survival (PFS) and overall survival. However (DW-MRI), perfusion MRI, and PET-CT with more specific tracers that visualize
also the combination did increase the incidence of characteristic adverse angiogenesis, tumour oxygenation or tumour cell proliferation have not yet
events like hypertension, arterial and venous vascular events, bleeding been broadly implemented, neither in clinical practice nor in phase I–III clinical
events, proteinuria and other (2). Recently two large randomised phase trials 6. In this context, Nishino et al.4 published an article on personalized
III trials revealed a significant increase in efficacy by the combination of tumour response assessment in the era of molecular treatment in oncology.
antiangiogenic agents and chemotherapy in pretreated patients with The authors showed that the concept of personalized medicine with regard
advanced NSCLC. In the LUME 1 trial the combination of the oral angiokinase to cancer treatment has been well applied in therapeutic decision-making
inhibitor nintedanib and docetaxel revealed a significant improvement of and patient management in clinical oncology. With regard to imaging
PFS (median PFS 3.4 vs 2.7 months, HR 0.79, 95% CI 0.68-0.92) and OS in techniques, however, it was criticized that the developments in tumour
patients with adenocarcinoma histology (median OS 12.6 vs 10.3 months, HR response assessment that should parallel the advances in cancer treatment
0.82, 95% CI 0.7-0.99) compared to docetaxel (3). The combination of the anti are not sufficient to produce state-of-the-art functional information that
VEGF receptor 2 antibody ramucirumab and docetaxel did show a significant directly reflect treatment targets. Functional information on tumour
improvement of response (response rate: 23% versus 14%, p<0.0001), PFS response is highly required because there is growing evidence that the
(median PFS 4.5 versus 3.0 months, HR 0.76, 95% CI 0.68-0.86) and OS current objective criteria for treatment response assessment may not reliably
(median OS 10.5 versus 9.1 months, HR 0.86, 95% CI 0.75-0.98) compared to indicate treatment failure and do not adequately capture disease biology.
docetaxel in pretreated patients with NSCLC regardless of histology (4). The Molecular-targeted therapies and novel immunotherapies induce effects
identification of potential predictive biomarkers remains a challenge due to that differ from those induced by classic cytotoxic treatment including
the complexity of angiogenesis, the interaction between the tumor and the intratumorale haemorrhage, changes in vascularity, and tumour cavitation.
host and due to dynamic changes of the system. In a very large trial (Abigail), Thus, conventional approaches for therapy response assessment such as
specifically designed to identify potential tissue based or blood based RECIST or WHO criteria that exclusively focus on the change in tumour size
markers of efficacy, no predictive markers could be determined. However are of decreasing value for drug response assessment in clinical trials.7,8
the relevant prognostic nature of angiogenesis marker could be confirmed Parallel to the development of novel imaging techniques automated and
(5). Recent analyses revealed that besides molecular markers clinical more detailed analysis of standard images is currently highly investigated
factors like rapid progressive diseases or tumors refractory to conventional and has led to the introduction of the term Radiomics. Radiomics refers
chemotherapy could be associated with improved outcomes of angiogenesis to the comprehensive quantification of tumour phenotypes by applying a
inhibitors. Preplanned as well as exploratory analyses did show pronounced large number of quantitative image features that are standardized collected
efficacy for the combination of antiangiogenic agents like nintedanib, with specific software algorithms. Radiomics features have the capability
ramucirumab and bevacizumab compared to chemotherapy alone supporting to further enhance imaging data regarding prognostic tumour signatures,
the hypothesis that fast progressing tumors are more dependant on neo detection of tumour heterogeneity as well as the detection of underlying gene
angiogenesis. The translational exploration of these clinical findings is on the expression patterns which is of special interest in patients with metastatic
way in several programs and trials. The understanding of this correlation will disease. The aim of of this presentation is to provide an overview on state-
be important for the optimal placement of antiangiogenic agents e.g. in the of-the-art imaging techniques for the initial staging, response evaluation
combination with immunotherapies. as well as surveillance in patients with lung cancer. The various techniques
will be discussed regarding their pros and cons to further provide functional
Folkman J, Merler E, Abernathy C et al. Isolation of a tumor factor responsible information that best reflects specific targeted therapies including anti-
for angiogenesis. J Exp Med 1971; 133: 275-288 angiogenetic treatment, immunotherapies and stereotactic body radiation
Soria JC, Mauguen A, Reck M et al. Systematic review and meta-analysis therapy. Moreover, imaging techniques and optimal time points after local
of randomised phase II/III trials adding bevacizumab to platinum based minimally invasive treatments with microwave ablation or novel irreversible
chemotherapy as first-line treatment in patients with advanced non-small- electroporation will be discussed. The second part of the presentation will
cell lung cancer. Ann Oncol 2013; 24: 20-30 focus on Radiomics and its potential value in lung cancer imaging. Literature:
1. Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging system
Reck M, Kaiser R, Mellemgaard A et al. Docetaxel plus nintedanib versus for lung cancer. Ann Thorac Cardiovasc Surg 2009;15:4-9. 2. Rengan R, Maity
docetaxel plus placebo in patients with previously treated non-small-cell lung AM, Stevenson JP, Hahn SM. New strategies in non-small cell lung cancer:
cancer (LUME-Lung 1): a phase 3, double blind, randomised controlled trial. improving outcomes in chemoradiotherapy for locally advanced disease. Clin
Lancet Oncol 2014; 15: 143-50 Cancer Res 2011;17:4192-9. 3. Miles K. Can imaging help improve the survival
of cancer patients? Cancer Imaging 2011;11 Spec No A:S86-92. 4. Nishino M,
Garon E, Ciuleanu TE, Arrieta O et al. Ramucirumab plus docetaxel versus Jackman DM, Hatabu H, Janne PA, Johnson BE, Van den Abbeele AD. Imaging
placebo plus docetaxel for second-line treatment of stage IV non-small-cell of lung cancer in the era of molecular medicine. Acad Radiol 2011;18:424-36. 5.
lung cancer after disease progression on platinum based therapy (REVEL): a Nishino M, Jagannathan JP, Ramaiya NH, Van den Abbeele AD. Revised RECIST
multicentre, double-blind, randomised phase 3 trial. Lancet 2014; 384: 665-773 guideline version 1.1: What oncologists want to know and what radiologists
need to know. AJR Am J Roentgenol 2010;195:281-9. 6. Henzler T, Goldstraw P,
Mok T, Gorbunova V, Juhasz E et al. A correlative biomarker analysis
Wenz F, et al. Perspectives of novel imaging techniques for staging, therapy
of bevacizumab and carboplatin-based chemotherapy for advanced
response assessment, and monitoring of surveillance in lung cancer: summary
nonsquamous non-small cell lung cancer: results of the phase II randomized
of the Dresden 2013 Post WCLC-IASLC State-of-the-Art Imaging Workshop.
ABIGAIL study (BO21015). J Thorac Oncol 2014; 9: 848-55.
J Thorac Oncol 2015;10:237-49. 7. Oxnard GR, Morris MJ, Hodi FS, et al. When
Keywords: Angiogenesis, Biomarker, NSCLC, rapid progressive tumors progressive disease does not mean treatment failure: reconsidering the criteria
for progression. J Natl Cancer Inst 2012;104:1534-41. 8. Stacchiotti S, Collini P,
Messina A, et al. High-grade soft-tissue sarcomas: tumor response assessment-
-pilot study to assess the correlation between radiologic and pathologic
SC26: ANGIOGENESIS INHIBITION: ADVANCES & PERSPECTIVES response by using RECIST and Choi criteria. Radiology 2009;251:447-56.
Keywords: functional imaging, Radiomics, Big data
SC26.04 NOVEL IMAGING TECHNIQUE

Stefan Schönberg
Institute of Clinical Radiology and Nuclear Medicine, University Medical Center
Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim/Germany
Lung cancer is still the leading cause of cancer-related death in both men SESSION SC27: P53 AND KRAS MUTATIONS IN NSCLC
and women with 80% to 85% of cases being non-small-cell lung cancer WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
(NSCLC).1The past fifteen years have brought significant breakthroughs
in the understanding of the molecular biology of lung cancer. Signalling
pathways and genetic driver mutations that are vital for tumour growth SC27.02 BIOLOGY OF KRAS MUTATIONS
have been identified and can be effectively targeted by novel pharmacologic
József Tímár

2nd Department of Pathology, Semmelweis University (SE), Budapest/Hungary I, Show AT. Crizotinib resistance: implications for therapeutic strategies.
Ann Oncol 273:iii42-iii50,2016 6. El-Osta H, Shahid K, Mills GM, Peddi P.
Molecular classification of lung cancer revealed that the most frequently Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer.
mutated oncogene in lung cancer is the KRAS due to smoking and this Oncotarget 9:5101-5016,2016
molecular subclass is exclusively occur in the adenocarcinoma histologic
variant and rarely in large cell variant. It also can be detected in the mixed Keywords: KRAS, lung adenocarcinoma, Prognosis, mutational profile
histological variants like the adenosquamous subtype. The incidence of
KRAS mutation in lung adenocarcinoma is 30% based on exon2 testing.
(1) However, it is expected that similar to colorectal cancer, a complex
SC27: P53 AND KRAS MUTATIONS IN NSCLC
RAS panel mutational analysis involving rare KRAS exon3 and 4 and NRAS WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
exon2-4 could increase this figure significantly (probaly by 5-10%). Since RAS
mutations are exclusive and do not occur together with other oncogenic
driver mutations the complett RAS panel mutation determination could SC27.03 TRANSFORMING KRAS INTO A CLINICALLY RELEVANT
help to clearly define a large set of adenocarcinoma patents where further BIOMARKER
molecular analysis is not necessary. Analysis of two large patient cohort of Kenneth O’Byrne
lung adenocarcinoma and colorectal cancer (500 pt each) revealed that the
Cancer Services, Princess Alexandra Hospital, Brisbane/Australia
alleic variations are highly similar in mutant KRAS exon2 in this two cancer
types. The TGT (G-C) transversion in codon 12 was proved to be lung cancer TP53 mutations represent the commonest mutation seen in NSCLC. Over
specific while the GAC (G-D) codon 13 alteration was colorectal cancer specific. 50% of NSCLC tumours harbour a TP53 mutations. TP53 mutations in
Since the RAS mutation in lung cancer is considered to be smoking-related, tobacco smokers are predominantly G-to-T transversions and deletions. In
this highly similar allelic profile in colorectal cancer can be the molecular non-smokers, however, these alterations are rare. p53 is a stress response
signature of smoking in this cancer type. Analysis of KRAS exon 2 aminoacid protein/transcription factor and is involved in cellular response to DNA
conversions by smoking status revealed that in non-smokers mutation is damage induced by oxidative stress and external factors such as sunlight and
rare and if it occurs it is most frequently G12V unlike in smokers where G12C radiation. Expression of p53 protein is largely controlled through degradation
is the predominant. G12V-type patients may respond better to conventional of the protein by the mouse double minute 2 (MDM2) E3 ligase and MDM4.
chemoterapy (2). RAS mutant lung cancer patients are resistant to EGFR Post-translational modification by various kinases/phosphatases and
TKI inhibitors (1). EGFR protein expression is highly similar in KRAS mutant acetylases/deacetylases also regulates p53 activity. Amongst the various
and wt lung adenocarcinoma but interestingly phosphorylated-EGFR is type of TP53 mutation that can occur, conformational TP53 mutations may
overexpressed in KRAS mutant tumors even overcoming EGFR mutated ones contribute to the emergence of new functions leading to genomic instability,
suggesting an aberrant RAS-driven signaling. (3) KRAS mutation in lung inhibition of apoptosis, cell migration, and drug resistance. These mutations
cancer is a poor prognostic factor. Analysis of the organ metastatic pattern of may result in the binding and inactivation of p53-related proteins such as p63
KRAS mutant lung adenocarcinoma revealed that brain and bone metastatic and p73, or with other transcriptional factors resulting in modification of their
potential of these tumors are similar to KRASwt ones while these tumors tend activity and, hence, altered gene expression. Apart from the loss of tumour-
to prefer pleural dissemination and liver. On the other hand, KRAS mutant suppressor functions, TP53 mutations may result in gain of function favouring
lung adenocarcinoma is less likely give rise adrenal- or lung metastasis, a cellular proliferation, inhibition of apoptosis, and genomic instability. As a
clearly indication a different biology as compared to KRASwt cancers. It result not all P53 mutations are the same with some more likely to affect the
is an important issue today the maintenance of the molecular profiles in pathogenesis of NSCLC than others. Broadly speaking TP53 mutations may
metastases as compared to the primary tumor. This issue may be less sensitive be divided into disruptive and non-disruptive cohorts. Many non-disruptive
in case of patients where surgical removal of the primary is impossible (a p53 mutations result in gain of function. In a recent series of 318 patients
significant proportion of lung cancers) while can be more significant where that included 125 with EGFR-mutations, non-disruptive TP53 mutations
only metastases are present in the patients. Analysis of the literature data were associated with a poor prognosis. A recent study using an ELISA
indicates that the discrepancy rate of RAS mutation status in lymphatic demonstrated p53 antibodies in 20.4% of lung cancer patients. A significant
metastases is low (below 10%), in case of visceral metastases increases to correlation between serum p53 antibodies and high levels of p53 expression
14-24% range while is was reported to be the highest in bone metastasis in the corresponding tumour samples was seen. In NSCLC, the presence of
(1). Lung cancer is reported to be a clonally heterogenous cancer and these p53 antibodies were significantly associated with poorly differentiated.
alterations are most probably due to clonal variations during metastatic High levels of p53 antibodies were also associated with high grade tumours,
dissemination. With the advent of liquid biopsy technology monitorization with squamous cell histology and with a poor prognosis in squamous cell
of this process is now feasible using circulating DNA. A major issue clinically carcinoma. Oncogenic KRAS mutations have been reported in up to 40% of
today is the development of resistance to target therapies. Both lung adenocarcinomas and 5% of squamous cell carcinomas of the lung. These
adenocarcinoma and colorectal cancer is treated by EGFR-targeted therapies mutations are found largely in lung adenocarcinomas with solid growth
where the molecular mechnisms of acquired resistance are now reported. It patterns. While KRAS mutations are classically associated with a significant
is interesting that in colorectal cancer patients the main cause of resistance smoking history, they are also identified in a substantial proportion of
to anti-EGFR antibody therapy is the emergence of RAS mutated clones in never-smokers. KRAS mutations are relatively mutually exclusive from EGFR,
progressing tumors which were in minority in the primary. Although RAS BRAF and ALK mutations/rearrangements but have considerable overlap
mutation is equally frequent in lung adenocarcinoma, EGFR-TKI resistance with both P53 and PIK3CA mutations. The commonest mutation is in codon
is most frequently due to EGFR T790M mutation or HER2 amplification 12 but mutations in codon 13 and 61 are also been described. Substitutions
but no report on the emergence of RAS mutated clones.(4) In case of ALK in these residues result in constitutively elevated levels of Ras-GTP due
mutated lung adenocarcinoma resistance to ALK inhibitors is mainly due to to reduced intrinsic GTP hydrolysis and resistance to GTPase-activating
novel mutations in ALK. In a small proportion of cases KRAS amplification or proteins and hence activation of the Raf and phosphatidylinositol 3-kinase.
NRAS mutation can be detected which suggest that in ALK-translocated lung Although controversy on the prognostic and predictive value of the presence
cancer no minor RAS mutant clones are present in the tumors. (5) Check point of a KRAS mutation in a tumour exists, recent studies indicate that patients
inhibitor therapy is a new modality of lung cancer management targeting with KRAS mutations are resistant re chemotherapy and radiotherapy,
CTLA4, PD1 or PDL1 as targets on immune cells or cancer cells (PDL1). Although with a lower objective response rate and worse progression free and overall
two drugs are registered in NSCLC, the significance of RAS mutations in this survival rates. A number of recent studies have allowed us to gain novel
new modality is not known yet. In case of Nivolumab it is known that smokers insights into the role of KRAS in the pathogenesis of lung cancer, in particular
are responding better to anti-PD1 therapy than nonsmokers suggesting that adenocarcinoma of the lung. Increasing evidence indicates a role for chronic
KRAS mutant tumors might be a better target but direct subgroup analysis inflammation in the pathogenesis of lung cancer, an observation being
is lacking. In case of Pembrolizumab even such an indirect data are missing exploited clinically through the use of immune checkpoint inhibitors such as
therefore the question cannot be answered yet. The fact that EGFR mutant pembrolizumab. A proportion of KRAS mutation positive tumours have been
tumors are tend to respond less to anti-PD1 therapy suggest that beside PDL1 found to have a high tumour mutation burden that may indicate sensitivity
status molecular classification can also be a predictive factor for selecting to such agents. KRAS mutations have also been associated with tumour-
patients for immunotherapy. (6)References 1.Tímár J: The clinical relevance of infiltrating lymphocytes. Recent work has demonstrated that KRAS mutation
KRAS gene mutation in non-small-cell lung cancer. Curr Opin Oncol 26: 138-144, in lung epithelial cells preferentially leads to recruitment of Th17 positive
2014 2. Cserepes M, Ostoros Gy, Lohinai Z, Rásó E, Barbai T, Tímár J, Rozsás immune cells that produce IL-17, a cytokine that promotes inflammation.
A, Moldvay J, Kovalszky I, Fabián K, Gyulai M, Ghanim B, László V, Klikovits IL-17 induces tumorigenesis by recruiting GR1C CD11bC immune cells. Recent
T, Hoda MA, Grusch M, Berger W, Klepetko W, Hegedűs B, Döme B: Subtype- work has demonstrated that miRs may play a role in the regulation of KRAS.
specific KRAS mutations in advanced lung adenocarcinoma: A retrospective For example miR-31 has recently been reported to be over-expressed in lung
study of patients treated with platinum-based chemotherapy. Eur J Cancer adenocarcinoma and to correlate with worse survival. Using a transgenic
50: 1819-1828, 2014 3.Moldvay J, Barbai T, Bogos K, Piurko V, Fillinger J, Popper mouse model that allows for lung-specific expression, induction of miR-31
HH, Tímár J: EGFR autophosphorylation but not protein score correlates with results in lung hyperplasia, followed by adenoma formation and later the
histologic and molecular subtypes in lung adenocarcinoma. Diagn Mol Pathol development of adenocarcinoma. Induced expression of miR-31 acts with
22: 204-209, 2013 4. Belchis DA, Tseng LH, Gmiadek T et. al. Heterogeneity mutant KRAS to accelerate lung tumourigenesis by down-regulating a
of resistance mutations detectable by next-generation sequencing in number of negative regulators of RAS/MAPK signaling. The expression of
TKI-treated lung adenocarcinoma. Oncotarget 2016 (in ress) 5. Dagogo-Jack
mesothelin, a cell surface glycoprotein that may have a role in cell adhesion stage of BATTLE-2. In BATTLE-2, we pre-specified an extremely limited set of
and metastases, is seen in several epithelial cancers and has recently been markers and our intent was to use the first half of the study (200 patients)
assessed in adenocarcinoma of the lung using immunohistochemistry. The to conduct prospective testing of biomarkers/gene signatures. Predictive
intensity of staining and the percentage of cells expressing mesothelin in markers were to be used to guide patient assignments in the second half
the report was blinded for molecular data and outcome. Mutations of EGFR, of the study. Although the design theoretically provided advantages,
KRAS, BRAF, AKT1, PIK3CA and HER2 were assessed by pyrosequencing; since clear predictive markers did not exist for any of the treatment Arms,
HER2 amplification and ALK translocation were assessed by fluorescence in activity was modest yielding no new predictive markers and not warranting
situ hybridization. Of the advanced lung adenocarcinomas, 53% expressed further exploration. The ISPY-2 trial (6) is a multicenter phase II trial in the
mesothelin to some degree. High mesothelin expression, defined as neoadjuvant setting for patients with breast cancer. The primary end point
mesothelin positivity in more than 25% of cells, was found in 24% of patients. is pathologic complete response (PCR) at the time of surgery. The patient
High mesothelin expression was associated with a worse survival (median population is partitioned into ten subgroups depending on hormone-receptor
18.2 months vs. 32.9 months; P = 0.014) and with wild-type EGFR, and was (HR) status, HER2 status and Mamma Print signature. Experimental drugs
strongly associated with mutant KRAS. The increased understanding of the are added to neoadjuvant therapy with the overall goal to prospectively
tumour promoting activities of KRAS mutations, and the association with learn as efficiently as possible which patients respond to each experimental
biomarkers, provides novel insights that will facilitate targeting of these treatment based on their biomarker profiles. Adaptive randomization
tumours with novel agents in the future. with interim analysis is used within each biomarker subgroup, with the
treatments that are performing better within a subgroup being assigned
with greater probability to patients belonging to that subgroup. The phase II
drug-screening stage is followed by a phase III confirmatory stage. The ISPY-2
trial has recently shown that two promising drugs improve response rates
in specific biomarker subsets and has graduated these two drugs veliparib
SESSION SC28: NOVEL CLINICAL TRIAL DESIGNS and neratinib for further development (7). The pharmaceutical industry and
regulatory agencies are therefore very interested in adaptive designs because
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 of their potential advantages and because they reflect medical practice in the
real world.
SC28.04 ADAPTIVE CLINICAL TRIAL DESIGNS To recapitulate, incorporation of adaptive designs in carefully designed and
Vassiliki Papadimitrakopoulou executed trials can enhance drug development, provide greater benefit to
the enrolled patients, and effectively address many research questions of
Thoracic/Head & Neck Medical Oncology, MD Anderson Cancer Center, Houston/TX/
United States of America interest. These designs require deep understanding of theoretical statistical
methodology, extensive modeling with simulations, specialized software and
Interest in adaptive design study methods stems from the principle that robust databases. Continued implementation in trials with guidance from
these methods hold promise for improving drug development compared regulatory agencies and innovative methods will contribute towards progress
to conventional study design (i.e., non-adaptive) methods. The theoretical in therapies.
advantages of adaptive designs are that (1) they provide similar information
more efficiently by reducing sample size and total cost, (2) increase the 1.Berry DA. Bayesian clinical trials. Nat Rev Drug Discov. 2006;5:27–36.
likelihood of success on the study objective, treating more patients with
2.Lee JJ, Chu CT. Bayesian clinical trials in action. Stat Med. 2012;31:2955–
more effective treatments or (3) lead to better improved appreciation of the
2972.
effects of therapy such as dose-response relationship or subgroup effects,
for example identifying efficacious drugs for specific subgroups of patients 3. Zhou X, Liu S, Kim ES, et al. Bayesian adaptive design for targeted therapy
based on their biomarker profiles, which may also lead to more impactful development in lung cancer-a step toward personalized medicine. Clin Trials.
subsequent studies). Adaptive designs use accumulating data to modify the 2008;5:181–193.
ongoing trial without undermining the integrity and validity of the trial. They
also hold the potential for shortening the time for drug development. Several 4. Kim ES, Herbst RS, Wistuba II, et al. The BATTLE Trial: Personalizing therapy
aspects of these trials including the dose-finding scheme, interim analysis, for lung cancer. Cancer Discov. 2011;1:44–53.
adaptive randomization, biomarker-guided randomization, and seamless
designs will be discussed. 5.Papadimitrakopoulou V, Lee JJ, Wistuba II et al. The BATTLE-2 Study: A
Biomarker-integrated targeted therapy study in previously treated patients
Many, but not all adaptive designs are devised under the Bayesian framework with advanced non-small cell lung cancer. J Clin Oncol Aug 1,2016 Epub ahead
incorporating principles such as (I) obtaining the prior distribution; (II) of print
collecting data to calculate the data likelihood; and then (III) computing the
posterior distribution. The Bayesian framework provides an ideal statistical 6.Barker AD, Sigman CC, Kelloff GJ, et al. I-SPY 2: An adaptive breast cancer
framework for adaptive trial designs (1, 2). trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther.
2009;86:97–100.
Examples of trials conducted with adaptive designs include the BATTLE
and BATTLE-2 trials and ISPY-2. The basic principle is that patients enrolling 7.Quantum Leap. I-SPY 2 Trial graduates 2 new drugs. 2013 Available
earlier in a trial are used to inform how subsequent patients are treated, thus online:http://www.quantumleaphealth.org/spy-2-trial-graduates-2-new-
improving the efficiency of the study; this means that fewer patients are drugs-press-release/
required to achieve the same answers regarding safe dosing and/or efficacy. Keywords: adaptive designs, clinical trials
The BATTLE and BATTLE-2 trials are prime examples of this approach. Both
trials have implemented adaptive randomization schemes to assign patients
to the more efficacious treatments based on their biomarker-guided profiles,
and use interim analyses to monitor the efficacy outcomes during the trial.
The BATTLE trial (3, 4) enrolled patients with stage IV recurrent non-small cell SESSION SC29: ACCESS, VALUE ASSESSMENTS AND AF-
lung cancer, employing a primary endpoint of eight-week disease control rate, FORDABILITY OF NOVEL THERAPIES
as a binary outcome. Four targeted therapies, erlotinib, vandetanib, erlotinib WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
plus bexarotene, and sorafenib, were evaluated, with one therapy targeting
each one of four biomarker profiles and it used an adaptive randomization
scheme to allocate patients to the different treatments; hence, patients
SC29.03 VALUE-BASED ASSESSMENTS IN LUNG CANCER THERAPY:
had higher probabilities of being assigned to better treatments based on
their biomarker profiles. The trial showed that adaptive design could work
THE ESMO PERSPECTIVE
in a complex trial that assessed multiple drugs and biomarkers and required Nathan Cherny
tissue collection and biomarker analysis. Based on the findings of the Oncology, Shaare Zedek Medical Center, Jerusalem/Israel
BATTLE trial, a follow-up BATTLE-2 trial (5) was started, that evaluated four
treatment regimens, erlotinib, sorafenib, erlotinib + MK2206, and MK2206 The value of any treatment is determined by the magnitude of its clinical
+ AZD6244, in a two-stage design with adaptive randomization. The first benefit (MCB) balanced against its cost. Whereas costs of procurement
stage was completed with 200 patients. Biomarker selection was planned in and out-of-pocket expenditures vary from country to country, the MCB, as
3 steps: training, testing and validation. In the training step, 10–15 potential derived from well-designed clinical trials, is a relative constant. Consequently,
prognostic and predictive markers were selected from the previous BATTLE meaningful discussion of value and relative value are predicated on an
experience, cell line data, and relevant literature information. In the testing understanding of the MCB. MCB in this context refers to the added benefit,
step, the selected markers are tested using the data acquired from stage 1 usually compared to a control (the best current standard care). Until recently
of the BATTLE-2 trial. In the validation step, the markers selected in the first there was no standard tool for grading the MCB of cancer therapies, which
stage of the BATTLE-2 trial are used for adaptive randomization in the second may range from trivial (median progression-free survival advantage of only
a few weeks) to substantial (improved long term survival). Recognising the

importance of presenting clear and unbiased statements regarding the CANCER

MCB from new therapeutic approaches derived from high quality clinical Sumitra Thongprasert
trials the European Society for Medical Oncology (ESMO) has developed a
Oncology, Bangkok Chiangmai Hospital, Chiangmai/Thailand
validated and reproducible tool to assess the MCB for cancer medicines, the
ESMO MCB Scale (ESMO-MCBS). This tool uses a rational, structured and With limited resources for health, Low and Middle Income Countries (LMICs)
consistent approach to derive a relative ranking of the magnitude of clinically struggle to guarantee all members of their society toget cancer treatments,
meaningful benefit that can be expected from a new anti-cancer treatment. especially the innovative but expensive cancer medicines[1, 2]. Cancer is a
The ESMO-MCBS is an important first step to the critical public policy issue leading cause of deathin Thailand, which is an upper-middle income country
of value in cancer care, helping to frame the appropriate use of limited public in South-East Asia. From 2003 to 2011, the mortality rate from cancer rose
and personal resources to deliver cost effective and affordable cancer care. from 79 to 95 per100,000 populations. [3].Since the Thai health care reform
The ESMO-MCBS v1.0 [1]has been developed and validated for solid cancers. in 2001[4, 5] several stakeholders have initiated policies andprogramsto
The tool is presented in two parts. Form 1 is used to evaluate adjuvant and facilitate access to medicines. The Thai NLEM is different from the one listed
other treatments with curative intent. Form 2 (a, b or c) is used to evaluate by WHO, due to the fact that WHO listed only the minimum required medicine,
non-curative interventions, with form 2a for studies with OS as the primary while the Thai list included an optimum list. At the present, the Thai NLEM has
outcome, form 2b for studies with PFS or TTP as primary outcomes, 2c for more than 700 items of active ingredients and 1000 dosage forms [6, 7]. When
studies with QoL, toxicity or response rate as primary outcomes and for the NLEM was first introduced in 1981, only cost, safety, and efficacy were
non-inferiority studies. Form 2a is prognostically sub-stratified for studies considered as criteria for inclusion whereas effectiveness was added to the
where the control arm produced OS greater or less than or equal to 1 year, and list of criteria in 2004. Since 2008, economic evidence has become important
form 2b is stratified for studies where the control arm PFS is <6m or >6mth. for the Sub-committee of the NLEM to justify the new costly medicines
Version 1.0 can be applied to comparative outcome studies evaluating the such as type E2 to be included in the list of NLEM. As of 2009, the NLEM can
relative benefit of treatments using outcomes of survival, QoL, surrogate be divided into six categories, which are A, B, C, D, E1, and E2. Type A: Basic
outcomes for survival or QoL (DFI, EFS, TTR, PFS and TTP) or treatment medicines that every health facility must make available Type B: Alternative,
toxicity in solid cancers. Eligible studies can have either a randomised or second line medicines of those in category A Type C: Medicines prescribed
comparative cohort design or a meta- analysis which report statistically only by specialists TypeD: Medicines used only for particular indications and
significant benefit (P>0.05, upper limit of 95th percentile for HR <1) from any diseases Type E1: Medicines used only for special or vertical programs Type
one, or more of the evaluated outcomes. For treatments with curative intent, E2: Medicines that are high costs but are important for particular groups of
the scale is graded A, B or C. Grades A and B represent a high level of clinical patients Heath Care Coverage for Thai residences are divided into 3 categories
benefit . For cancers treated without curative intent, the scale is graded 5, 4, 1. Universal Coverage Scheme (UCS) Cover 75% of Thai population 2. Social
3, 2, 1, where grades 5 and 4 represent a high level of proven clinical benefit. Security Scheme (SSS) Cover 19%, Private sector employees, excluding
The scale incorporates a “dual rule” taking into account the variability of the dependants 3. Civil Servant Medical Benefit Scheme (CSMBS) Cover 9%,
estimated HR from a study, the lower limit of the 95% Confidence Interval (CI) Government employees plus dependants (parents, spouse and up to two
for the HR is compared to specified threshold values; and second the observed children age <20) The CSMBS has covered most of the cancer drugs including
absolute difference in treatment outcomes is compared to the minimum the expensive drugs, however UCS and SSS have covered only drugs listed
absolute gain considered as beneficial. Different candidate threshold values in the NELM; thus there are unmet need for cancer patients with these two
for HR and absolute gains for survival, DFS and PFS, adjusted to represent as healthcare schemes. Thai government set up several policies to enable access
accurately as possible the expert opinion of the oncology community, have to the cancer drugs such as Compulsory Licensing, Pooled purchasing (price
been explored through extensive simulations. In all forms HR thresholds refer negotiation), Special marketing arrangement (price negotiation), and E2
to the lower extreme of the 95% CI, analogous to the convention of evaluating access program. Several pharmaceutical companies provide their own scheme
null effect by the upper limit of the 95%CI <1. The performance of the for patients who are willing to pay for the drug by themselves (patient access
evaluation rule based on the lower limit of the 95% CI of HR, was compared to program) Even with all the programs available, the problem of accessibility
the simpler rule of using a cut-off for the point estimate of HR, in conjunction of costly anticancer drugs still persists. There should be more input into
with the additional rule on the minimum absolute gain in treatment outcome. this problem.References 1. Kanavos P, Das P, Durairaj V, Laing R, Abegunde
The simulation results under different HR values and corresponding power, DO (2010) Options for financing and optimizing medicines in resource-poor
favoured the proposed approach to use the lower limit of the 95% CI which countries World Health Organization. 2. American College of Physicians
takes into account the variability of the estimate. The concern that small (2011) How can our Nation Conserve and Distribute Health Care Resources
studies generate wider confidence intervals is real and justified, however Effectively and Efficiently? Philadelphia: American College of Physicians.
in the ESMO-MCBS v1.0 all high grading scores in a non-curative setting 3. MoharaA, Youngkong S, Pérez Velasco R, Werayingyong P, Pachanee
incorporate both HR and absolute gain to mitigate against over valuing small K,et al. (2012) Using health technology assessment for informing coverage
studies with wide HR. This structured and disciplined approach to deriving decisions in Thailand. J Compar Effect Res.1:137–146. 4. Damrongplasit K,
estimates of clinically meaningful benefit from published data can be used in Melnick GA (2009) Early results from Thailand’s 30 Baht Health Reform:
a range of settings: it can help public policy-makers advance “accountability something to smile about. Health Aff (Millwood). 28: w457–466. doi: 10.1377/
for reasonableness” in resource allocation deliberations, contribute to hlthaff.28.3.w457 PMID: 19336469 5. Towse A, Mills A, Tangcharoensathien
formulation of clinical guidelines, in the clinic it can help clinicians to weigh V (2004) Learning from Thailand’s health reforms. BMJ. 328: 103–105. PMID:
the relative merits of competing relevant therapeutic options in situations in 14715608 6. Yoongthong W, Hu S, Whitty JA, Wibulpolprasert S, Sukantho K,
which there is no direct comparative data and grading may also be of benefit et al. (2012) National drug policies to local formulary decisions in Thailand,
when explaining the relative merit of therapeutic options to patients and China, and Australia: drug listing changes and opportunities. Value Health. 15:
their families. Finally ESMO-MCBS may be of use to editors, peer reviewers s126–131. doi: 10.1016/j.jval.2011.11.003 PMID: 22265059 7. Turongkaravee S,
and commentators in considering the clinical significance of research findings Rattanavipapong W, Khampang R, Leelahavarong P, Teerawattananon Y, et al.
from randomised clinical studies, cohort studies and meta-analyses with (2012) Evaluation of high-cost medicine scheme (Category E2) under the 2008
statistically significant positive findings. Experience accrued in evaluating National List of Essential Medicines. Nonthaburi: Health Intervention and
trials in the management of non small-cell lung cancer have been critical in the Technology Assessment Program.
development process of v1.0, particularly with regard to the interpretation
of PFS is studies with extensive crossover on progression that precludes Keywords: Thai Health Care System, National List of Essential Medicine,
meaningful OS survival results. In this cohort of studies, the inclusion of Compulsory License, E2 access
QoL evaluation was able to generate confirmatory secondary evidence to
support the clinical significance of the PFS findings. The proliferation of new
agents targeting NSCLC with specific mutations that have been approved
on the basis if Phase I-II data have challenged the working group to expand
the scope of the scale to include single arm studies. This new subscale will be
among the amendments in the planned revision that is under development SESSION SC30: NOVEL APPROACHES AND REGULATION IN
and scheduled for publication early next year. 1. Cherny NI, Sullivan R, Dafni U SURGICAL EDUCATION
et al. A standardised, generic, validated approach to stratify the magnitude WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45
of clinical benefit that can be anticipated from anti-cancer therapies: the
European Society for Medical Oncology Magnitude of Clinical Benefit Scale
(ESMO-MCBS). Annals of oncology 2015; 26: 1547-1573. SC30.03 E-LEARNING IN THORACIC ONCOLOGY
Jalal Assouad
Keywords: ESMO, Value, Clinical Benefit
Thoracic Surgery, Tenon Hospital Sorbonne University, Paris/France
Advances in modern technologies allows for an increasing opportunities in

surgical and medical education. The main advantages for e-learning process
SC29: ACCESS, VALUE ASSESSMENTS AND AFFORDABILITY OF NOVEL THERAPIES
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 are: accessibility and flexibility. A range of platforms offers educational
programs accessible at work or home with total temporal and spatial freedom.
Trainees are allowed to access their learning environment at a convenient
SC29.05 THE THAI EXPERIENCE TO OVERCOME HIGH COST DRUG IN
time and relevant to their own training needs. Several techniques are be accurately communicated in a handoff. While patient safety data is not
available: web-based data, interactive online modules, and virtual reality. conclusive there is data on worse outcomes in spinal and meningioma surgery
This is especially true within surgical training where the development of new post implementation of duty hour regulations. These data may serve to
techniques constantly evolves. The rapid and constant evolution in oncology corroborate the perceived concerns.
knowledge’s makes it relevant for e-leaning process. E learning allows
trainees to apply and be assessed on the new information in a safe setting. In Keywords: Education, duty hour regulation, working time directives
addition, all contents can be discussed and debated around the medical world
without any limits. The level of trainees recall can be significantly increased
by e-learning techniques because it stimulates multi-sensory experiences. E SESSION SC31: TOGETHER AGAINST LUNG CANCER
learning offers also large possibilities for decision making based on available
– A STRATEGY FOR SUCCESS IN THE 21ST CENTURY
information and interactive decision-making process. Surgical e-learning
programs include the development of knowledge, technical skills, non- WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45
technical skills and decision-making process. The content of all the e-learning
modules should be relevant; best available, up to date and critically appraised
evidence should supports the information contained within the modules. SC31.01 THE ROLE OF SCIENTIFIC ORGANIZATIONS
E-learning surgical programs should be based on an understanding of Paul Bunn, Jr.
educational principles, peer review resources associated to creativity. It could Department of Medical Oncology, University of Colorado Denver, Aurora/CO/United
be highly interactive. Immersive questions and answers for clinical setting States of America
permit to trainee to progress through scenarios and makes the relevant
decisions and choices. Trainees have to evolve with their decisions and receive The goal of scientific organizations is to facilitate progress in a specific area
feedback as to the choices they have made. These interactive models can be through promotion of research, training and education. In some instances the
created with text on the page or with simulators. E-learning modules should scientific area may be a single discipline such as medical, surgical or radiation
be used as a complementary tool to traditional learning methods. Authors will oncology, pathology, radiology and so on. In some instances the scientific
present their e-learning thoracic platform created at September 2013 : “Tenon area may be a single geographic region such as Europe, North America or Asia.
Thoracic Institute“ (www.tenon-thoracic-institute).This e-leaning thoracic Examples of such organizations would be the European Respiratory Society
platform develops several e-learning tools: live from OR with interactive (ERS), the American College of Radiology, the College of American Pathology
discussion with faculty, round table with exerts, didactic session for young (CAP) and many, many others. In some instances the organization might
trainees. All the aspects around thoracic pathology are treated: oncology, focus its efforts on training and research grants and in other instances the
surgery, anaesthesiology, radiology, etc. Authors will discuss the relevance of organization might focus on education of the public and in public programs
such a platform, the lack of its content and future e-leaning projects. such as prevention. In some instances the organization may conduct
research or may solely sponsor research to be done by others. Some scientific
Keywords: thoracic oncologic surgery, oncology, e-learning, education organization chose to develop guidelines for clinical care. All of these efforts
are important and different organizations focus on different aspects of a
problem. In this presentation I will focus my attention on The International
Association for the Study of Lung Cancer (IASLC) since it is the sponsor of
SC30: NOVEL APPROACHES AND REGULATION IN SURGICAL EDUCATION
WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45 the World Conferences on Lung Cancer and since is programs are dedicated
to reducing the world wide burden of thoracic cancers. Lung Cancer is the
leading cause of cancer death worldwide and the most preventable. When
SC30.04 IMPACT OF WORKING TIME DIRECTIVES ON THORACIC the IASLC was organized in 1974 it was recognized not only that lung cancer
SURGICAL TRAINING: THE NORTH-AMERICAN EXPERIENCE was the leading cancer killer but also that it would take an international
Claude Deschamps 1, Ara Vaporciyan2 and multidisciplinary effort to make progress. The very international and
1
Surgery, University of Vermont Medical Center, Burlington/United States of multidisciplinary nature of the IASLC are what set it apart from other
America, 2Thoracic and Cardiovascular Surgery, UT MD Anderson Cancer Center, organizations. Many of the unique contributions of the IALSC rely on these
Houston/TX/United States of America differentiating aspects. For example, the IASLC has contributed all the cases
and evaluation of the world wide lung cancer, mesothelioma and thymoma
The following is in part the STS, TSDA and AATS combined response to ACGME TNM staging classifications. The IASLC Pathology committee has formulated
(collated and written up by Dr. Ara Vaporciyan) regarding the effect of Duty all of the changes to the pathologic classification of thoracic cancers. The
hour regulations on resident education in Thoracic Surgery in North America. IASLC has worked with other organizations such as the College of American
A greater reliance on midlevel providers and physician extenders. This has pathology and Association of Molecular Pathology to develop guidelines
impacted the profession in terms of additional cost from their much higher on molecular characterization of lung cancer. To enhance worldwide
salaries, which are anywhere from 50% to 100% higher, but also a subtle but collaboration and education the IASLC began the World Conferences on
steady transfer of bedside teaching previously focused on the trainee to Lung Cancer and rotated these conferences to different regions around the
bedside teaching focused on the mid-level provider. Limited exposure to our world. Originally, these conferences were held every 3 years as progress was
field. Our profession still fills the bulk of its training position from general slow but as research and research advances have quickened, the WCLCs are
surgery graduates. Duty hour restrictions have contracted the ability of ow held annually. In addition the IASLC sponsors regional meetings on a
those programs to provide elective rotations in thoracic and cardiac. Limited routine basis including the European Lung Cancer Conference (ELCC), the
exposure translates into limited interest and diminished applications. Quality Latin America Lung Cancer Conference (LALCA), the Asia Pacific Lung cancer
of Surgical and postoperative teaching. This is where we have felt the greatest conference and the Chicago Multidisciplinary Lung Cancer conference. The
impact. We, like all surgical professions, have developed an increasing variety IASLC also sponsors workshops on various timely topics such as a conference
of procedures necessitating expansion of our case log requirements. This puts on Small cell lung cancer held in 2015. To support its educational and research
pressure on trainees to participate in every available case. Appropriate cases missions the IASLC publishes a scientific journal entitled Journal of Thoracic
are harder to find due to increasing case complexity and outcome reporting. Oncology which has continually increased its circulation and impact factor.
Therefore, the inability to scrub on just one or two of these cases can be More recently, the IALSC has reinstituted a weekly newsletter and has
significant. While some large surgery programs have implemented float published monographs on time issues such as ALK and PD-L1 testing. The
pools to ensure that all cases provide someone a learning experience most CT IASLC has sponsored research grants especially for junior faculty and fellows
training programs are small and cannot implement that solution Even more to support and nurture their research careers. The IASLC has also sponsored
difficult to overcome is when a trainee misses a rare postoperative event. As travel fellowship awards for junior investigators and for young faculty from
a high acuity specialty our patients will frequently develop rapid changes in developing countries. The IASLC had worked with advocacy groups from
their condition which, if not recognized, can quickly become catastrophic. around the world to provide information and support to these groups and
Most occur in the immediate postoperative period at night. The use of to individuals and families afflicted by lung cancer. These efforts have led
mid-level providers and other services to cover call in an effort to preserve a to a sharing of efforts and to publications directed to patients and their
trainee’s ability to do cases the next day prevents them from taking part in families. The IASLC’s tobacco committee has worked tirelessly to combat
the bedside assessment and management of these rare events. One solution the worldwide tobacco epidemic.References: Tan DS, Yom SS, Tsao MS, Pass
is to lengthen training to allow more opportunities but there is concurrent HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes
pressure to reduce what is already one of the longest training paradigms (up MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone
to 9 years for congenital surgeons without considering any time for research). DP, Bunn PA Jr, Mok TS, Hirsch FRThe International Association for the Study
Alternatively simulation has been used but these are expensive and are not of Lung Cancer Consensus Statement on Optimizing Management of EGFR
easily implemented at all programs. Finally, issues of patient safety and Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016. J Thorac
outcomes. While there is no clear study demonstrating documented impact Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May
on patient safety there are many surveys of resident and faculty perceptions 23. Review Bunn PA Jr, Minna JD, Augustyn A, et al. Small Cell Lung Cancer:
of patient safety. The majority of these, especially in surgery, have shown Can Recent Advances in Biology and Molecular Biology Be Translated into
that the perception is that safety is compromised. The increased number Improved Outcomes?J Thorac Oncol. 2016 Apr;11(4):453-74. doi: 10.1016/j.
of handoffs, especially of high acuity cases, is frequently the target of that jtho.2016.01.012. Epub 2016 Jan 30. Review Goldstraw P, Chansky K, Crowley
perception. The subtle aspects of the intraoperative findings cannot always J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell

A, Bolejack V; International Association for the Study of Lung Cancer Staging trial participation. Site data will also be monitored to provide a contextual
and Prognostic Factors Committee, Advisory Boards, and Participating picture of the program including total patients seen, demographics, insurance
Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision mix, rates and outcomes of molecular testing among other metrics. Data
of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the is analyzed across the COE community and against comparator groups to
TNM Classification for Lung Cancer.J Thorac Oncol. 2016 Jan;11(1):39-51. doi: demonstrate impact of the COE program3. Accelerating Clinical Trial Accrual
10.1016/j.jtho.2015.09.009 The U.S. National Institutes of Health database currently lists over 45,000
cancer-related clinical trials worldwide4. Unfortunately, more than 20% of
Hirsch FR.International Association for the Study of Lung Cancer (IASLC): these trials will never complete, for reasons unrelated to the effectiveness of
celebrating 40 years with scientific and educational achievements!J Thorac the intervention that’s being tested. The most common reason for 20% of all
Oncol. 2014 Oct;9(10):1424-5. doi: 10.1097/JTO.0000000000000340. Bhora FY, clinical trials never finishing is poor patient accrual. One of the most common
Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, Giaccone G, Huang reasons for low accrual is procedural inefficiencies such as complexities
J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, in enrolling in the trial itself and the informed consent process. In 2014,
Ruffini E, Van Schil P; Staging and Prognostic Factors Committee; Advisory ALCMI launched a prospective study to characterize somatic and germline
Boards. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A genomics of adolescents and young adult (AYA) patients5. It is estimated
Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming that less than 2% of those newly diagnosed with lung cancer globally are AYA,
8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. thus presenting a striking recruitment challenge. To address this challenge,
2014 Sep;9(9 Suppl 2):S88-96. doi: 10.1097/JTO.0000000000000293. Tsao ALCMI’s study workflow included building a dedicated website3 enabling
MS, Travis WD, Brambilla E, Nicholson AG, Noguchi M, Hirsch FR; IASLC remote screening and e-consenting so patients could participate from their
Pathology Committee. Forty years of the international association for study homes anywhere in the world while, in parallel, ALCF employed social media to
of lung cancer pathology committee.J Thorac Oncol. 2014 Dec;9(12):1740-9. educate patients on the importance of comprehensive genomic profiling and
doi: 10.1097/JTO.0000000000000356. Leighl NB, Rekhtman N, Biermann WA, increasing awareness of the study via grass-roots patient blogging. Together,
Huang J, Mino-Kenudson M, Ra malingam SS, West H, Whitlock S, Somerfield ALCMI and ALCF bring “research to the patient”. Accrual opened July 23, 2014
MR. Molecular testing for selection of patients with lung cancer for epidermal and in the first 5 weeks of the study, 37 subjects consented. Of the 37 initially
growth factor receptor and anaplastic lymphoma kinase tyrosine kinase consented, 35 enrolled via the remote web-portal. As of June 15 2016, 104
inhibitors: American Society of Clinical Oncology endorsement of the College subjects are enrolled (128 consented) in the study from 10 countries following
of American Pathologists/International Association for the study oflung a social media campaign. Of the 104 subjects enrolled to date, 49% entered
cancer/association for molecular pathology guideline. J Clin Oncol. 2014 Nov the study via the remote study portal with the balance recruited locally
10;32(32):3673-9. doi: 10.1200/JCO.2014.57.3055. Epub 2014 Oct 13 Hung JJ, Yeh by participating ALCMI study sites Conclusion As briefly outlined above,
YC, Jeng WJ, Wu KJ, Huang BS, Wu YC, Chou TY, Hsu WH. Predictive value of patient advocacy organizations have moved well beyond their original patient
the international association for the study of lung cancer/American Thoracic supportive role and have become key players in the oncology healthcare
Society/European Respiratory Society classification of lung adenocarcinoma delivery and clinical research ecosystems. As the healthcare system continues
in tumor recurrence and patient survival. J Clin Oncol. 2014 Aug 1;32(22):2357- to evolve and become more complex so will the role of patient advocacy
64. doi: 10.1200/JCO.2013.50.1049. Epub 2014 May 5 Detterbeck FC, Asamura organizations. To address these challenges, there will be even greater need
H, Crowley J, Falkson C, Giaccone G, Giroux D, Huang J, Kim J, Kondo K, for innovation, sharing of data and resources, increased infrastructure and
Lucchi M, Marino M, Marom EM, Nicholson A, Okumura M, Ruffini E, van mission sophistication, the need to avoid overlap and duplication, and a laser
Schil P, Stratton K; Staging and Prognostic Factors Committee; Members of focus on providing meaningful improvement in the availability, transparency
the Advisory Boards; Participating Institutions of the Thymic Domain The and affordability of healthcare.References: 1. Ruth R. Faden, Tom L.
IASLC/ITMIG thymic malignancies staging project: development of a stage Beauchamp, A History and Theory of Informed Consent, (Oxford University
classification for thymic malignancies. J Thorac Oncol. 2013 Dec;8(12):1467-73. Press, 1986), 93 2. http://www.gotoper.com/publications/ajho/2015/2015feb/
doi: 10.1097/JTO.000000000000001 lung-cancer-disparities-in-the-era-of-personalized-medicine 3. Leah Fine 1,
Guneet Walia1, Raymond U. Osarogiagbon2; 1Addario Lung Cancer Foundation,
Keywords: Organizations,IASLC
San Carlos/United States of America, 2Baptist Cancer Center, Memphis, TN/
United States of America. The ALCF Centers of Excellence Model Delivers
a Standard of Care to the Community Similar to Academic and Research
SC31: TOGETHER AGAINST LUNG CANCER – A STRATEGY FOR SUCCESS IN THE 21ST Centers. World Conference on Lung Cancer, Abstract 6334, December 2016 4.
CENTURY https://clinicaltrials.gov. 5. Barbara J. Gitlitz, Alicia Sable-Hunt, Steven W.
Young, Andreas Kogelnik, Danielle Hicks, Deborah Morosini, Tiziana Vavala,
Marisa Bittoni, S. Lani Park, Silvia Novello, Geoffrey R. Oxnard, Bonnie
SC31.02 THE ROLE OF PATIENT ADVOCACY GROUPS Addario (in press). Employing Remote Web Consenting and Social Media to
Facilitate Enrollment to an International Trial on Young Lung Cancer. World
Bonnie Addario
Conference on Lung Cancer, Abstract 4180, December 2016 6. https://www.
Founder and Chair, Bonnie J. Addario Lung Cancer Foundation/alcmi, San Carlos/
openmednet.org/site/alcmi-goyl
Keywords: disparities, advocacy, accrual, Patients
The role of Patient Advocacy organizations in the oncology health care
delivery ecosystem is ever evolving and has moved well beyond its original
role of solely advocating for services, research, care and understanding. The
current field of patient advocacy has its roots in the patient rights movement TOGETHER AGAINST LUNG CANCER – A STRATEGY FOR SUCCESS IN THE 21ST CENTURY
of the 1970’s with groups like The National Welfare Rights Organization WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45
being instrumental in getting a patient bill of rights accepted by the Joint
Commission on Accreditation of Healthcare Organizations in 19721. The
SC31.03 THE ROLE OF MEDICAL JOURNALS
transformation was further accelerated in 1991 with the formation of the FDA
Patient Representative Program and has continued to expand over time with David Collingridge
patient advocates now being involved in the entire care continuum. In this The Lancet Oncology, The Lancet, London/United Kingdom
presentation I will focus my attention on examples of the ever evolving and
expanding role of patient advocacy highlighted by projects developed and For many years the traditional peer-reviewed medical journal was seen
led by “partner” foundations the Bonnie J. Addario Lung Cancer Foundation to be the only reliable place to obtain the latest advances in science and
(ALCF) and the Addario Lung Cancer Medical Institute (ALCMI). Addressing medicine. But, with the advent of online depositiories, information services
Disparities in Care The disparities in lung cancer treatment and outcomes and feeds, news services, preprint servers, data-sharing, and open access,
among underserved populations are well documented2. Further, 80% of to name just a few recent innovations, the role of the medical journal is
cancer patients are treated in the community hospital setting yet may not changing. Whilst it is true to say that for many physicians, certain journals
receive the same level of care as those treated at leading academic centers. are still seen as an authorative voice and a vital source of validated data to
The ALCF Community Hospital Centers of Excellence (COE) program addresses inform practice, this isn’t the case for all—indeed, any reasonably reputable
this unmet need. The COE program is a patient-centric model for lung cancer source of information, especially if easily available online, is increasingly
that establishes a standard of care for community hospitals which often treat considered to be a valid fount of medical evidence. So what is the role of the
underserved patient populations. The COE program, which currently includes medical journal in the online era? How do medical journals remain relevent,
13 hospitals in regions of high unmet need, aims to improve the standard continue to offer a valuable resource of practice-defining information, and
of care, patient experience and patient outcome by offering patients and play a important and collaborative role with their respective communities?
caregivers the same type of multi-disciplinary and comprehensive care How do medical journals not succumb to the fate of the newspaper or
provided at leading academic centers. ALCF also provides lung cancer music industries, in which the online revolution has caused considerable
education and services to patients, caregivers and the community. The COE upheaval—which many might argue has not resulted in a postive evolutionary
program tracks patient process data longitudinally for multiple quality-of- change for the betterment of all stakeholders? The central tenet for any
care metrics, including disease stage at diagnosis; molecular testing; tumor medical journal is publication of trustworthy data that have been thoroughly
board review; time from diagnosis to treatment; treatment type; and clinical reviewed and challenged prior to publication to ensure the interpretation is
accuate, honest, and will not cause harm if used in the real world. Moreover,
a good medical journal should be much more than this, and must show developing field of early diagnosis (in risk groups). Inform about advancing
leadership; take risks; distil the most important information to a time-poor science and medical procedures to overcome this old nihilistic view of lung
readership; provide innovative ways of linking disparate, but inter-related, cancer as something too poor and bad to speak and write about.
strands of information to a readership that no longer reads cover-to-cover;
and encourage scientific debate rather than simply reporting it. A good
contemporary medical journal therefore needs to be more than just a mirror
reflecting the lastest research or thinking without contest: it must inform
and drive research and clinical practice forwards. There are multiple ways in
which this can be achieved. First, a journal must offer a impartial platform for
presentation of data and discussion of ideas without prejudice, and ensure
studies are reported rigourously, transparently, and honestly. The activities
of an unconflicted editorial team and well-qualified peer reviewers are vital
in this regard, as is the application of reporting standards to ensure all data
and analyses are captured accurately. Second, journals have a responsibility
to ensure the ethical integrity of everything they publish. Journals should be
active members of independent ethics organisations and uphold the highest
standards. If any suspicion of misconduct occurs surrounding a published
article, reputable journals should always investgiate such allegations, which
often relate to issues such as: research conduct; reproducibility of data;
unethical behaviour in the laboratory or institution; plagarism; withholding of
pertinent data and misreporting; conflicts of interests; authorship disputes;
or compliance with prevailing governance structures. Academic institutions
take these issues very seriously because of the ramifications for their own
integity, and thus journals and instititions must work together to root-
out any misconduct and ensure the medical literature is trustworthy and
organisations practice science and medicine of the highest standards. Third,
journals can help further the practice of good science by taking a leadership
role in forward-focused programmes. Recent examples include the team
science programmes in the UK and USA, and the REWARD initiative. The
UK Academy of Medical Sciences Team Science project has been focused on
how biomedical researchers can be encouraged, supported, and rewarded
for participating in team-based collaborations—editors and publishers are
clear stakeholders in this debate; whilst the REWARD (REduce research
Waste And Reward Diligence) campaign encourages everyone involved
in biomedical research to critically examine the way they work to reduce
waste and maximise efficiency via five guiding principles: setting the right
research priorities; using robust research design, conduct, and analysis;
making sure regulation and management are proportionate to risks; ensuring
all information on research methods and findings are accessible; and
guaranteeing reports of research are complete and usable. Finally, a fifth role
for medical journals is to take an dynamic part in advocating change, leading
the direction of future research, and actively participating in health policy
reform and in initiatives to promote universal access to medicine. The Lancet
Oncology’s advocacy programme, for example, maps out the inequalities
and inequities in health systems worldwide, and highlights deficiencies in all
aspects of cancer care, health policy, structural organisation, and leadership.
The programme offers a impartial platform that brings together thought-
leaders from across different disciplines and organisations to offer solutions
to those barriers that hinder provision of high quality cancer control,
irrespective of socioeconomic status or country of residence. The journal
achieves this via specific, dedicated undertakings including Commissions,
series of inter-related papers on specific themes, targeted articles,
conferences, and events. The medical journal in the 21st century must evolve
from being a simple record of research to an engaged stakeholder advocating
and leading change in the practice of medicine. Journals should aim to be
platforms that bring together communities and thought-leaders rather than
disenfranchise groups in to silos. The world has never been as interconnected
as it is today, and it is only by working together with a clear vision that
journals, hand-in-hand with the communities they serve, will achieve the
progress needed to promote the best research and health policies to improve
healthcare for all.
Keywords: Medical publishing, Journals
SC31: TOGETHER AGAINST LUNG CANCER – A STRATEGY FOR SUCCESS IN THE 21ST
CENTURY
SC31.04 THE POSSIBILITIES OF PRINT & SOCIAL MEDIA

Wolfgang Wagner
General News/science/medicine, Austria Press Agency Apa, Vienna/Austria
Lung Cancer – What media can/should do Oncology today is one of the main
topics of health/medicine media coverage. With the advent of targeted and
immunotherapies there’s been a shift towards presenting the rapid advances
in this field. But contrary to topics like skin cancer, breast and colorectal
cancer lung cancer has stayed in the shadows of reporting until now. It has all
been anti tobacco campaigns often regarding smokers immoral, stigmatizing
the patients. Late diagnosis and advanced disease plus bad prognosis have
not made lung carcinoma a hot topic – and patient advocacy groups, often
key players in getting topics into the broad public, are rare. What we have
to do (besides non smoking campaigns): Produce valid information on the

like Uruguay for their progress in tobacco control. The Swiss government
MEET THE EXPERT SESSIONS prepared amendments for the tobacco law without considering the EU
tobacco directive. Tighter restrictions on tobacco advertising will probably be
SESSION MTE01: STRATEGIES TO IMPROVE TOBACCO eliminated from the Swiss law. A ban of sponsoring by tobacco companies was
not even considered within Switzerland. Lobbies in the Federal parliament
CONTROL IN CENTRAL EUROPEAN COUNTRIES and the government were able to block also comprehensive smoking bans.
(TICKETED SESSION) Fortunately, the country offers other political tools to progress, namely
MONDAY, DECEMBER 5, 2016 - 07:30-08:30 that counties can go for better policies, and Federal “initiatives” can be
launched to bring issues to the ballots. In fact, 8 out of 26 Swiss Counties
successfully adopted comprehensive smoking bans with no exemption. The
MTE01.01 STRATEGIES TO IMPROVE TOBACCO CONTROL IN Swiss parliament, however, was not even enabled to raise minimum prices of
CENTRAL EUROPEAN COUNTRIES tobacco. If the Track-and-Tracing-System of TPD-II is not joined, Switzerland
might become a platform for international tobacco smuggling. In restaurants
Martina Pötschke-Langer 1, Manfred Neuberger2
smaller than 80 square meters employers can still choose to permit smoking.
1
German Cancer Research Center, Heidelberg/Germany, 2Preventive Medicine, The largest progress of tobacco control in Switzerland was due to a tobacco
Medical University of Vienna, Vienna/Austria
prevention fund, financed from tobacco taxes (2.6 Rappen per pack of
Tobacco use is the single most preventable cause of death and disease, cigarette sold) since 2004. This fund finances also tobacco monitoring and
especially of lung cancer. Approximately 1.6 million people in the WHO smoking cessation (training of professionals). Swiss health insurance covers
European Region die of tobacco-related diseases every year and the Region both counseling and pharmaceutical support of smoking cessation. The
has the highest proportion of deaths (16%) attributable to tobacco use. largest progress of tobacco control in Central Europe was seen in Hungary,
Globally, Europe also has the highest prevalence of tobacco smoking which received the WNTD reward by WHO in 2013 and improved its ranking
among adults (28%), including one of the highest smoking prevalence rates by the European Cancer Leagues from place 27 in 2010 to place 11 in 2013.
among women (19%). In the meantime it is wellknown that a wide range of Only in Hungary there is a total ban on smoking in all enclosed public places
political decisions can stop the tobacco epidemic and reduce substantially (except prisons and psychiatric wards) since 2012, and tobacco shops (reduced
smoking. According to the first health treaty in history, the WHO Framework from 40 000 to 6 045) must not be entered below age 18. There is no tobacco
Convention on Tobacco Control, following strategies are the most effective: advertising outside these shops, no vending machine for cigarettes and plain
raising cigarette prices through higher cigarette taxe and combating packaging was introduced in 2016. The main obstacle against improvement
illicit trade of cigarettes, protecting from secondhand smoke through of tobacco control in the EU is corruption of certain politicians and media
comprehensive smoke-free air laws, enforcing bans on advertising, promotion by the tobacco industry and the subsidiarity principle in public health. The
and sponsorship, placing warnings (pictures and text as big as possible) on Green Paper of the EU “Towards a Europe free from tobacco smoke” showed
tobacco packages and communicate the warnings through media/educational policy options. 24 ministers of health voted on November 30, 2009 in favor
programmes and finally offering greater access to smoking cessation services. of implementing the WHO- FCTC until 2012, but not the representatives of
WHO Europe has established a database on countries of the WHO European Austria, Czech Republic and Slovak Republic. Up to now the implementation
region showing the effects of the reduction in smoking prevalence as a result of FCTC and the EU Council Recommendation on Smoke-free Environments
of implementing tobacco control policies. This presentation will analyse the is voluntary. All countries of Central Europe except Switzerland ratified the
current situation in this Region and showing the lessons learnt from past FCTC treaty, but nonsmoker’s protection follows article 8 only in Hungary.
years with regards to future prevention of smoking. In Central and Eastern Europe tobacco taxes and cigarette prices are much
lower than in Northern and Western Europe. In a European ranking according
Keywords: Strategies for effective tobacco control, WHO European region, to tobacco price increase by taxes, smoking restrictions at work and in public
especially Central Europe, Tobacco prevention places, consumer information, tobacco advertising bans, health warnings
and access to smoking cessation therapy, Austria, Germany, Cyprus, Czech
Republic, Greece and Lithuania had the poorest score and would need help by
more advanced EU members to reach Western standard. In summary, tobacco
MTE01: STRATEGIES TO IMPROVE TOBACCO CONTROL IN CENTRAL EUROPEAN control in Central Europe needs enforcement of FCTC, in particular article 5.3,
COUNTRIES (TICKETED SESSION) to stop interference of tobacco industry; application of strategies formulated
MONDAY, DECEMBER 5, 2016 - 07:30-08:30
by WHO (Monitor tobacco use & prevention, Protect from passive smoking,
Offer help to quit, Warn about dangers, Enforce bans on ads & promotion,
MTE01.02 STRATEGIES TO IMPROVE TOBACCO CONTROL IN Raise tobacco tax) and the World Bank (Curbing the Epidemic: Governments
CENTRAL EUROPEAN COUNTRIES and the Economics of Tobacco Control); financing of tobacco prevention and
cessation by tobacco taxes; comprehensive bans on advertising, promotion
Manfred Neuberger
and sponsorship of tobacco products and e-cigarettes (including ban of
Preventive Medicine, Medical University of Vienna, Vienna/Austria
vending machines, display ban at point of sales, plain packaging, stop of state
Up to now strategies of tobacco control, which were successful in Australia, funding for media violating article 13 FCTC); enforcement of smoke-free public
North America and Western Europe, have been introduced only in few places (without exceptions for hospitality industry), workplaces, schools,
Central European countries. Implementing the EU Tobacco Product Directive kindergartens, playgrounds, public transportation and private cars carrying
Austria extended existing smoking bans, advertising bans and mailing bans minors and promotion of nonsmoking by schools and media campaigns.
for tobacco products to e-cigarettes. Still missing is an enforced smoking
Keywords: prevention, cessation, Central Europe, Tobacco Control
ban without exceptions in the hospitality industry, an advertising ban and
display ban at point of sale, ban of vending machines, increase of age limit
for buying any cigarettes and tobacco products to 18 years, enforcement of
age control by regular test purchases, ban of free cigarettes (still allowed for
introduction of new sorts), extension of warnings and ban of aromas to cigars SESSION MTE03: BASICS OF MOLECULAR BIOLOGY FOR
and pipes, smoke-free hospitals and health care centers, smoke-free school
premises without exceptions, smoke-free playgrounds and cars carrying
THE CLINICIAN (TICKETED SESSION)
children, smoke-free public transportation including stations, increase of MONDAY, DECEMBER 5, 2016 - 07:30-08:30
tobacco tax earmarked for tobacco prevention (up to now only the quitline
has regular funding), stop of state funding for media violating article 13 FCTC,
enforcement of article 5.3 FCTC (transparency law), obligatory TV air time MTE03.01 BASICS OF MOLECULAR BIOLOGY FOR THE CLINICIAN
(e.g. 90 min/month like in Turkey) for promotion of non-smoking, inclusion Antonio Marchetti
of smoking prevention and cessation in the curricula of health professionals,
Center of Predictive Molecular Medicine, University of Chieti, Chieti/Italy
covering of counseling for smokers by health insurance, more frequent
surveys on smoking prevalence, including cotinine tests for risk groups The rapid development of molecular biology in recent years has allowed us
(pregnant women) and opinion leaders (journalists, health care workers), to understand the main molecular steps involved in the development and
scientific evaluations of efficacy and effectiveness of smoking prevention progression of lung cancer. The identification of molecular alterations in
and smoking cessation programs. Other Central European countries are facing specific tumor genes that function as key drivers for neoplastic growth has
similar problems. 13 of 16 federal states of Germany, the Czech Republic, laid the foundations for new therapeutic approaches with targeted agents.
Slovakia and most cantons of Switzerland did not succeed to pass and enforce An accurate detection of target mutation is mandatory for an efficient
smoking bans without exceptions in the hospitality industry. Germany treatment. The main limitation of targeted therapies is the occurrence of
is still violating the EU tobacco advertising ban and the Czech Republic acquired resistance that makes cancer unresponsive to treatment. In many
recently failed to ban the use of water-pipes and e-cigarettes in enclosed cases, through the acquisition of additional (secondary) mutations the tumor
spaces. Austria was the only Central European state, which ratified the FCTC is able to acquire the heterogeneity which may enable it to adapt to various
smuggling protocol up to now. Switzerland did not even ratify FCTC and was conditions of the microenvironment, including those determined by the
abused by the tobacco industry as a base to sue and intimidate small countries effect of treatment with specific drugs. New generation drugs are constantly
under development to overcome tumor resistance and increase survival of on the optimal treatment strategy for this subset of patients. When N2
lung cancer patients. In this process, a constant monitoring of the mutational disease is detected during thoracotomy, this is referred to as incidental,
status of the tumor is required. Different types of genetic alterations are unsuspected, unforeseen or “surprise” N2 [4]. When found intraoperatively, a
involved in tumor development, progression, and induction of resistance, resection should be performed as long as it can be complete. Adjuvant
including single nucleotide variants, indels, amplifications, fusions etc. chemotherapy prolongs survival and is currently recommended in this setting.
Mutation detection before first line treatment is usually performed on tissue However the role of radiotherapy remains controversial and is currently
or cytological samples. Resected tumor samples, biopsies and cytological evaluated in the randomized LungART trial (NCT00410683) [5]. In quite a large
specimens are available in about 25%, 35% and 40% of NSCLC patients, subgroup of patients, N2 disease is suspected on PET-CT scanning and
respectively. At progression, a re-byopsy should be obtained to detect the subsequently confirmed by minimally invasive or invasive staging techniques.
emergence of resistance-inducing mutations. Transbronchial tissue biopsy Although the term “potentially resectable N2” is often utilized, no precise,
is the most common sampling method used for re-biopsy. However, several internationally accepted definition is available. Most patients in this
factors limit the success rate of re-biopsy, such as the performance status of sub-group will be treated by concurrent chemo-radiotherapy alone or
the patient, the difficulty of accessing some tumor sites, and the invasiveness induction therapy followed by surgery or definitive radiotherapy. Whether
of sampling methods. When the amount and/or quality of the biological induction chemo-radiotherapy yields better results than chemotherapy alone
material is insufficient for molecular analysis, circulating free DNA (cfDNA) was studied in the recently published, randomised trial NCT00030771 of the
can represent a valid alternative in selected patients. Liquid biopsies have Swiss Cancer League [6]. No significant differences were found. However, this
several advantages over tissue or cells: they are less invasive, can be repeated study was not adequately powered to show non-inferiority between the two
over time, and have a more rapid turnaround time. However, there are some strategies. There are different restaging techniques to evaluate response
critical issues that must be considered: 1) the possibility to detect a mutation after induction therapy. In contrast to imaging or functional studies,
in cfDNA is dependent on several clinicopathological parameters, including remediastinoscopy provides pathological evidence but is technically more
tumor type, tumor burden, and particularly tumor stage (a locally advanced difficult and less accurate than mediastinoscopy done prior to induction
tumor has a significantly lower probability to spread mutant DNA in the blood treatment [3]. An alternative approach consists of the use of minimally
than a metastatic tumor); 2) a large amount of wild-type DNA circulates in the invasive staging procedures to obtain an initial proof of mediastinal nodal
plasma with only trace amounts of the mutant allele; therefore, the analysis involvement. Mediastinoscopy is subsequently performed after induction
of genetic aberrations in cfDNA is challenging, requiring well standardized therapy to evaluate response [3]. In patients with proven mediastinal
pre-analytical/analytical protocols and dedicated techniques with high downstaging after induction who can preferentially treated by lobectomy,
sensitivity and specificity. Different technologies/protocols are required for surgical resection may be recommended. Whether radiotherapy yields similar
the detection of these genetic aberrations. Robust and sensitive molecular results has not been established yet. One of the reasons is that in patients
biology techniques are nowadays available to detect mutations in driver undergoing chemo-radiotherapy pathology to evaluate response is not
genes before initiating a targeted treatment or to identify the emergence of available making comparison with surgery quite difficult. A recent meta-
secondary mutations at disease progression. The use of multimarker assays, analysis tried to better clarify the outcome of surgery compared to
and in particular next generation sequencing, is progressively becoming radiotherapy after induction treatment in patients with N2 disease [7]. Six
popular, allowing on one hand to reduce the working time, costs per single trials including a total of 868 patients were included. Main outcome was
assay, and the amount of nucleic acids required for testing and increasing, in overall survival. The authors concluded that when bimodality treatment is
the other hand, throughput and overall quality. Recently, semi-quantitative or applied, both surgery and radiotherapy options are valid with a pooled hazard
quantitative detection methods for the assessment of genetic aberrations in ratio for mortality in the surgery group of 1.01 (p not significant). In contrast,
cfDNA have been developed with a number of potential clinical implications. in trimodality regimens results support surgical resection as part of
An accurate quantification of mutated alleles in cfDNA during the first days multimodality management with a pooled hazard ratio for mortality in the
of treatment could: a) complement or replace more expensive and invasive surgery group of 0.87 indicating a 13% relative improvement in overall survival
methods to assess response in treated patients; b) represent a new way (p= 0.068). In the recently published ESPATUE trial, patients with resectable
to compare the effectiveness of different drug; c) be an additional tool to stage IIIA-N2 and selected stages IIIB NSCLC were included [2]. No significant
evaluate the best treatment regimen for patients. In addition, a periodic differences were found between the control arm consisting of induction
quantification of the mutation burden during all the treatment time could chemotherapy followed by definitive chemo-radiotherapy, and the
allow an early detection of resistance-inducing mutations for possible experimental arm administering induction chemotherapy followed by
changes to therapy. chemo-radiotherapy with a dose of 45 Gy, followed by surgical resection. Both
treatment options are considered acceptable strategies for these highly
Keywords: Targeted Therapies, Acquired resistance, Lung cancer molecular selected patients with a relatively good prognosis. North American (American
biology College of Chest Physicians 2013) [8] and European guidelines (European
Society of Medical Oncology 2015) [1] recommend that in NSCLC patients with
N2 involvement the treatment plan should be made with the input of an
experienced multidisciplinary team. The ESMO guidelines include induction
chemotherapy followed by surgery, induction chemoradiotherapy followed by
SESSION MTE05: WHERE IS THE PLACE OF SURGERY FOR surgery, or concurrent definitive chemoradiotherapy as possible treatment
N2 DISEASE? (TICKETED SESSION) strategies for potentially resectable stage IIIA-N2 However bulky N2 disease is
MONDAY, DECEMBER 5, 2016 - 07:30-08:30 mostly treated with chemo-radiotherapy as these patients do not qualify for
surgical resection due to extensive extracapsular involvement [1].
Furthermore complete resection, which is a major prognostic factor, is mostly
MTE05.01 WHERE IS THE PLACE OF SURGERY FOR N2 DISEASE? not achievable in this subset of N2 disease. The standard of care in patients
with good performance status is concurrent chemoradiotherapy [1]. Of
Paul Van Schil1, Corinne Faivre-Finn2 particular interest to thoracic surgeons is the relatively new concept of
1
Thoracic and Vascular Surgery, Antwerp University Hospital, Edegem (Antwerp)/ “salvage” surgery after full-dose chemo-radiotherapy in stage IIIA-N2 NSCLC
Belgium, 2Radiotherapy Research Related, The University of Manchester and the
[9, 10]. These patients present with recurrent or progressive locally advanced
Christie NHS Foundation Trust, Manchester/United Kingdom
disease, in some cases complicated by an infected cavity, rendering surgical
The diagnostic and management strategies for stage IIIA-N2 non-small cell resection technically difficult. Furthermore, a systematic nodal dissection
lung cancer (NSCLC), which represents locally advanced disease with may be challenging, especially when bulky lymph nodes were initially present.
involvement of ipsilateral mediastinal lymph nodes, remain controversial In conclusion, although randomised controlled trials are available, no definite
despite results from several randomized controlled trials [1-2]. There are answer can be provided regarding the optimal strategy for staging, restaging
various reasons for this ongoing debate. First, stage IIIA-N2 represents a very and treatment of the different subsets of stage IIIA-N2 disease. Every patient
heterogeneous patient population ranging from incidental discovery of with locally advanced NSCLC should be discussed within a multidisciplinary
positive N2 nodes during lung resection, to single mediastinal nodal tumour board including radiation oncologists and thoracic surgeons who have
involvement and bulky N2 disease where individual lymph nodes are hard to a large experience with major lung resections. The best available diagnostic
identify. In this setting, the precise diagnostic algorithm remains and treatment strategies should be discussed with the patient. Salvage
controversial. Currently, patients with proven or suspected lung cancer are surgery should be reserved for those centres having a large experience in
mainly staged by integrated positron emission tomography – computed thoracic surgery where a dedicated team is available as management of these
tomography (PET-CT). However pathological proof of nodal involvement patients requires multidisciplinary cooperation preoperatively,
should be obtained by a minimally invasive or invasive technique due to a intraoperatively and postoperatively.References 1. Eberhardt WE, De
relatively high rate of false positive nodes, owing to mainly inflammation [3]. Ruysscher D, Weder W, Le Péchoux C, De Leyn P, Hoffmann H et al. 2nd ESMO
Secondly, the optimal restaging strategy after induction therapy is heavily Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell
debated. Thirdly, specific controversy relates to the role of surgery versus lung cancer. Ann Oncol 2015; 26:1573-88. 2. Eberhardt WE, Pöttgen C, Gauler
radiotherapy and the precise extent of resection after induction therapy. TC, Friedel G, Veit S, Heinrich V et al. Phase III study of surgery versus
Randomized trials included different subsets of N2 disease making the definitive concurrent chemoradiotherapy boost in patients with resectable
interpretation of results quite difficult. As a result of the limitations of stage IIIA-N2 and selected IIIB non-small-cell lung cancer after induction
available data heated discussions have been taking place for several decades chemotherapy and concurrent chemoradiotherapy (ESPATUE). J Clin Oncol

2015; 33:4194-201. 3. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, and cetuximab results crossed protocol specified futility boundaries. We
Rami-Porta R et al. Revised ESTS guidelines for preoperative mediastinal recorded no statistical differences in grade 3 or worse toxic effects between
lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg radiotherapy groups. By contrast, the use of cetuximab was associated with
2014; 45:787-98. 4. Van Schil P. Stage IIIA-N2 non-small-cell lung cancer: from a higher rate of grade 3 or worse toxic effects (205 [86%] of 237 vs 160 [70%]
“surprise” involvement to surgical nightmare. Eur J Cardiothorac Surg 2016; of 228 patients; p<0.0001). There were more treatment-related deaths in
49:1613-4. 5. Le Péchoux C, Dunant A, Faivre-Finn C, Thomas PA, Pourel N, the high-dose chemoradiotherapy and cetuximab groups (radiotherapy
Lerouge D et al. Postoperative radiotherapy for pathologic N2 non-small cell comparison: eight vs three patients; cetuximab comparison: ten vs five
lung cancer treated with adjuvant chemotherapy: need for randomized patients). Severe esophagitis was more common in patients who received
evidence. J Clin Oncol 2015; 33:2930-1. 6. Pless M, Stupp R, Ris HB, Stahel RA, high-dose chemoradiotherapy than in those who received standard-dose
Weder W, Thierstein S et al. Induction chemo-radiotherapy in stage IIIA/N2 treatment (43 [21%] of 207 patients vs 16 [7%] of 217 patients; p<0.0001).
non-small cell lung cancer: a phase 3 randomised trial. Lancet 2015; This study did not mandate 4D simulation and possibly GTV was not well
386(9998):1049-56. 7. McElnay PJ, Choong A, Jordan E, Song F, Lim E. Outcome covered by the dose prescribed. There was higher local failure in the 74 Gy
of surgery versus radiotherapy after induction treatment in patients with N2 arm because of tighter margin in this group. We assumed from this study
disease: systematic review and meta-analysis of randomised trials. Thorax that 74 Gy radiation given in 2 Gy fractions with further improvements are
2015; 70:764-8. 8. Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, expected from the use of charged particle therapy with protons or other
Balekian AA et al. Treatment of stage III non-small cell lung cancer: diagnosis particles; randomized comparisons of proton therapy vs. intensity-modulated
and management of lung cancer, 3rd ed: American College of Chest Physicians photon radiation therapy for lung cancer are underway in the United States
evidence-based clinical practice guidelines. Chest 2013; 143 (5 Suppl): .A secondary analysis was performed to compare IMRT with 3D-CRT in NRG
e314-30S. 9. Van Schil P. Salvage surgery after stereotactic radiotherapy: a Oncology clinical trial RTOG 0617. The median follow-up was 21.3 months.
new challenge for thoracic surgeons. J Thorac Oncol 2010; 5:1881-2. 10. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The
Schreiner W, Dudek W, Sirbu H. Is salvage surgery for recurrent non-small-cell IMRT group had larger planning treatment volumes (median, 427 v 486 mL;
lung cancer after definitive non-operative therapy associated with reasonable P =.005); a larger planning treatment volume/volume of lung ratio (median,
survival? Interact Cardiovasc Thorac Surg 2015; 21: 682-4. 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056).
Two-year OS, progression-free survival, local failure, and distance metastasis
Keywords: induction therapy, Chemo-radiotherapy, Surgery, stage IIIA-N2 were not different between IMRT and 3D-CRT. IMRT was associated with
disease fewer grade 3 or greater pneumonitis (7.9% v 3.5%, P = .039) and a reduced
risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046).
IMRT also produced lower heart doses (P <0 .05), and volume of heart
receiving 40 Gy (V40) was significantly associated with OS on adjusted
analysis (P<0.05). Lung V5 was not associated with any toxicity equal or
SESSION MTE06: RADIOTHERAPY TECHNIQUES IN LUNG greater than grade 3, whereas lung V20 was associated with increased grade
3 or greater pneumonitis risk on multivariable analysis (P = .026). IMRT was
CANCER (TICKETED SESSION) associated with lower rates of severe pneumonitis and cardiac doses in
MONDAY, DECEMBER 5, 2016 - 07:30-08:30 NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT
for locally advanced NSCLC. We have evidence that severe pneumonitis
and esophagitis have been reduced by proton compared to IMRT with
concurrent chemotherapy for stage III NSCLC. However it is difficult to
MTE06.01 RADIOTHERAPY TECHNIQUES IN LUNG CANCER do a randomized trials. In conclusion, screening by low dose spiral CT scan
Ritsuko Komaki for among previous or current smokers to detect early lung cancer. Early lung
Radiation Oncology, Unit 97, MD Anderson Cancer Center, Houston/TX/United cancer can be curable by SBRT Lung cancer treatment planning requires 4D
States of America simulation. The technical advancement such as IMRT or Proton Treatment
compared to 2 or 3 dimensional radiotherapy with concurrent chemotherapy
Recent Advances in Radiation Treatment Technique for Lung Cancer Lung
reduced normal tissue toxicity among patients with locally advanced lung
cancer is the leading cause of cancer-related death in the United States and
cancer which will improve their outcome in future. We are testing this
throughout the world. Advancement of Radiation Treatment have been
hypothesis by a randomized prospective study.
parallel to imaging capability to target cancer and avoid surrounding normal
tissue structure which associated with volume and dose. We can cure most Keywords: Advances, Technique, Lung, Cancer
of early lung cancer if it is well staged early cancer and targeted correctly by
stereotactic body radiation therapy (SBRT). Because of high dose per fraction,
technical aspects and quality assurance to deliver the radiation to the
tumor precisely and avoid high dose of radiation to the critical surrounding MTE06: RADIOTHERAPY TECHNIQUES IN LUNG CANCER (TICKETED SESSION)
normal tissue are critical issues organs in addition to controlling tumor MONDAY, DECEMBER 5, 2016 - 07:30-08:30
motion. Technologic advancements of imaging and radiotherapy to conform
the gross target volume(GTV) with tighter margins but adequate clinical
MTE06.02 RADIOTHERAPY TECHNIQUES IN LUNG CANCER
targeted volume (CTV) and planning tumor volume (PTV) considering daily
set up variations which are supposed to minimize the dose to nearby normal Martin Stuschke, Christoph Pöttgen
tissues. We have tried to answer higher radiation dose improve survival by West German Cancer Center, University of Duisburg-Essen, Essen/Germany
the RTOG 0617 which compared overall survival after standard-dose versus
Dose escalation with conventional fractionation and concurrent platin-
high-dose intensity-modulated radiation therapy (IMRT) or three-dimensional
based chemotherapy within the RTOG 0617 trial has failed to show a
conformal radiation therapy (3DCRT) with concurrent chemotherapy +/-
survival benefit. Proton therapy has failed to show a reduction in radiation
cetuximab for patients with inoperable stage III non-small-cell lung cancer.
pneumonitis in comparison to intensity modulated photon radiotherapy at
In this open-label randomized, phase 3 study in 185 institutions in the USA
the same total dose according to the NCT 00915005 trial. Randomized trials
and Canada, we enrolled patients (aged ≥18 years) with unresectable stage
for comparison of IMRT and 3D conformal radiotherapy are lacking. While
III non-small-cell lung cancer, a Zubrod performance status of 0–1, adequate
randomized trials conducted so far failed to show an increment in survival by
pulmonary function, and no evidence of supraclavicular or contralateral
newer radiotherapy concepts on one hand, the old standard of giving 60 Gy
hilar adenopathy. We randomly assigned (1:1:1:1) patients to receive either
with conventional fractionation and concurrent chemotherapy consolidated
60 Gy (standard dose), 74 Gy (high dose), 60 Gy plus cetuximab, or 74 Gy plus
on the other. So where does the hope come from that technological advances
cetuximab. All received concurrent chemotherapy with 45 mg/m2 paclitaxel
in radiotherapy lead to an improved survival in locally advanced lung cancer, if
and carboplatin once a week (AUC 2); 2 weeks after chemoradiation, two
not from randomized trials? It comes from many small precious components
cycles of consolidation chemotherapy separated by 3 weeks were given
that can lead to an increase of loco-regional control by radiotherapy in
consisting of paclitaxel (200 mg/m2) and carboplatin (AUC 6). Radiation dose
locally advanced NSCLC, the primary goal of radiotherapy. First of all, the
was prescribed to the PTV and was given in 2 Gy daily fractions with either
determination of tumor spread has been substantially improved by the
IMRT or 3DCRT. For patients assigned to receive cetuximab, 400 mg/m2
introduction of FDG-PET/CT, by systematic mediastinal evaluation with
cetuximab was given on day 1 followed by weekly doses of 250 mg/m2, and
EBUS-TBNA, and by brain MRI. The determination of tumor position during
was continued through consolidation therapy. 166 patients were randomly
irradiation has been improved by stereoscopic KV imaging during irradiation
assigned to receive standard-dose chemoradiotherapy, 121 to high-dose
or real-time magnetic resonance imaging and therefore tumor targeting
chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab,
can be optimized. Volumetric modulated arc therapy can deliver conformal
and 110 to high-dose chemoradiotherapy and cetuximab. Median follow-up
dose distributions within a breath hold of 20 s. With hyperfractionated
for the radiotherapy comparison was 22.9 months (IQR 27.5–33.3). Median
acceleration and concurrent chemotherapy, high biologically effective doses
overall survival was 28.7 months (95% CI 24.1–3.9) for patients who received
can be given for patients with locally advanced NSCLC resulting in similar
standard-dose radiotherapy and 20.3 months (17.7–25.0) for those who
survival and local control rates than with trimodality treatment. Integrated
received high-dose radiotherapy (hazard ratio [HR] 1.38, 95% CI 1.09–1.76;
boost radiotherapy controlling dose gradients form gross tumor volume
p=0.004). Median overall survival in patients who received cetuximab was
towards organs at risk as the contra-lateral bronchial wall or the esophagus
25.0 months (95% CI 20.2–30.5) compared with 24.0 months (19.8–28.6)in
has become feasible and is tested within prospective trials. Immunotherapy
those who did not (HR 1.07, 95% CI 0.84–1.35; p=0.29). Both the radiation-dose
and molecular targeted therapies are upcoming as combination partners with established training and validation sets. Tissue microarrays were scored for
radiotherapy in selected tumors. Proper patient selection criteria resulted stromal CD8 TLI’s; stromal CD8 TIL density was found to be an independent
long term survival as high as 30-45% in multicenter prospective trials in prognostic factor and retained significant prognostic impact within each
locally advanced NSCLC. These advantages have to be bundled into new stage. The value of PD-L1 as a biomarker in NSCLC has been investigated
radiotherapeutic concepts and tested against the standard of conventional primarily in advanced disease and focused on prediction of response and/
fractionated radiotherapy up to 60 Gy and simultaneous chemotherapy in or survival. Studies investigating the value of PD-L1 as a prognostic marker
future well designed randomized trials. in early stage NSCLC have many limitations. These studies are small, include
heterogenous populations, assess PD-L1 using different antibodies and
Keywords: dose painting, dose escalation, image guidence, IMRT scoring systems and included PD-L1 on tumour cells only or tumour cells
and TLI’s. It is not surprising that these studies show conflicting results.
Based on the available evidence, the prognostic value of PD-L1 expression in
early stage NSCLC remains uncertain. The adjuvant trials of anti-PD1/PD-L1
therapy currently being conducted may clarify the value of PD-L1 as both
SESSION MTE08: IMMUNOTHERAPY IN EARLY AND prognostic and predictive biomarkers in this setting. Challenges One of the
LOCALLY ADVANCED NSCLC: CHALLENGES AND PERSPEC- fundamental challenges to developing effective cancer immunotherapies is
TIVES (TICKETED SESSION) our limited understanding of the human immune system in steady state and
MONDAY, DECEMBER 5, 2016 - 07:30-08:30 its response to stress. Animal models do not necessarily translate to humans.
The Human Vaccines Project (8) is a global initiative that has as one of its
primary objectives the decoding of the human immune system and providing
a map of the human “immunome”. This private-public partnership uses state-
MTE08.01 IMMUNOTHERAPY IN EARLY AND LOCALLY ADVANCED of-the-art machine learning and technologies to elucidate the principles of
NSCLC: CHALLENGES AND PERSPECTIVES immunogenicity to accelerate the development of new immunotherapies
Charles Butts 1, Frank Griesinger 2 against infectious diseases and cancer. A second challenge is how best to
1
Medical Oncology, Cross Cancer Institute, Edmonton/Canada, 2Oncology, Pius- target micrometastases in the adjuvant and locally advanced setting. While
Hospital Oldenburg, Oldenburg/Germany the primary tumor and metastatic lesions have many mutations in common,
metastatic tumors possess mutations that are distinct from the primary.
The demonstration that therapies directed at the programmed death-1 Do adjuvant therapies need to target the metastatic cascade and if so,
(PD-1) receptor or its ligand (PD-L1) result in durable responses and improved which steps are the most susceptible to intervention? (9) The complex of the
survival in a number of solid tumours including non-small cell lung cancer TME would predict that focusing on TIL’s or PD-L1 is likely to result in only
has awakened interest in cancer immunotherapy. The activity of PD-1/PD-L1 modest improvements in outcome. Blank et al (10) argue that it will take a
therapy in NSCLC implies that endogenous T-cells can recognize antigens combination of biomarkers, the “cancer immunogram” , to determine the best
on tumour cells and eliminate those cancer cells. The success of checkpoint approach in individual patients.References:
inhibitor therapy in the metastatic setting has led to a immunotherapy
trials in early stage (adjuvant) and stage lll NSCLC. This session will provide Lancet Oncol 2016. 17;(8): 22-35
perspective on the current state and challenges facing immunotherapy in
these settings. Current perspectives: The concept of using immunotherapy Lancet Oncol 2014; 15 : 59-68
to prevent recurrence of NSCLC after resection of early stage NSCLC is not
Ann Oncol 2015; 26: 2213-2220
new. More recently, two randomized phase lll trials of therapeutic cancer
vaccine strategies have been completed in resected, early stage NSCLC Nat Rev Immunology, 2015; 15: 73-86
(MAGRIT) or after chemoradiation in stage lll disease (START). The MAGRIT
trial (1) assessed the efficacy of an active, specific cancer immunotherapy Clin Cancer Res 2011; 17(16): 5247-56
(ASCI) against the MAGE-A3 cancer testis antigen in completely resected
stage IB-IIIA NSCLC. Tumors from more than 13,000 patients were screened J Clin Oncol 2016; 34:1223-30
for MAGE-A3 expression and 2312 patients whose tumours expressed MAGE
Clin Cancer Res 2015; 21(11): 2635-43
A3 were randomized 2:1 to MAGE-A3 (ASCI) or placebo. The MAGRIT trial failed
to meet its primary end-point of improvement in disease free survival with Science Translational Medicine 2016; 8(334): 334-339
MAGE-A3 ASCI. The START trial(2) assessed a MUC1 vaccine in stage III NSCLC
patients who had response or stable disease after standard chemoradiation. Nature Reviews Cancer 2015; 16: 201-218
The chemoradiation could have been delivered concurrently or sequentially.
The modified intention to treat population included 1239 patients. The Science 2016; 352(6286):658-660
primary end-point was not met (adj. HRO .88, 95% CI 0.75 -103, p=0.123).
Keywords: non-small cell lung, early stage, adjuvant, immunotherapy
Further development of this agent has been abandoned. The failure of these
two large global phase III studies raises doubt about vaccine strategies used in
isolation in early stage NSCLC. There are a number of possible explanations for
these negative results (3). One of the primary reasons is that cancer vaccines
, when used alone, fail to address the many immunosuppressive factors
SESSION MTE09: BIOMARKERS FOR TARGETED THERAPIES
operating in the tumour microenvironment (TME). Clinical trials evaluating
anti PD-1/PD-L1 therapy in early stage or locally advanced NSCLC have not AND IMMUNE CHECKPOINT INHIBITORS IN ADVANCED
yet reported results. The PACIFIC trial (NCT 20125461) is a randomized phase NSCLC (TICKETED SESSION)
III trial of MEDI4736 versus placebo following concurrent chemoradiation MONDAY, DECEMBER 5, 2016 - 07:30-08:30
in patients with stage III NSCLC. The primary outcome measures are OS and
PFS. This trial completed accrual in April 2016 and has randomized more than
700 patients. In addition to the important efficacy outcomes, a number of MTE09.01 BIOMARKERS FOR TARGETED THERAPIES AND IMMUNE
exploratory objectives will assess tissue and blood for potential biomarkers.
CHECKPOINT INHIBITORS IN ADVANCED NSCLC
The Canadian Cancer Clinical Trials Group is assessing MEDI 4736 versus
placebo in completely resected stage IB-IIIA NSCLC (NCT 02273375). This trial Jie Wang
will randomize 1100 patients with the primary outcome measure being DFS Thoracic Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences,
in PD-L1 positive patients. PD-L1 positive is defined as > % positive tumour Beijing/China
cells. Immune Based Prognostic Markers: The TME consists of stromal cells
The targeted therapy based on genotyping has become an important
including endothelial cells and fibroblasts and a number of immune cell
treatment approach for advanced non-small cell lung cancer (NSCLC),
types. Tumours may escape immune recognition in large part by modulating
especially adenocarcinoma. It is reported that nearly fifty to sixty percent
the recruitment and function of various immune cells into the TME (4). A
of Asian patients with lung adenocarcinoma could have survival benefit
comprehensive review of the prognostic value of different immune cells in
from the first generation epidermal growth factor receptor-tyrosine kinase
NSCLC has been reported (5). Two recent studies have separately assessed
inhibitors (EGFR-TKI) and Anaplastic Lymphoma kinase (ALK)-TKI. However,
tumour lymphocytic infiltration (TLI) (6) or stromal CD8+ T-cell density
the targeted therapy has apparently reached a plateau due to the drug
(7) as potential prognostic markers in early stage NSCLC. Using the large,
resistance. The spatial and temporal heterogeneity of tumors are regarded
relatively homogenous population of curative resected NSCLC patients
as the foundation of both primary and acquired resistance. Multiple studies
from the LACE-Bio collaboration, Brambilla et al examine the prognostic and
show that the mechanism of acquired resistance to first generation EGFR-
predictive value of TLI. Patients were separated into discovery and validation
TKI is complicated, including T790M mutation, PI3KCA mutation, c-MET
sets. An intense TLI (>50% stromal lymphocytes in tumour bulk) was strongly
amplification, and histologic transformation from NSCLC to SCLC et al, some
prognostic of favourable overall survival and disease free survival. Based
of which could co-exist in the same patient. Although the third generation
on previous work, Donner et al selected stromal CD8+ tumour infiltrating
EGFT-TKI targeted at T790M mutation has been proved with dramatic
lymphocyte as the most promising immuno-based prognostic marker.
efficacy, most patients become resistant after 10 months of therapy, the
Using four separate cohorts of curatively resected stage I-III patients, they

mechanism of which is even more complicated. Recently, by conducting next an overall objective tumor response rate of about 60%. Another molecular
generation sequencing (NGS) through peripheral blood samples of patients aberration which is of importance for treatment decision in patients with
treated with AZD9291 and CO1686 in clinical trials, newly drug-resistant advanced NSCLC is the rearrangement of the anaplastic lymphoma kinase
mutations such as C797S and C693I have been found and functionally (ALK) gene. It was demonstrated that patients with an ALK rearrangment do
verified. This has laid a solid foundation for developing the fourth generation benefit from therapy with the ALK inhibitor crizotinib. Second generation ALK
medicine in future undoubtedly. In the meanwhile, the resistant mechanism inbibitors (e.g. alectinib, brigatinib, ceritinib) can overcome resistance which
to ALK-TKI is also very complex. Multiple drug-resistant mutations could not may be mediated by secondary ALK mutations. Moreover, third generation
only occur in ALK kinase domain, but also in alternative signal pathways. ALK inhibitors (e.g. lorlatinib) were developed and are currently being tested.
Therefore, we should establish a real-time, dynamic and quantitative Similar to patients with an ALK rearrangement also patients with a ROS1
detecting system for multiple targetable genes to fulfill detecting and rearrangement may benefit from treatment with crizotinib. The relevance
monitoring the drug resistance during treatment, and on the other hand, of other molecular characteristics like KRAS or BRAF mutations, c-met
to explore novel drug-resistant mutations through NGS of peripheral blood amplification and HER2 abnormalities as potential biomarkers for targeted
samples in future. Checkpoint inhibitors have been studied and utilized therapies is currently under investigation. Programmed death 1 (PD-1)
in various cancers, which has changed the perennially stagnant situation immune checkpoint inhibitor antibodies like nivolumab or pembrolizumab are
of immunotherapy and opened a new chapter in the treatment of cancers. used in the clinical routine, however, only about 20% of patients do benefit
Studies have shown an objective response rate of approximately 20%-30% from this treatment. To use resources as effective as possible, a biomarker
with a prolonged survival period of 3-6 months to a series of programed death to predict tumor response to these type of drugs would be enormous helpful
(PD1)/ programed death-ligand 1(PD-L1) inhibitors immunotherapy in lung in order to save costs. So far, the impact of expression of the PD ligand 1
cancer patients, with adenocarcinomas, squamous cell carcinomas and small (PD-L1) regarding clinical benefit to PD1 and PD-L1 inhibitor therapy was,
cell carcinomas. While the biggest challenge of immunotherapy currently is to besides efficacy of these drugs in comparison to chemotherapy, investigated
establish a powerful predictive system for efficacy. The existing researches in several randomized clinical trials. While in the CheckMate 017 study the
mostly focus on exploring whether the PD-L1 expression or tumor infiltrating overall survival of squamous cell carcinoma patients treated with nivolumab
lymphocytes (TIL) status could predict the efficacy of PD1/PD-L1 inhibitors. was independent from PD-L1 expression on tumor cells, in the CheckMate 057
The results varied from different agents of PD1/PD-L1 inhibitors and results study there seems to be some association between the PD-L1 expression level
of different trails. For instance, PD-L1 expression was associated with and the overall survival of adenocarcinoma patients treated with nivolumab.
response to Nivolumab in patients with lung adenocarcinoma, while this kind In the KEYNOTE-010 trial especially patients (both squamous cell and
of relationship was not observed in squamous cell NSCLC. The inconsistency adenocarcinoma histology) with high (≥ 50% score) PD-L1 expression on tumor
between different trails may be attributed to the heterogeneity of PD-L1 cells did benefit from treatment with pembrolizumab. PD-L1 expression on
expression, the unstandardized sample collecting and storing, and issue in tumor cells as well as on tumor infiltrating immune cells were investigated in
IHC evaluation system. So the future investigation should lay more emphasis patients treated with the PD-L1 inhibitor atezolizumab in the POPLAR study.
on overcoming tumor heterogeneity, standardization and optimization of The overall survival benefit from atezolizumab increased with increasing
detection techniques and sample collections, based on which we are looking PD-L1 expression on tumor cells, tumor infiltrating immune cells or both.
forward to more effective predictive biomarkers. Both tumor and host Overall, currently the impact of PD-L1 expression and the use of certain cut-off
microenvironment should be equally important as the foundation of precision levels to predict response to PD-1 and PD-L1 inhibitors is still under discussion.
medicine for cancer. More and more studies show that mutation loads of Different findings may, at least partly, be explainded by the use of variables
somatic cells contribute to immunogenicity of tumors, so as to be associated regarding tissue fixation and storage as well as by different antibodies for
with the efficacy of checkpoint inhibitors. One research showed that different detection of PD-L1. Alternative biomarker approaches are currently being
types of mutations, such as EGFR mutation, ALK fusion gene and PI3KCA investigated. In particular, the mutational load as well as the number of
mutation, possess different levels of mutation loads. And another research predicted neoantigens may be of importance. An association between
indicated that lung adenocarcinoma with higher neoantigen-load responded a higher nonsynonymous mutation burden in tumors and an improved
better to checkpoint inhibitors than the lower ones. There has been a study objective reponse, durable clinical benefit as well as progression-free survival
to calculate mutation loads and neoantigens in adenocarcinoma or squamous in patients treated with pembrolizumab was reported and, in addition,
carcinoma by whole Exome sequencing based on the Cancer Genome Atlas the efficacy was associated with the molecular smoking signature, higher
(TCGA). The future studies should pay close attention to exploring the neoantigen burden and DNA repair pathway mutations. Overall, additional
dynamic change patterns of mutation loads and neoantigens prior and during studies are necessary to definitely define the impact of PD-L1 expression as
the treatment strategies, including PD-1/PD-L1 inhibitors immunotherapy, biomarker for PD-1 and PD-L1 inhibitors as well as to investigate the value of
targeted therapy and traditional chemotherapy, and also to investigate the alternative biomarkers. In conclusion, strong biomarkers are able to predict
relationship between regulatory immune factors in the microenvironment, response to certain therapies. Thus, ineffective treatment strategies may
to further establish the predictive system for immunotherapy integrating be prevented and resources including costs may be saved. So far, a few
PD-L1,PD-L2, TIL mutation loads of somatic cells, and neoantigens which are biomarkers are known which are very well established in the clinical routine
in great expectations. and are important for treatment decisions in NSCLC patients. Regarding
immunotherapy, it seems that the expression of PD-L1 may has some impact
Keywords: Immune checkpoint inhibitors, biomarker, dynamic change, to predict response to PD-1 and PD-L1 inhibitors, however, its role needs to
Targeted Therapies be completely clarified. Several candidate biomarkers exist, however, their
impact needs to be futher investigated.
Keywords: EGFR, ALK, ros1, PD-L1

MTE09: BIOMARKERS FOR TARGETED THERAPIES AND IMMUNE CHECKPOINT
INHIBITORS IN ADVANCED NSCLC (TICKETED SESSION)
MONDAY, DECEMBER 5, 2016 - 07:30-08:30
MTE09.02 BIOMARKERS FOR TARGETED THERAPIES AND IMMUNE SESSION MTE10: UNIQUE BIOLOGIC ASPECTS OF TOBAC-
CHECKPOINT INHIBITORS IN ADVANCED NSCLC CO-INDUCED LUNG CANCER (TICKETED SESSION)
Sabine Zöchbauer-Müller TUESDAY, DECEMBER 6, 2016 - 07:30-08:30
Department for Internal Medicine I, Medical University of Vienna, Vienna/Austria
Targeted therapies or immune checkpoint inhibitors may be the adequate MTE10.01 UNIQUE BIOLOGIC ASPECTS OF TOBACCO-INDUCED
treatment in some patients with advanced non-small cell lung cancer (NSCLC).
LUNG CANCER
So far, certain biomarkers are known which may predict tumor response to
these drugs. Of major importance is the detection of activating epidermal Mauro Papotti, Giorgio Scagliotti
growth factor receptor (EGFR) mutations. They occur more frequently Oncology, University of Turin, Orbassano Turin/Italy
in the asian compared to the caucasian population and are usually found
Lung cancer is the leading cause of cancer death worldwide and cigarette
within exon 18-20 of the EGFR gene. Most of them are either a deletion at
smoking is a major causative environmental factor. Some unique biologic
exon 19 or the L858R point mutation at exon 21. Activating EGFR mutations
profiles are associated to tobacco-induced lung cancer, including clinical,
are predominantly detected in female patients with adenocarcinoma
pathological and genetic features. Lung cancer in never smokers (up to 20%
histology and never (or low) smoking history. The efficacy of first (erlotinib,
of cases worldwide) has been suggested to represent a distinct disease,
gefitinib) and second (afatinib) generation EGFR tyrosine kinase inhibitors
compared to tobacco-induced lung cancer. Cigarette smoke is a mixture
(TKI) in patients with advanced NSCLC and an activating EGFR mutation
of more than 5000 chemical compounds, among which more than 60 are
was demonstrated in several clinical studies. However, at some time during
recognized to have a specific carcinogenic potential. Carcinogens and their
treatment with a first- or second generation TKI usually resistance to these
metabolites (i.e., N-nitrosamines and polycyclic aromatic hydrocarbons,
drugs occurs which is mediated by the EGFR T790M mutation in about 50%.
among others) can activate multiple pathways, contributing to pulmonary
Recent trials demonstrated that third generation EGFR TKIs like osimertinib
cell transformation in different ways. Nicotine, originally thought to be
and olmutinib may be effective in T790M mutation positive patients with
responsible for tobacco addiction, only, is also involved in tumor promotion
and progression with anti-apoptotic and indirect mitogenic properties (Tonini Keywords: PATHOLOGY, LUNG CANCER, TOBACCO, GENETIC
et al. Future Oncol 2013;9:649-55). Preclinical models were employed to define
epigenomic alterations and gene expression profiles in respiratory epithelia
exposed to cigarette smoke condensate. In a study, smoke condensate
significantly repressed miR-487b, that directly targets several genes,
including SUZ12, BMI1, WNT5A, MYC, and KRAS. Such repression correlated SESSION MTE11: THE CLINICAL IMPACT OF THE 2015 WHO
with overexpression of the above targets in lung cancer and coincided CLASSIFICATION OF LUNG TUMORS (TICKETED SESSION)
with DNA methylation within the miR-487b genomic locus, indicating this
molecule as a tumor suppressor microRNA silenced by epigenetic mechanisms
during tobacco-induced pulmonary carcinogenesis. These findings may
potentially pave the way for DNA demethylating agent treatment, in order
to re-activate miR-487b in lung cancer therapy (Xi et al. JCI 2013; 123:1241-61). MTE11.01 THE CLINICAL IMPACT OF THE 2015 WHO CLASSIFICATION
Among other effects of cigarette smoking, a synergy was described with the OF LUNG TUMORS
aryl hydrocarbon receptor (AHR), which is partially responsible for tobacco- Andrew Nicholson1, Masayuki Noguchi2
induced carcinogenesis through incompletely understood mechanisms. It was 1
Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London/
reported that smoking induces AHR activating ligands, which in turn induced United Kingdom, 2Pathology, Tsukuba University, Tsukuba/Japan
adrenomedullin both in vitro and in vivo, thus significantly contributing to the
carcinogenicity of tobacco-activated AHR. These effects were not reproduced There are many important changes in the 2015 WHO classification of lung
in fibroblasts and mice lacking the aryl hydrocarbon receptor (Portal-NuÑez tumours, reflecting the numerous advances in tumour genetics and therapy
et al. Cancer Res 2012; 72:5790-800). Genetic factors involved in tobacco- over the past decade.1 Many have been in the field of adenocarcinoma, with
induced lung cancers have been widely investigated to determine the genetic discontinuation of the term bronchioloalveolar carcinoma and the concept
susceptibility to lung cancer, including epigenomic alterations (Fujimoto et of stepwise progression accepted for adenocarcinoma.1 Adenocarcinoma in
al. PlosOne 2010;5:e11847. Liu et al. Oncogene 2010;29:3650-64). In addition, situ (AIS) is a small (less than 3 cm in diameter), pure lepidic adenocarcinoma;
tobacco-induced lung cancer is characterized by a deregulated inflammatory minimally invasive adenocarcinoma (MIA) is also a small lepidic
microenvironment (Spitz et al. Cancer Epidemiol Biomark Prev 2012; 21:1213- adenocarcinoma but has small invasive areas less than 5 mm across. As both
21). Therefore variants in inflammation pathway associated genes, as well entities have a very favorable outcome, with an expected 5-year survival rate
as a number of genetic polymorphisms have been identified as putative of 100%, AIS and MIA are targets for reduction surgery, and are frequently
candidates predisposing to lung cancer development. The effects of single detected by low-dose CT screening. High-resolution (HR)-CT demonstrates
polymorphisms on lung cancer development risk have been investigated, these tumours as a pure ground glass nodule (GGN) or a part-solid nodule
with inconsistent results. Most currently identified polymorphisms involve (PSN), being closely correlated with their pathological features.2 Therefore,
genes encoding proteins associated with the metabolic processing of AIS and MIA can be assessed by HR-CT. However, the size of the solid
tobacco smoke carcinogens and the repair of mutations induced by those component in HR-CT images does not necessarily correspond to the extent
carcinogens. Polymorphisms on chromosomes 5p15.33, 6p21, and 15q24-25.1 of histological invasion, since features such as alveolar collapse and fibrosis
were identified, being the former specifically associated to a higher risk for are also included in the solid part demonstrated by HR-CT.1 Although the
adenocarcinoma (Yokota et al. Adv Cancer Res 2010;109:51-72). Regarding new WHO classification defines the histological criteria for MIA invasion,
inflammation genes, analyzing a comprehensive panel of over 11,000 the degree of inter-observer agreement regarding the histological definition
inflammation pathway single-nucleotide polymorphisms (SNP), six SNPs were of invasion in MIA has still not been fully studied, and a consensus trial will
significantly (p < 0.05) associated to a higher risk of lung cancer development, be needed in the near future. More advanced adenocarcinoma is subdivided
including two SNP variants in former smokers (BCL2L14) and in current into five categories: lepidic, papillary, acinar, solid and micropapillary.
smokers (IL2RB) (Spitz et al. Cancer Epidemiol Biomark Prev 2012; 21:1213-21). These subtypes are diagnosed according to the predominant component
The above genetic alterations are observed in all histological subtypes of lung and the group comprising lepidic, papillary and acinar adenocarcinomas
cancer with several differences, especially between small cell lung carcinoma shows a better prognosis than those with solid and micropapillary patterns.
(and the other neuroendocrine tumors) and non-small cell lung cancers. Therefore the presence of solid and/or micropapillary adenocarcinoma
Though all lung cancers are generally tobacco related, changes of incidence should be reported, even if the predominant component is lepidic, papillary
of different histological types (with an increase of adenocarcinoma in both or acinar adenocarcinoma. These patterns also predict response to adjuvant
sexes) are well known, reflecting modifications of smoking habits, cigarette chemotherapy,3 and the above changes overall have also led new proposals
types, filter types and content of tar, among others. Wide sequencing of for both clinical and pathologic staging in the 8th TNM revision in terms of
single cancer histotypes has provided a relatively complete map of most multiple primary tumours and measurement of tumour invasive size.4,5 For
common alterations in each tumor. In adenocarcinoma, a mean exonic somatic the other three major tumour types (large cell carcinoma (LCC), squamous cell
mutation rate of 12.0 events/megabase was identified, which included most carcinoma (SQCC) and neuroendocrine (NE) tumours), the classification has
previously reported genes in adenocarcinoma as significantly mutated, as well evolved from mainly morphological to a more biologically based system, which
as recurrent mutations in U2AF1, RBM10 and ARID1A genes, and structural allows more appropriate decisions in relation to adjuvant therapy and better
rearrangements within EGFR and SIK2 kinases (Imielinski et al. Cell 2012; defined subgroups for studies into molecular characterisation and the search
150, 1107–1120). Regarding squamous cell carcinoma, the Cancer Genome for potentially treatable targets. LCC is now restricted to resected tumours
Atlas Network profiled 178 tumors and found complex genomic alterations, that lack clear morphologic and immunohistochemical differentiation, with
with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 reclassification of those that do to solid adenocarcinoma (TTF-1 positive)
segments of copy number alteration per tumor. Recurrent mutations were and non-keratinising SQCC (P40 and/or CK5/6 positive). This has already
found in 11 genes, with TP53 mutations occurring in nearly all specimens and been shown to correlate with molecular data.6 For SQCC, classification is
novel alterations affecting a proportion of cases, including HLA-A class I simplified to keratinizing, nonkeratinizing and basaloid subtypes, with
major histocompatibility gene, NFE2L2, KEAP1, phosphatidylinositol-3-OH- the non-keratinizing tumours ideally requiring immunohistochemical
kinase pathway genes, CDKN2A, RB1 and specific squamous differentiation confirmation. Criteria for diagnosing NE tumours remain essentially
genes (Cancer Genome Atlas Res Network. Nature 2012;489:519-525). As far unchanged but these tumours are now grouped in one category, with further
as small cell lung cancer is concerned, high mutation rates (up to 8.6 non- subdivision into carcinoids, and large cell neuroendocrine carcinoma and
synonymous mutations per million base pairs) were identified. Of these, up to small cell carcinoma. Molecular studies based on these definitions are already
28% were found to be C:G>A:T transversions, a type of alteration associated identifying interesting subgroups.7 In relation to rarer entities, the definition
to heavy smoking, although the smoking history was not correlated with of pleomorphic carcinomas is also being shown to have clinical relevance in
the type and number of mutations. Other genes exhibiting mutations and terms of correlating with potential therapies, both in relation to specific
inactivating translocations included the histone acetyltransferase genes molecular abnormalities (exon 14 skipping mutations)8 and immunoodulatory
CREBBP and EP300, genes with functional roles in the centrosome (ASPM, therapy with high levels of PD-L1 expression.9 Molecular characterisation
ALMS1 and PDE4DIP), in the RNA-regulating gene XRN1 and the tetraspanin is also increasingly important in the accurate diagnosis and potential
gene PTGFRN. Damaged genes were commonly found, including the known treatment of other rare tumours, such as NUT-carcinoma and inflammatory
TP53, RB1, but also TP73, CREBBP and COL22A1, as well as FMN2 and NOTCH myofibroblastic tumours (ALK and ROS1/RET gene rearrangements).10 A
family genes (mostly inactivation in the latter) (George et al. Nature 2015; classification system for small biopsies and cytology is provided for the first
524: 47–53). Whether the identified genetic signatures and peculiar biological time, with emphasis on integration of molecular testing and usage of a limited
features will produce a corresponding reproducible therapeutic “signature” panel of immunohistochemistry when needed (table 1). The presence of such
is still not the case, but the way is paved for stratifying patient groups based a system for the first time provides a system for consistent classification
on their unique pathological and genetic tumor characteristics, among of the majority (unresectable) of lung cancer cases, both in terms of clinical
different histotypes and also within individual neoplastic variants. The management, assignment to pathways for molecular and immunomodulatory
future challenge will be to define the biological profile of immunocheckpoint characterisations, and for assessment of the results of clinical trials that
molecule expression in tobacco related lung cancers, in order to identify a have sometimes been confounded by inaccurate subgrouping. The book also
reliable predictive marker of response to treatments targeting PD1 or PDL1, in emphasises how to obtain the greatest value from small sample via efficient
relationship with the different mutational burden and immunological status usage and avoidance of inappropriate testing.1 Table 1: Classification of non-
of individual cases. small cell lung carcinoma in small biopsies and cytology specimens when there
is no morphologic evidence of differentiation

2015 WHO Small drugs. DNA Repair Pathway: Genomic DNA encodes all biochemical
2015 WHO Classification in processes that drive cellular function and biology. Extensive damage to DNA
Biopsy/Cytology Morphology/Stains
resection specimens encoding proteins/enzymes involved in cell proliferation will result in cell
Terminology
cycle arrest and cell death. DNA damage may also induce replicative errors
Morphologic
and mutations, which leads to constitutive activation of oncogenes, or
adenocarcinoma
Non-small cell inactivation of tumor suppressor genes. DNA repair mechanisms are crucial
patterns (lepidic, acinar, Adenocarcinoma, solid
carcinoma, favour for mitigating catastrophic chromosomal damage during DNA synthesis
papillary, micropapillary) pattern (may only be a
adenocarcinoma and replication, thus allowing tumor cells to survive chemotherapy or
not present, but component)
using IHC radiotherapy. New targeted anti-cancer agents being developed include
supported by special
those that inhibit the activity of critical molecules involved in DNA repair,
stains (+TTF-1)
or inhibit cell cycle checkpoint proteins that allow DNA repair mechanisms
Morphologic squamoid to occur. EGFR and downstream pathways: The proliferation of epithelial
Non-small cell
features (keratinization cells depends on growth stimuli arising from either factors produced by the
carcinoma, favour Squamous cell carcinoma,
and/or clear intercellular tumor cells themselves (autocrine), factors produced by cells from distant
squamous cell (non-keratinizing pattern
bridging) not present, organs (endocrine), or factors from neighboring tumor or non-tumor cells
carcinoma using may be just one component)
but supported by stains in the tumor microenvironment (paracrine). For lung epithelial cells, a
IHC
( +p40) major growth stimulating pathway involve the epidermal growth factor
No clear receptor (EGFR) family members. EGFR (HER1) is highly expressed in >90%
Non-small cell adenocarcinoma, of squamous cell carcinoma and in 60-80% of adenocarcinoma. EGFR has
carcinoma, squamous or many ligands, including EGF, TGF-a, amphiregulin, HB-EGF, etc. Binding of
not otherwise neuroendocrine Large cell carcinoma the ligands to the EGFR induces homo or hetero dimerization of EGFR and its
specified NSCLC- morphology or staining family members, activates the cytoplasmic tyrosine kinase of the receptor,
NOS using IHC pattern (IHC or mucin and promotes auto-phosphorylation. This sequentially leads to binding of
stains). SOS1, activation of downstream RAS, RAF, MEK and ERK/MAPK. Targeting
EGFR by monoclonal antibodies and small molecule kinase inhibitors have
REFERENCES 1. WHO Classification of Tumours of the Lung, Pleura, Thymus demonstrated clinical efficacy in subpopulation of NSCLC patients. Targeted
and Heart. Lyons, France.: International Agency for Research on Cancer agents against KRAS, BRAF and MEK are in clinical trials. MET, ALK, and ROS1
(IARC); 2015. 2. Kakinuma R, Noguchi M, Ashizawa K, et al. Natural History of pathways: Other tyrosine kinase receptors (RTKs) that may play important
Pulmonary Subsolid Nodules: A Prospective Multicenter Study. J Thorac Oncol. role in lung cancers include hepatocyte growth factor (HGF) receptor MET
Jul 2016;11(7):1012-1028. 3. Tsao MS, Marguet S, Le Teuff G, et al. Subtype and fibroblast growth factor receptor (FGFR) family members. In contrast
Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant to EGFR, the ligands for MET and FGFRs appear to be produced by the tumor
Chemotherapy in Patients Undergoing Complete Resection. J Clin Oncol. stromal fibroblasts. While attempts to inhibit MET signaling pathway by
Oct 20 2015;33(30):3439-3446. 4. Detterbeck FC, Nicholson AG, Franklin neutralizing antibody have not been successful, more recent data suggest
WA, et al. The IASLC Lung Cancer Staging Project: Summary of Proposals for that MET kinase inhibitors may be highly effective in patients with MET exon
Revisions of the Classification of Lung Cancers with Multiple Pulmonary Sites 14 splice site mutations. Such mutations cause the loss of exon 14, which
of Involvement in the Forthcoming Eighth Edition of the TNM Classification. encode the Cbl binding site of the receptor, a crucial domain required for
J Thorac Oncol. Feb 29 2016. 5. Travis WD, Asamura H, Bankier AA, et al. The the degradation of MET receptor. The RTKs with close homology to MET are
IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for ALK and ROS1. Constitutive activation of ALK and ROS1 occurs by formation
Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in of new chimeric protein through translocation involving these genes.
the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. Inhibitors to ALK and ROS1 are now clinically approved for treatment of lung
J Thorac Oncol. Aug 2016;11(8):1204-1223. 6. Clinical Lung Cancer Genome P, cancers that express fusion proteins resulting from the rearrangement of
Network Genomic M. A genomics-based classification of human lung tumors. the ALK and ROS1 genes. PI3K/AKT/mTOR pathway: Aside from activating
Sci Transl Med. Oct 30 2013;5(209):209ra153. 7. Rekhtman N, Pietanza MC, the MAPK pathway, tyrosine kinase receptors may also activate the PI3K/
Hellmann MD, et al. Next-Generation Sequencing of Pulmonary Large Cell AKT/mTOR pathway, which plays a crucial role in the survival of lung cancer
Neuroendocrine Carcinoma Reveals Small Cell Carcinoma-like and Non-Small cells. This pathway is commonly activated in NSCLC through amplification
Cell Carcinoma-like Subsets. Clin Cancer Res. Jul 15 2016;22(14):3618-3629. 8. or activating mutation of the PIK3CA gene, or inactivation of PTEN by
Schrock AB, Frampton GM, Suh J, et al. Characterization of 298 Patients with gene deletion, mutation or methylation. While there is intense research to
Lung Cancer Harboring MET Exon 14 Skipping Alterations. J Thorac Oncol. develop targeted therapies that inhibit this important survival pathway,
Sep 2016;11(9):1493-1502. 9. Chang YL, Yang CY, Lin MW, Wu CT, Yang PC. High the efforts have so far met little success, revealing the complexity of this
co-expression of PD-L1 and HIF-1alpha correlates with tumour necrosis in pathway. There is also evidence that alternative RTK and PI3K signaling play
pulmonary pleomorphic carcinoma. Eur J Cancer. Jun 2016;60:125-135. 10. an important role as bypass mechanisms for the development of resistance
Antonescu CR, Suurmeijer AJ, Zhang L, et al. Molecular characterization to kinase inhibitor therapies. Angiogenesis pathways: Because an adequate
of inflammatory myofibroblastic tumors with frequent ALK and ROS1 blood supply is regarded as essential for tumor development, there had been
gene fusions and rare novel RET rearrangement. Am J Surg Pathol. Jul overwhelming optimism initially that blocking angiogenic pathways would
2015;39(7):957-967. represent an effective treatment strategy in solid malignancies, including
Keywords: lung cancer, classification, WHO, Adenocarcinoma primary and metastatic lung tumors. However, clinical trials investigating
antivascular drugs have been both encouraging and disappointing. Success
with antivascular strategies therefore requires a deeper knowledge of the
clinical significance of the different angiogenic machineries that control
lung tumors. VEGF (vascular endothelial growth factor) is the key molecular
SESSION MTE12: CLINICALLY RELEVANT SIGNAL TRANS- regulator of new tumor blood capillary formation (i.e. angiogenesis) and its
high expression is associated with poorer survival in NSCLC. Bevacizumab,
DUCTION PATHWAYS (TICKETED SESSION) a humanized monoclonal anti-VEGF antibody, is currently approved for the
TUESDAY, DECEMBER 6, 2016 - 07:30-08:30 first-line treatment of advanced stage non-squamous NSCLC in combination
with chemotherapy. Ramucirumab (a fully human monoclonal antibody
against VEGFR2) has been approved for use in combination with docetaxel
MTE12.01 CLINICALLY RELEVANT SIGNAL TRANSDUCTION for the treatment of metastatic NSCLC patients who progressed after
PATHWAYS platinum-based chemotherapy. Nintedanib (an oral RTK inhibitor against
Ming Tsao 1, Balazs Dome 2 VEGFRs, platelet-derived growth factor receptors (PDGFR) and FGFRs
1 in combination with chemotherapy has been approved by the EMEA in
Pathology, Princess Margaret Cancer Centre, Toronto/Canada, 2Thoracic Surgery,
Medical University of Vienna, Vienna/Austria
NSCLC patients with locally advanced, metastatic or locally recurrent lung
adenocarcinoma after first-line chemotherapy. Additional anti-vascular
Up to a decade ago, the main non-surgical treatment modalities in oncology strategies including vascular disrupting agents (VDAs) to destroy the
have been cytotoxic chemotherapy and/or radiation therapy. These established tumor vasculature and other investigational antiangiogenic
therapies are aimed at inducing DNA damage, thus selectively killing the antibodies and small molecule RTK inhibitors are also under clinical testing
highly proliferative cancer cells. More recently, new therapies are targeting for NSCLC therapy, though enthusiasm is tempered by short disease control
signaling pathways that are critical to support cancer cell proliferation and/ and modest overall survival benefit. Angiogenesis Resistance Mechanisms
or survival, including micro-environmental factors that sustain tumor. The and Biomarkers: Unfortunately, resistance against antivascular therapies
first part of our presentation will review pathways operating mainly in the is poorly understood. The possible resistance mechanisms include
tumor cells, and how they constitute targets for lung cancer therapies. The increased intratumoral hypoxia, the activation of compensatory angiogenic
second part will focus on the vascularization mechanisms in primary and machineries, the release of myeloid or endothelial progenitor cell populations,
metastatic lung tumors, antivascular drugs, potential biomarkers and on the downregulation of target receptors in endothelial and/or tumor cells,
mechanisms through which tumors can become resistant to antivascular limited tumor tissue drug penetration, and also a switch to an alternative
vascularization mechanism such as intussusceptive angiogenesis or vessel- 17.3 and 14.9 months when received pembrolizumab at 10 mg/kg and 2 mg/kg,
cooption. Reliable biomarkers for the prediction of response to antivascular respectively. Again, grade 3-5 treatment-related AEs were less common for
drugs are also yet to be identified and clinically validated. both pembrolizumab doses than for docetaxel. Recently, press release on
KEYNOTE-024 phase III study, reported OS in favor of pembrolizumab over
platinum-based doublet in first-line therapy for advanced NSCLC patients
with PD-L1 expression. The clinical results from KEYNOTE-024 may change the
landscape of lung cancer treatment at first-line for advanced NSCLC. Also in
SESSION MTE13: BASIC IMMUNOLOGY FOR THE CLINICIAN development are the PD-L1 inhibitors which affect the interaction between
(TICKETED SESSION) PD-L1 and B7.1 and PD-1 receptor and PD-L2; the later interactions are not
affected by PD-1 inhibitors. Atezolizumab and darvulumab have several phase
III trials ongoing in first line for advanced NSCLC. Phase II trials for both
compounds have shown promising results. The role of PD-L1 as predictive
biomarker is still not well defined. PD-L1 expression is a dynamic process and it
MTE13.02 BASIC IMMUNOLOGY FOR THE CLINICIAN also varies as part of an adaptive immune resistance exerted by the tumor.
Edgardo Santos There are other possible predictive biomarkers such as higher nonsynonymous
Florida Atlantic University, Eugene M. and Christine E. Lynn Cancer Institute, Boca mutation burden, molecular smoking signature, higher neo-antigenic burden,
Raton/FL/United States of America DNA repair pathway mutations, high levels of PD-L1 expression, T-helper type
1 gene expression, and others. There is no question that we must continue
Lung cancer remains the number one cause of cancer-related death worldwide. looking for a better predictive biomarker which can help us to determine the
Cancer immunotherapy nowadays has become not only a growing field but therapeutic benefit of PD-1/PD-L1 inhibitors.References. 1. Nemunaitis J,
also a fascinating area as recent clinical trials have improved both PFS and OS Dillman RO, Schwarzenberger PO, et al. Phase II study of belagenpumatucel-L,
in first line and second line treatment for patients with advanced NSCLC. The a transforming growth factor beta-2 antisense gene-modified allogeneic
idea of immunotherapy in cancer is to modify the host immune system, so tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol. 24, 4721–30
cytotoxic T-cells (CTCs) can recognize tumor-associated antigens (TAAs) as (2006). 2. González G, Crombet T, Neninger E, Viada C, Lage A. Therapeutic
abnormal and be destroyed by an immune response. For many decades, we vaccination with epidermal growth factor (EGF) in advanced lung cancer:
have tried unsuccessfully many vaccines against different lung cancer analysis of pooled data from three clinical trials. Hum Vaccin. 3(1), 8-13 (2007).
antigens. It was thought at one point that lung cancer was a non immunogenic 3. Vansteenkiste J, Zielinski H, Linder A, et al. Final results of a multi-center,
tumor very different from melanoma and kidney cancers. Whole-cell vaccines double-blind, randomized, placebo-controlled phase II study to assess the
(e.g. belagenpumatucel-L) and antigen-specific vaccines (e.g., CIMAvax, efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II
MAGE-A3, L-BPL25) showed just promising results in clinical trials, but failed non-small cell lung cancer (NSCLC). J Clin Oncol. 25(18S), 7554 (2007). 4. Palmer
to significantly improve clinical outcomes [1-4]. The major reason why vaccines M, Parker J, Modi S, et al. Phase I study of the BLP25 (MUC1 peptide) liposomal
failed in lung cancer was due to tumor escape mechanisms from host immune vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung
surveillance [5, 6]. One of this mechanisms was recently elucidated, cancer. Clin Lung Cancer. 3(1), 49-57 (2001). 5. Gross S, Walden P.
checkpoint pathway. Lung cancer has been found to have high levels of CTLA-4 Immunosuppressive mechanisms in human tumors: why we still cannot cure
expression, programmed death-1 (PD-1), PD ligand 1 (PD-L1), B7-H3 and B7-H4 cancer. Immunology Letters. 116(1), 7–14 (2008). 6. Dunn GP, Bruce AT, Ikeda H,
expression on tumor-infiltrating lymphocytes (TILs), and regulatory CD4+ Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to
T-cells (Tregs) suggesting that lung cancer is immunogenic. For many years, tumor escape. Nat Immunol. 3, 991–8 (2002). 7. Egen JG, Kuhns MS, Allison JP.
cancer immunology was centered on the adaptive immune system and T-cell CTLA-4: new insights into its biological function and use in tumor
activation. Stimulation of the T-cell response involves antigen presenting cells immunotherapy. Nat immunol 3(7):611-618, 2002. 8. Zang X, Allison JP. The B7
(APCs), or dendritic cells (DCs), expressing tumor antigens from the tumor family and cancer therapy: costimulation and coinhibition. Clin Cancer Res
microenvironment, which then bind to the T-cell receptor (TCR) on CD4+ or 13(18):5271-5279, 2007. 9. Blank C, Mackensen A. Contribution of the PD-L1/
CD8+ T-cells. Meanwhile, B7-1/CD80, or B7-2/CD86 on the APC, bind to CD28 on PD-1 pathway to T-cell exhaustion: an update on implications for chronic
the T-cell in a costimulatory fashion to stimulate tumor-antigen specific T-cells infections and tumor evasion. CancerI Immunol Immunother 56(5):739-745,
to proliferate. However, cross talk between APCs and T-cells at the 2007. 10. http://www.businesswire.com/news/home/20160616005393/en/
immunological synapse is regulated very closely and can be attenuated. One Merck%E2%80%99s-KEYTRUDA%C2%AE%C2%A0-pembrolizumab-
of this attenuation signal is mediated by CTLA-4, which is also stimulated by Demonstrates-Superior-Progression-Free-Survival. Access online September
CD80 and CD86. Although CTLA-4 and CD28 have the same ligands, CTLA-4 has 20, 2016.
a much higher affinity for them; hence, T-cell proliferation occurs despite the
effects of CTLA-4 because of the intracellular location, short half-life and Keywords: lung cancer, checkpoint pathway, Immunotherapy, PD-L1
quick degradation of CTLA-4 [7, 8]. Another example of a tumor immune
checkpoint is PD-1 which binds B7-H1/PD-L1 and B7-DC/PD-L2 [9]. By using PD-1
inhibitors, we are able to remove the interaction between PD-1 receptor
located in the T-cells and its ligand expressed in the tumor cells which causes
inhibitory signaling over the T-cells. Hence, an immune response cannot be SESSION MTE15: LYMPH NODE MAPPING IN LUNG CANCER
mounted. CTLA-4 has been studied in lung cancer in combination with (TICKETED SESSION)
platinum-based doublet (carboplatin/paclitaxel). Outcomes from that study
were not enough to grant approval from regulatory entities. However,
investigators found better response to CTLA-4 inhibition in patients with
squamous cell histology; this population has higher percentage of TILs than
their non-squamous counterparts. Why the combined therapy (chemotherapy MTE15.02 LYMPH NODE MAPPING IN LUNG CANCER
plus ipilimumab) had limited effect remains unclear. Conversely, studies using David Waller
PD-1 inhibitors pembrolizumab and nivolumab have shown OS advantage over Thoracic Surgery, Glenfield Hospital, Leicester/United Kingdom
docetaxel in second line therapy, and more recently, OS and PFS advantage in
first line against chemotherapy when tumor cells expressed > 50% of PD-L1 The How and Why? The Aim will be to outline the various methods to map
[10]. We also understand that PD-L1 is not the perfect predictive biomarkers the extent of lymph node metastasis from a primary NSCLC and to assess
the clinical application and implications of each intervention. The Aim will
so efforts are directed to discover more specific markers which can help us to
also be to highlight the following areas of clinical debate and controversial
tailor checkpoint inhibitors in lung cancer. The approval of nivolumab in
issues 1.Preoperative Non-invasive – Lymph node mapping may start with
NSCLC came from two phase III trials CheckMate 017 and CheckMate 057
simple Ultrasound guided cervical node aspiration cytology [1] . Can this be
which studied nivolumab vs docetaxel in second-line for squamous and
all that is needed in some advanced cases? c Can computed tomography/
non-squamous advanced NSCLC, respectively. The CheckMate 017 reached the
positron emission tomography (CTPET) be relied upon to obviate the need for
“trifecta” proving that nivolumab was statistically superior to docetaxel for
invasive nodal mapping ? Can newer techniques including CT lymphography
OS, PFS and response rate (RR). Interestingly, OS benefit was independent of
[2] improve the accuracy of mapping ? Does magnetic resonance imaging (MRI)
PD-L1 expression. The CheckMate 057 showed OS and RR in favor of
have a role in preoperative lymph node mapping. Invasive – We will consider
nivolumab. There was no difference in PFS between nivolumab and docetaxel
in detail the debate between endobronchial and endoluminal ultrasound
in non-squamous NSCLC patients. In this study, PD-L1 expression levels at
(EBUS/EUS) and surgical lymph node mapping. What role, if any, does cervical
different cut-off matter for OS. For those patients who had ≥1%, ≥ 5%, and
mediastinoscopy have in addition to EBUS/EUS [3] ? Does the increased
10%, the hazard ratio (HR) for OS were 0.59 (p < 0.06), 0.43 (p < 0.001), and 0.40
sensitivity of more invasive surgical mediastinal procedures like VAMLA
(p < 0.001), respectively. In both studies, nivolumab was well tolerated and
[4] and TEMLA contribute significantly to preoperative mapping ? We will
had better treatment-related adverse event profile. In case of pembrolizumab,
discuss why these investigations should influence primary therapy and which
it was KEYNOTE-010 study which proved OS advantage over docetaxel in
patients should undergo induction therapy and which should have primary
second line therapy. Herein, pembrolizumab at a dose of 10 mg/kg and 2 mg/kg
resection. Evidence from the latest TNM revision suggest that mediastinal
shown an OS of 12.7 months (HR 0.61; p < 0.001) and 10.4 months (HR 0.71; p <
nodal disease needs more accurate mapping than previously appreciated. We
0.001); OS for docetaxel was 8.5 months. Noteworthy, OS was better in
will consider how many of these stages of mapping are required before making
patients whose tumors expressed PD-L1 ≥50%; these patients had an OS of

a decision to operate and will propose a controversial algorithm for surgical gradually increased over time by the incorporation of a number of approved
treatment of N2 disease [5]. 2.Intraoperative We will discuss the arguments molecules for 1st, 2nd -, subsequent line therapy (Peters, 2012; Masters, 2015;
surrounding the necessary extent of intraoperative lymph node dissection. NCCN, 2016). NSCLC – 1st-line-therapy - wild-type: For patients with wild-type
We will consider the relative merits of the methods for intraoperative non-squamous NSCLC it is generally accepted that upfront platinum based
sentinel node identification including Near Infrared thoracoscopy and doublet chemotherapy (DCT) remains the backbone for individuals with
radiolabelling [6,7]. We will ask whether the investment in technology and good performance and that this approach should be modified according to
time is beneficial for the patient. Is the added information about metastases feasibility and tolerability, co-morbidity, and age over 70 years. Progress
of clinical value ? We will evaluate the argument between nodal sampling vs has been made through pemetrexed, which is recommended as the favorite
systematic nodal dissection [8] and attempt to formulate an intraoperative partner of platinum-based components (Scagliotti; 2008/2011). In addition, it
mapping algorithm. Intraoperative nodal mapping has been proposed as a has lately been demonstrated that the extension of induction chemotherapy
prerequisite to direct the extent of lung resection. We will examine how the by single agent pemetrexed until progression - in case of non-progression
findings of nodal disease have been used to discriminate between lobectomy under four cycles of DCT not containing pemetrexed (switch maintenance)
vs pneumonectomy or between lobectomy vs segmentectomy. We will (Ciuleanu, 2009) or containing pemetrexed (continuation maintenance)
consider the argument that nodal metastatic disease is not a justification (Paz-Ares, 2012/2013) - prolongs survival. In this case survival may also be
for more extensive sacrifice of functioning lung tissue. Is there any role prolonged by erlotinib, when used in the switch maintenance setting, but
for intraoperative nodal analysis in determining the extent of resection? erlotinib’s benefit seem to be restricted to patients, which have experienced
How reliable is this method of nodal mapping. 3.Postoperative Once the disease stabilization to induction chemotherapy (Cappuzzo, 2010; Coudert,
pathologist has the resected lymph nodes we will attempt to rationalize 2012). Bevacizumab, when added to platinum-based to DCT, significantly
how they should be analysed, asking the question : “ What are the minimum improves response rate, progression free survival, as well as overall survival
sampling requirements ?”. We will also analyse whether the more detailed in eligible patients (Sandler, 2006/2010; Reck, 2009/2010). In wild-type
nodal mapping of micrometastatic disease by immunohistochemistry squamous NSCLC platinum based DCT (no pemetrexed, no bevacizumab)
significantly influences patient management or outcome [10] ? Finally we will remains standard. Nonetheless, necitumumab has recently shown to
discuss how these pathological results could influence the use of adjuvant improve survival when combined with cisplatin/gemcitabine (Thatcher,
chemotherapy/ radiotherapy or more interestingly targeted therapies. We 2015). Maintenance therapy in squamous tumors with docetaxel or erlotinib
intend the session to be interactive between presenters and delegates with (switch) or gemcitabine (continuation) may be justified in some patients even
a free exchange of ideas and experience. We hope to stimulate delegates so study evidence is weaker than for non-squamous tumors (Fidas, 2009;
to re-evaluate their own approach to lung cancer staging.References 1. Perol, 2012). NSCLC – 1st-line-therapy - mutant: For patients with advanced
Chang DB, Yang PC, Yu CJ, Kuo SH, Lee YC, Luh KT.Ultrasonography and NSCLC expressing specific molecular features – mainly non-squamous tumors
ultrasonographically guided fine-needle aspiration biopsy of impalpable – 1st- line treatment with targeted agents has been established. In tumors
cervical lymph nodes in patients with non-small cell lung cancer.Cancer. 1992 with EGFR mutations gefitinib, erlotinib, and afatinib have shown to prolong
Sep 1;70(5):1111-4 2. Suga K, Yuan Y, Ueda K, Kaneda Y, Kawakami Y, Zaki M, progression free survival over standard chemotherapy (Mok, 2009; Rosell,
Matsunaga N Computed tomography lymphography with intrapulmonary 2012; Sequist, 2013). In tumors bearing ALK-/ROS1-gene-rearrangements
injection of iopamidol for sentinel lymph node localization. Invest Radiol. crizotinib has also shown to prolong progression free survival when
2004 Jun;39(6):313-24. 3. Annema JT, van Meerbeeck JP, Rintoul RC, Dooms C, compared to platinum/pemetrexed. (Solomon, 2014). Therefore, erlotinib,
Deschepper E, Dekkers OM, De Leyn P, Braun J, Carroll NR, Praet M, de Ryck F, gefitinib or afatinib should be prescribed for patients with tumors bearing
Vansteenkiste J, Vermassen F, Versteegh MI, Veseliç M, Nicholson AG, Rabe EGFR-mutations. For patients with tumors bearing ALK-/ROS1 crizotinib
KF, Tournoy KG. Mediastinoscopy vs endosonography for mediastinal nodal should be prescribed. However, for these patients molecular testing is
staging of lung cancer: a randomized trial .JAMA. 2010 Nov 24;304(20):2245- critical and should be used to select patients for EGFR/ALK/ROS1 targeted
52 4. Witte B, Hürtgen M.Video-assisted mediastinoscopic lymphadenectomy therapy. Patients with lung adenocarcinoma should not be excluded from
(VAMLA).J Thorac Oncol. 2007 Apr;2(4):367-9 5. De Leyn P, Dooms C, Kuzdzal J, testing on the basis of clinical characteristics (ethnicity, gender, smoking
Lardinois D, Passlick B, Rami-Porta R, Turna A, Van Schil P, Venuta F, Waller D, status) (Lindeman, 2013). NSCLC - 2nd /subsequent-line therapy - wild-type:
Weder W, Zielinski M. Revised ESTS guidelines for preoperative mediastinal In patients with disease progression during or after completion of 1st -line
lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg. chemotherapy, 2nd -, subsequent-line therapy is indicated when the patient
2014 May;45(5):787-98 6. Hachey KJ, Colson YL. Current innovations in remains in good clinical condition. Approved older treatment options
sentinel lymph node mapping for the staging and treatment of resectable include docetaxel, pemetrexed and erlotinib. Two anti-angiogenic agents
lung cancer. Semin Thorac Cardiovasc Surg. 2014 Autumn;26(3):201-9 7. and two immune-checkpoint inhibitors have recently been added. These
Tomoshige K, Tsuchiya T, Otsubo R, Oikawa M, Yamasaki N, Matsumoto K, include nintedanib and ramucirumab (Reck, 2014; Thatcher, 2015), as well
Miyazaki T, Hayashi T, Kinoshita N, Nanashima A, Nagayasu T.Intraoperative as nivolumab and pembrolizumab (Brahmer, 2015; Borghaei, 2015; Herbst,
diagnosis of lymph node metastasis in non-small-cell lung cancer by a semi-dry 2016). Nintedanib/docetaxel increases significantly survival in patients with
dot-blot method.Eur J Cardiothorac Surg. 2016 Feb;49(2):617-22 8. Darling adenocarcinoma who specifically progressed within 9 months after the
GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, Jones DR, start of 1st-line therapy, who have experienced disease progression as best
McKenna RJ, Landreneau RJ, Rusch VW, Putnam JB Jr. Randomized trial of response to 1st-line therapy and decreases tumor burden and decelerates
mediastinal lymph node sampling versus complete lymphadenectomy during tumor growth. Nintedanib/docetaxel has been approved in the EU for the
pulmonary resection in the patient with N0 or N1 (less than hilar) non-small treatment of patients with adenocarcinoma. Ramucirumab/docetaxel has
cell carcinoma: results of the American College of Surgery Oncology Group also been approved in the US and EU for patients with disease progression on
Z0030 Trial . J Thorac Cardiovasc Surg. 2011 Mar;141(3):662-70 9. Nomori H, or after DCT for wild-type non-squamous and squamous NSCLC. This approval
Cong Y, Sugimura H. Utility and pitfalls of sentinel node identification using has been based on phase III study evidence indicating survival advantage
indocyanine green during segmentectomy for cT1N0M0 non-small cell lung in non-squamous NSCLC (statistically significant) and squamous NSCLC
cancer. Surg Today. 2016 Aug;46(8):908-13 10. Deng XF, Jiang L, Liu QX, Zhou D, (numerically longer). Comparing head-to head nivolumab and docetaxel in
Hou B, Cui K, Min JX, Dai JG Lymph node micrometastases are associated with patients with squamous and non-squamous NSCLC after failure of DCT has
disease recurrence and poor survival for early-stage non-small cell lung cancer demonstrated superior overall survival in patients receiving nivolumab.
patients: a meta-analysis. J Cardiothorac Surg. 2016 Feb 16;11:28. Nivolumab has received US and EU approval for advanced NSCLC with
progression on or after DCT. Nivolumab appears to be most effective in
Keywords: lung cancer. lymph node metastasis. nodal mapping patients with more than 6 months from completion of the latest treatment
regimen to randomization in comparison to patients with less than 3 months
to randomization. Pembrolizumab has received approval in the US and EU
for patients with advanced NSCLC who’s tumors expressed PD-L1 and who
have disease progression on or after chemotherapy. Approval has been based
SESSION MTE16: PRECISION MEDICINE IN NSCLC: LESSONS on head-to-head comparison of pembrolizumab and docetaxel in patients
LEARNED AND PERSPECTIVES (TICKETED SESSION) with previously treated PD-L1 positive squamous and non-squamous NSCLC,
TUESDAY, DECEMBER 6, 2016 - 07:30-08:30 which has demonstrated a significant survival benefit for pembrolizumab.
NSCLC-2nd/subsequent-line therapy - mutant: Resistance to first and second
generation EGFR-TKIs is a multifactorial process with a variety of clinically
MTE16.02 PRECISION MEDICINE IN NSCLC: LESSONS LEARNED patterns. Its management requires different, case adapted approaches.
Several strategies are currently under investigation, but some have already
AND PERSPECTIVES
find its way into todays practice although study evidence is still rather weak.
Christian Manegold In case of oligoprogression the EGFR-TKI therapy may continue but local
Surgery, Medical Faculty Mannheim, University of Heidelberg, Mannheim/Germany therapies (radiation, surgery) should be added. In case of diffuse progression
EGFR-TKI therapy may continue, but in combination with chemotherapy;
Medical therapy in advanced NSCLC in 2016 is characterized by
EGFR-TKI therapy may be switched to chemotherapy, but at the moment
personalization, individualization, and therapy precision. Not only clinical
of chemotherapy resistance patients may be re-exposed to EGFR-TKI
factors are used for treatment differentiation but also the histological
therapy; admission to clinical trials offering investigational agents may be
type (squamous versus non-squamous) and the molecular profile (mutant
a valid option for some patient. Osimertinib has just been approved and is
versus wild type). In addition, the complexity of the treatment algorithm has
recommended for tumors expressing P790M (Jänne, 2015). In tumors bearing maintenance (4.8 vs 2.6 months, HR=0.42; 95% CI: 0.33–0.55; p <0.0001). No
ALK-/ROS-gene-rearrangements ceritinib is approved and recommended in overall survival benefit has been found for squamous cell patients. However, a
case of crizotinib resistance (Shaw, 2014). Conclusion: During the past ten PFS benefit was seen in IFCT-GFPC 0502 for continuation maintenance with
years the complexity of the treatment algorithm of advanced NSCLC has gemcitabine and in SATURN for sequential erlotinib. The ABOUND study with
gradually increased by the incorporation of several approved molecules. Novel carboplatin/ nab-paclitaxel is exploring the nab-paclitaxel maintenance in
immunotherapies have recently changed the management of advanced wild- squamous-cell and results are awaited. The SQUIRE trial evaluated the
type NSCLC. Treatment by histo-type and geno-type has been established and anti-EGFR monoclonal antibody necitumumab in combination with
it can be assumed by the given speed of growth of molecular information that cisplatin-gemcitabine followed by maintenance necitumumab. It modestly
the process of treatment differentiation will fast continue. Identification improved overall survival and PFS over chemotherapy alone (median OS 11.5 vs
of new prognostic and predictive factors undoubtedly will accelerate this 9.9 months, HR 0.84, p=0.012; PFS HR 0.85, p=0.02). The contribution of
process. bevacizumab maintenance phase was not prospectively been established.
However, a retrospective landmark analysis of E4599 evaluated the patients
who were alive without progression for at least 3 weeks after completion of 6
cycles of chemotherapy. The PFS favored bevacizumab maintenance (4.4 vs
2.8 months; HR 0.64). OS was also longer (median 12.8 vs 11.4 months). ECOG
SESSION MTE17: MAINTENANCE THERAPY VERSUS EARLY 5508 is an important ongoing study, as mentioned previously Another
SECOND-LINE THERAPY IN ADVANCED NSCLC ongoing study (MO 22097) is evaluating the role of continuing bevacizumab in
combination with a second line chemotherapy, beyond progression to
(TICKETED SESSION)
maintenance bevacizumab. In a phase III placebo-controlled study,
TUESDAY, DECEMBER 6, 2016 - 07:30-08:30 carboplatin and paclitaxel were given with or without concurrent and
maintenance sorafenib, but no improvement in overall survival was shown
and the results were detrimental in patients with squamous cell histology.
MTE17.02 MAINTENANCE THERAPY VERSUS EARLY SECOND-LINE CALGB 30607 of maintenance sunitinib versus placebo met its primary
THERAPY IN ADVANCED NSCLC endpoint of improving PFS (4.3 versus 2.8 mos), including squamous histology.
Panos Fidias There was no effect on OS. EORTC 08092 evaluated pazopanib given as
Massachussets General Hospital, Boston/United States of America maintenance treatment following standard first line platinum-based
chemotherapy in patients with advanced NSCLC. This study was stopped due
Several trials have evaluated the appropriate initial duration of platinum to lack of efficacy by stringent criteria for PFS at a futility interim analysis. A
based chemotherapy: 3 versus 6 cycles, 4 versus continuous cycles, or 2 versus phase III trial of carboplatin, paclitaxel with or without concomitant and
4 cycles after non-progression to the initial 2 treatments. In all situations maintenance ipilimumab (an anti-CTLA4 agent) is ongoing, and was initiated
there was no benefit to longer duration of chemotherapy and both ASCO and taking into account the positive results obtained adding maintenance
NCCN recommend no more than 6 cycles of initial treatment. Continuation of ipilimumab to the platinum doublet in a previous phase II study. Vaccine
lower intensity therapy (typically with a single agent from the initial doublet) therapy has also been studied as maintenance treatment in NSCLC.
was also tested. Studies of weekly paclitaxel after carboplatin-paclitaxel Belagenpumatucel-L (Lucanix) is an allogeneic cancer vaccine, obtained from
(Belani et al) or gemcitabine after cisplatin-gemcitabine (Brodowicz et al) TGF-beta2 antisense gene modified whole NSCLC cell lines. There was no
showed no OS difference, but a possible benefit in PFS. Studies evaluated the difference in overall survival between arms (median survival 20.3 versus 17.8
introduction of a non-cross resistant agent (early second line) in patients months with belagenpumatucel-L versus placebo, respectively. Tecemotide
without progression after initial chemotherapy. Westeel et al. randomized (L-BLP-25) is a vaccine against MUC1 antigen. START trial randomized patients
patients after MIC x 3 to either observation versus vinorelbine; Fidias et al. with stage III NSCLC who completed chemoradiotherapy between tecemotide
evaluated immediate versus delayed docetaxel after carboplatin-gemcitabine injections or placebo. No significant difference in overall survival with the
x 4 and JMEN study looked into pemetrexed versus placebo after four cycles of administration of tecemotide after chemoradiotherapy was found - median
platinum doublet. For the latter two studies, about 50% of patients OS was 25.6 months with tecemotide versus 22,3 months with placebo.
completed 6 maintenance cycles and 50-60% of patients in the observation References 1. Cost-utility analysis of maintenance therapy with gemcitabine
arm received second line therapy; this is consistent with rates of second line or erlotinib vs observation with predefined second-line treatment after
therapy in multiple studies of NSCLC. Results showed a 2-3 month difference cisplatin–gemcitabine induction chemotherapy for advanced NSCLC:
in PFS favoring immediate therapy. In terms of overall survival, there was no IFCT-GFPC 0502-Eco phase III study. I Borget, M Pérol, D Pérol, A Lavolé, L
difference with vinorelbine, and a 2.6-2.8 month difference with either Greillier, P Dô, V Westeel, J Crequit, H Léna, I Monnet, H Le Caer, P Fournel, L
docetaxel or pemetrexed (significant only with pemetrexed). QoL was not Falchero, M Poudenx, F Vaylet, S Chabaud, A Vergnenegre, G Zalcman, C
affected by continuous chemotherapy and tumor related symptoms improved Chouaïd. BMC Cancer2014,14:953 DOI: 10.1186/1471-2407-14-953) 2.
with pemetrexed. Erlotinib has been evaluated in 3 randomized trials against Maintenance pemetrexed plus best supportive care versus placebo plus best
placebo (SATURN), observation (IFCT-GFPC 0502) or in combination with supportive care for non-small-cell lung cancer: a randomised, double-blind,
bevacizumab against placebo-bevacizumab (ATLAS). In all studies there was a phase 3 study. Tudor Ciuleanu, Thomas Brodowicz, Christoph Zielinski, Joo
PFS benefit (HR 0.71-0.82), but OS was only significant in the SATURN trial (HR Hang Kim, Maciej Krzakowski, Eckart Laack, Yi-Long Wu, Isabel Bover,
0.81). PFS benefit was limited to non-squamous histology for pemetrexed, as Stephen Begbie, Valentina Tzekova, Branka Cucevic, Jose Rodrigues Pereira,
opposed to the docetaxel and erlotinib trials. Despite the initial negative Sung Hyun Yang, Jayaprakash Madhavan, Katherine P Sugarman, Patrick
trials, continuation pemetrexed following platinum-pemetrexed doublet has Peterson, William J John, Kurt Krejcy, Chandra P Belani. Lancet Vol 374: 1432,
emerged as a standard option for non-squamous NSCLC. PARAMOUNT 2009 3. Maintenance therapy with pemetrexed plus best supportive care
randomized between pemetrexed and placebo following four cycles of versus placebo plus best supportive care after induction therapy with
cisplatin pemetrexed. It showed a PFS benefit (HR 0.64) and also an OS pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung
benefit (2.9 month difference, HR 0.78) in favor of continuation maintenance. cancer (PARAMOUNT):a double-blind, phase 3, randomised controlled trial.
AVAPERL used a similar design, however with the addition of bevacizumab Luis Paz-Ares, Filippo de Marinis, Mircea Dediu, Michael Thomas, Jean-Louis
throughout therapy, i.e. initial cisplatin-pemetrexed-bevacizumab followed Pujol, Paolo Bidoli, Olivier Molinier, Tarini Prasad Sahoo, Eckart Laack, Martin
by pemetrexed-bevacizumab versus bevacizumab. PFS significantly favored Reck, Jesús Corral, Symantha Melemed, William John, Nadia Chouaki,
pemetrexed (10.2 versus 6.6 months), and although OS was also superior (19.8 Annamaria H Zimmermann, Carla Visseren-Grul, Cesare Gridelli. Lancet Vol 13:
versus 15.9 months) it was not statistically significant. The IFCT-GFPC 0502 247, 2012 4. PointBreak: A Randomized Phase III Study of Pemetrexed Plus
trial also evaluated continuation gemcitabine and demonstrated a PFS Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and
advantage, but no OS benefit in an underpowered study. Bevacizumab Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed
continuation is an accepted approach based on the design of E4599, although by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous
its contribution has never been established in a randomized trial. However, a Non–Small-Cell Lung Cancer. Jyoti D. Patel, Mark A. Socinski, Edward B. Garon,
direct comparison between E4599 (carboplatin-paclitaxel-bevacizumab Craig H. Reynolds, David R. Spigel, Mark R. Olsen, Robert C. Hermann, Robert
followed by bevacizumab) and carboplatin-pemetrexed-bevacizumab M. Jotte, Thaddeus Beck, Donald A. Richards, Susan C. Guba, Jingyi Liu, Bente
followed by pemetrexed-bevacizumab was undertaken in the POINTBREAK Frimodt-Moller, William J. John, Coleman K. Obasaju, Eduardo J. Pennella,
study. It showed no OS differences (numerically favored E4599: 13.4 versus Philip Bonomi, and Ramaswamy Govindan. JCO 31:4349, 2013
12.6 months), although in pre-specified analysis of patients going through
maintenance (as opposed to ITT) there was a 2-month difference favoring the Keywords: Maintenance chemotherapy
combination of pemetrexed-bevacizumab. E5508 [ClinicalTrials.gov
identifier:NCT01107626] is attempting to answer this question by directly
randomizing patients to either bevacizumab, pemetrexed or the combination
after carboplatin-paclitaxel-bevacizumab. Subset data from the SATURN trial
strongly supports switch maintenance with erlotinib for EGFR mutant SESSION MTE18: PERSPECTIVES IN THE SYSTEMIC
patients, who had an impressive three fold higher median PFS (44 vs 14 weeks; TREATMENT OF SMALL-CELL LUNG CANCER
HR: 0.10; 95% CI: 0.04–0.25). INFORM included 296 asian patients, who were (TICKETED SESSION)
randomized between gefitinib and placebo. PFS favoured gefitinib TUESDAY, DECEMBER 6, 2016 - 07:30-08:30

TRIALS AND IN ROUTINE PRACTICE

MTE18.01 PERSPECTIVES IN THE SYSTEMIC TREATMENT OF SMALL- Dimitra Grapsa, Kostas Syrigos
CELL LUNG CANCER Oncology Unit, 3rd Internal Medicine Dpt, University of Athens, Athens/Greece
Mary O’Brien
Medical Oncology, Royal Marsden Hospital, Rs/United Kingdom Monitoring of treatment efficacy and treatment-related toxicity –both
in the real-world and the clinical trial setting- is a crucial, complex and
Small cell lung cancer is the prototype of a smokers cancer and therefore with constantly evolving aspect in the field of modern personalized oncology.
changing smoking patterns and decreasing prevalence of smoking this is a The expansion of our lung cancer armamentarium, due to continuous
tumour that happily we are seeing less frequently. However the nature of implementation of novel (and costly) targeted and immunotherapeutic
the disease, the morbidity and suffering it causes, and the tantalising chemo agents, along with their companion diagnostics, has inevitably led not only
and radiotherapy sensitivity of this tumour make it of great medical and to substantial improvements in clinical outcomes, but also to increasing
academic interest to us. More attention is now given to the morphology of demands for a more accurate prediction and prevention of toxicities and
small cell lung cancer and the blurred boundary with large cell neuroendocrine more robust evaluation of cost-effectiveness. Furthermore, transition to
tumours and non small cell lung cancer with neuroendocrine features. At the targeted therapies displaying modes of action and biologic behavior vastly
end of the EGFR mutation driven lung cancer natural history, small cell lung distinct to those of traditional cytotoxic agents, has necessitated the need
cancer appears once resistant has developed to EGFR mutation therapies. to revisit our concept of what constitutes “tumor response” in lung cancer
If we start from the early stage disease and look at radical approaches and treatment (and solid tumors in general). Vital issues that need to be urgently
how these have changed in the last 20 years we see that the gains made by -albeit concertedly- addressed include –but are not limited to- the need to
systemic treatment have been stable while outcomes have been improved adapt response evaluation criteria, monitoring tools and techniques to this
by intensive local and focused treatments in the form of prophylactic cranial rapidly changing landscape of lung cancer treatment and to increase our focus
irradiation and consolidation radiotherapy to the mediastinum. Small gains towards a patient-centered standard of care. Monitoring of treatment efficacy
have also been made by the timing of radiotherapy both quickly after last using imaging modalities Monitoring of tumor size changes -as evidenced
chemotherapy or when given in a concurrent fashion. The Convert study on quantitative imaging modalities such as CT and MRI scans and typically
has now given us a faster twice a day delivery with equal effectiveness and assessed by the unidimensional RECIST criteria- remains the cornerstone of
toxicity to a higher dose once daily schedule. Surgery has never really taken treatment response evaluation and decision-making in oncology practice and
off as a widely used treatment for SCLC. For all the anecdotal cases who a strong surrogate endpoint for overall survival in clinical trials. Limitations
have been cured with combined treatment involving surgery, we will also of this approach are, nevertheless, significant and increasingly recognized.
remember those patients who have failed to recover or have delayed recovery First, measurement inaccuracies and considerable inter-observer variability
from surgery and lost the window of opportunity for systemic treatment in should be pointed out. Second, considerable time and cycles of cytotoxic
a disease that can rapidly change from asymptomatic to very symptomatic. drugs are needed prior to the appearance of any clinically meaningful tumor
Despite little change in systemic therapies, it is important that what we size changes on standard imaging studies, meaning that a reduction of tumor
have, we use well and to this end patients with SCLC should be carefully volume alone may not represent an early indicator of treatment response.
monitored during treatment for treatment induced neutropenia as this is Third, antitumor activity of targeted agents, which may not necessarily
readily treated and prevented by the use of GCSF which has become cheap and result in significant tumor size modification, cannot be accurately assessed
readily available in most countries. In addition SCLC was also one of the solid or predicted with the use of these conventional strategies; multiparametric
tumours that benefited from denosumab in the trials of patients with bone imaging –evaluating both anatomical and functional parameters of tumors-
metastases and thus denosumab or zometa should be added to patients with is thus required for optimal assessment of tumor behavior (stability,
SCLC who have bone metastases to decrease bone morbidity. Extensive stage progression or regression). Within this context, functional imaging modalities
small cell lung cancer is still a challenge and currently a graveyard for drugs (i.e. dynamic contrast-enhanced MRI, diffusion weighted imaging or FDG-
development. The drugs that are looking promising are the PD-L1 inhibitors, PET and FLT-PET ) with the potential to visualize physiologic changes in
although PD-L1 in itself does not appear to be a biomarker. Anti- PD1 and PD-L1 the molecular level, have been investigated for their ability to influence
antibodies, while active in some cases of SCLC are not as broadly active as in decision-making by predicting or monitoring response to molecularly targeted
NSCLC. Indeed it does not appear that PD-L1 expression on tumour cells is agents or their value as surrogate outcome measures in the trial setting.
not a predictors of response. On could argue that the patients with SCLC who Notably, FDG-PET is increasingly used for the evaluation of treatment
have a response to anti PD1 therapies may have heterogeneous disease and response (mainly with PET response criteria /PERCIST) in lung cancer, while
have areas of NSCLC which drive the response. It has always been thought it is generally acknowledged that combined use of both RESIST and PERSIST
that SCLC must be a problem of proliferation of abnormalities at the stem cell criteria might lead to increased accuracy of prediction of treatment response
level. Indeed now it is no surprise that an anti DDL3 antibody (rovalpituzumab in the earlier treatment stages. Evidently, earlier recognition of tolerance to
tesirine) is showing activity in relapsed disease – a situation where responses treatment is vital for reduction of unnecessary toxicity and increase of cost-
are few but results of trials are rapid. It also appears that DDL3 expression is effectiveness. The barriers of complexity, high cost and limited availability,
a biomarker to predict response. Once again this biological pathway like the with regard to the above functional imaging techniques, should nevertheless
PD1 pathway, is unpatentable and thus we can expect a florry of antibodies also be emphasized. Evaluation of response to immune checkpoint inhibitors
targeting in and around these receptors on stem cells. The PARP inhibitors represents an emerging challenge in the field of immuno-oncology; since the
are again a group of drugs that held much promise but as yet have failed to specific patterns of tumor response to these agents cannot be accurately
deliver a treatment option at any point in the SCLC pathway. Further trials are described using conventional imaging criteria, immune-related response
ongoing. Positive benefits from radiotherapy in extensive stage as in limited criteria (irRC) were first defined in 2009, so as to provide a “common
SCLC, tells us that any treatment that can control a site of disease and can language”, enabling the application of a unified assessment of response
improve outcome, and suggests that removal of clones is important as either to immunotherapy. Controversy with regard to the use of bidimensional
a form of debulking treatment or indeed these clones are a future source of measurements (according to the WHO criteria) in the irRC nevertheless
resistance. Thus research on the treatment of oligometastatic sites either at ensued; immune-related RECIST 1.1 criteria are now increasingly used in clinical
presentation, residual after treatment or on relapse, as in the ongoing work in studies. Immune-related response evaluation remains to be implemented
NSCLC (e.g the Saron study) may lead to future gains in survival. The biology in routine practice and seems to represent an emerging endpoint in clinical
of SCLC should be approached in the same way as NSCLC i.e. when disease trials. Monitoring of treatment efficacy using non-imaging modalities
relapses, rebiopsies should become the norm with as large a piece of tissue as Monitoring of response to biomarker-driven therapies targeting specific
possible. SCLC also sheds tumour cells into the circulation, which are a source molecular alterations in the lung cancer genome remains a major challenge
of material for interrogation. Despite the negative trials, it is still rewarding to in the field of personalized oncology, mainly due to shortage of tissue for
treat SCLC patients – for the rapid improvement in symptoms with treatment the performance of genetic profiling of tumors. Liquid biopsies –detecting
and the small but real group who get long term responses, in addition the circulating tumor cells/CTCs and fragments of cell-free circulating tumor
rapid results makes this still an area for many more years of research. DNA/ctDNA- carry much promise for becoming an excellent and non-invasive
alternative to tissue-based testing for the identification of genetic mutations
Keywords: small cell lung cancer, heterogenous, neuroendocrine, with prognostic or therapeutic relevance. As a blood-based biomarker,
chemosensitive ctDNA analysis offers the potential of serial investigations at any time point
during the course of treatment, and thus of real-time dynamic monitoring
of treatment response and early identification of acquired resistance to
treatment or even early detection of recurrence (ideally prior to visible tumor
size changes on imaging). The first liquid biopsy test approved by the FDA as
SESSION MTE19: MONITORING OF TREATMENT OUTCOME a companion diagnostic, cobas® EGFR Mutation Test v2, is now increasingly
IN CLINICAL TRIALS AND IN ROUTINE PRACTICE used in routine practice for EGFR mutation testing in patients with advanced
(TICKETED SESSION) non-small cell lung cancer, expanding the access of this population to
potential disease-modifying treatments. Comprehensive molecular profiling
of tumors using next-generation sequencing (NGS) analysis of ctDNA is
another major advancement in personalized lung cancer oncology, with
tremendous potential for monitoring of dynamic tumor behavior in response
MTE19.02 MONITORING OF TREATMENT OUTCOME IN CLINICAL
to targeted therapy. Other simple and innovative tools for monitoring of (NSCLC).1Over the past years, the IASLC Staging and Prognostic Factors
treatment response are also being explored. For example, recent data showed Committee has collected a new database of 94,708 cases of lung cancer as
that breath analysis using nanoarray technology may represent a quick and the backbone for the upcoming 8th edition of the TNM classification for lung
patient-friendly monitoring tool for earlier recognition of treatment failure cancer due to be published late 2016 2,3. The 8th edition will significantly
and thus potentially serve as a surrogate marker for response to lung cancer impact lung cancer staging with CT and/or PET-CT due to the subclassification
therapy. Monitoring of treatment-related toxicity Subjective toxicity -which of T1 and T2 into a,b and c categories, the reclassification of tumors more than
cannot be assessed by current toxicity scales- is frequently under-reported 5 cm but not more than 7 cm in greatest dimension as T3, the reclassification
in clinical trials, with important negative implications on drug safety of tumors more than 7 cm in greatest dimension as T4, the grouping of the
evaluations and patient care in general. Recent data highlight the need to involvement of the main bronchus as a T2 descriptor, regardless of distance
improve the current system of toxicity assessment in the trial setting, mainly from the carina, but without invasion of the carina, the grouping of partial
via implementation of patient-reported outcomes (PROs). Self-reported and total atelectasis or pneumonitis as a T2 descriptor, the reclassification of
(and, ideally, real-time) monitoring of toxicity is increasingly investigated diaphragm invasion as T4 and the elimination of mediastinal pleura invasion
in the setting of routine oncology practice as well. As of yet it remains to be as a T descriptor 2,3. Moreover, the upcoming 8th edition will also lead to a novel
firmly established whether this system may significantly contribute to earlier classification of distant metastasis, in which single extrathoracic metastasis
identification and better management of adverse events, improved patient- will be classified as M1b whereas multiple extrathoracic metastasis are
physician communication and higher quality of life. Suggested reading classified as M1c. The changes made within the proposal of the 8th edition of
1.Nishino M, Hatabu H, Johnson BE, McLoud TC. State of the art: response the TNM will be discussed within the presentation using clinical examples.
assessment in lung cancer in the era of genomic medicine. Radiology 2014; Beside the accurate staging of patients with lung cancer early detection
271: 6-27. 2.Bennett CW, Berchem G, Kim YJ, El-Khoury V. Cell-free DNA and using CT screening with novel low radiation dose CT technologies will also
next-generation sequencing in the service of personalized medicine for lung be discussed. Within this context, a special focus will be given on novel
cancer. Oncotarget 2016; doi: 10.18632/oncotarget.11717. 3.Nishino M, Giobbie- methods that may improve a more accurate characterization of detected
Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a common lung nodules using deep machine learning and Radiomics. Radiomics refers to
language for tumor response to immunotherapy: immune-related response the comprehensive quantification of lung nodule and tumour phenotypes by
criteria using unidimensional measurements. Clin Cancer Res 2013; 19: 3936- applying a large number of quantitative image features that are standardized
43. 4.Di Maio M, Basch E, Bryce J, Perrone F. Patient-reported outcomes in the collected with specific software algorithms. Radiomics features have the
evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol 2016; 13: capability to further enhance imaging data regarding prognostic tumour
319-25. signatures, detection of tumour heterogeneity as well as the detection of
underlying gene expression patterns which is of special interest in patients
Keywords: clinical trials, Monitoring, treatment outcome, oncology practice with metastatic disease. The third part of the presentation will focus on
novel techniques in lung cancer imaging. The past fifteen years have brought
significant breakthroughs in the understanding of the molecular biology of
lung cancer. Signalling pathways and genetic driver mutations that are vital
for tumour growth have been identified and can be effectively targeted by
SESSION MTE21: NEXT GENERATION SEQUENCING (TI- novel pharmacologic agents, resulting in significantly improved survival of
CKETED SESSION) patients with lung cancer4. Parallel to the progress in lung cancer treatment,
WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30 imaging techniques aiming at improving diagnosis, staging, response
evaluation, and detection of tumour recurrence have also considerably
advanced in recent years5. However, standard morphologic computed
MTE21.01 NEXT GENERATION SEQUENCING tomography (CT) and magnetic resonance imaging (MRI) as well as fluor-18-
fluorodeoxyglucose (18F-FDG) positron emission tomography CT (PET-CT)
Ignacio Wistuba1, Xuefei Li2
1
are still the currently most frequently utilized imaging modalities in clinical
Translational Molecular Pathology, The University of Texas MD Anderson practice and most clinical trials 6,7. Novel state-of-the-art functional imaging
Cancer Center, Houston/United States of America, 2Medical Oncology, Shanghai
techniques such as dual-energy CT (DECT), dynamic contrast enhanced CT
Pulmonary Hospital, Shanghai/China
(DCE-CT), diffusion weighted MRI (DW-MRI), perfusion MRI, and PET-CT with
Non small cell lung cancer(NSCLC) with sensitive epidermal growth factor more specific tracers that visualize angiogenesis, tumour oxygenation or
receptor (EGFR) mutations invariably develop resistance to EGFR tyrosine tumour cell proliferation have not yet been broadly implemented, neither in
kinase inhibitors (TKIs). 20%-30% of NSCLC patients haboring sensitive clinical practice nor in phase I–III clinical trials. In this context, Nishino et al.4
mutations have no good initial clinical response to EGFR-TKIs, which is defined published an article on personalized tumour response assessment in the era
as having intrinsic resistance to EGFR-TKIs; while the rest of patients with of molecular treatment in oncology. The authors showed that the concept
activating mutations who are initially responsive to EGFR-TKIs eventually of personalized medicine with regard to cancer treatment has been well
develop acquired resistance after 10–12 months of consistent clinical beneft, applied in therapeutic decision-making and patient management in clinical
followed by disease progression. The drug resistance is a really tough and oncology. With regard to imaging techniques, however, it was criticized
urgent clinical problem. Part of resistant mechanisms have been reported, that the developments in tumour response assessment that should parallel
including BIM deletion polymorphism, combined with other bypass signal the advances in cancer treatment are not sufficient to produce state-of-
pathway activation, epithelial-mesenchymal transition (EMT) for primary the-art functional information that directly reflect treatment targets.
resistance; T790M, cMET amplification, SCLC transformation for acquired Functional information on tumour response is highly required because
resistance. However, partial resistant mechanisms still unknown. In contrast there is growing evidence that the current objective criteria for treatment
to acquired resistance to EGFR-TKIs, intrinsic resistance is more complicated. response assessment may not reliably indicate treatment failure and do
Next-generation sequencing (NGS) is a promising tool for analysis of tumor not adequately capture disease biology. Molecular-targeted therapies and
mutations. We aimed to investigate the intrinsic resistant mechanisms to novel immunotherapies induce effects that differ from those induced by
EGFR-TKIs by NGS, further to optimize treatment strategies and improve classic cytotoxic treatment including intratumorale haemorrhage, changes
clinical outcome in EGFR activating mutant patients having intrinsic in vascularity, and tumour cavitation. Thus, conventional approaches for
resistance to EGFR-TKIs. At present, the study is underway, and the results therapy response assessment such as RECIST or WHO criteria that exclusively
will be presented at the 2016 WCLC. focus on the change in tumour size are of decreasing value for drug response
assessment in clinical trials8,9. In summary, the aim of of this presentation
Keywords: next-generation sequencing, NSCLC, EGFR-TKIs, drug resistance is to provide an overview on the changes made within the upcoming 8th of
the TNM classification as well as to provide an overview on state-of-the-art
imaging techniques for lung cancer screening, staging, response evaluation
as well as surveillance in patients with lung cancer. The various techniques
will be discussed regarding their pros and cons to further provide functional
information that best reflects specific targeted therapies including anti-
SESSION MTE22: PERSPECTIVES IN LUNG CANCER angiogenetic treatment, immunotherapies and stereotactic body radiation
IMAGING (TICKETED SESSION) therapy. Literature: 1. Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM
WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30 staging system for lung cancer. Ann Thorac Cardiovasc Surg 2009;15:4-9. 2.
Asamura H, Chansky K, Crowley J, et al. The International Association for the
Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision
MTE22.01 PERSPECTIVES IN LUNG CANCER IMAGING of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification
for Lung Cancer. Journal of thoracic oncology : official publication of the
Thomas Henzler
International Association for the Study of Lung Cancer 2015;10:1675-84. 3.
Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Rami-Porta R, Bolejack V, Crowley J, et al. The IASLC Lung Cancer Staging
Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim/Germany
Project: Proposals for the Revisions of the T Descriptors in the Forthcoming
Lung cancer is still the leading cause of cancer-related death in both men Eighth Edition of the TNM Classification for Lung Cancer. Journal of thoracic
and women with 80% to 85% of cases being non-small-cell lung cancer oncology : official publication of the International Association for the Study

of Lung Cancer 2015;10:990-1003. 4. Rengan R, Maity AM, Stevenson JP, Hahn Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, Ercan D,
SM. New strategies in non-small cell lung cancer: improving outcomes in Matthews SE, Cantarini M, Barrett JC, Janne PA, Oxnard GR (2015) Acquired
chemoradiotherapy for locally advanced disease. Clin Cancer Res 2011;17:4192- EGFR C797S mutation mediates resistance to AZD9291 in non-small cell
9. 5. Miles K. Can imaging help improve the survival of cancer patients? Cancer lung cancer harboring EGFR T790M. Nat Med 21 (6):560-562. doi:10.1038/
Imaging 2011;11 Spec No A:S86-92. 6. Nishino M, Jackman DM, Hatabu H, Janne nm.3854 http://www.nature.com/nm/journal/v21/n6/abs/nm.3854.
PA, Johnson BE, Van den Abbeele AD. Imaging of lung cancer in the era of html - supplementary-information 5. Sunshine J, Taube JM (2015) PD-1/
molecular medicine. Acad Radiol 2011;18:424-36. 7. Nishino M, Jagannathan PD-L1 inhibitors. Current opinion in pharmacology 23:32-38. doi:10.1016/j.
JP, Ramaiya NH, Van den Abbeele AD. Revised RECIST guideline version 1.1: coph.2015.05.011 6. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder
What oncologists want to know and what radiologists need to know. AJR Am JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn M-J, Felip E, Lee
J Roentgenol 2010;195:281-9. 8. Oxnard GR, Morris MJ, Hodi FS, et al. When J-S, Hellmann MD, Hamid O, Goldman JW, Soria J-C, Dolled-Filhart M, Rutledge
progressive disease does not mean treatment failure: reconsidering the RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator
criteria for progression. J Natl Cancer Inst 2012;104:1534-41. 9. Stacchiotti S, K, Gandhi L (2015) Pembrolizumab for the Treatment of Non–Small-Cell Lung
Collini P, Messina A, et al. High-grade soft-tissue sarcomas: tumor response Cancer. New England Journal of Medicine 372 (21):2018-2028. doi:doi:10.1056/
assessment--pilot study to assess the correlation between radiologic NEJMoa1501824 7. Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE,
and pathologic response by using RECIST and Choi criteria. Radiology Dediu M, Ramlau R, Galiulin RK, Balint B, Losonczy G, Kazarnowicz A, Park
2009;251:447-56. K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R,
Paz-Ares L, Socinski MA (2015) Necitumumab plus gemcitabine and cisplatin
Keywords: Imaging of lung cancer, lung cancer, Radiomics, functional imaging versus gemcitabine and cisplatin alone as first-line therapy in patients with
stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label,
randomised, controlled phase 3 trial. The Lancet Oncology 16 (7):763-774.
doi:10.1016/s1470-2045(15)00021-2
SESSION MTE23: BIOMARKER CHARACTERIZATION: CHAL-

LENGES AND PERSPECTIVES (TICKETED SESSION)
WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30 MTE23: BIOMARKER CHARACTERIZATION: CHALLENGES AND PERSPECTIVES (TICKETED
SESSION)
MTE23.01 BIOMARKER CHARACTERIZATION: CHALLENGES AND

PERSPECTIVES MTE23.02 BIOMARKER CHARACTERIZATION: CHALLENGES AND
PERSPECTIVES
Leonhard Müllauer
Rafael Rosell
Institute of Pathology, Medical University Vienna, Vienna/Austria
Director, Cancer Biology & Precision Medicine Program, Catalan Institute of
The treatment of lung adenocarcinomas has improved with the identification Oncology, Germans Trias I Pujol Health Sciences Institute and Hospital, Badalona,
of driver gene mutations and the development of drugs tackling the altered Barcelona/Spain
driver gene proteins [1]. The interrogation of EGFR mutations as well as ALK
Early adaptive resistance in EGFR mutant NSCLC. Small molecule inhibitors
and ROS1 translocations is nowadays part of the routine diagnostic workup
are the current treatment for non-small-cell lung cancer (NSCLC), especially
of lung adenocarcinomas. Further therapies aiming at mutations in driver
for tumours harbouring an active mutation of epidermal growth factor
genes like RET, HER2, BRAF and MET are emerging. The main techniques
receptor (EGFR). Approximately 90% of EGFR mutations are exon 19
currently employed in molecular pathology laboratories for mutation
deletions or exon 21 single-point L858R substitutions and are associated
detection are mutation specific PCR, conventional capillary (Sanger)
with sensitivity to EGFR tyrosine kinase inhibitors (EGFR TKIs), like gefitinib
sequencing and next generation sequencing (NGS) [2]. The basic principles
or erlotinib. However, less than 5% of EGFR-mutant NSCLC patients achieve
of these methods, advantages and disadvantages with a special emphasis
a complete response to EGFR TKI and the overall median progression-free
on NGS and its potency for cancer diagnostics will be discussed. Recently
survival is no longer than 9-11 months. Accumulated studies report several
the detection of driver gene mutations in DNA that is derived from cancer
mechanisms of early adaptive resistance that can occur as early as two hours
cells and released into the blood has become feasible (so-called „liquid
after starting EGFR TKI therapy. The activation of signal transducer and
biopsy“) [3]. It has already entered routine diagnostics with the detection
activator of transcription 3 (STAT3) signalling is among these mechanisms
of the T790M mutation in circulating tumor DNA of primary EGFR mutated
of resistance. Furthermore, EGFR blockage enriches lung cancer stem
lung cancers, that developed resistance to first or second generation
cells through Notch3-dependent signalling pathway. We have previously
tyrosine kinase inhibitors [4]. The verification of a T790M mutation either
demonstrated that NF-κB contributes to gefitinib resistance in EGFR-mutant
by liquid biopsy or the analysis of tumor tissue is a prerequisite for therapy
NSCLC. The efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-
of lung adenocarcinomas with third generation tyrosine kinase inhibitors
mutant non-small cell lung cancer (NSCLC) is jeopardized by the activation
like osimertinib. The principles of liquid biopsy, employed techniques and
of signalling pathways. We examined the relevance of co-targeting EGFR,
potential applications will be introduced. The recent advent of cancer
signal transducer and activator of transcription 3 (STAT3) and Src-YES-
immunotherapy that interferes with immune checkpoint molecules like
associated protein 1 (YAP1) signalling. We conducted clinical and preclinical
programmed death 1 (PD-1) offers a new treatment for subgroups of lung
studies of key components of signalling pathways limiting EGFR TKI efficacy
cancer patients. A biomarker that would predict responsiveness to this
in EGFR-mutant NSCLC. High levels of STAT3 or YAP1 mRNA expression were
expensive therapy is greatly needed. The expression of the PD-1 ligand
associated with worse outcome to EGFR TKI in two independent cohorts of
(PD-L1) by tumor or immune/stromal cells is a potential biomarker, however
EGFR-mutant NSCLC patients. In the initial cohort of 64 patients, median
its utility is heavily debated [5]. The confusion on PD-L1 as a biomarker is
progression-free survival was shorter among the patients with high STAT3
partly caused by technical difficulties in the determination of expression,
than among those with low STAT3 (hazard ratio [HR] for disease progression,
such as the antibody used for immunohistochemistry and the determination
3·02; 95% confidence interval [CI], 1·54-5·93; P=0·0013). Median progression-
of a treshold of expression that correlates with response [6]. A further
free survival was shorter among the patients with high YAP1 than among
biomarker that is determined by immunohistochemistry is the expression
those with low YAP1 (HR for disease progression, 2·57; 95%CI, 1·30-5·09;
of EGFR in lung squamous cell carcinoma. A therapy with the recently
P=0·0067). The results were similar in the validation cohort of 55 patients.
approved anti-EGFR antibody necitumumab requires the demonstration
We demonstrated that gefitinib augments STAT3 signalling in EGFR-mutant
of EGFR expression by the cancer cells [7]. The methods and pitfalls in PD-1
NSCLC cells. Gefitinib with TPCA-1 (STAT3 inhibitor) blocked STAT3, but not
and EGFR immunohistochemistry will be presented. The requirement for
the YAP1 phosphorylation on tyrosine residue 357 by Src family kinases (SFKs)
biomarkers increases. This poses a challenge for diagnostics in respect to
that occurs downstream of IL-6. The triple combination of gefitinib, TPCA-1
availabiltity of techniques, infrastructure and budget. Particularly in lung
and AZD0530 (SFK inhibitor) ablated both STAT3 and YAP1 phosphorylation
cancer often very little tissue is available, but different assays should be
and markedly and safely suppressed tumour growth. Added value of our
run. To fulfill the increasing demand for a plethora of biomarker analysis
research: We found that EGFR TKI therapy activates STAT3 and that EGFR
multiplexing techniques that simultaneously interrogate a large number
blockage enriches lung cancer stem cells with up-regulation of the YAP1 and
of gene mutations, gene fusions, gene amplification and deletions, as well
Notch downstream effectors connective tissue growth factor (CTGF) and
as RNA and protein expression will be needed. An outlook on available and
hairy-enhancer of split-1 (HES1), respectively. We sought to demonstrate
emerging multiplexing techniques will be provided.References 1. The Cancer
that EGFR TKI treatment cannot abrogate STAT3 and Src-YAP1-Notch
Genome Atlas Research N (2014) Comprehensive molecular profiling of lung
activation in EGFR-mutant NSCLC cell lines, leading us to examine whether
adenocarcinoma. Nature 511 (7511):543-550. doi:10.1038/nature13385 2.
the combination of gefitinib with compounds targeting STAT3 and Src,
Buermans HP, den Dunnen JT (2014) Next generation sequencing technology:
supresses the mechanisms of resistance. Nine days after gefitinib treatment,
Advances and applications. Biochimica et biophysica acta 1842 (10):1932-
STAT3 mRNA level was significantly increased, as well as the fraction of ALDH
1941. doi:10.1016/j.bbadis.2014.06.015 3. Diaz LA, Jr., Bardelli A (2014) Liquid
positive cells. TPCA-1, a compound that targets STAT3, increases sensitivity
biopsies: genotyping circulating tumor DNA. Journal of clinical oncology :
to gefitinib in PC-9 and H1975 cells; however, neither gefitinib nor TPCA-1
official journal of the American Society of Clinical Oncology 32 (6):579-586.
inhibits Src or YAP1. The addition of the Src inhibitor, saracatinib, to the
doi:10.1200/JCO.2012.45.2011 4. Thress KS, Paweletz CP, Felip E, Cho BC,
doublet of gefitinib and TPCA-1, was highly synergistic and abrogated STAT3, was used. Only immune PD-L1 expression was correlated with a highly intense
and Src-YAP1-Notch signalling. Implications: Treatment with single EGFR immune infiltrations. Previous published evaluations of prognostic value were
TKI can no longer be considered adequate for patients with EGFR mutant discordant likely because immune checkpoints modulators play both positive
NSCLC. Our findings ultimately suggest that a clinical trial evaluating the and negative roles in the immune inhibitory pathways with some redundancy,
co-targeted inhibition of STAT3 and Src is warranted. As a result, STAT3 and and patients series and assays were not comparable. The two meta-analyses
YAP1 mRNA levels could become important predictive biomarkers.References: with different antibodies, cutoffs, patient series, ethnicities and contribution
We searched PubMed for English language reports published up to December, of oncogene driven cancers, initial resection sample or contemporary biopsy
2015 using the terms “non-small-cell lung cancer”, “STAT3”, “interleukin-6”, rendered their interpretation extremely problematic. Global result was
“NF-κB”, “aldehyde-dehydrogenase (ALDH)”, “integrin-linked kinase (ILK)”, supporting a poor prognosis of “PD-L1 positivity” on tumor cells.
“glycoprotein 130 (gp130)”, “Src-homology 2 domain-containing phosphatase
2 (SHP2)”, “the complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing PD-L1 as a Predictive Biomarker for Checkpoint Inhibitors. Most of phase
protein-1 (CDCP1)”, “AXL”, “ephrin type-A receptor-2 (EphA2)”, “Src family I trials works with four antibodies targeting PD-1 or its primary ligand PD-
kinases (SFK)”, “YES-associated protein 1 (YAP1)”, “Notch”, “cell migration, L1, response taxes appear higher in patients with increased tumor PD-L1
invasion and metastases” and “STAT3 inhibitors”. membrane expression by IHC. However, different antibody assays, absence
of standardization, different score to determine PD-L1 positivity, companion
Keywords: STAT3, EGFR TKI, YAP1, NSCLC test type, and a short number of specimens available for testing, accopled
to the variability of the intervals between biopsy and test, has certainly
disadvantaged the conclusion and prevent consensus to be reached (10). The
best threshold was provided by Garon et al, with ≥ 50% of tumor cells PD-L1
positive to allow the highest response rate of 45% to pembrolizumab (3). In
SESSION MTE24: IMMUNOHISTOCHEMICAL ASSESSMENT most trial series, biopsies or resected specimen were used and considerable
OF BIOMARKERS FOR IMMUNE CHECKPOINT INHIBITORS difference between these samples occurs due to tumor heterogeneity. The
reliability of small biopsy samples is questioned (10). Indeed lung tumor
(TICKETED SESSION)
heterogeneity is characteristic and PD-L1 is typically heterogeneous in its
WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30 distribution in the tumor majority as is PD-L1 positive immune cells. Multiple
questions are still addressed before PD-L1 is considered as a definitive
molecular predictor of effectiveness. As for prognostic evaluations,
MTE24.01 IMMUNOHISTOCHEMICAL ASSESSMENT OF thresholds of ≥ 1%, ≥ 5%, ≥ 10%, ≥ 50% or continuous H score have been used.
BIOMARKERS FOR IMMUNE CHECKPOINT INHIBITORS In addition, in a few trials, PD-L1 expression in TILs was predictive more than
Vera Capelozzi PD-L1 on tumor cells but the best cut off was not revealed.
Pathology, Faculty of Medicine, University of SÃo Paulo, SÃo Paulo/Brazil
Conclusion. PDL1 expression predicts response to immune checkpoint
Immune checkpoint inhibitors in cancer immunotherapy. Programmed inhibitors. Concordant results showing a better response if PDL1 + in several
death receptor-1 (PD-1) is a type 1 membrane protein of the immunoglobulin trials, using drug specific test and for Nivolumab also histology specific.
superfamily that has an important role in restrincting immune-mediated We should evaluate membranous staining in tumor sample with at least
tissue danage secondary to inflammation and/or infection (1). The clinical 100 tumors cells and immune cells. Perspective for upgrading includes:
advantage of antibodies that target either PD-1 or PD-L1 to block this 1) heterogeneity of the expression of PDL1 within tumor, primitive vs
ligand-receptor interface, allowing cancer killing by T cells became clear metastases number and size of samples; 2) surgical tissue versus biopsy and 3)
when CTLA4, an antagonist against the T-cell, such as ipilimumab, and archival versus new biopsy and 4) standardize the assays. Published abstracts
afterward PD-1, showed an increase survival in patients with metastatic showed high rates of concordance between primary and metastases (81%).
melanoma (2). Clinical investigations in lung cancer have demonstrated the Obtaining multiple biopsies from different areas of the tumor would enhance
benefit of PD-1 inhibitors pembrolizumab in advanced non–small cell lung the validity of the results of IHC evaluation (160 patients=48% discordance).
cancer (NSCLC) and nivolumab in advanced squamous and nonsquamous
References
NSCLC; both approved as second-line therapies by the US Food and Drug
Administration (FDA) (3-5). Others PD-L1 inhibitors such as atezolizumab and 1. Sholl LM, Aisner DL, Allen TC, Beasley MB, Borczuk AC, Cagle PT, Capelozzi
durvalumab have demonstrated effectiveness in several tumor types (6-7) V, Dacic S, Hariri L, Kerr KM, Lantuejoul S, Mino-Kenudson M, Raparia K,
but they were not approved for clinical use until now. PD-1 inhibitors induce Rekhtman N, Roy-Chowdhuri S, Thunnissen E, Tsao MS, Yatabe. Programmed
around of 20% of complete response frequency in patients with NSCLC, and Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A
persistent response in a subgroup of patients treated by immune checkpoint Perspective From Members of the Pulmonary Pathology Society. Arch Pathol
inhibitors. Garon et al (3) showed that tumors with PD-L1 expression ≥ 50% Lab Med. 2016;140(4):341-4.
by immunohistochemistry (IHC) were significantly more expected to respond
to pembrolizumab than those with less than 50% malignant cell expression. 2.Couzin-Frankel J. Breakthrough of the year 2013: cancer immunotherapy.
In contrast, response rates to nivolumab are significantly greater in patients Science 2013;342:1432–1433.
with nonsquamous NSCLC, showing ≥ 1% tumor cell positivity (5). These
differences are related to the combination of antibody clone and detection 3.Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non–
system as a companion diagnostic for selecting lung cancer patients for small-cell lung cancer. N Engl J Med 2015;372:2018–2028.
pembrolizumab therapy. Previous investigations reported response taxes 4.Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel
in PD-L1–positive tumors of 31% to 52%, but particularly more than 16% of in advanced squamous-cell non-small-cell lung cancer. N Engl J Med
PD-L1–negative tumors also showed treatment response (1). This finding 2015;373:123–135.
indicates that PD-L1 expression improves for responders but the absence of
expression is not a complete indicator of advantage. PD-L1 expression did not 5.Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in
predict differential response to nivolumab in lung squamous cell carcinoma as advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373:
compared with docetaxel (4). 1627–1639.
Immunohistochemical Assessment of Immune Checkpoint Inhibitors. PD-L1 6. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response
in NSCLC is expressed on the membrane of tumor cells, and/or on immune to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014;
infiltrating cells dendritic cells, antigen-presenting cells and T lymphocyte. 515:563–567.
PD-1, the PDL1 receptor, is expressed on tumor infiltrating lymphocytes,
mainly CD4 T cells, T and B regulatory, NK, monocytes and DC. Concerning 7.Stewart R, Morrow M, Hammond SA, et al. Identification and
PD-L1 binding, PD-1 inhibits kinases involved in T cell activation. Two potential characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal
mechanisms are involved in expression of immune checkpoints on tumor cells antibody. Cancer Immunol Res 2015;3:1052–1062.
and their immune stromal component: oncogenic signaling, and response to
8. Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A, Graziano S,
inflammatory signals (8). Tumor cells express multiple ligands and receptors
Pirker R, Douillard JY, Le Chevalier T, Filipits M, Rosell R, Kratzke R, Popper
and antitumor immune response can be enhanced by multi-level blockade of
H, Soria JC, Shepherd FA, Seymour L, Tsao MS. Prognostic Effect of Tumor
immune checkpoints. PD-1/PD-L1 commitment leads to HSP-2 phosphatase
Lymphocytic Infiltration in Resectable Non-Small-Cell Lung Cancer. J Clin
activity which dephosphorylates Pi3K and thus downregulate AKT (8).
Oncol. 2016;34:1223-30.
The positive score on tumor cells has not been evaluated nor enhanced or
standardized (3; 8). Brambilla and Ming (8) assessed a score of positivity for 9. Soria JC, Marabelle A, Brahmer JR, Gettinger S. Immune checkpoint
prognosis analysis using E1L3N Cell Signaling antibody commercially available. modulation for non-small cell lung cancer. Clin Cancer Res. 2015;21: 2256-62.
They found that 20% of lung tumors cell expressed PD-L1 (≥ 20% intensity
2+3+), and 29% the immune stromal cells (T, macrophages, DC ) ≥ 10% intensity 10. Kitazono S, Fujiwara Y, Tsuta K, Utsumi H, Kanda S, Horinouchi H,
2+3+. PD-L1 positivity in both tumor and immune cells were seen in only 9% of Nokihara H, Yamamoto N, Sasada S, Watanabe S, Asamura H, Tamura T, Ohe Y.
NSCLC, 20,7% were both negative. There was no prognostic relevance of PD-L1 Reliability of Small Biopsy Samples Compared With Resected Specimens for
(tumor cells or stroma) whatever cut off by 10% increment or linear scoring the Determination of Programmed Death-Ligand 1 Expression in Non--Small-

Cell Lung Cancer. Clin Lung Cancer 2015;16:385-90. tissue needed, reducing time and costs. Development of EGFR inhibitors
also led to a different approach for treating lung cancer. For the first time
Keywords: Lung Cancer, Immunotherapy, PD-L1, Immunohistochemistry physicians faced with oligo-progressing diseases, consisting in disease
slowly progressing under EGFR-TKI therapy. Often the disease remains
asymptomatic and it is still partially sensitive to the therapy. The possibility
to control disease outcome by continuing the targeted agent led to the
concept of “treatment beyond progression”, an approach that is preserving
patient quality of life with also a favorable impact on duration of life. Finally,
SESSION MTE26: EGFR TARGETED THERAPIES:
anti EGFR therapies also highlighted the new opportunity for treating brain
LESSONS LEARNED (TICKETED SESSION) metastases. Brain metastases (BM) are a frequent complication of NSCLC,
WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30 with 25–40% of patients developing BM during the course of the disease,
often within the first 2 years after the primary tumor diagnosis. A review
of 1,127 NSCLC patients found that those with EGFR mutations were more
MTE26.02 EGFR TARGETED THERAPIES: LESSONS LEARNED likely to develop BM than those without such mutations. The frequency of
Shun Lu1, Federico Cappuzzo2 BM was thus 31.4% for the mutation-positive patients but only 19.7% for
1 the negative ones. Improvements in neurologic symptoms and performance
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University,
Shanghai/China, 2Department of Oncology, Ausl Romagna, Ravenna/Italy
status have been reported with whole-brain radiation therapy (WBRT) in
combination with steroid therapy in these patients. However, due to their
poor performance status, many patients with BM are not eligible for surgery
or radiosurgery. Furthermore, the role of systemic chemotherapy for the
treatment of BM is controversial due to the impenetrable nature of the blood
brain barrier (BBB), with reported response rates to chemotherapy ranging
from 15–30% (overall survival [OS] 6–8 months). Response rates of brain
metastases to EGFR tyrosine kinase inhibitor (TKI) treatment (e.g. gefitinib,
erlotinib, afatinib) in patients with NSCLC harboring EGFR mutations
reach 60–80%, with a complete response rate as high as 40%. Median OS is
15–20 months, and progression-free survival in the brain reaches 6.6–11.7
months, demonstrating improved clinical outcome (Table I). Nevertheless,
first and second generation EGFR-TKI may have limited BBB penetration.
New EGFR-TKIs including the third-generation EGFR-TKI osimertinib and
AZD3759, an oral reversible inhibitor of EGFR activating mutations, recently
showed impressive activity in presence of BM. The possibility to obtain a long
lasting brain disease control together with the positive impact on duration
of life is also impacting on the strategy of BM treatment, with preference
for therapies not or modestly impacting on cognitive functions, such as
stereotaxic radiotherapy, and a lower usage of WBRT. Reference: 1. Porta R,
et al. Eur Respir J 37: 624-631, 2011. 2. BPark SJ, et al. Lung Cancer 77: 556-560,
2012. 3. Li Z. J Clin Oncol 29 (Suppl): abstract e18065, 2011. 4. Kim JE, et al. Lung
Cancer 65: 351-354, 2009. 5. Welsh JW, et al. J Clin Oncol 31: 895-902, 2013. 6.
Iuchi T, et al. Lung Cancer 82: 282-287, 2013. 7. Hoffknecht P, et al. J Thorac
Oncol 10: 156-163, 2015.
Keywords: EGFR, brain metastases
SESSION MTE27: TREATMENT OF LUNG CANCER PATIENTS

WITH POOR PERFORMANCE STATUS (TICKETED SESSION)
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) are

MTE27.01 TREATMENT OF LUNG CANCER PATIENTS WITH POOR
the standard therapy for patients with Non-Small-Cell Lung Cancer (NSCLC)
harboring activating EGFR mutations. During the last 10 years several trials PERFORMANCE STATUS
demonstrated that first and second generation EGFR-TKIs such as erlotinib, Rogerio Lilenbaum
gefitinib or afatinib are superior to standard platinum-based chemotherapy Yale Cancer Center, New Haven/CT/United States of America
in terms of efficacy and tolerability and quality of life. Development of
EGFR-TKIs led to a dramatic change in mentality of physicians treating Performance status (PS) captures a patient’s ability to perform daily
NSCLC. For many years NSCLC has been treated with chemotherapy and activities and provides a measure of impairment as a function of tumor
platinum-based doublets were offered to all patients irrespective of biological burden. The Eastern Cooperative Oncology Group (ECOG) scale is the most
characteristics. Knowledge in the field of molecular biology were limited frequently used and ranges from 0 (fully ambulatory without symptoms) to
and even a small cytological sample was sufficient for defining the therapy. 5 (dead). Typically, patients with an ECOG PS of 0 and 1 are labeled as “good
Tumor biopsy was recommended only at the time of initial diagnosis and PS”, are typically treated with combination regimens, and are the focus
changes in tumor biology as a consequence of therapy exposure were largely of the majority of the clinical trials. Patients with “poor PS”, mostly ECOG
unknown. Discovery of EGFR mutations and the impressive activity observed 2, but also 3 and occasionally 4, have been largely excluded from clinical
with EGFR-TKIs in EGFR mutated patients led clinicians to understand the trials. Patients with a PS of 2 account for approximately 30-40% of patients
relevance of patient selection based on biomarker assessment and therefore diagnosed with advanced non-small cell lung cancer (NSCLC) in clinical
the importance of tumor tissue analysis. Since EGFR-TKI approval, EGFR practice (1). As a result of the lack of dedicated research, current guidelines
testing entered onto clinical practice and today several biomarkers are are equivocal with respect to the optimal therapy for these patients and
routinely tested in NSCLC patients for defining the best therapeutic strategy. their management remains inconsistent, ranging from best supportive care
In addition to EGFR, other biomarkers such as ALK or ROS1 rearrangements to combination chemotherapy. Cooperative group studies in the 1980’s
or PD-L1 expression are guiding physician for therapy choice and additional and 1990’s suggested that poor PS patients (ECOG ≥2) derived little or no
tests are expected to reach the clinic in the next future. As a consequence, benefit from systemic chemotherapy and had high rates of treatment-related
tumor biopsy and tissue collection become relevant in clinical practice and morbidity and mortality (2). This perspective permeated clinical research
also in trial design, since modern studies often claim for tumor tissue. In and clinical practice for over 2 decades. While concerns about safety and
addition, identification of mechanisms responsible for acquired resistance benefit remain appropriate, the advent of better supportive care, along
led to repeat tumor biopsies. Unfortunately, in NSCLC, the amount of tissue with more effective and tolerable carboplatin-based doublets have led to
obtained at the time of primary diagnosis is often not abundant and tumor new trials in this subset of patients. Two large phase III randomized trials
re-biopsy if feasible in the minority of patients. Such limitations are leading in PS 2 patients in the mid-2000’s provide insights into this heterogeneous
to development of the so-called “liquid biopsy”, allowing physicians to cohort. In one trial, 400 patients were assigned to standard carboplatin
obtain biomarker information in circulating tumor DNA. In addition, new plus paclitaxel or carboplatin plus another formulation of paclitaxel (3). In
technologies are implementing the possibility to test for multiple biological the other trial, 400 patients were assigned to single agent gemcitabine or
events using a single experiment, with a significant reduction in amount of vinorelbine (4). The identical eligibility criteria led to a separate publication
comparing single agent vs. combination chemotherapy (5). The response SESSION MTE28: IMPLEMENTATION OF PRECISION MEDI-
rate (38 versus 16 percent) and the median time to progression (4.6 versus CINE IN ROUTINE PRACTICE: THE LATIN AMERICAN EXPE-
3.5 months) were statistically superior with combination chemotherapy.
Overall survival trended in the same direction, but the difference was not
RIENCE (TICKETED SESSION)
significant (8.0 versus 6.6 months). Toxicity, as expected, was higher with WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30
combination chemotherapy. The question of single agent vs combination
chemotherapy was addressed in a definitive manner by a phase III randomized
trial that compared pemetrexed alone or in combination with carboplatin MTE28.01 IMPLEMENTATION OF PRECISION MEDICINE IN ROUTINE
in 205 eligible patients with PS 2 (6). Respectively, the response rates were PRACTICE: THE LATIN AMERICAN EXPERIENCE
10% vs 24%; the median progression free survival was 2.8 vs. 5.8 months; Mercedes Dalurzo
and the median survival was 5.3 vs. 9.3 months, all statistically significant in
Pathology, Hospital Italiano de Buenos Aires, Ciudad Autonoma de Buenos Aires/
favor of the combination regimen. Toxicity was manageable but 4 treatment- Argentina
related deaths were observed in the combination arm. This trial has set a
new standard for treatment of advanced NSCLC patients with a PS of 2. Technology for molecular testing in lung cancer is a highly demanding aspect
The advent of targeted agents led to the exploration of these agents as a to tackle in the LATAM countries. Molecular testing requires incorporation
“gentler approach” to PS 2 patients, irrespective of the presence or absence of new technologies usually involving expensive equipment, reagents
of the mutation. In a phase II randomized trial, patients were assigned to and supplies. Moreover, these items are commonly imported from other
either erlotinib or a combination of carboplatin and paclitaxel (7). Patients countries and are subjected to custom regulation and heavy taxes. Therefore,
treated with erlotinib had a significantly shorter median survival compared LATAM labs commonly face unpredictable delays in the legal processing of
to chemotherapy (6.5 vs 9.7 months, HR 1.73, 95% CI 1.09-2.73). As shown purchase orders, are constantly adjusting to changes in regulations and in
in other trials, EGFR inhibitors should not be given to untreated patients the country’s financial status, and suffer from slow and sometimes poor
without the mutation, regardless of the PS. Guidelines from the American support from companies that do not see them as preferred clients. As an
Society of Clinical Oncology (ASCO) state that the data for patients with example of consequences of some of this points, in Argentina the agents
PS 2 are insufficient to make a strong recommendation for combination Nivolumab and Pembrolizumab were approved by government agencies
chemotherapy, and single agent therapy may be appropriate if the perception for immunotherapy for NSCLC before the molecular testing laboratories
of risk outweighs the perception of benefits (8). The European Society of had conditions to purchase the DAKO platform and the CDx antibodies for
Medical Oncology (ESMO), after reviewing the same body of data, came up appropriate IHC testing. Some technical devices such as automated IHC
with a straightforward recommendation for carboplatin-based combinations platforms are more widely available. They were initially integrated onto large
to all eligible PS 2 patients (9). The National Comprehensive Cancer Network pathology labs in the main cities of several countries but smaller automated
(NCCN) merged PS 2 patients into the PS 0-1 group for recommendations platforms are currently available in a number of other cities. There are
regarding first line therapy, with no obvious distinction between the laboratories equipped for fluorescence in situ hybridization (FISH) and for
subsets (10). This progressive approach recognizes the advances made in the DNA sequencing in most countries. Sanger sequencing is still commonly used,
management of PS 2 patients in the past decade and extends the benefits of but the main laboratories already incorporated newer technologies such
systemic therapy to a large group of patients who were, until recently, offered as RT-PCR allele-specific technology (usually Cobas platform) and tailored
inferior treatments.References: panels of next generation sequencing (NGS) or have them in the short list
for implementation. Additionally to the challenges in the laboratories
Lilenbaum RC, Cashy J, Hensing TA, et al. Prevalence of poor performance organization, two other main issues obstruct the implementation of lung
status in lung cancer patients: implications for research. J Thorac Oncol 2008; cancer molecular testing in the LATAM countries: the lack of a stable logistic
3:125 infra-structure necessary to ship biological samples to the molecular
Sweeney CJ, Zhu J, Sandler AB, et al. Outcome of patients with a performance laboratories in a cheap, reliable and rapid way, and the hurdle of cost
status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II reimbursement for the tests. In the past 10 years, expenses and logistics
trial in patients with metastatic nonsmall cell lung carcinoma . Cancer 2001; for transfer of biological specimens and reimbursement for molecular
92:2639 test costs, in most countries such as Mexico, Brazil and Argentina, were
sponsored by pharmaceutical companies. Companies such as AstraZeneca,
Langer CJ, O’Byrne KJ, Socinski MA, et al. Phase III trial comparing paclitaxel Roche, Boehringer Ingelheim, and Pfizer have acted through clinical trials
poliglumex (CT-2103, PPX) in combination with carboplatin versus or special access programs. In a smaller scale, molecular tests have been
standard paclitaxel and carboplatin in the treatment of PS 2 patients with supported by governmental health agencies or covered by private health
chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol care insurance companies. A restricted number of patients are paying the
2008; 3:623 tests out of the pocket, mostly sending to US laboratories. Least but not
least, the implementation of lung cancer molecular testing relies in the
O’Brien ME, Socinski MA, Popovich AY, et al. Randomized phase III trial adequate quantity and, most importantly, in the good quality of the available
comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single- biological sample. Subsequent to the intense interdisciplinary work by the
agent gemcitabine or vinorelbine for the treatment of PS 2 patients with laboratory personnel, significant progress has been detected in the last years
chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol in the amount of tumor cells present in the testing specimens. However,
2008; 3:728 proper quality is only achieved in a fraction of specimens. Most LATAM
countries do not have local regulations for quality control (QC) of pathology
Lilenbaum R, Villaflor VM, Langer C, et al. Single-agent versus combination
laboratories, and a limited number of those laboratories are taken external
chemotherapy in patients with advanced non-small cell lung cancer and a
QC certification. Moreover, there is no financial support for the adequate
performance status of 2: prognostic factors and treatment selection based
validation of the assays at their implementation and for the competency
on two large randomized clinical trials. J Thorac Oncol 2009; 4:869
checking periodically thereafter. In consequence, the risk of having
Zukin M, Barrios CH, Pereira JR, et al. Randomized Phase III trial of single- laboratories testing in substandard quality conditions is high. Institutions
agent pemetrexed versus carboplatin and pemetrexed in patients with that are well-structured administratively, technically and scientifically
advanced non-small cell lung cancer and Eastern Coopertaive Group and that handle large volumes of clinical specimens usually participate
performance status of 2. J Clin Oncol 2013; 31:2849–2853 in external QC for molecular tests. They engage in accredited proficiency
testing activities or, at least, send material to reference laboratories for
Lilenbaum R, Axerold R, Thomas S, et al. Randomized Phase II Trial of Erlotinib investigation of reproducibility of results. Unfortunately, this does not occur
or Standard Chemotherapy in patients with Advanced Non-Small Cell Lung in the majority of the LATAM laboratories. Therefore, it is critical to reach
Cancer and a Performance Status of 2. J Clin Oncol 2008; 26:863-869 potential sponsors to assist the LATAM molecular testing laboratories in
overcoming these challenges and rapidly jump to the future. Efforts leading
Masters GA, Temin S, Azzoli G, et al. Systemic therapy for stage IV non- to improve tissue quality, to facilitate local optimization of assays and to
small cell lung cancer: American society of clinical oncology clinical practice ensure assay validation by international standards are needed. A group of
guideline update. J Clin Oncol 2015; 62:1342 regional laboratories have been trying to organize a collaborative project to
face these issues and also to come up with an affordable strategy to ensure
Reck M, Popat S, Reinmuth N, et al. Metastatic non-small cell lung cancer
good quality in pathology and molecular laboratories. Multiple barriers are
(NSCLC): ESMO clinical practice guidelines for diagnosis, treatment, and
making it difficult to succeed in this effort. The patient advocate groups have
follow-up. Ann Oncol 2014; 25 (suppl 3): iii27
proved effective in sensitizing governments and regulatory agencies in the
National Comprehensive Cancer Network. Non-Small Cell Lung cancer USA, but those groups are still very under-represented in LATAM. Professional
(Version 4.2016). http://www.nccn.org/professionals/physician_gls/pdf/ institutions such as the IASLC are specially tailored to help. IASLC congregates
bone.pdf. Accessed September 15, 2016 internationally conscious personnel and lung cancer experts and would
excel, for instance, in matching experts with laboratories requesting
Keywords: Advanced NSCLC PS 2 specific assistance and in coordinating a regional consortium of laboratories
interested in rounds of specimen exchange for proficiency testing and
in validated sets of control specimens for implementation of new tests.

Data from at least 15 of the highest populated LATAM countries regarding Nevertheless, the continuous update with the evolving field required from the
their lung cancer test menu, the technical platforms used, and efforts for pathologists, the scarceness of trained bioinformaticians for data sequencing
investigation of the assay performance characteristics have been surveyed analysis, and the vigorous integration of the entire professional team are still
and results will be discussed. challenging personnel issues to be addressed. Data from at least 15 of the
highest populated LATAM countries regarding their efforts in initiating and
Keywords: Precision Medicine Latin America expanding molecular testing for lung cancer and the strengths and challenges
faced have been surveyed and results will be discussed.
Keywords: Pathology, Latin-America, molecular testing

MTE28: IMPLEMENTATION OF PRECISION MEDICINE IN ROUTINE PRACTICE: THE LATIN
AMERICAN EXPERIENCE (TICKETED SESSION)
MTE28.02 IMPLEMENTATION OF PRECISION MEDICINE IN SESSION MTE29: ADVANCES IN MALIGNANT PLEURAL ME-
ROUTINE PRACTICE: THE LATIN AMERICAN EXPERIENCE SOTHELIOMA (TICKETED SESSION)
Marileila Varella-Garcia WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30
Medicine/ Medical Oncology, University of Colorado School of Medicine, Aurora/
The increasing application of the concept of precision medicine (PM) in the

MTE29.01 ADVANCES IN MALIGNANT PLEURAL MESOTHELIOMA
last decade has revolutionized health care. Under this concept, the approach Paolo Boffetta1, Matteo Malvezzi2, Enrico Pira3, Carlo La Vecchia2
1
to disease treatment and prevention takes into account individual variability Tisch Cancer Institute, ICAHN School of Medicine at Mount Sinai, New York Ny/
in genes, environment, and lifestyle to more accurately predict treatment NY/United States of America, 2Dept. of Clinical Sciences and Community Health,
and prevention strategies for a particular disease in specific patient subsets. University of Milan, Milan/Italy, 3University of Turin, Turin/Italy
PM has been progressing faster among infectious diseases and neoplasia,
Background More than 30 years have passed since industrialized countries
with emphasis in non-small cell lung cancer (NSCLC) among the solid tumors.
started to strictly regulate the use of asbestos, including, in several of them,
However, we are still far away from a stable scenario to which we should
introducing a total ban on import of raw material and of asbestos-containing
adjust. The field is in continuous evolution with constant new discoveries
products. The use of the International Classification of Diseases (ICD) to
and proposals. The implementation of PM for lung cancer has dramatically
classify deaths from mesothelioma has been a source of concern in the past
impacted several medical areas mainly in two basic aspects: the molecular
because, before the 10th version of ICD (ICD-10), no specific code existed
diagnosis and the therapy regimen. The first involves questions such as
for this type of neoplasm, and analyses based on entities such as ‘pleural
how to collect and process specimen for testing, which tests to apply and
cancer’ were subject to misclassification. Since the late 1990s ICD-10 has
in which level, how to define scoring criteria and cut-offs for variables with
been used for death certification in many developed countries. Methods We
continuous distribution in the population, how to interpret and validate
analyzed age-specific mesothelioma mortality rates (all sites), calculated
clinical assays, and how to properly communicate with the multidisciplinary
on the basis of the data of the WHO Mortality Database, among men from
team. The second involves questions pertinent to understanding the
Canada (2000-2011), USA (1999-2013), Japan (1995-2008), France (2000-2011),
molecular diagnostic, access to and cost of new and old drugs, evaluation
Germany (1998-2013), Italy (2003-2012), the Netherlands (1996-2013), Poland
of side effects, selection of combination or sequential regimens, definition
(1999-2013), United Kingdom (2001-2013) and Australia (1998-2011), based
of clinical progression and resistance, and proper communication with the
on ICD-10, to identify temporal patterns following reduction of asbestos
multidisciplinary team. Our discussion will primarily address molecular
exposure. Results Mortality in the age groups 35-54 and 55-64 decreased
testing in lung cancer in Latin America countries (LATAM). One of the medical
throughout the study period in all countries (median decrease, 7.9% per year
areas most largely affected by the changes accompanying PM is Pathology.
and 4.1% per year, respectively) except in Poland and (up to 2007) in Japan, two
The new specialty of Molecular Pathology has emerged to focus on the
countries which started from lower rates. In the age group 65-74, mortality
sub-microscopic aspects of disease by examination of molecules within
decreased in the USA and, since 2009, in the Netherlands, was stable in
tissues and bodily fluids. Molecular Pathology encompasses aspects of
Australia, and increased in other countries (median increase, 3.0% per year).
anatomic and clinical pathology as well as molecular biology, biochemistry,
In the age group above age 74, a decrease was apparent only in the USA after
genetics, and bioinformatics. Molecular lung cancer testing in LATAM is
2003 (median increase in the other countries, 3.5% per year). Conclusions
centralized in the main cities of several countries and usually performed
Our analysis, based on consistent mortality data for mesothelioma, provide
in laboratories of few large, private or public hospitals, mostly belonging
strong evidence for a decrease in mortality in the young age groups in most
to academic institutions. Examples of those laboratories are located in
high-income countries: these birth cohorts experienced reduced opportunity
the Hospital Italiano and Hospital Roffo in Buenos Aires, Argentina; in the
for exposure to asbestos during their occupational life. In the case of older age
Instituto Nacional do Cancer in Rio de Janeiro and Instituto AC Camargo
groups, whose members had greater opportunity of exposure, in particular
in Sao Paulo, Brazil; in the Universidad Catolica de Chile; in the Fundacion
to amphiboles, the evidence of a decrease in mortality is present only in a few
Santa Fe de Bogota and Fundacion Valle de Lili in Colombia, and in the
countries. Overall, these results stress the importance of early-life exposure
Instituto Nacional de Cancerologia in Mexico City. There are also few
circumstances to determine mesothelioma risk throughout life.
commercial laboratories that offer standard tests under good laboratory
practices. Examples are the laboratories Hermes Pardini and Consultoria Keywords: Mesothelioma, epidemiology
em Patologia in Brazil, Argenomics and Biomarkers in Argentina, and ROE in
Peru. The implementation of molecular testing poses important challenges
to pathology practices in commercial and academic institutions, and efforts
to overcome them have been extensively discussed. It is well recognized that MTE29: ADVANCES IN MALIGNANT PLEURAL MESOTHELIOMA (TICKETED SESSION)
changes in two organizational levels are required, one related to personnel WEDNESDAY, DECEMBER 7, 2016 - 07:30-08:30
and another related to equipment and technology. In terms of personnel,
there is a need to increase multi-disciplinary communication affecting all
MTE29.02 ADVANCES IN MALIGNANT PLEURAL MESOTHELIOMA
areas including oncologists or surgeons requesting the tests, professionals
(surgeons, pulmonologists, interventionists) collecting the specimens, Nico Van Zandwijk, Matthew Soeberg, Glen Reid
technologists processing and handling the specimens, pathologists University of Sydney, Asbestos Diseases Research Institute, Concord/NSW/
performing histology diagnosis and molecular testing interpretation, lab Australia
scientists (biologists, biotechnologists, biochemists) executing assays and
Epidemiology: MPM, representing around 90% of all mesothelioma cases
interpreting the results, and bioinformaticians handling computer-generated
diagnosed, is an aggressive tumour with a poor prognosis, and relatively few
data. The interdisciplinary work in the anatomic and clinical pathology
treatment options. The association of mesothelioma with asbestos exposure
laboratory must be intensified and personnel with distinct expertise and no
is well established. The latency period, the interval between first asbestos
clinical experience must be added and integrated to the team. The role of the
exposure to the diagnosis is long (around 40 years), and explains why in many
pathologist in the communication and integration among team members
instances the effect of banning asbestos from the workplace has yet to be
(clinical/medical and laboratory group) is crucial. Interestingly, the work
seen. At the same time there is evidence accumulating that non-occupational
environment in a complex molecular testing laboratory has changed to
asbestos exposure may significantly contribute to mesothelioma incidence [1]
demand personnel not only with excellent hard technical skills but also with
and it is most worrying that unrestricted use of this carcinogen is allowed in
soft skills such as active listening, coordination, adaptability, punctuality,
Russia and most Asian, African and South American countries. Unfortunately
problem solving, and friendly personality. The lab success relies in that each
the multilateral treaty to promote shared responsibilities in relation
team member clearly understands his/her role and the value of efficient
hazardous chemicals (Rotterdam convention) has become paralyzed by the
communication among team members, which is mainly modulated by the
veto of asbestos producers and considering the rapid surge of asbestos
pathologists. Most of the LATAM laboratories already performing molecular
consumption in developing countries the end of the mesothelioma epidemic is
testing have increased and strengthened this interdisciplinary work
not in sight [2]. Molecular biology: Major efforts have been undertaken to
using biologists and biotechnologists originally trained in research fields.
explore the genomic alterations responsible for the development of pleural mesothelioma: identification of a poor prognosis subgroup linked to the
malignant pleural mesothelioma. Recent next-generation sequencing efforts epithelial-to-mesenchymal transition. Clin Cancer Res, 2014. 20(5): p. 1323-34.
have confirmed the frequent loss of tumour suppressor genes identified in 5. Williams, M., et al., Tumour suppressor microRNAs regulate PD-L1 expression
earlier studies. Deletion and loss of function mutation of CDKN2A, NF2 and in malignant pleural mesothelioma., in International Mesothelioma Interest
BAP1 are common molecular events in MPM, but the overall mutational load Group (iMig) 2016. 2016: Birmingham 6. Linton, A., et al., Factors associated
tends to be lower in MPM than in lung cancer. Mutation, aberrant splicing, and with survival in a large series of patients with malignant pleural mesothelioma
gene fusions occur in additional genes such as SF3B1, TRAF7 and SETD2, but at in New South Wales. Br J Cancer, 2014. 111(9): p. 1860-9. 7. Stahel, R.A., et al.,
lower frequency [3]. Expression analyses suggest that there are subgroups of Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant
tumours both within and between the traditional histopathological subtypes pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04):
of MPM [3, 4], and this has potential implication for prognosis. Although still a randomised, international, multicentre phase 2 trial. Lancet Oncol, 2015.
to be published, the results from a TCGA mesothelioma study paint a similar 16(16): p. 1651-8. 8. de Perrot, M., et al., Accelerated hemithoracic radiation
picture of the mutational and transcriptional landscape. Investigation of followed by extrapleural pneumonectomy for malignant pleural mesothelioma.
microRNA expression reveals a general downregulation of microRNAs with J Thorac Cardiovasc Surg, 2016. 151(2): p. 468-73. 9. Berghmans, T., et al.,
tumour suppressor activities. In addition to miR-31, frequently co-deleted Activity of chemotherapy and immunotherapy on malignant mesothelioma: a
with CDKN2A, the miR-15/16 family is consistently downregulated in MPM systematic review of the literature with meta-analysis. Lung Cancer, 2002.
tumours. This family controls expression of targets such Bcl-2, CCND1 and 38(2): p. 111-121. 10. Zalcman, G., et al., Bevacizumab for newly diagnosed
VEGF, and thus plays a role in the regulation of proliferation, apoptosis and pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed
angiogenesis. Recent data suggest that these microRNAs also play role in Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet,
controlling the levels of PD-L1 expression in MPM cells [5], targeted by 2016. 387(10026): p. 1405-14. 11. Schunselaar, L.M., et al., A catalogue of
immune checkpoint inhibitors. Treatment Options: MPM is notoriously treatment and technologies for malignant pleural mesothelioma. Expert Rev
refractory to localized and systemic treatment. Meta-analyses (multivariate Anticancer Ther, 2016. 16(4): p. 455-63. 12. Alley, E.W., et al., Clinical safety and
analyses) of large series of patients confirm that the prognosis of the select efficacy of pembrolizumab (MK-3475) in patients with malignant pleural
group of patients able to undergo radical surgery is significantly better than mesothelioma: Preliminary results from KEYNOTE-028. Cancer Research, 2015.
without surgery [6]The debate about the extent of radical surgery has for 76(18): p. CT 103. 13. Kindler, H.L., et al., Tremelimumab as second- or third-line
some time been governed by the significant risks associated with radical treatment of unresectable malignant mesothelioma (MM): Results from the
surgery as noted in the MARS trial. Therefore, when radical multimodality global, double-blind, placebo-controlled DETERMINE study. Journal of Clinical
treatment approaches are considered, it seems prudent to involve an Oncology, 2016. 34(15 (May Suppl)): p. #8502. 14. Cornelissen, R., et al.,
experienced team at a high volume centre. While the important palliative role Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose
of radiotherapy in MPM has been accepted by the oncological community, Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural
consolidation radiotherapy after radical surgery [7] has not been shown to Mesothelioma. Am J Respir Crit Care Med, 2016. 193(9): p. 1023-31. 15. Reid, G.,
provide major benefits in terms of local control. To define the role of (intensity et al., Clinical development of TargomiRs, a miRNA mimic-based treatment for
modulated) accelerated radiotherapy in MPM comparative studies are patients with recurrent thoracic cancer. Epigenomics, 2016. 8(8): p. 1079-85. 16.
needed. The impressive data (median overall survival of 51 months) from the Kao, S.C., et al., A Significant Metabolic and Radiological Response after a
SMART study [8] combining pre-operative intensity modulated radiation Novel Targeted MicroRNA-based Treatment Approach in Malignant Pleural
therapy (IMRT) immediately followed by extra-pleural pneumonectomy in 62 Mesothelioma. Am J Respir Crit Care Med, 2015. 191(12): p. 1467-9.
patients MPM patients with epithelial histology suggests that such an
approach may have the potential to become an alternative for induction Keywords: combined modality treatment, malignant mesothelioma,
chemotherapy followed by radical surgery. Almost every chemotherapy agent chemotherapy, Immunotherapy
has been tested in MPM. Cisplatin, methotrexate, pemetrexed and the
anthracyclines doxorubicin and daunorubiucin were most active, but single
agent activity seldomly exceeded a 20% response rate. A systematic review of
the chemotherapy literature carried out in the early 2000s concluded that
combination therapy was likely to be more effective than single agent therapy
[9]and shortly thereafter Vogelzang’s randomized comparison between
cisplatin and cisplatin/pemetrexed confirmed cisplatin/pemetrexed as the
new therapy standard. Thirteen years later this standard has been augmented
by a large comparative French intergroup study revealing that the addition of
bevacizumab to the cisplatin/pemetrexed standard is associated with a 2.7
months advantage in median overall survival [10]. However, it important to
note that a not insignificant number of negative phase II and III studies with a
range of inhibitors of growth factors including EGFR, VEGF and PDGF had
preceded this positive result. Other targeted agents investigated in phase II
and III studies including bortezomib, vorinostat, everolimus, and defactinib,
the inhibitor of the NF2/mTOR/FAK pathway, have also failed to show notable
activity in pre-treated MPM patients [11]. It has become clear that MPM is an
immunogenic tumour type and the preliminary data showing responses after
immune checkpoint (PD-L1) inhibition [12] seem to indicate that reversing the
immunosuppression induced by advancing disease is likely to represent a
major step forward. However, monotherapy with Tremelimumab, inhibitor of
CTLA-4 and considered active in phase II studies, failed to produce a survival
benefit over placebo in 2nd and 3rd line, underlining the importance of
comparative studies [13]. Independent research groups have reported
‘spontaneous’ regression of MPM, revealed a relation between infiltrating
lymphocytes and plasma cells and prognosis and presented promising early
clinical results with mesothelin-targeting antibodies [11]. Most recently
dendritic cell vaccination combined with pulsed (metronomic)
cyclophosphamide to deplete regulatory T cells resulted in prolonged tumour
control in a limited group of MPM patients [14]. It is not excluded that
targeting multiple compartments involved in immune surveillance will lead to
increased efficacy. Early signs of efficacy of experimental treatment with
tumour suppressive microRNAs packaged in minicells [15, 16] and the
interaction between the microRNA 15/16 family and PD-L1 expression point to
the complexity of immune checkpoint regulation and underlines the need for
additional translational studies to unravel the resilient drug resistance
mechanisms operable in MPM. 1. Marinaccio, A., et al., Malignant
mesothelioma due to non-occupational asbestos exposure from the Italian
national surveillance system (ReNaM): epidemiology and public health issues.
Occup Environ Med, 2015. 72(9): p. 648-55. 2. Takahashi, K., P.J. Landrigan, and
R. Collegium, The Global Health Dimensions of Asbestos and Asbestos-Related
Diseases. Ann Glob Health, 2016. 82(1): p. 209-13. 3. Bueno, R., et al.,
Comprehensive genomic analysis of malignant pleural mesothelioma identifies
recurrent mutations, gene fusions and splicing alterations. Nat Genet, 2016.
48(4): p. 407-16. 4. de Reynies, A., et al., Molecular classification of malignant

procedure, but published studies suggest an increase in sensitivity up to 10%.

PRO-CON SESSIONS Overall, a confirmatory VAM is still warranted for the individual patient with a
negative combined linear endosonography as this further lowers the post-test
SESSION PC01: PRO CON SESSION: INVASIVE MEDIAS- probability. This has been shown within ASTER for patients with clinical N2/3
disease on PET-CT (prevalence of mediastinal nodal disease 63%), as the post-
TINAL STAGING FOR N2 DISEASE test probability of a negative linear combined endosonography of 20% could
MONDAY, DECEMBER 5, 2016 - 14:30-15:45 be lowered to 5% by adding a cervical mediastinoscopy.9 A recent prospective
cohort study on clinical stage II lung cancer based on N1 disease on imaging
(prevalence of mediastinal nodal disease 24%) showed that the post-test
PC01.02 INVASIVE STAGING AND RESTAGING probability of a negative endosonography was 19%, which could be lowered
Christophe Dooms to 9% by adding a cervical mediastinoscopy.10 In conclusion, combined EBUS-
University Hospitals KU Leuven, Leuven/Belgium
EUS(-B) linear endosonography is the standard for initial baseline mediastinal
nodal staging, but a VAM is still recommended after a negative (or incomplete)
The aim of mediastinal staging is to exclude with the highest certainty and combined linear endosonography. Mediastinal restaging after induction
the lowest morbidity patients with mediastinal nodal disease. The concepts therapy for locally advanced stage III NSCLC is an important prognostic factor.
of decision analysis and Bayes’ theorem form the basis for a mediastinal In the context of a 40-50% prevalence of residual mediastinal disease after
staging strategy. The goal of the clinical staging strategy is to lower the induction therapy, a first cervical VAM as a restaging technique seems to be
post-test probability sufficiently so that it falls below a testing threshold, the most accurate method for nodal assessment.1 Overall, limited literature
which ascertains the clinician that the result is accurate. The ESTS working reported a sensitivity and NPV for linear endosonography that is lower than
group considers a rate of unforeseen mediastinal nodal disease at the time of for a first mediastinoscopy.
anatomic resection with lymph node dissection less than 10% as acceptable.1
Contrast-enhanced multi-detector CT (computed tomography) scanning Keywords: NSCLC, mediastinal nodal staging, mediastinal nodal restaging,
has an excellent spatial resolution but is an imperfect means of staging the invasive
mediastinum. A Cochrane review evaluated integrated positron emission
tomography (PET) - CT for assessing mediastinal lymph node involvement in
NSCLC.2 The review showed that the accuracy of PET-CT is insufficient to allow
management on PET-CT alone, but PET-CT can be used to guide clinicians in
the next step (either a biopsy or direct to surgery). The suboptimal specificity
SESSION PC02: BY 2030 CHEMOTHERAPY WILL REMAIN
of mediastinal lymph nodes positive on PET-CT requires a tissue confirmation. STANDARD OF CARE FOR THE MAJORITY OF PATIENTS
There are conditions where invasive staging is also mandatory despite a WITH NSCLC STAGES I-IV
normal mediastinum on PET-CT as the prevalence of N2/N3 disease remains TUESDAY, DECEMBER 6, 2016 - 14:30-15:45
significant. These conditions include a primary tumour >3 cm, any central
primary tumour, PET/CT hilar N1 disease, or low FDG uptake in the primary
tumour.1 Cervical Mediastinoscopy. A conventional cervical mediastinoscopy
PC02.02 PRO CHEMOTHERAPY
through a pretracheal suprasternal incision was introduced in 1959 and
for decades considered the gold standard for invasive mediastinal nodal Nasser Hanna
staging. Recently, a very large (N=721 patients; prevalence of mediastinal Simon Cancer Center, Indiana University School of Medicine, Indianapolis/IN/
nodal disease 47 %) retrospective single center study reported on safety and United States of America
efficacy of cervical mediastinoscopy performed by general thoracic surgeons.3
Despite the reduction in cigarette consumption in many parts of the world,
There was no mortality, a low perioperative complication rate at 1.3 %, and an
the incidence and mortality rate of lung cancer will remain high in the year
unexpected hospital (re)admission rate of 0.46 %. The sensitivity, negative
20301. Over the last 50 years major advances in the treatment of lung cancer
predictive value and post-test probability were 0.90 (95% CI 0.87-0.92), 0.92
have included early detection by screening CT, improved cure rates with
(95% CI 0.90-0.94), and 0.09 (95% CI 0.07-0.11), respectively. It is performed
neo-adjuvant and adjuvant chemotherapy, the successful integration of
under general anesthesia and allows a full mapping of the ipsilateral and
chemotherapy with radiation for locally advanced disease, and prolonged
contralateral superior mediastinal lymph nodes. Since 1995, the use of video
survival times with chemotherapy in the metastatic setting. More recently,
techniques has been introduced leading to video-assisted mediastinoscopy
the discovery of targetable mutations and development of a myriad of small
(VAM) clearly improving visualization and teaching. In addition, VAM allows
molecule tyrosine kinase inhibitors have transformed the natural history of
bimanual dissection with possibilities to perform nodal dissection and
lung cancer in select subsets. Furthermore, immunotherapy is now a reality
removal rather than sampling or biopsy. The ESTS working group recommends
in the treatment of patients with stage IV non-small cell lung cancer (NSCLC).
performing VAM.1 Endoscopic ultrasonography (EUS) en endobronchial
Today, the integration of targeted agents and immunotherapy are being
ultrasonography (EBUS). In the last decade, the predominant role of cervical
investigated in earlier stages of disease. With these recent advances, what
mediastinoscopy has been challenged by EUS and EBUS using a convex probe.
does the future of chemotherapy hold in the treatment of stage I-IV NSCLC? Is
When mediastinal nodal staging is required, systematic nodal sampling seems
there a future at all? Can we eliminate the need for chemotherapy altogether
feasible but some primary choices have to be made. At least mediastinal nodal
for most patients at any point in their disease history? The dream of replacing
stations 4R, 4L and 7 should be sought. To avoid contamination, the order
chemotherapy with more active, less toxic, and more convenient therapy for
of sampling should begin at the level of N3 stations followed by N2 stations
patients with stage I-IV NSCLC is a laudatory goal. Is it realistic by the year
before N1. There is no evidence to suggest that sampling of all visible nodes
2030? Certainly not. Chemotherapy is currently the only systemic therapy
in each nodal station is superior to a systematic nodal sampling of the largest
that has ever been known to cure patients in the neo-adjuvant or adjuvant
measuring ≥5 mm or PET-positive node in each station. It must be stressed
setting for stage I-III NSCLC 2. While many targeted agents can prolong
that EBUS cannot access the prevascular nodes (station 3a), the subaortic
life in the metastatic setting, to date all of those tested in the adjuvant
and para-aortic nodes (stations 5 and 6) as well as the paraesophageal and
setting have failed to improve upon standard therapy3-5. The graveyard of
pulmonary ligament nodes (stations 8 and 9). Some of these nodes (stations
negative trials in the adjuvant setting includes those evaluating angiogenesis
8 and 9) can however be reached from the esophagus. Therefore the use
inhibition, epidermal growth factor tyrosine kinase inhibition, and vaccine
of the EBUS scope is extended to an esophageal exploration with EUS-B
therapy. The same can be said for locally advanced, unresectable NSCLC.
sampling of stations 4L, 7, 8 and 9. In terms of safety, EBUS and EUS have a low
While the integration of chemotherapy with radiation improves survival rates
complication or serious adverse event rate of 1.4 and 0.3%, respectively.4,5 The
compared with radiation alone6, thus far no other agents have successfully
two staging strategies, surgical staging alone on the one hand and combined
done so, including tyrosine kinase inhibitors, angiogenesis inhibitors, or
EUS/EBUS followed by surgical staging whenever endosonography was
monoclonal antibodies7-8. In the metastatic setting, chemotherapy improves
negative on the other hand, were compared in a pivotal randomized controlled
survival whether given as induction therapy or as maintenance therapy.
trial (RCT).6 It was concluded that invasive mediastinal nodal staging
Chemotherapy is also more active than targeted therapy in the vast majority
should start with combined linear endosonography, as the trial showed
of patients who do not harbor targetable mutations. Even with the stunning
that a staging strategy starting with combined linear endosonography
success of immunotherapy for some patients with advanced NSCLC, it
(EUS+EBUS) detected significantly (P=0.02) more mediastinal nodal N2/
appears this will not be curative in this setting and nearly all patients will
N3 disease compared to cervical mediastinoscopy alone, resulting in a
still be getting chemotherapy at some point of their disease history. In other
significantly higher sensitivity of 0.94 (95%CI 0.85-0.98) compared to 0.79
words, chemotherapy works for patients with stage I-IV NSCLC. Just as we
(95%CI 0.66-0.88), respectively.6 Another RCT suggested that EBUS-TBNA
will do with targeted therapy and immunotherapy, we will not abandon
is the preferred primary procedure in combined linear endosonography for
what works, but rather we will improve upon it. Chemotherapy works in a
mediastinal nodal staging of resectable stage I-III lung cancer.7 There is no
broad group of patients with lung cancer. It targets DNA, topoisomerase,
RCT comparing combined EBUS-EUS(-B) to EBUS-TBNA alone for mediastinal
and the mitotic spindle, which are the key targets in all cells. The majority of
nodal staging, but a recent meta-analysis suggested that the combined
patients’ tumors do not have targetable mutations and most patients do not
EBUS-EUS is more sensitive than EBUS-TBNA alone to detect mediastinal
respond to immunotherapy. While gains are expected over the next 15 years
nodal disease.8 The absolute increase in sensitivity of the combined approach
in targeted therapy and immunotherapy, it is likely that we will discover the
compared to EBUS-TBNA alone depends on the quality of the EBUS-TBNA
plateau in the benefit to these strategies and eventually nearly all patients
will develop resistance. While predicting the future is usually only a fool’s application based on general tumor biology principles and not on the
errand, the past is prologue. So, what is the future of chemotherapy in underlying biology of lung cancer has hampered its ability to dramatically
NSCLC? Better drug delivery systems; developing combination therapy with improve survival and cures for lung cancer. Over the last twenty years we
DNA repair agents, cell cycle checkpoint modulators, and immunotherapy; have seen multiple examples of how molecular characterization of lung
and improved biomarkers for efficacy and toxicity are each on the tumors coupled with advances in drug development, have led to astonishing
horizon. Improved targeting of the cancer cell, increased cancer cell drug improvements in cancer outcomes. Hence, it is time to set a course toward
concentrations, and reduction of normal cell toxicity can be accomplished abandoning chemotherapy. In addition to their superior efficacy, targeted
through nano-carriers9. Nano-carriers can deliver chemotherapy directly to therapies and immunotherapy have milder toxicity profiles compared to
cancer cells by protecting these agents from being degraded in the circulation chemotherapy that all patients appreciate. We have already made significant
and being excessively protein bound, limiting active drug exposure. Nano- progress in this quest. Our journey began with the discovery of EGFR
carriers include liposomes, carbon nanotubes, dendrimers, and polymeric (epidermal growth factor receptor) mutations and their exquisite sensitivity
compounds (micelles, conjugates, nanoparticles). These carriers are to EGFR-TKI (tyrosine kinase inhibitors). This observation was confirmed in
typically 100-150 nm in size but have large surface-to-surface volume ratios, the landmark IPASS trial that demonstrated the superiority of EGFR-TKIs
enabling them to encapsulate cytotoxic agents and enhancing drug deliver over platinum-based chemotherapy for the first line treatment of patients
to tumors. Thus far 8 have been FDA approved, including 2 polymer-protein whose tumors harbor these mutations (1). On the heels of this therapeutic
conjugates, 5 liposomal formulations, and 1 polymeric nanoparticle, in various advancement came the discovery of ALK (anaplastic lymphoma kinase) gene
cancers. Another strategy to enhance drug delivery to tumors is through rearrangements and the replacement of doublet chemotherapy with an
antibody-drug conjugates (ADC). These agents link an antibody to a protein ALK-TKI in patients with ALK positive tumors (2). To date actionable driver
overexpressed on the surface of a cancer cell to a potent cytotoxic such as a mutations are found in at least 50% of patients with adenocarcinoma (3)
microtubule inhibitor or an alkylating agent. The cytotoxic is released only and inhibitors to all of these mutations are in clinical development with the
in the cancer cell after the ADC complex is internalized. Examples include hope that they will have similar success as their predecessors. Of particular
TDM-1 and Brentuximab. Over 30 ADC’s are under clinical investigation, interest is developing inhibitors to KRAS (V-Ki-ras2 Kirsten rat sarcoma
including several against lung cancer including Rova-T and Sacituzumab. viral oncogene homolog) because it is the most frequent driver mutation
Another promising strategy for the future treatment of lung cancer involves occurring in approximately 20-25% of tumors. Today there is optimism
combining chemotherapy with drugs that interfere with DNA repair, that we will achieve this goal given it is the focus of the Stand Up To Cancer
silence DNA repair genes, or inhibit cell cycle arrest 10. Examples of this (SU2C) lung cancer dream team initiative and several novel agents are in
approach include PARP inhibitors, DNA methylation agents, and checkpoint development including direct KRAS therapy. Driver mutations are typically
modulators. Combination trials of chemotherapy and immunotherapy are identified in patients who are never smokers, light former smokers or have a
also underway. In this regard, ADC technology may prove a more effective lengthy quit time. The remaining groups of patients’ (i.e. current smoker or
strategy when combining cytotoxic drugs with immunotherapy. By improving recent former smokers) have a different biology that has been successfully
chemotherapy drug delivery to cancer cells and reducing off-target toxicities, exploited with immunotherapy. Immune checkpoint inhibitors have replaced
nanotechnology has the potential to most effectively combine chemotherapy single agent docetaxel as the standard of care for second line treatment
with immunotherapy. Lastly, despite decades of clinical investigation, of lung cancer for all histological subtypes of NSCLC (4-6). Most recently
most patients are empirically treated with chemotherapy, regardless of the the KEYNOTE-024 a randomized trial of pembrolizumab versus doublet
molecular characteristics of the tumor and the pharmacogenomics of the chemotherapy for untreated patients with advanced NSCLC whose tumor
patient. Refinements in these areas are expected in the upcoming years. In have > 50% PD-L1 (programmed death-ligand 1) IHC (immunohistochemistry)
conclusion, for better or worse, in the year 2030 chemotherapy will remain expression met its primary progression-free survival (PFS) endpoint and
standard of care for the majority of patients with stage I-IV NSCLC. But, the also improved overall survival (7). This will represent a new standard of
year 2040 or 2050 may be a different story. care for approximately 25% of patients and will serve as the backbone for
immune combinations. We are anxiously awaiting the results of a randomized
References 1. Rahib L, Smith B, Aizenberg R, et al. Projecting cancer incidence trial of a PD-1 (programmed cell death protein 1) inhibitor plus a CTLA-4
and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas (cytotoxic T-lymphocyte-associated protein 4) inhibitor versus platinum-
cancer in the United States. Cancer Res 2014;74(11):2913-2921. 2. Burdett S, based chemotherapy that is expected to report out in mid 2017. A similar
Pignon J, Tierney J, et al. Adjuvant chemotherapy for resected early-stage study is actively accruing patients. The preliminary results on this dual
non-small cell lung cancer. Cochrane Database Syst Rev 2015;2(3):doi: immune combination were very promising and if positive would increase the
10.1002/14651858.CD011430 3. Wakelee H, Dahlberg S, Keller S, et al. E1505: number of patients receiving upfront immune therapy over chemotherapy
Adjuvant chemotherapy +/- bevacizumab for early stage NSCLC—Outcomes (8). Additionally, there are numerous immune combinations involving drugs
based on chemotherapy subsets. J Clin Oncol 2006;34(abstract 8507). 4. Kelly that target immune evasion and even more drugs that stimulate the immune
K, Altorki N, Eberhardt W, et al. Adjuvant Erlotinib Versus Placebo in Patients system including cellular therapies that are being evaluated. The success of
With Stage IB-IIIA Non–Small-Cell Lung Cancer (RADIANT): A Randomized, targeted therapy and immunotherapy in the advanced setting has quickly led
Double-Blind, Phase III Trial. J Clin Oncol 2015;33:4007-4014. 5. Van Steenkiste to their evaluation in earlier stages of disease. There is a lot of enthusiasm for
J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 Immunotherapy in Resected combining immunotherapy with radiation for patients with locally advanced
Non–Small-Cell Lung Cancer: Phase II Randomized Study Results. J Clin lung cancer given the well-known immune modulatory effects of radiation.
Oncol 2013;31(19):2396-2403. 6. O’Rourke N, Roque i Figuls M, Farre Bernado Moreover the bar for replacing weekly low dose concurrent chemotherapy
N, et al. Concurrent chemoradiotherapy in non-small cell lung cancer. with immunotherapy is low. In the adjuvant setting our Asian colleagues
Cochrane Database Syst Rev 2010; DOI: 10.1002/14651858.CD002140. 7. designed and conducted two randomized phase III trials in patients whose
Kelly K, Chansky K, Gaspar L, et al. Phase III trial of maintenance gefitinib or tumors have an EGFR sensitizing mutation to replace chemotherapy with an
placebo after concurrent chemoradiotherapy and docetaxel consolidation EGFR-TKI. Accrual is completed and we are awaiting the results. In regard to
in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol immunotherapy, enrolling phase III trials are evaluating immune checkpoint
2008;26(15):2450-6. 8. Bradley J, Paulus R, Komaki R, et al. Standard-dose inhibitors as maintenance therapy but the pursuit of immunotherapy as a
versus high-dose conformal radiotherapy with concurrent and consolidation replacement for chemotherapy will follow. Beyond treatment of lung cancer,
carboplatin plus paclitaxel with or without cetuximab for patients with stage on the horizon is the exploration of targeted agents and immunotherapy as
IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two preventive agents. It is important to emphasize that our current and future
factorial phase 3 study. Lancet Oncol 2015;16(2):187-199. 9. Fanciullino R, success is the consequence of many factors: 1) the exponential advances in
Ciccolini J, Milano G. Challenges, expectations and limits for nanoparticles- technology that has driven the science and drug development 2) rapid trial
based therapeutics in cancer: a focus on nano-albumin-bound drugs. Crit Rev accrual and 3) regulatory authorities’ responsiveness to bringing efficacious
Onc Hemat 2013;88:504-513. 10. Helleday T, Petermann E, Lundin C, et al. DNA treatments to patients as quickly as possible. This momentum is what will
repair pathways as targets for cancer therapy. Nature Rev 2008;8:193-204. lead us to replacing chemotherapy for lung cancer. With 20%+ of patients
with driver mutations and 25% of all NSCLC with high PD-L1 already benefiting
Keywords: nano-carriers, antibody-drug conjugates, chemotherapy
from non-chemotherapy treatment, we are well on our way to ousting
chemotherapy in NSCLC by 2030.References
Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or Carboplatin-Paclitaxel in

PC02: BY 2030 CHEMOTHERAPY WILL REMAIN STANDARD OF CARE FOR THE MAJORITY Pulmonary Adenocarcinoma. N Engl J Med 2009, 361:947-57.
OF PATIENTS WITH NSCLC STAGES I-IV
Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in
advanced ALK-positive lung cancer. N Engl J Med 2013, 368:2385-94.
PC02.03 CONTRA CHEMOTHERAPY
Vigneswaran J, Tan YH, Murgu SD, et al. Comprehensive genetic testing
Karen Kelly
identifies targetable genomic alterations in most patients with non-small
Department of Hematology and Oncology, UC Davis Cancer Center, Sacramento/ cell lung cancer, specifically adenocarcinoma, single institute investigation.
CA/United States of America
Oncotarget 2016, 7:18876-86.
Cytotoxic chemotherapy has undeniably provided benefit for our patients
Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced
with non-small cell lung cancer (NSCLC). However its nondiscriminatory

Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015, 373:123-35.
Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced

Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015, 373: 1627-39.
Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for
previously treated, PD-L1-positive, advanced non-small-cell lung cancer
(KEYNOTE-010): a randomized controlled trial. Lancet 2016, 387:1540-50.
MERCK press release, July 2016
Hellman MD, Gettinger SN, Goldman JW, et al. CheckMate 012: Safety and
efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced
(adv) NSCLC. J Clin Oncol 34, 2016 (suppl; abstr 3001).
Keywords: Immunotherapy, Targeted therapy, lung cancer
Thoracic Surgery, Buenos Aires British Hospital, Ciudad de Buenos Aires/Argentina

INTERACTIVE SESSIONS
The definition of staging in Lung Cancer is the determination of the anatomic
extent of three tumor components: the primary tumor (T), the lymph nodes
SESSION IA01: MULTIDISCIPLINARY DIAGNOSIS OF LUNG (N), and the metastases (M). Their accurate evaluation allows grouping
CANCER IN THE ERA OF MOLECULAR MEDICINE patients in stages that is one, and perhaps the single most important, of
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 several prognostic factors that guide the appropriate treatment option(s) to
offer the patient. The clinical classification cTNM (Pre-treatment clinical
classification), is based on evidence acquired before treatment The
IA01.04 DOES CYTOLOGICAL MATERIAL FIT ALL - LESSONS FROM pathological classification pTNM (Post-surgical histopathological
classification), is based on the evidence acquired before treatment,
EBUS/BRONCHOSCOPY
supplemented or modified by the additional evidence acquired from surgery
Wlodzimierz Olszewski and from pathological examination. A minimum number of tests is not
Pathology, Institute of Oncology, Warsaw/Poland required to define the extent of the disease, but it’s very clear that as more
exhaustive the explorations more accurate and precise the staging will be.
In the diagnosis of lung cancer the primary diagnostic approach is microscopic
This may be strongly affected by the availability of physical and human
evaluation of tissue biopsy. However, in many cases the only material for
resources, multidisciplinary work and adherence to clinical practice
microscopic evaluation is cytological one. There are numerous types of
guidelines. After the changes proposed by the new IASLC-ATS-ERS lung
cytological material in evaluation of lung tumors including sputum, bronchial
adenocarcinoma classification and the IASLC proposals for revision of the T, N
brush, bronchial washing, transthoracic and transbronchial fine needle
and M descriptors and stage groupings in the forthcoming (Eighth) edition of
aspirates. Historically sputum was the most common diagnostic material
the TNM Classification for Lung Cancer, we must incorporate this new
but at present the most common types of cytological specimen are bronchial
information into our clinical practice. (1, 2) The changes that The IASLC
brush, and transthoracic or transbronchial FNAB. Nowadays worked out and
Staging Committee recommends for the T, N and M components and the
recognized cytological criteria allows not only to diagnose carcinoma but
resulting new stage grouping and their survival are summarized in table 1 and
in majority of cases to specify the histologic type of a tumor. This approach
figure 1. The main changes in T components are the relevance of the size of the
to microscopic diagnosis of lung carcinoma was incorporated to the latest
tumor for each cm, grouping of the involvement of the main bronchus or
WHO classification of lung tumors (ref). The key reason that cytodiagnosic
partial and total atelectasis or pneumonitis as a T2 descriptor and the
criteria and terminology were included into WHO classification was that
reclassification of diaphragm invasion as T4. (3) N component remains
in about 30% cases of lung tumors the cytological specimen is the only
without changes. (4) In M component a new M1b category includes patients
material for microscopic evaluation. Similarly to evaluation of small tissue
with a single metastatic lesion in a single organ site and a new M1c category
biopsies in cytopathology, in doubtful cases, immunocytochemistry may be
was introduce for patients with multiple lesions in a single organ or multiple
implemented to determine histologic type of tumor. Most useful in evaluation
lesions in multiple organs. (5) Some new stage groupings are proposed. The
of cytological specimen are IHC antibodies with nuclear presentation. (e.g.
new size cut points of T1-N0-M0 tumors has been assigned to stage IA1, IA2,
p40 for squamous cell carcinoma and TTF1 for adenocarcinoma). Cytological
and IA3. The new stage IIIC (T3 and T4-N3-M0) reflects their worse outcome.
material may be utilized in evaluation and in differential diagnosis between
Finally, stage IV disease has been divided into IVA (M1a, M1b) and IVB (M1c).
primary and metastatic lung tumor. The panel of the antibodies (e.g. CDX2,
The new IVA stage grouping should be used in trials analyzing patients with
PSA, Melan A ) may be used to indicate location of primary tumors mainly
oligo-metastasis or pleural or pericardial disease. (2) For the newly described
adenocarcinomas. Since cytological smears are of limited diagnostic
types of adenocarcinoma of the lung, The IASLC recommends incorporating
value for immunocytochemistry, the so-called cell blocs technique is
the coding of AIS as Tis (AIS) and of MIA as T1mi into the traditional TNM
recommended. This technique allows to use larger panel of antibodies for
classification. For part-solid tumors, the size of the invasive component
immunohistochemical evaluation. Cytology become very useful for clinical
should be used to assign a T category, but the whole tumor size should also be
staging of lung carcinoma routinely utilizing EBUS and EUS technique for
recorded. However, the measurements will be influenced by a number of
obtaining material from parahilar and mediastinal lymph nodes. Cytological
observer-dependent and technical factors. It is important to perform the
criteria are similar to that used for specimens obtained by transthoracic
measurements for clinical staging on contiguous thin CT sections
FNAB. In our center practice cooperation with adequately trained thorax
reconstructed with a high-resolution algorithm with multiplanar
surgeons provides adequate material for microscopic evaluation from EBUS
reconstruction. (6) For pathologic staging, attention should be given to the
and EUS obtained specimens in 94% cases. Currently one of the important
assessment of invasive and lepidic components. It can be helpful to correlate
task for pathologist in evaluating material from lung carcinoma is adequate
microscopic findings with measurements made on gross examination,
selection of the material for molecular test. In case of lung carcinoma or to be
particularly in inflated specimens or with CT findings. Patients who present
specific lung adenocarcinoma â material is selected for evaluation of EGFR
with more than one pulmonary site of lung cancer may represent different
and K-RAS mutation. In our experience cytological material particularly
patterns of disease as synchronous primary lung cancers, those with a
fine needle aspirates - fulfill such demands. Percentages of tumors cells in
separate solid tumor nodule(s) (intrapulmonary metastases), multifocal lung
the sample is often even higher than in tissue sections especially in fine
cancer presenting as multiple nodules with ground glass/lepidic features, and
needles of peripherally location lesions. Cytological material may be useful
diffuse pneumonic-type adenocarcinoma. It is proposed that the T category of
in evaluation of EGFR and K-RAS mutation as well as in determination of
patients presenting ground glass/lepidic (GG/L) tumors be classified using the
presence of translocations of ALK and ROS1 using FISH technique. Evaluation
T category of the highest T lesion and in parentheses either the number of
of ALK and ROS1 translocation remained in the hands of cytopathologists
GG/L tumors or simply m for multiple (#/m). A single N and M category is
since the crucial point is the location of translocation in nuclei of tumors
assigned for all GG/L tumors combined. (7) Both clinical information (the
cells. Latest challenge for pathologists evaluating lung carcinoma specimen
presence of additional lesions identified by imaging) and the pathologic
is to determine predictive criteria for immunotherapy in those tumors. At
information (from resected lesions) should be used to determine the TNM
the moment it seems that cytological material may be not satisfactory for
classification. Lesions smaller than 5 mm or AAH are not counted. The
adequate evaluation of immunocytochemical expression of PD-L1 and PD-1.
pneumonic type of adenocarcinoma should be classified according to the size
In summary cytological material from lung carcinoma is useful in establishing
of the area of lung involved, or as T4 or M1a in the case of involvement of more
the firm microscopic diagnosis of malignancy, to determine histologic type
than one lobe (i.e., either ipsilateral or contralateral). A single N and M
and to be used for molecular tests. It also allows to differentiated between
category is assigned. In patients with separate tumor nodules
primary and metastatic lung malignancies as well as determined primary
(intrapulmonary metastases), it is proposed that the seventh edition
location of metastatic lung carcinoma. Cytological specimens obtained
classification of same-lobe nodules as T3, same side (different lobe) nodules
by EBUS and EBUS techniques are very useful in clinical staging of lung
as T4, and other-side nodules as M1a be carried forward. (8) It is easier to
carcinoma. Reference Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG
establish that two pulmonary foci of cancer are separate primary tumors than
eds. WHO Classification ofÂ Tumours of the Lung, Pleura, Thymus and Heart.
that they are metastatic from one another. Few features are sufficiently
4th ed. Lyon, France: IARC Press; 2015
reliable by themselves, such as different histologic type and differences by a
Keywords: cytology, lung carcinoma, molecular testing comprehensive histologic assessment of resected specimens or by matching
breakpoints by DNA sequencing. Most criteria can be suggestive, but are
associated with potential misclassification. These include biomarker
patterns, imaging characteristics, and the presence or absence of nodal
involvement. The fact that generally only biopsy specimens are available at
SESSION IA05: THE PRACTICAL USE OF THE TNM CLASSIFI- the time of clinical decision making further adds to the uncertainty and
difficulty of the assessment. A constellation of factors is better than any
CATIONS FOR THORACIC CANCERS
single factor; it is best to make a determination of separate primary versus
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 metastatic lesions through a collective judgment of a multidisciplinary tumor
board after taking into account all of the available information. (9)
Synchronous primary cancers are classified with a T, N, and M category for
IA05.01 LUNG CANCER CASES each tumor; separate tumor nodules result in a T3, T4, or M1a category
Gustavo Lyons depending on the separate nodule’s location relative to the primary tumor.

(10) Despite these proposals of staging, there will always be areas of difficulty Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming
and tumors that are challenging to classify. The prognostic value of clinical Eighth Edition of the TNM Classification for Lung Cancer. Journal of Thoracic
and pathological TNM staging in patients with SCLC was also confirmed, and Oncology, Vol. 11, Issue 3, p300–311
the continued usage is recommended for SCLC in relation to proposed changes
to T, N, and M descriptors for NSCLC in the eighth edition. (11) Table 1 Keywords: lung cancer, Staging
Descriptors and T and M categories in the seventh edition and as proposed for
the eighth edition.
IA05: THE PRACTICAL USE OF THE TNM CLASSIFICATIONS FOR THORACIC CANCERS
IA05.02 MESOTHELIOMA CASES

Mir Hoda
Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria
Malignant pleural mesothelioma (MPM) is a highly lethal malignancy arising

from the serosal lining of the pleural cavity [1]. In up to 80% of patients,
asbestos is considered to contribute to the development of this tumor
within about 20 to 40 years of exposure time [2]. The incidence of MPM is
expected to increase dramatically over the next few decades. It has been
estimated that 250 000 people will die of MPM in Europe in the next three
decades, and 2500–3000 new cases are diagnosed each year in the USA [3].
The macroscopic appearance of MPM depends on disease stage. In early
stage MPM, the cancer presents as multiple small nodules on the surface of
both pleural linings. In advanced stages, the multiple small nodules form a
*Where there is a change, the resultant stage groupings proposed for the
tumor plate which surrounds the lung like a cage and in most cases invades
eighth edition are in bold, and the stage in the seventh edition is given in
the lung parenchyma, diaphragm and pericardium [4]. The establishment
parenthesis. Figure 1 Overall survival by clinical and pathological stage
of the pathological diagnosis of MPM and the classification in three main
according to the proposed eighth edition groupings using the entire database
histological subtypes (namely epitheloid, biphasic and sarcomatoid) is
available for the eighth edition.
important and has an impact on therapy and prognosis. Epitheloid MPM is
more therapy responsive and associated with better outcome compared to
biphasic and sarcomatoid histotypes. Other very important simple prognostic
factors for MPM are disease stage and lymph node involvement. Therefore
an adequate staging of MPM patients is crucial for therapy decision-making.
The currently widely used staging system is the one according to International
Mesothelioma Interest Group (IMIG) established in 1996 [5]. Based on the
TNM (tumor-node-metastasis) system for malignant tumors, this staging
system describes: the extent and size of the primary tumor, lymph node
involvement and distant metastases. By the different TNM descriptors,
MPM can be classified and summarized in four different tumor stages (IMIG
I-IV). Patients suffering from stage I-III are considered for surgery within
multimodality protocols, while palliative systemic or local treatment is
indicated for stage IV in accordance with the current classification. Butchart
et al. [6]proposed in 1976 an alternative staging system, referred to as
References: 1. Travis WD, et al. The New IASLC/ATS/ERS international the Butchart Staging. Contrary to the IMIG system (based on lung cancer
multidisciplinary lung adenocarcinoma classification. J Thorac Oncol. 2011;6: staging) the Butchart system is particularly set up for MPM. Therefore,
244–285. 2. Goldstraw P et al. The IASLC Lung Cancer Staging Project: several differences between both staging systems exist. However, the IMIG in
Proposals for Revision of the TNM Stage Groupings in the Forthcoming collaboration with the International Association for the Study of Lung Cancer
(Eighth) Edition of the TNM Classification for Lung Cancer Journal of Thoracic (IASLC) have proposed a new T, N and M descriptors for in the forthcoming
Oncology, Vol. 11, Issue 1, p39–51 3. Rami-Porta R et al. The IASLC Lung Cancer 8th edition of the TNM classification for MPM with significant changes to the
Staging Project: Proposals for the Revisions of the T Descriptors in the 7th TNM edition and proposals have been very recently published [7-9]. With
Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. Journal regard to the T descriptor, a fusion of both, clinical and pathological T1a and
of Thoracic Oncology, Vol. 10, Issue 7, p990–1003 4. Asamura H et al. The T1b into a T1 was recommended [7]. Regarding the N descriptor, a summary
International Association for the Study of Lung Cancer Lung Cancer Staging of the clinical and pathological N1 and N2 categories into a single category
Project: Proposals for the Revision of the N Descriptors in the Forthcoming with the classification into ipsilateral, intrathoracic nodal metastases (N1)
8th Edition of the TNM Classification for Lung Cancer. Journal of Thoracic was proposed [8]. No changes have been recommended for the M descriptor
Oncology, Vol. 10, Issue 12, p1675–1684 5. Eberhardt W E.et al. The IASLC Lung in the 8th edition of the TNM [9]. In this presentation, 4 patient cases of
Cancer Staging Project: Proposals for the Revision of the M Descriptors in different stages of MPM patients will be presented and the newly proposed
the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. TNM descriptors and IMIG staging will be applied. Cases and changes in the
Journal of Thoracic Oncology, Vol. 10, Issue 11, p1515–1522 6. Travis WD, et al. staging system will be discussed together with the attending audience in
The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories an interactive manner. After the presentation, the participants will be able
for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in to understand and practically apply the forthcoming changes in the TNM
the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. system for staging of MPM patients. 1. Whitaker, D., J.M. Papadimitriou, and
Journal of Thoracic Oncology, Vol. 11, Issue 8, p1204–1223 7. Detterbeck FC et M.N. Walters, The mesothelium and its reactions: a review. Crit Rev Toxicol,
al. The IASLC Lung Cancer Staging Project: Background Data and Proposals 1982. 10(2): p. 81-144. 2. Lanphear, B.P. and C.R. Buncher, Latent period for
for the Application of TNM Staging Rules to Lung Cancer Presenting as malignant mesothelioma of occupational origin. J Occup Med, 1992. 34(7): p.
Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type 718-21. 3. Peto, J., et al., The European mesothelioma epidemic. Br J Cancer,
of Involvement in the Forthcoming Eighth Edition of the TNM Classification. 1999. 79(3-4): p. 666-72. 4. Rudd, R.M., Malignant mesothelioma. Br Med
Journal of Thoracic Oncology, Vol. 11, Issue 5, p666–680 8. Detterbeck FC et Bull, 2010. 93: p. 105-23. 5. Rusch, V.W., A proposed new international TNM
al. The IASLC Lung Cancer Staging Project: Background Data and Proposals staging system for malignant pleural mesothelioma from the International
for the Classification of Lung Cancer with Separate Tumor Nodules in the Mesothelioma Interest Group. Lung Cancer, 1996. 14(1): p. 1-12. 6. Butchart,
Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. E.G., et al., Pleuropneumonectomy in the management of diffuse malignant
Journal of Thoracic Oncology, Vol. 11, Issue 5, p681–692 9. Detterbeck FC et mesothelioma of the pleura. Experience with 29 patients. Thorax, 1976. 31(1):
al. The IASLC Lung Cancer Staging Project: Background Data and Proposed p. 15-24. 7. Nowak, A.K., et al., The IASLC Mesothelioma Staging Project:
Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci Proposals for Revisions of the T descriptors in the forthcoming Eighth edition of
in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the the TNM classification for pleural mesothelioma. J Thorac Oncol, 2016. 8. Rice,
TNM Classification for Lung Cancer. Journal of Thoracic Oncology, Vol. 11, Issue D., et al., The IASLC Mesothelioma Staging Project: Proposals for Revisions of
5, p651–665 10. Detterbeck FC et al. The IASLC Lung Cancer Staging Project: the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification
Summary of Proposals for Revisions of the Classification of Lung Cancers for Pleural Mesothelioma. J Thorac Oncol, 2016. 9. Rusch, V.W., et al., The
with Multiple Pulmonary Sites of Involvement in the Forthcoming Eighth IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for
Edition of the TNM Classification. Journal of Thoracic Oncology, Vol. 11, Issue 5, Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the
p639–650 11. Nicholson AG et al. The International Association for the Study TNM Classification for Mesothelioma. J Thorac Oncol, 2016.
of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the
Keywords: Staging, TNM, Mesothelioma
depends in part on whether there are inequalities in participation which

NURSES SESSION has the potential to exacerbate disparities in lung cancer survival. Given the
impact of lung cancer stigma on satisfaction with care and patient outcomes
SESSION NU01: PREVENTION it is imperative that further research explore the association of perceived lung
cancer stigma and the decision to have LDCT.
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
NU01.04 STIGMA IN LUNG CANCER

NU01: PREVENTION
Janine Cataldo MONDAY, DECEMBER 5, 2016 - 11:00-12:30
Physiological Nursing, University of California, San Francisco, San Francisco/CA/
NU01.05 INDIGENOUS POPULATION WITH LUNG CANCER
Despite substantial reductions in smoking prevalence, lung cancer is the Gail Garvey
leading cause of cancer-related mortality for both genders in the United
Preventable Chronic Diseases and Wellbeing, Menzies School of Health Research,
States. In 2016, lung cancer is expected to be responsible for 158,080 deaths. Brisbane/Australia
Tobacco smoking is still the number one risk factor for lung cancer and has
been linked to 90% of all lung cancer cases. Currently, only 15% of all lung Background: As the most common cancer and the leading cause of cancer
cancer cases are diagnosed at an early stage. Historically, these poor rates deaths worldwide, lung cancer has garnered increasing attention and efforts
were due to the lack of effective routine screening. This changed dramatically to reduce its toll. In contrast to the wealth of information on lung cancer
in November 2011 when the National Lung Cancer Screening Trial (NLST), burden for the general population, a rapid review of the academic literature
released their results that showed low-dose computed tomography (LDCT) (published in the past 10 years) to identify articles about lung cancer in
could reduce lung cancer mortality by 20%. LDCT is now widely recommended Indigenous populations of four comparable OECD countries, found a paucity
for current and former smokers. Identification of all barriers and facilitators of information. The reasons for the paucity of articles are multi-faceted and
is essential for the successful promotion of lung cancer screening. most likely related to the lack of indigenous identification in health and
Denormalization of smoking has been one of the most successful tobacco cancer administrative datasets, among other issues. The search identified 62
control measures and is associated with a sharp decrease in the prevalence articles which documented disparities in lung cancer outcomes for Indigenous
of smoking. However, smoking is now concentrated in the most vulnerable peoples, identified likely reasons and made recommendations for better
populations (e.g. lower income groups and the mentally ill) who have the targeted prevention and management strategies. Indigenous people in all
least ability and/or willingness to quit. In addition, denormalization has the four countries, namely Aboriginal and/or Torres Strait Islanders in Australia;
effect of sanctioning smoking related stigma. A majority (95 %) of lung cancer Māori in New Zealand; First Nations, Métis or Inuit in Canada; American
patients experience stigma, with 48 % of lung cancer patients specifically Indians and/or Alaskan Natives (AIs/ANs) in the United States (US), have
reporting feeling stigmatized by their medical providers. Perceived lung significantly lower life expectancy than their non-Indigenous counterparts, to
cancer stigma is defined as a personal experience characterized by exclusion, which their lung cancer burden must surely contribute. The burden of lung
rejection, blame or devaluation. Lung cancer conjures up attributions of cancer for Indigenous populations: Lung cancer is one of the most commonly
blame because it is associated with smoking cigarettes and is perceived to be occurring cancers for indigenous people across all four countries. It has
a controllable behavior. Perceived lung cancer stigma is a risk factor for poor recently been reported that lung cancer incidence is higher in Indigenous men
psychosocial and medical outcomes in the context of lung cancer diagnosis in Australia, Canada’s Métis and in Alaskan Natives than in their non-
and treatment. People often associate lung cancer with previous smoking indigenous counterparts, and in Māori women, Alaskan Native women and
behavior, regardless of whether the person with lung cancer was a smoker or Indigenous women in some Australian States [1]. Lung cancer is the leading
not. There is growing body of evidence that patients, caregivers, healthcare cause of cancer deaths in Indigenous Australians (1 in 4 cancer deaths) and
providers, and members of the general public have negative implicit attitudes Māori where mortality rates were three times those of non-Māori (nearly 1 in 3
toward lung cancer. Perceived lung cancer stigma is one barrier that can delay cancer deaths) [1, 2]. Lung cancer mortality among the Alaskan Native
the detection of lung cancer because of fear of health professionals’ censure population is higher than the US white population, and among the highest of
associated with smoking. any racial/ethnic group in the US [3]. Survival following a diagnosis of lung
cancer was lower for indigenous people in all four countries compared to their
In our previous work we found that there were four beliefs associated with non-indigenous counterparts [4, 5, 6]. For example for Indigenous Australians
whether older (>55)current and former smokers would agree to lung cancer five year survival following a diagnosis of lung cancer was 7% compared with
screening (LDCT): Perceives accuracy of the LDCT as an important factor in the 11%. Indigenous Australians are 1.7 times more likely to die from lung cancer
decision to have a LDCT scan; Believes that early detection of LC will result in than non-Indigenous Australians. In Australia, lung cancer accounted for 25%
a good prognosis; Believes that they are at high risk for lung cancer; and is not of all Indigenous deaths from cancer [2]. In the USA and Canada lung cancer
afraid of CT scans. This study showed that older smokers are aware of the risks survival rates improved over time for non-indigenous populations but
of smoking, are interested in smoking cessation, and most are interested in remained unchanged or declined for the AI/AN and First Nations cohorts [6, 8],
and positive about LDCT. There are no studies that have examined the impact increasing disparities. Explaining the disparities: The greater burden of lung
of perceived lung cancer stigma on the decision to have an LDCT. To address cancer in indigenous populations is largely attributable to the higher
this gap, we conducted a secondary analysis in which lung cancer stigma was prevalence of tobacco smoking. In both Australia and New Zealand, 39% of the
measured by five true or false items: doctors treat smokers badly; doctors Indigenous populations aged 15 and over were daily smokers – almost 3 times
have a bias against smokers; cigarette smokers keep their smoking a secret the rate of the non-Indigenous populations [4, 9]. AI/AN populations had the
from important people in their lives; cigarette smokers avoid talking about highest tobacco use (29%) of any population group in the USA [10]. Smoking
smoking with their doctor; cigarette smokers feel guilty about their smoking; rates among Canada’s Aboriginal populations are on average twice as high as
and friends and family are upset that I smoke. Four variables demonstrated those of non-Aboriginal Canadians, with nearly half of Inuit adults smoking
a significant association with LDCT agreement: People treat smokers badly; daily or regularly [11]. While smoking rates in all four countries have decreased,
Doctors have a bias against smokers; Smokers feel guilt about smoking; the decline in indigenous smoking prevalence has occurred at the same or
and Friends and family do not approve of my smoking. Only two of the slower rate than for non-indigenous people, meaning the gap in smoking rates
independent variables made a unique statistically significant contribution to has remained. Although higher lung cancer incidence and mortality rates for
the model. A test of the model against a constant only model was statistically indigenous peoples is related to patterns of tobacco use, they also reflect the
significant, indicating that the predictors as a set, reliably distinguished significant disparities in terms of socio-economic disadvantage, social
between those who would agree to an LDCT and those who would not agree dislocation, geographic/remoteness and related stressors indigenous people
(chi square = 8.5 p. = <.1 with df = 4). The model as a whole explained between face [1]. Poorer survival of indigenous people with lung cancer is attributed to
43% of the variance in agreement to have a CT scan, and correctly classified a greater likelihood of advanced disease at diagnosis [12], lower rates of
83.2% of cases. The strongest predictor for agreeing to a LDCT was “People treatment, not receiving optimal lung cancer care concordant with clinical
treat smokers badly”, (OR 3.7, 95% CI .143-.971). Participants with this belief guidelines care [1, 7, 13, 14], and higher prevalence of comorbidities [2]. But
were almost 4 times less likely to agree to a CT scan than those who did not these factors do not explain all the survival disparities. Recent research has
have the belief. The odds ratios for the remaining predictor, Doctors have shifted focus from patient and community-level factors to examining
bias against smokers, was OR 1.7, 95% CI 1.47- 4.90); Believes that they are at system-level and societal factors that affect lung cancer care and outcomes
high risk for LC (OR 2.1, 95% CI 1.8 – 3.12). DISCUSSION The decision to agree for indigenous patients including difficulty accessing health services and the
to a LDCT is negatively associated with two indicators of perceived stigma, cultural appropriateness of healthcare services [6]; lack of coordination and
“people treat smokers badly” and “doctors have a bias against smokers.” These follow-up processes [15, 16]; health professional behaviours including
findings suggest that stigma is a barrier to preventative care utilization much knowledge about lung cancer, relationships with patients and carers,
like it is for patients with HIV, STDs, TB and mental health problems. Smokers communication and responsiveness to needs [15, 16]; and the impact of stigma
from deprived communities are an important group to engage with lung and shame on delays in medical help-seeking and lung cancer patients’ quality
cancer screening but thus far participation in trials has been skewed towards of life [16]. Strategies to reduce the disproportionate burden: The current
former smokers and better educated smokers. With the current demographic evidence highlights that significant disparities exist in lung cancer outcomes
profile of smokers, the effectiveness of a lung cancer screening program between indigenous and non-indigenous peoples and that multiple strategies

are required to reduce the burden of lung cancer for indigenous people. At the 1
Dept. of Psycho-Oncology, Institute of Oncology Ljubljana, 2Cancer Patients’
systems level, inclusion of an indigenous identifier in administrative data is Association of Slovenia, Ljubljana/Slovenia
required to accurately identify and monitor lung cancer outcomes. The
provision of and timely access to medically effective and culturally accepted Background: Lung cancer and its treatment have a major physical impact, as
diagnostic, treatment and support services, and personalised care that well as emotional, social, psychological, spiritual, functional and practical
addresses the social-cultural needs of indigenous patients, is required to challenges and consequences, both for the patient and his relatives. While
improve indigenous patients engagement with cancer care services and, in coping with the disease they become aware of vulnerability and mortality, they
turn, cancer outcomes [12]. Tobacco control and smoking cessation initiatives are balancing hope and the realisation of mortal danger(1). Preconceptions
are critical – but there is limited evidence about what works in indigenous which patients are harbouring could be an important factor at coping with the
populations. While public policy initiatives have reduced overall smoking lung cancer. Both smokers (or former smokers) and non-smokers are being
prevalence, they appear to have had less impact on smoking rates among stigmatised, and lung cancer is connected with stereotype representation of
indigenous populations. Well-targeted tobacco control strategies need to incurable disease(2). Life is never the same as before the diagnosis. In the
consider historical, social, economic and cultural reasons why indigenous comprehensive approach to lung cancer, team work is of paramount
people smoke – factors that also can undermine efforts to reduce smoking importance. Beside the standard oncological treatment, for the patient there
uptake and encourage indigenous people to quit. The use of both is a benefit of an early palliative care. This benefit beside better quality of life
comprehensive and tailored interventions has been recommended, including (due to better quality of life, less depression and less aggressive treatment)
culturally appropriate health materials and activities, with indigenous confers also an increase of survival(3). Here, the nurse is an important member
peoples’ engagement and control [17]. It is also essential to increase symptom of comprehensive care team, and is the one spending the greatest amount of
awareness to expedite diagnoses, and there are novel initiatives aimed at time at bedside. Methods: We reviewed the literature and the current clinical
improving awareness of lung cancer risk factors and symptoms among practice. Results: In operationalising psychosocial care in oncology many
indigenous communities and health professionals. Reducing the authors are advocating so called tiered approach(4,5). Providing psycho-social
disproportionate burden of lung cancer on indigenous peoples requires support to lung cancer patients is the task of all medical workers included in
targeted and multifaceted approaches that recognise and address the broad the multidisciplinary care. And all cancer patients have the basic psycho-social
and interconnected web of factors at patient, provider and system levels that needs, such as informational needs, basic emotional support, adequate
impact on optimal care and outcomes.References: 1. Moore, S.P., et al., Cancer communication, screening of needs on on-going basis and the symptom
incidence in indigenous people in Australia, New Zealand, Canada, and the USA: management. Patients experiencing more profound distress or have more
a comparative population-based study. Lancet Oncol, 2015. 2. Australian unmet needs, should be directed into the specialist care provided by the
Institute of Health and Welfare, Cancer in Australia: an overview 2014. Cancer mental health professionals or other professionals needed. At the psycho-
series No 90. Cat. no. CAN 88. 2014, AIHW: Canberra. 3. Lanier, A.P.D., G. social care of the lung cancer patients entering the treatment, there should be
E.;Kelly, J. J.;Provost, E., Disparities in cancer mortality among Alaska Native an emphasis on the adequate patient information concerning the disease,
people, 1994-2003. Alaska Med, 2008. 49(4): p. 120-5. 4. Australian Institute of planned treatment, side effects and their management, the possibilities of
Health and Welfare & Cancer Australia 2013. Cancer in Aboriginal and Torres patient’s contribution to the treatment, and also patients’ fears and
Strait Islander peoples of Australia: an overview. Cancer series no 78. Cat. No. existential issues should be addressed. It is important for the patient to get as
CAN 75. Canberra:AIHW 5. NZ Ministry of Health (2015) Cancer Patient many information as he deems necessary, being careful about the pace the
Survival: 1994 to 2011 Wellington 6. Nishri, E.D.S., A. J.;Withrow, D. R.;Marrett, information is given. Despite the amount of information offered in media in
L. D., Cancer survival among First Nations people of Ontario, Canada the recent time – many of them unfortunately also untested – many patients in
(1968-2007). Int J Cancer, 2015. 136(3): p. 639-45. 7. Smith CB, Bonomi M, their search for information prefer getting information in one-to-one
Packer S, Wisnivesky JP. Disparities in lung cancer stage, treatment and communication with health provider, in relation with whom they are
survival among American Indians and Alaskan Natives. Lung Cancer. 2011 experiencing confidence, safety, care and professionalism(1). It is important to
May;72(2):160-4. doi: 10.1016/j.lungcan.2010.08.015 8. White, M.C.E., D. present the information, at the same time accurate and still preserving the
K.;Swan, J.;Wiggins, C. L.;Eheman, C.;Kaur, J. S., Disparities in cancer mortality hope even in the face of the odious situation, thus giving the patient and his
and incidence among American Indians and Alaska Natives in the United States. relatives emotional support and strengthening their functional coping
Am J Public Health, 2014. 104 Suppl 3: p. S377-87. 9. Ministry of Health, Tobacc strategies. Therefore, medical professionals should develop good
use 2012/13: New Zealand health survey. 2014, Ministry of Health: Wellington. communication skills; these are proven to be associated with less unmet
10. Centers for Disease Control and Prevention, Current Cigarette Smoking needs(6)by the patient and also with the increase of informed decisions
Among Adults—United States, 2005–2014. Morbidity and Mortality Weekly regarding treatment(7). In patients with poorer communication skills,
Report, 2015. 64(44): p. 1233-40. 11. Statistics Canada, Select health indicators assertiveness support can help with the communication with the medical
of First Nations people living off reserve, Métis and Inuit. Catalogue no. professionals but also with the relatives. The cognitive behavioural therapy
82-6240X. 2013. 12. Moore, S.P.G., Adèle C.;Bray, Freddie;Garvey, Gail;Coory, strategies can take a pivotal place. Cognitive interventions are focused on the
Michael;Martin, Jennifer;Valery, Patricia C., Survival disparities in Australia: an way of thinking about a situation and through it influences the behavioural
analysis of patterns of care and comorbidities among indigenous and and emotional response, like cognitive restructuration, helping the patient in
non-indigenous cancer patients. BMC Cancer, 2014. 14: p. 517-517. 13. Javid, SH, development of positive alternative to negative thought, or distraction,
Varghese TK, Morris AM, Porter MP, He H, Buchwald D, Flum DR; Collaborative changing the patient focus. Behavioural interventions, such as relaxation
to Improve Native Cancer Outcomes (CINCO). Guideline-concordant cancer techniques, can help controlling physiological responses in stressful
care and survival among American Indian/Alaskan Native patients. Cancer. situations. An important place in the support of patient’s psycho-social needs
2014 Jul 15;120(14):2183-90. 14. Whop, LJ, Bernardes CM, Kondalsamy- is taking into consideration emotional and social support. In addition to
Chennakesavan S, Darshan D, Chetty N, Moore SP, Garvey G, Walpole E, Baade patient’s relatives, friends and peers, medical workers represent an integral
P, Valery PC. Indigenous Australians with non-small cell lung cancer or cervical part of it. In the patient’s preparation for treatment, it is important to
cancer receive suboptimal treatment. Asia Pac J Clin Oncol. 2016 Mar 21. doi: recognize those experiencing more profound distress or having more unmet
10.1111/ajco.124632016 15. Dunn, J. , Garvey, G., Valery, P. C., Ball, D., Fong, K.M. needs, thus needing more help. Research has shown that cancer patients are
, Vinod, S., O’Connell, DL. & Chambers, S.K. Barriers to Lung Cancer Care: experiencing more physical problems - the most common are pain, dyspnoea,
Health Professionals’ Perspectives. Accepted for publication 24th September fatigue, cough(8) - and also have more unmet needs than other patients. In
2016. Journal of Supportive Care in Cancer 16. Chambers, S.K.B., P.;Youl, excess of 80 % of lung cancer patients are experiencing some degree of
P.;Aitken, J.;Occhipinti, S.;Vinod, S.;Valery, P. C.;Garvey, G.;Fong, K. M.;Ball, psychological distress. This is more than other cancer type patients are
D.;Zorbas, H.;Dunn, J.;O’Connell, D. L., Psychological distress and quality of life experiencing. Depression estimates are ranging between 11 and 44 % and the
in lung cancer: the role of health-related stigma, illness appraisals and social fear of recurrence is ranging from 5 % up to the 89 %(8). The severity of distress
constraints. Psychooncology, 2015. 24(11): p. 1569-77. 17. Minichiello, A., et al., is varying through the process of treatment and rehabilitation; the time of
Effective strategies to reduce commercial tobacco use in Indigenous diagnosis is a period during which more patients are entering psycho-social
communities globally: A systematic review.(Report). 2016. 16(21). treatment than later during treatment(1,5). With the aim of early recognition
of patients with more profound distress, screening procedures are being
Keywords: lung cancer, Indigenous implemented. Beside different questionnaires, International Psycho-Oncology
Society is striving to implement the distress thermometer with 10 grades(9).
The psycho-social interventions, performed by mental health professionals are
proven to increase wellbeing, improve adjustment and coping, and reduce
distress in people with cancer. In the field of psycho-oncology, the most
SESSION NU02: PREPARING PATIENTS FOR TREATMENT commonly used methods are cognitive behavioural therapy, learning of
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 relaxation skills, psycho education, and also partnership and family therapy(4).
Providing psycho-social treatment for patients with more profound distress is
connected with multiple challenges. Beside patient recognition and
implementation of screening programmes, the next challenge is patient’s
NU02.01 PREPARING PATIENTS FOR TREATMENT. PROVIDING
compliance, as psychological treatment can for a patient still be stigmata.
PSYCHOSOCIAL SUPPORT FOR LUNG CANCER PATIENTS
Despite limited evidence of its efficacy patients prefer emotional and social
PREPARING TO ENTER TREATMENT help from the nurse than from allied professionals, because their medical
Andreja Cirila Škufca Smrdel expertise is seen as an advantage(5). In many healthcare systems the
availability of psycho-social treatment, to the patient who needs it in the effective preoperative teaching program. Collaborating with nurses and
proper time, and the development of required resources, still in many cases advanced practice providers across the care continuum is ideal: these
underutilised, is the next challenge. This, despite proven ethical, emotional as members of the team have both the knowledge base and the access to
well as economic benefits of psycho-social treatment. Conclusion:The nurse is patients and their families needed to provide effective patient education.
playing one of the crucial roles in comprehensive treatment of lung cancer Method: “A Patient’s Guide to Thoracic Surgery” is a thoracic teaching manual
patients. She is indispensable in providing psycho-social support to the lung that was customized to fit our thoracic patient population. It was developed
cancer patients, preparing to enter treatment. She is providing the basic by a group of nurses and advanced practice providers who were interested in
psycho-social support, such as patient’s need for relevant information, basic developing thoracic patient education at our institution. The booklet includes
emotional support, communication, screening for needs on an ongoing basis, basic information concerning how to prepare for thoracic surgery, as well as
symptom management. She is also pivotal in recognizing patients, what to expect before and after the surgery. Our thoracic team saw the need
experiencing more profound distress or has more unmet needs and can run a for additional education and developed a patient education video, “A Patient’s
screening programme.References: 1. Missel M, Pedersen JH, Hendriksen C, Guide to Thoracic Surgery Video” that includes pre-operative teaching, what
Tewes M, Adamsen L. Diagnosis as the First Critical Point in the Treatment to expect after surgery, and after discharge. The video was funded by a grant
Trajectory: An Exploration of Operable Lung Cancer Patients’ Lived that our hospital provides annually, funding various projects that support
Experiences. Cancer Nurs. 2015;38(6):E12-21. 2. Pujol J-L, Mérel J-P, Roth C. How research, education, and clinical care. The team wrote a script and worked
preconceptions about lung cancer treatment interact with medical discourse with the hospital IT department to create the video. Patients receive both
for patients who accept chemotherapy? Psychooncology. 2016 Jul 23 [cited the pre-operative teaching booklet and video during the initial office visit
2016 Aug 21]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/27449209 and the major points of the teaching material are reviewed at this time. The
Accessed August 20, 2016 3. Temel JS, Greer JA, Muzikansky A, Gallagher ER, patient is instructed to read through the information and watch the video at
Admane S, Jackson VA, et al. Early palliative care for patients with metastatic their convenience. They are also encouraged to call the office to discuss what
non-small-cell lung cancer. N Engl J Med. 2010;363(8):733–42. 4. Hutchison SD, they learned and answer any questions they may have. The outpatient nurse
Steginga SK, Dunn J. The tiered model of psychosocial intervention in cancer: a practitioner calls and sometimes meets with the patients at least once again
community based approach. Psychooncology. 2006;15(6):541–6. 5. Brebach R, prior to surgery to review the patients’ pre-operative studies, update their
Sharpe L, Costa DSJ, Rhodes P, Butow P. Psychological intervention targeting pre-operative paperwork, and to answer any questions or concerns about
distress for cancer patients: a meta-analytic study investigating uptake and their upcoming surgery. The patients are asked if they have read through the
adherence. Psychooncology. 2016;25(8):882–90. 6. Walling AM, Keating NL, material and watched the video. During this encounter, updates on smoking
Kahn KL, Dy S, Mack JW, Malin J, et al. Lower Patient Ratings of Physician cessation and exercise are documented and discussed. Following surgery,
Communication Are Associated With Unmet Need for Symptom Management additional teaching is done by the nursing staff and the teaching video and
in Patients With Lung and Colorectal Cancer. J Oncol Pract. 2016;12(6):e654-69. discharge instructions are again reviewed. Furthermore, the patient is phoned
7. Janssens A, Kohl S, Michielsen T, Van Langendonck S, Hiddinga BI, van for a “day after discharge” call by a thoracic team member to check on the
Meerbeeck JP. Illness understanding in patients with advanced lung cancer: patient’s progress and answer any questions the patient or family may have.
curse or blessing? Ann Palliat Med. 2016;5(2):135–8. 8. Pozo CLP, Morgan MAA, The patients and their families are seen in the office for a post-operative
Gray JE. Survivorship issues for patients with lung cancer. Cancer Control. visit usually 2-3 weeks after discharge. A 10 question “Thoracic Video Patient
2014;21(1):40–50. 9. Bultz BD. Guide to implementing screening for distress, Satisfaction Survey” is completed during this initial post-op visit. This survey
the 6th vital sign: Background, recommendations, and implementation. Cancer asks the patients to rate the educational video on content and how helpful
Journey Action Gr. 2009;(May):4–43. they felt the video was in preparing them for surgery and for what to expect
after surgery. Results: A “Thoracic Video Satisfaction Survey” has been given
Keywords: psychosocial support, nurses, Preparing for treatment to all patients undergoing thoracic surgery at Penn Presbyterian Medical
Center; Philadelphia, Pennsylvania over the past several months. Preliminary
results have shown that since the implementation of the thoracic teaching
video in conjunction with the written material there has been an increase
NU02: PREPARING PATIENTS FOR TREATMENT in patient’s satisfaction and a decrease in anxiety associated with thoracic
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
surgery Conclusion: Providing patients with multi-format education materials
and the ability to review them on their own time has proven successful at
NU02.02 PREOPERATIVE THORACIC SURGERY PATIENT EDUCATION achieving the stated goals. Moving forward we intend to build upon this
PROGRAM DEVELOPMENT resource to improve the patient education program at our institution.
Additionally, we hope to conduct a formal research project in conjunction with
Katherine Kuhns
other institutions such as the University of Maryland to continue to develop
Thoracic Surgery/nursing, Penn Presbyterian Medical Center, Philadelphia/PA/
thoracic patient education and to help identify which programs work best in
promoting patient education and changing behaviors in the thoracic surgery
Purpose: To develop a cost-effective preoperative patient teaching program population.
that includes a patient teaching video along with written material that
Keywords: Patient Education Thoracic Surgery
improves patient satisfaction, decreases patient anxiety, decreases
readmission rates associated with post-operative complications, and
optimizes overall outcomes of thoracic surgery patients. Overview: Patients
undergoing surgery usually have little knowledge of what to expect during
NU02: PREPARING PATIENTS FOR TREATMENT
the preoperative, postoperative, and recovery period following thoracic MONDAY, DECEMBER 5, 2016 - 16:00-17:30
surgery. Multiple studies have shown that good quality preoperative
teaching increases patient satisfaction, improves patient outcomes, and
decreases patient readmission rates following surgery. Although the benefit NU02.03 ETHICAL DECISION MAKING
of preoperative education is widely recognized in the literature, finding Sabine Ruppert
the resources available to provide efficient and effective teaching is a Department of Medicine Ii and Department of Medicine III, Division of Nephrology
challenge. Patients who are diagnosed with a suspicious lung nodule or lung and Dialysis, Vienna General Hospital, Vienna/Austria
cancer are usually overwhelmed when attempting to navigate through the
health care system. During the initial surgical visit a battery of studies and Ethical decision making is very important in the context of treatment of
often additional diagnostic procedures are ordered for staging and surgical cancer patients. These decisions can lead to withdrawal or withholding of
clearance. The details of the surgery are discussed and the surgical consent life-sustaining therapy, or change the goal of the therapy from curative to
is obtained. The patient and family are inundated with so much information palliative. “Do-not-reanimate” or “allow-natural-death” orders are also part
that pre-operative teaching is not effective at this time. Further, in outpatient of ethical decision making. Sometimes pain treatment is adapted or palliative
health care settings there is a finite amount of time within a visit for a sedation is started. It is necessary to make these decisions to ensure dignity
provider to promote all of the pre-operative patient education. It has been the at the end-of-life, which is a human right. Ethical decision making is usually
experience of this thoracic surgery practice that providing the patients and done state-of-the-art in the context of Palliative Care, which means dialogue
families an opportunity to undergo pre-operative teaching in another setting, with the patient, the next of kin and other health-care-professionals involved
such as in their own homes, typically results in increased retention of the in the treatment. The decision making process is structured, documented
information, and patients do better not only in the pre-operative period but and can be replicated for everyone. Most of the time, these decisions are
in the post-operative and recovery stages as well. Developing a well-designed made by physicians only, without a dialogue, especially in Austria in hospitals
preoperative teaching program requires a multidisciplinary approach and or nursing homes. Sometimes patients are involved, but more often only
utilization of resources already available to build upon and promote better their relatives. Physicians rarely ask other health-care-professionals for
programs that optimize patient and caregiver learning and retention. Pre- their opinion. End-of-life-decision-making seldom occurs as a structured
operative education and teaching is not just to provide information, but well documented process. But the fact, that by law physicians have to take
also to help patients acquire the knowledge needed to change behaviors and the final decision, does not prevent them from listening to and involving
to promote better health. Individuals within the care team with particular the perspective of the different persons concerned. If the discussion stops
interest in patient education should be utilized in helping to develop an with the question “Who is allowed to decide?” then decisions would only be

made because of having legal authority and not because of ethical reasons. ethischen Entscheidungen. In: Imago Hominis 19 (2), S. 97-105.
(Vanlaere & Gastmans, 2008, Arndt, 2007) From an ethical perspective
these decisions are often decisions between the autonomy of patients and Steinkamp, Norbert (2012): Methoden ethischer Entscheidungsfindung
the care of health care professionals. It is crucial to preserve the dignity im Pflegealltag. In: Monteverde Settimio (Hrsg.): Handbuch Pflegeethik.
of the suffering human being. It is a challenge to make reasonable ethical Ethisch denken und handeln in den Praxisfeldern der Pflege. Stuttgart: W.
decisions in a context characterized by strong pressure for efficient and Kohlhammer Verlag, S. 175-192.
flexible organisational structures on the one side and complex values on
Valentin, Andreas; Druml, Wilfred & Steltzer, Heinz (2004): Konsensuspapier
the other side. (Gastmans & Vanlaere, 2005). It is not always clear what is
der Intensivmedizinischen Gesellschaften Österreichs (2004): Empfehlungen
right and what is wrong, or what is good and what is bad. Sometimes health
zum Thema Therapiebegrenzung und -beendigung an Intensivstationen. In:
care professionals, especially physicians, try to avoid these decisions by
Wiener Klinische Wochenschrift, 116/21-22: 763-767.
not to deciding anything, but avoidance is also a decision. Ethical decision
making is much more difficult, if the suffering person cannot express his Van der Arend, Arie & Gastmans, Chris (2009): Ethisch zorg verlenen.
wishes anymore. Then, physicians and other health care professionals, who Handboek voor de verpleegkundige beroepen. Baarn: Hbuitgevers, 4.
are included in the decision-making-process, have to find out the person`s korrigierte Druck, 5. Auflage.
wishes. It is very important that ethical decision making is based on indication
for treatment, futility and the wish of patient. (Bundeskanzleramt, 2015) Vanlaere, Linus & Gastmans, Chris (2008): Een goed gesprek voor een zo goed
Ethical decision making should include all persons involved – physician, mogelijke zorg. Een zorgethische en personalistische overlegmethode. In:
patient, relatives, nurses and also, if appropriate pastor or other religious Tijdschrift voor Gezondheitdszorg en ethiek 18(2), S. 45-49.
leader, social workers and other health care professionals. The involvement
of patients and – if they wish – their next of kin is necessary. Austrian Zentrale Ethikkommission bei der Bundesärztekammer (2006): Ethikberatung
medical guidelines (Valentin et al. 2004) recommended that nurses and in der klinischen Medizin. Deutsches Ärzteblatt 103 (24): A1703-1707.
other members of the multidisciplinary team had to be involved in such
Keywords: end-of-life-decisions, decision making process, role of nurses,
decisions. The decision making process should be structured, documented
palliative care
and - depending on the context – regularly evaluated. Several models exist
for ethical decision making and help to guide and structure the dialogues.
Individual ethical case conferences could be part of clinical ethical counseling,
which also includes ethical education and providing guidelines. (Zentrale
Ethikkommission, 2006). Examples of such decision-making-models are the
SESSION NU03: SUPPORTING PATIENTS RECEIVING TREAT-
model of Gastmans and Vanlaere (Vanlaere & Gastmans, 2008) based on the
personalism and care-ethic, the Nijmwegener-model of Steinkamp and Gordijn MENT
(Steinkamp, 2012) and the model of Arndt (2007). Decision-making-models TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
are not simply checklists. Health care professionals have to use them with
empathy in the context of their own experience and values. (Körtner, 2012).
General guidelines could deviate from frequently arising problems, but there NU03.01 SUPPORTING PATIENTS UNDERGOING RADICAL
always would be individual cases, which represent marginal cases because TREATMENTS EPD – MARS STUDY
they burst all limits (Körtner, 2012). By using decision-making-models health
Angela Tod
care professionals have to be alert, not to use those strictly according to
School of Nursing and Midwifery, The University of Sheffield, Sheffield/United
the written instructions. The sensitivity for the individual and his special
Kingdom
situation has to be preserved. A discussion or counselling, where all persons
concerned make a choice together according to their values and principles, is Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer
the best guarantee for a well-grounded ethical decision and gives more sense of the lining of the chest wall and lung, its aetiology lies in asbestos exposure.
of security for a good result. Nevertheless, there is no guarantee for a right or With over 2,500 people diagnosed each year, the UK has the highest incidence
good action. (Körtner, 2012). Because of the emotional burden of end-of-life- of mesothelioma in the world. Chemotherapy is an established treatment
decisions, these models are also helpful to include all important aspects. The for MPM but response rates are variable, evidence is lacking in new drug
participants of these dialogues have to respect the values of the others and therapies and mortality remains high (in the UK half of patients die within
to see the situation from their point of view. Using decision-making-models 8.5 months of diagnosis) (Maggioni 2016, HSCIC 2015). Surgery is therefore
guarantees to involve all relevant individuals. Furthermore, the decision an important option. Very little robust, randomised controlled trial evidence
making process becomes repeatable and visible. Finally, it is important to (RCT) exists regarding surgical interventions for mesothelioma and many
mention that ethical-decision-making can’t be reduced to using decision- studies are observational (Cao et al 2014). This has prompted global variations
making-models. Ethical thinking is a result of dynamic mutual reactions in surgical approaches (Mclean 2013). Extended Pleurectomy Decortication
between emotions, intuition, standardization and rational reasoning. (Van (EPD) is a surgery for patients considered to have resectable MPM. EPD
der Arend & Gastmans, 2009) The role of nurses in this decision making involves the removal of the lining of the chest wall, lining of the lung, with
process and also in the realization of these decisions is rarely recognized. the sac of the heart and / or diaphragm (as required to achieve complete
But nurses play an important role in ethical decision making - as national tumour removal) but leaving the lung in-situ. However, evidence on survival
(Ruppert et al., 2012) studies show. Nurses have the closest relationship to or symptom improvement benefits of this surgery is limited (Cao et al 2014,
the patient compared to all health care professionals. They communicate Teh et al 2011). Challenges in surgical research are the lack of clinical trials
daily with patients, know their problems, emotions, understand the social and few patients choosing to enter RCTs for surgery (Treasure & Morton,
context and values. Furthermore, nurses execute the end-of-life-decisions, 2012, Horton 1996). Potential explanations for this include restrictive trial
by, for example, not calling the rescue team. Therefore, it is very important, regulation, patients declining randomisation, and difficulties in recruitment
that nurses reflect and create actively their role in the ethical decision making practice such as presenting trial arm options neutrally (Treasure & Morton
process. They have to know which end-of-life-decisions are available and legal 2012). The Mesothelioma and Radical Surgery 2 (MARS 2) Trial, a UK based
in the country where they work. Furthermore, they need knowledge in nursing study, will evaluate whether EPD can improve the length and / or quality of
ethics and ethical frame conditions of their organisations. Nurses have to life in patients with surgically treatable disease and its cost-effectiveness. It
become part of the ethical-decision-making; especially, if discussing ethical will randomise participants to chemotherapy or chemotherapy plus surgery.
problem with the help of decision-making-models becomes routine because The feasibility stage has demonstrated the ability to recruit and randomise
this has a vital impact on the daily nursing practise. Then nurses get used to to this study and the plan is to proceed to full trial. This paper presents
reflect their acts, the values and principles laying behind and to involve the findings from a nested qualitative patient experience sub-study within MARS
perspectives, values and norms of other individuals. If decision-making is 2 that investigated patient experience of the study interventions. It more
consciously trained, it has a positive impact on situations, where reflection specifically identifies the support and information needs for people regarding
isn’t possible. (Arndt, 2007) Literature: i) the interventions (surgery and chemotherapy) and ii) trial recruitment,
consent and participation. This paper focuses on the findings related to
Arndt, Marianne (2007): Ethik denken. Maßstäbe zum Handeln in der Pflege.
support needs of the trial interventions. A summary of results will be provided
Stuttgart: Thieme Verlag, 2. Unveränderte Auflage.
along with reflections on the implications for future practice. Methods: An
Bundeskanzleramt (2015): Sterben in Würde. Empfehlungen zur Begleitung in-depth longitudinal qualitative study with interviews of 16 participants
und Betreuung von Menschen am Lebensende und damit verbundene randomised to chemotherapy (n=8) and chemotherapy + surgery (n=8).
Fragestellungen. Stellungnahme der Bioethikkommission. Interviews were conducted after randomisation (but before surgery in the
surgical cohort). Surgical patients had an additional interview post-surgery.
Gastmans, Chris & Vanlaere, Linus (2005): Cirkels van zorg. Ethisch omgaan Framework analysis methods were used (Ritchie and Lewis, 2014). Follow-up
met ouderen. Leuven: Ten Have. interviews were at 6 and 12 months post-randomisation. This paper presents
findings up to and including the 6 months follow-up. Results: Participants
Körtner, Ulrich (2012): Grundkurs Pflegeethik. Wien: Facultas Verlag, 2. reported being well informed about their illness, but had struggled to absorb
Auflage. and understand the extent of information delivered at diagnosis. This was
influenced by the range of significant subjects that were covered in a number
Ruppert Sabine; Heindl Patrik & Kozon Vlastimil (2012): Rolle der Pflege bei
of consultations with different healthcare staff providing distinct specialist THERAPY

services. The topics discussed included diagnostic information about Tanja Cufer
mesothelioma, treatment options and consequences, trials processes and
Medical Oncology Unit, University Clinic Golnik, Golnik/Slovenia
logistics, and legal and financial information regarding classification of MPM
as an industrial disease. Despite feeling well informed about their treatment Introduction Systemic therapy (ST) with chemotherapy (Cht), targeted agents
some participants reported not being prepared for the full extent of the or immunotherapy (IT) represents the mainstay therapy for patients with
problems they experienced. Both chemotherapy and surgery were challenging advanced lung cancer; while adjuvant systemic therapy is recommended in
treatments although they were associated with different physical effects. a majority of patients with operable and locally advanced disease. The goal
Adverse consequences of treatment were described including neutropenic of ST is to prolong life without compromising quality of life (QoL). Despite
sepsis and dehydration post chemotherapy, and bleeding, prolonged the ability of ST to prolong life or even cure patients, QoL and life span might
pneumothorax and infection post-surgery. For most participants pain and be compromised due treatment toxicity. In addition, uncontrolled adverse
breathlessness were experienced post-surgery while nausea, anorexia, taste events (AEs) might lead to treatment interruption or discontinuation.
changes and constipation were associated with chemotherapy. Fatigue that Therefore, effective management of adverse events of anti-cancer drugs, the
impacted on daily living was experienced by both groups. Interventions to so-called “supportive care to systemic therapy” is extremely important for a
manage the consequences of treatment were recounted; some had been true benefit, i.e. treatment effectiveness in a routine practice. During the last
recommended by healthcare staff while others had been developed by decade several improvements in prevention, treatment and amelioration of
patients from their own initiative. Participants reported struggling to cope ST AEs been achieved. To implement them in everyday clinic practice a good
with the effect of treatment whilst trying to deal with the broader context of understanding of adverse events, supportive care measures and professional
coming to terms with their illness. Uncertainty was expressed in relation to skills of all team members are needed. Registered nurses, specialized in the
treatment plans (exacerbated by the logistics surrounding participation in a oncology, the so called “oncology nurses” are key providers of supportive care
clinical trial), severity and duration of side effects, rehabilitation and recovery in everyday clinical practice. Supportive care for prevention and treatment
and treatment outcomes. Participants employed a number of strategies of adverse events Chemotherapy-induced nausea and vomiting (CINV)
to help with coping. These included ‘playing things down’, ‘weighing the has been a priority in the supportive care of cancer patients ever since the
balance’, ‘managing expectations’, ‘taking control’ ‘manning up’ and ‘trust in first use of Cht (1). The introduction of 5-HT3 and NK1 antagonists into
the doctor and/or treatment’. Many of these strategies facilitated staying anti-emetic therapy resulted in much better control of CINV in lung cancer
positive, maintaining hope and finding comfort which was important to patients receiving highly emetogenic, platinum-based therapy. With proper
participants. Family members played a key role in coping. A diverse range of use of available drugs complete control of vomiting could be achieved in
healthcare staff provided information, advice and practical interventions up to 90% of these patients. However, despite the efficacy of new anti-
across the care pathway from community, surgical, respiratory and oncology emetic therapies a proper us of anti-emetics and other preventive measures
services. Discussion: Patient’s perspectives on the experience of receiving are vital. Chemotherapy-induced neutropenia with febrile neutropenia
radical surgery and/or chemotherapy for mesothelioma were identified by (FN) as its ultimate and most serious complication are often observed in
the study. This provided valuable insights into their impact on patient’s patients receiving Cht. The risk of FN can be predicted by assessing patient
feelings about their illness and treatment and how they coped with the characteristics and mylotoxicity of the Cht regimen; and granulocyte-colony-
challenges they were presented with. Multiple sources of uncertainty were stimulating factors (G-CSF) can be used to prevent it (2). Even thought,
expressed by participants. The contribution of healthcare staff to supporting most of the regimens for lung cancer do not classify to high, i.e. more than
coping and providing information and advice was appraised positively by 20% risk of febrile neutropenia, the primary prophylaxis with G-CSF is often
participants. However, we identified that fragmentation could occur due to necessary due to high comorbidity index, poor PS or extensive disease often
the diverse services involved in providing care with no single point of contact present in lung cancer patients. In case of FN, a risk-base approach provided
or co-ordination. Conclusion: Understanding the patient’s perspective of the by MASCC helps us to decide which patients need hospitalization and which
challenges associated with treatment, alongside their strategies for coping, can be treated by antimicrobial therapy at home (3). Oral mucositis and
provides insights for the services that can support patients undergoing diarrhea related to mucosal damage are frequent complications of Cht as
arduous treatments for mesothelioma. The study reveals ways to facilitate well as targeted therapy with TKIs that can significantly affect patient’s QoL
strategies to help patients manage the condition, as well as treatment side- and the ability to deliver full doses and complete therapy. Oral care protocols
effects. Interventions to reduce uncertainty have been identified as a priority are essential components in prevention and treatment of stomatitis, while
for service improvement. intensive local therapy protocols with antibiotics, anesthetics and/or
corticosteroids help to ameliorative symptoms (4). Diarrhea is quite common
Keywords: Radical surgery, Mesothelioma, patient experience, Qualitative
in lung cancer patients receiving Cht with an even higher occurrence in
research
patients treated with TKIs (5). It could be life threatening in elderly, fragile
patients and in patients with concurrent neutropenia, thus requiring a rapid
and effective control. When dietary strategy does not work, or when patients
present with severe grade 3/4 diarrhea pharmacologic intervention with
NU03: SUPPORTING PATIENTS RECEIVING TREATMENT
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 loperamide or even somatostatin analogues should be initiated quickly. Skin
changes (rash, dry skin, paronychia) are the most frequent AEs associated
with targeted therapy for lung cancer next to diarrhea. Even though, they
NU03.03 EHEALTH AND REMOTE PATIENT MONITORING AND are usually mild or moderate they hava negative impact on patient’s QoL
SUPPORTIVE CARE IN THORACIC ONCOLOGY and might lead to dose modifications or even discontinuation. Prophylactic
Roma Maguire measures with regular use of moisturizing products, sunshine protection and
School of Health Sciences, University of Surrey, Glasgow/United Kingdom careful skin hygiene are necessary. In case of severe but still localized changes
topical corticosteroids/antibiotics are indicated while a severe and prolonged
Lung cancer is the commonest cancer worldwide with 1.6 million people toxicity usually requires TKIs dose interruptions (6). Fatigue is a common
diagnosed each year. People with lung cancer experience a high level of symptom reported in up to 80% of LC patients. In most cases it is impossible
supportive care needs and many of these needs are unmet. Systematic to distinguish to what extend it is the adverse event of ST and to what of
supportive care is therefore vital in this patient group. Patient Reported disease. It is increasingly reported in patients receiving targeted therapy or
Outcome Measures (PROMs) can be used to identify the supportive care needs immunotherapy, and major improvements in recognition and treatment of
of people with lung cancer and the collection of PROMs data is reported to fatigue have been achieved recently (7). Immunotherapy with checkpoint
have a number of positive effects on patient outcomes. Enhancing the utility inhibitors (CPIs) represents a novel approach. By breaking of immune
of PROMs within clinical practice is the use of health technologies that have self-tolerance it might lead to autoimmune/inflammatory adverse events,
the ability to collect PROM data remotely from patients in their own homes designated as immune-related adverse events (irAEs), mainly including rash,
and send this information in ‘real time’ immediately to relevant health/social diarrhea, hepatitis and endocrinopathies (8). Although most of irAEs are of
care professionals for subsequent intervention. The Advanced Symptom low grade, some of them progress rapidly and prompt medical attention with
Management System is one of the most evolved remote patient monitoring treatment interruption and the administration of glucocorticoids is critical.
systems in cancer care. This presentation will initially focus on remote Implications for nursing Oncology nurses should have in-depth knowledge on
patient monitoring within the context of lung cancer before considering the adverse events of systemic therapy and must be familiar with the supportive
implications for the future and the ultimate vision of connected health for all. care protocols. Nursing interventions for prevention and treatment of
particular adverse events are presented in Table 1. Oncology nurses play a
Keywords: Technology, connected health, lung cancer, supportive care key role in continuous education of patients, their families and caregivers
on adverse events. They are valuable members of the multidisciplinary team
performing ongoing assessment of AEs and monitoring of patients and
actively discussing potential solutions and improvements with other team
NU03: SUPPORTING PATIENTS RECEIVING TREATMENT members, thus providing a high-quality patient-centered care.
NU03.04 SUPPORTIVE CARE IN PATIENTS RECEIVING SYSTEMIC

diagnosed with advanced non-small cell lung cancer (NSCLC) (either squamous
or non-squamous) have previously had limited treatment options. With the
emergence of new drugs, particularly in the immune-oncology setting, this
is now changing. Recent clinical trial evidence demonstrates that compared
with docetaxel, patients who received Nivolumab or Pembrolizamab had
better overall survival and also significantly fewer Grade 3-4 adverse events
(AEs). However the nursing experience of caring for lung cancer patients on
an immunotherapy remains quite limited. Up to recent times immunotherapy
drugs were limited to the clinical trial setting or early patient access schemes.
Often patients on clinical trials are managed and monitored by research
nurses which can further limit the experience for Lung Cancer Clinical Nurse
Specialists caring for patients on immunotherapy. The two main clinical
trials for immunotherapy in the UK were CHECKMATE (Nivolumab) and
KEYTRUDA (Pembrolizamab). The aim of this presentation is to look at two
patient case studies and review their experience of taking an immunotherapy.
The presentation will focus on how immunotherapy has impacted on their
lung cancer and also on their life. As part of the patient case studies there
will be a focus on the nursing role in supporting and caring for patients on
immunotherapy in a safe and effective manner. The presentation will examine
the main adverse event profiles of immunotherapy and how these differ to
chemotherapy. The presentation will open with a brief synopsis of the mode
of action of immunotherapy which is a 2 minute film. The main focus of the
presentation however, will be on the patient experience and the nurses’ role.
Currently in the UK there is a scarcity of information available to oncology
nurses on the nursing care of patients on immune-oncology treatments.
However, there are many transferable skills which can be utilised when caring
and supporting patients and their carers who either about to commence on
immune-oncology. According to Reiger (2003) oncology nurses have a better
opportunity than any other member of the healthcare team to develop the
required rapport for effective educational pre-treatment consultations with
both the patient and the carer. With regards to lung cancer clinical nurse
Keywords: Systemic therapy, supportive care, Nursing implications specialists this rapport is often developed from the point of meeting the
patient and carer at diagnosis and then supporting them through first line
treatment and beyond to follow up. Often oncology nurses will build a rapport
with patients when they attend to undergo treatment and are often a point
of contact for patients to report side effects to. Including the patient’s carer
SESSION NU04: MANAGING TOXICITY in pre-treatment consultations and at key points in the patient pathway is
TUESDAY, DECEMBER 6, 2016 - 14:30-15:45 very important. Often patients will be receive a lot of information about their
diagnosis and proposed treatment plans and this can be very overwhelming
(Malton 2002). Having the carer present means that they can ask questions
NU04.01 MANAGEMENT OF TOXICITIES ASSOCIATED WITH about treatment side effects, how long the intended benefit of the treatment
IMMUNOTHERAPY IN THE LUNG CANCER PATIENTS is and how the patient will be monitored during treatment. The pre-treatment
consultation should be undertaken separately to the consent to treatment
Michelle Turner
appointment to allow both the patient and the carer to digest information
Radiation Oncology, Maryland Proton Treatment Center Affiliated with the Marlene
and write down any questions about the treatment they may have. In the
& Stewart Greenebaum Cancer Center, Baltimore/MD/United States of America
current setting patient information for Nivolumab is under design meaning
Chronicity is a word that over the past few years has been utilized when there may be limited information available to give the patient. There are
talking about lung cancer treatments. From the developments of the TKIs in patient alert cards which patients can keep in their wallets which detail
the early 2000’s to the approval of immunotherapy for lung cancer in 2015, the main side effects of Nivolumab. However, it is also important the nurse
we are seeing that progression free survival and in some instances overall undertaking the pre-treatment consultation has a good understanding of
survival continues to be on the rise. So what does this mean for the medical Nivolumab, how it works and the potential side effects to monitor for so that
oncology community? Patients can be on therapies longer than a year and they can counsel the patient and their carer accordingly and be able to answer
sometimes for several years. We now as providers face the challenge of any questions they may have. A clear and concise approach should be used in
becoming experts in the management of long-term toxicity of these agents. the pre-treatment consultation with key communication skills of planning,
Side effects of the targeted and immunotherapy drugs are not as predictable preparation and delivering the message, listening and questioning skills
as their chemotherapy predecessors, and we are now dealing onset times should also be implemented (Wiffen 2007).References. Malton S (2012) How
ranging from days to years after beginning therapy. Immunotherapy drugs are to counsel cancer patients about their oral chemotherapy. Clinical Pharmacist
the newest treatment craze and rightfully so, as we have seen documented 12 4: 171 Wiffen P, Mitchell M, Snelling M, Stoner N (2007) Oxford Handbook of
month overall survival in both non-squamous and squamous cell carcinoma Clinical Pharmacy. 1st edn. Oxford University Press, Oxford Rieger P, Yarbro
for some of these agents and even up to 24 months for some patients. C (2003) Role of the oncology nurse. In: Cancer Medicine. 6th edn. Kufe DW,
Although this has brought optimism to both providers and patients alike, Pollock RE, Weichselbaum RR, eds. BC Decker, Hamilton
it has also brought forth a multitude of side effects that remind us that we
Keywords: Immunotherapy, patient experience, nursing care
are still novices in this field and necessitate the collaboration with our non-
oncologic colleagues as some of these side effects can be life-long. This lecture
will review the mechanism of action of the immunotherapy agents as well as
review those that are currently available for NSCLC with review of the data
NU04: MANAGING TOXICITY
leading to their approval and the current and potential future challenges that TUESDAY, DECEMBER 6, 2016 - 14:30-15:45
lie ahead.
Keywords: Chronicity, immunotherapy, lung cancer NU04.03 WHERE ARE WE WITH TKI TOXICITIES
Beth Eaby-Sandy
Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia/
PA/United States of America
NU04: MANAGING TOXICITY
Thoracic oncology nursing is now entering over 10 years of experience
with managing tyrosine kinase inhibitor (TKI) toxicities, most notably,
NU04.02 EXPERIENCE OF LUNG CANCER PATIENTS RECEIVING epidermal growth factor receptor (EGFR) inhibitor associated rash. The three
IMMUNOTHERAPY approved EGFR inhibitors used to treat non-small cell lung cancer (NSCLC)
are afatinib, erlotinib, and gefitinib. Most recently, the drug Osimertinib,
Rachel Thomas for EGFR mutation resistance known as T790M, has now been approved for
Palliative Care, Guy’s and St Thomas’ NHS Trust, London/United Kingdom use. Grading of the EGFRI rash has been difficult due to its inconsistency
in comparison to non-EGFRI rashes in the general medical community
With the emergence of immunotherapy in lung cancer, patients now have
and other oncologic rashes. Consensus guidelines for the management of
access to treatments that have the potential to improve prognosis. Patients
EGFR inhibitor associated rash have been produced and disseminated in The Hong Kong Polytechnic University, Kowloon/Hong Kong Prc, 3The Christies
the oncology community.1,2 There is a correlation between EGFRI rash and NHS Foundation, Manchester/United Kingdom, 4University Hospitals of South
overall survival in NSCLC patients, making it imperative to keep patients Manchester NHS Trust, Manchester/United Kingdom
with rash on the EGFRI therapy.3,4 It remains a challenge for oncology nurses
Lung cancer, the most common cause of cancer-related death in men and
to understand and manage this sometimes severe rash (see figure 1). Figure
women, is responsible for 1.3 million deaths worldwide annually. Lung cancer
1. Other cutaneous toxicities such as scalp rash, paronychia, hypertrichosis-
(LC) patients face many symptoms throughout the cancer trajectory and
namely trichomegaly (see figure 2), fissuring, pruritis, and xerosis have all
these often co-occur. Among the most prevalent (ranging from 21–90%),
been reported. The Multinational Association for the Supportive Care in
burdening and debilating symptoms that patients face is dyspnoea. Although
Cancer (MASCC) has produced recommendations for these toxicities as well.2
this symptom tends to become more frequent and persistent towards end-
While they are often a minor annoyance, they can sometimes also become
of-life, evidence show that even in early stage NSCLC patients who are most
severe and cause dose reductions and a significant impact on activities
likely to be cured may also be faced with debilitating dyspnoea that results
of daily living (ADL’s). Identification, prevention, and management are
in poor QOL during survivorship (Sarna et al 2008). Dyspnoea in the setting
important tasks for oncology nurses to master to allow patients to remain
of lung cancer has a complex aetiology that includes: direct involvement
on therapy. Figure 2. Other classes of TKI toxicities include the Anaplastic
of lung tissue by cancer, indirect respiratory complications related to the
Leukemia Kinase (ALK) inhibitors, where there are currently 3 drugs approved
cancer, treatment related complications (fibrosis secondary to chemotherapy
for use, alectinib, ceritinib, and crizotinib. Each of the ALK inhibitors carries
or radiation), respiratory co-morbidities (pulmonary embolism) and other
different yet important toxicities, ranging from nausea/vomiting, diarrhea,
co-morbid conditions (i.e. COPD)(Kvale et al 2007). Due to its complex
edema, bradycardia, pneumonitis, myalgias with elevated CPK levels, and
aetiology, dyspnoea also has a multimodal management strategy including
hepatotoxicity. Several other TKI’s are in development for potential use in
both pharmacological and non-pharmacological interventions (Kloke &
lung cancer, such as HER2 inhibitors, BRAF inhibitors, and drugs targeting
Cherny 2015). Pharmacological management options include bronchodilators,
pathways dealing with RET, MET and KRAS (see table 1).5-7
corticosteroids, anxiolytics, antidepressants, opiods and oxygen (Ferrell et
al 2011; Kloke & Cherny 2015). The non-pharmacological interventions include
4% NSCLC patient’s education on measures for ameliorating the symptom, such as
opening windows, using small ventilators, adequate positioning, respiratory
BRAF mutations Most common is V600E
training and relaxation techniques (Galbraith et al 2010; Molassiotis et al
Drugs in trials: dabrafenib, vemurafenib, dasatinib, 2015). A non-pharmacological intervention that has been widely used for
the management of respiratory symptoms in asthma and COPD but not
1-2% NSCLC lung cancer is Inspiratory Muscle Training (IMT). This method can reduce
dyspnoea mainly through two distinct ways. Firstly, by strengthening
RET Highly associated with young, never-smokers
the inspiratory muscles therefore lessening the effort during a given task
rearrangements
Drugs in trials: vandetanib, cabozantinib, sunitinib, (dyspnoea) and secondly by providing a means for controlled breathing. An
ponatinib improved inspiratory muscle strength and endurance can lead to the better
management of dyspnoea and therefore facilitate the increase in the level
MET Drugs in trials: crizotinib, tivantinib, onartuzumab, MET of activity and improving the quality of life for patients. Despite the wealth
amplification inhibitors of data on the effect of IMT on inspiratory muscle strength and endurance,
Drugs in trials: trastuzumab, afatinib, dacomitinib, exercise capacity, dyspnoea and quality of life for adults with COPD, there are
HER2 mutations no available data for lung cancer patients. Whilst the literature shows that
neratinib
COPD and lung cancer are correlated (Sekine et al 2012), this is not sufficient
25-30% NSCLC, most common mutation to advocate towards the use of IMT in lung cancer patients experiencing
KRAS mutations dyspnoea. Despite the scarcity of evidence, the fact that both COPD and lung
MEK, PI3K, FAK inhibitors
cancer patients face many common problems such as increased resistance
It is important for thoracic oncology nurses to have a firm understanding of to airflow, air trapping and hyperventilation of the lung , increases the
these drugs and their toxicities. Management strategies must be tailored to likelihood that IMT can also have a positive effect on lung cancer patients’
the patient’s symptoms and side effects, as well as to the specific drug and dyspnoea. Aim: This randomised study aimed to assess the feasibility and
dosage.References: 1. Burtness B, Anadkat M, Basti S, et al (2009). NCCN task effectiveness of inspiratory muscle training in patients with lung cancer
force report: management of dermatologic and other toxicities associated regarding their dyspnoea, psychological distress and quality of life. Design:
with EGFR inhibition in patients with cancer. JNCCN, 7(suppl 1):S5-S21. The trial is a two-arm, non-blinded, randomised controlled, proof-of-principle
Available at http://www.nccn.org/JNCCN/PDF/2009_Derm_Tox_TF.pdf study. Patients were randomly assigned to IMT or a control group. The IMT
2. Lacouture ME, Anadkat MJ, Bensadoun RJ, et al (2011). Clinical practice group received standard care and additionally included the intervention with
guidelines for the prevention and treatment of EGFR inhibitor-associated home follow-up every month for 3 months. Patients were recruited from the
dermatologic toxicities. Support Care Cancer, 19(8):1079-1095. DOI:10.1007/ outpatients’ clinics of two large cancer centres in the UK and one in Cyprus.
s00520-011-1197-6 3. Lee SM, Khan I, Upadhayay S, et al (2012). First-line Participants were eligible if they a) were adults with histological diagnosis
erlotinib in patients with advanced non-small-cell lung cancer unsuitable of primary LC or mesothelioma; b) had refractory dyspnoea not responding
for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 to current treatment for the past 2 weeks (breathlessness daily for 3 months
trial. Lancet Oncol, 13(11):1161-1170. DOI:10.1016/S1470=2045(12)70412-6 4. at rest or on minimal exertion where contributing causes have been treated
Liu H, Wu Y, Lv T, et al (2013). Skin rash could predict the response to EGFR maximally); c) expected prognosis of >3 months as judged by the clinicians
tyrosine kinase inhibitor and the prognosis for patients with non-small cell and d) had oxygen saturation above 85 % at rest. Patients were excluded if:
lung cancer: a systematic review and meta-analysis. PLOS One. DOI:10.1371/ they suffered from unstable COPD with frequent or acute exacerbations,
journal.pone.0055128 5. Cardarella S, Ogino A, Nishino M, et al. (2013). Clinical, had rapidly worsening dyspnoea requiring urgent medical intervention,
pathologic, and biologic features associated with BRAF mutations in non- they received palliative radiotherapy to the chest received within 4 weeks
small cell lung cancer. Clin Cancer Res. 2013; 19:4532-4540. 6. Tsuta K, Khono or chemotherapy within 2 weeks, they were experiencing intractable cough,
T, Yoshida A, et al. (2014). RET-rearranged non-small-cell lung carcinoma: a and those having unstable angina or clinically significant pleural effusion
clinicopathological and molecular analysis. Br J Cancer. 110:1571-1578. 7. Awad needing drainage. Intervention: A pressure threshold device was used to
MM, Oxnard GR, Jackman DM, et al. (2016). MET Exon 14 mutations in Non- deliver IMT, which controls a constant inspiratory pressure training load
small-cell lung cancer are associated with advanced age and stage dependent that is maintained unless the patient drastically alters his/her breathing
MET genomic amplification and c-MET overexpression. J Clin Oncol. 34(7):721- pattern. Based on the literature on COPD patients, the intervention protocol
30. included five sessions weekly for 12 weeks for 30 mins/day, divided over two
sessions (the actual intervention had duration of 3-5 min for each session
Keywords: TKI toxicities, EGFR rash and progressively the time was increased to 30mins/day). The IMT resistance
level was set to a low level (baseline) that allowed the patient to inhale
comfortably. Progressively, the resistance level was increased according to
the patient’s performance. Outcome measures: Outcome measures were
completed at baseline and monthly for 3 months, and included: physiological
SESSION NU05: SURVIVORSHIP parameters (FEV1,FVC); perceived severity of breathlessness using six
WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45 10-point NRS; modified Borg Scale; quality of life using the short form Chronic
Respiratory Disease Questionnaire; Hospital Anxiety and Depression Scale,
and safety. Results: The final sample included 46 patients (M=37, F=9) at a
mean age of 69.5 years old and a mean of 16 months post-diagnosis mainly
NU05.01 USE OF INSPIRATORY MUSCLE TRAINING IN MANAGING
with NSCLC and advanced disease (70%). Statistical and clinically important
DYSPNOEA IN LUNG CANCER PATIENTS
differences were seen with regard to distress from breathlessness (p=0.03),
Andreas Charalambous 1, Alexander Molassiotis2, Yvonne Summers3, Zoe ability to cope with breathlessness (p=0.01), satisfaction with breathlessness
Stamataki3, Paul Taylor4 management (p=0.001), fatigue (p=0.005), emotional function (p=0.011),
1
Nursing, Cyprus University of Technology, Limassol/Cyprus, 2 School of Nursing, breathlessness mastery (p=0.015) and depression (p=0.028). Changes were

more evident in the 3-month assessment where the effect of the intervention
came to its peak. Discussion: This trial showed that the IMT is feasible and
potentially effective in patients with lung cancer. A larger trial will provide
more concrete conclusions on the usefulness of IMT in the management of
dyspnoea in lung cancer patients with relatively stable disease, relatively
higher performance status and life expectancy of >3 months. However,
those patients with acute or severe dyspnoea should be treated according
to established protocols rather than IMT.References: Sarna L, Cooley ME,
Brown JK, Chernecky C, Elashoff D, Kotlerman J (2008). Symptom Severity 1 to
4 Months After Thoracotomy for Lung Cancer. Am J Crit Care; 17(5):455–467.
Simon ST, Müller-Busch C, Bausewein C (2011). Symptom management of
pain and breathlessness. Internist (Berl); 52: 28, 30–35. Galbraith S, Fagan
P, Perkins P et al (2010). Does the use of a handheld fan improve chronic
dyspnea? A randomized, controlled, crossover trial. J Pain Symptom Manage;
39: 831–838 Kloke M & N. Cherny N (2015). Treatment of dyspnoea in advanced
cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology 26
(Supplement 5): v169–v173, 2015 doi:10.1093/annonc/mdv306. Kvale PA,
Selecky PA, Prakash UB (2007). Palliative care in lung cancer: ACCP evidence-
based clinical practice guidelines (2nd edition) Chest; 132(3 Suppl):368S–403S
Ferrell B, Koczywas M, Grannis F, Harrington A. (2011) Palliative Care in Lung
Cancer. Surg Clin North Am. 91(2): 403–ix. Molassiotis A, Charalambous A,
Taylor P, Stamataki Z, Summers, Y (2015). The effect of resistance inspiratory
muscle training in the management of breathlessness in patients with
thoracic malignancies: a feasibility randomised trial. Support Care Cancer,
23:1637–1645.
Keywords: Inspiratory muscle training, Integrative medicine, lung cancer,

dyspnoea
recommendations7. At a national level, campaigns to raise public awareness of

PATIENT ADVOCACY SESSION the signs and symptoms of lung cancer can help promote earlier presentation
to primary care, whilst the adoption of lung cancer screening programmes
SESSION PA01: LUNG CANCER DIAGNOSIS AND CARE: IDEN- has the potential to reduce the number of lung cancer patients diagnosed
late. Lung cancer risk assessment and clinical decision support tools can
TIFYING AND IMPROVING COMMUNITY STANDARDS
assist the GP. System-based tools use patients’ current symptoms to provide
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 an indication as to who should be referred for further investigations, whilst
lung cancer risk prediction models identify high risk individuals without
symptoms for CT screening. These require further testing and validation, but
PA01.01 THE IMPORTANCE OF PATIENT ACCESS TO MOLECULAR if proven successful, should be available in primary care practices. Improving
TESTING AND NOVEL THERAPIES communication between primary and secondary care is critical. Direct
Janet Freeman-Daily telephone or email access between GPs and secondary care consultants
would speed discussion about high risk cases. Meanwhile GPs should be able
Lung Cancer Patient Advocacy, #lcsm Chat (Lcsm = Lung Cancer Social Media),
Federal Way/WA/United States of America to make direct referrals for CT scans for patients with suspected lung cancer
without the need for specialist authorization. Other innovative schemes
Advances in lung cancer diagnosis and treatment are enabling many have pioneered open-access patient self-referral for chest radiographs. The
metastatic cancer patients to live months or years longer than ever before. ED is often used as a safe and quick access point to secondary care, even for
Best practices in lung cancer detection, diagnosis, and treatment are changing those patients who do not require emergency medical care. Developing new
so fast that keeping current with new developments is difficult for many outpatient pathways can prevent EP by providing GPs with access to rapid-
healthcare providers-- more new drugs have been approved for lung cancer access clinics for patients with, for example, clinical suspicion of cancer but
in the past five years than in the previous five decades. While testing for who are too unwell to wait 2 weeks for an urgent outpatient appointment,
useful biomarkers such as EGFR, ALK and ROS1 is becoming more common, or those in whom the likely tumour type is not clear6. The Danish pathway
such tests are not yet standard procedure in many settings. Some patients for patients with serious but non-specific symptoms and signs of cancer is
who have limited tissue or who are interested in pursuing clinical trials might one of the pioneers in this area8 . To support the patient through their whole
benefit from liquid biopsies or next generation sequencing (NGS) panels, but journey and expedite the diagnostic process, a clinical nurse specialist (CNS)
such tests might not available to them for a variety of reasons: the healthcare should be available to all patients undergoing investigations for suspected
provider may be unfamiliar with the test or unconvinced of its merits, the lung cancer. Those who present via EP should be seen within 24 hours by a
facility may not have the technology or expertise to conduct the testing, CNS who then acts as their key worker. The patient should be registered on
or insurance may not cover the test. Even if the testing finds an actionable a timed, multi-disciplinary pathway, so that diagnosis is efficient and the
biomarker, patients may have difficulty obtaining novel therapies if those patient is afforded the same treatment opportunities as those presenting
therapies are not approved or covered by insurance, or they may have trouble via elective routes. Although there is not one solution to the problem of EP
identifying and accessing appropriate clinical trials. Some biomarkers, such as in lung cancer, and different approaches are needed for different health
PD-L1, are also less ‘definitive’ or standardized than others. This presentation systems, there are common themes by which survival can be improved by
discusses ways that patient access to molecular testing and novel therapies changing the system for this vulnerable patient group.References: 1. Elliss-
can not only improve lung cancer outcomes, but also help engage patients Brookes L, McPhail S, Ives A, et al. Routes to diagnosis for cancer - determining
as partners in their own care and accelerate research through patient-driven the patient journey using multiple routine data sets. British journal of cancer
data sharing. 2012;107(8):1220-6. doi: 10.1038/bjc.2012.408 2. Newsom-Davis T, Berardi
R, Cassidy N, et al. Emergency diagnosis of lung cancer: an international
Keywords: biomarkers, patient access, data sharing, novel therapies problem. American Society of Clinical Oncology Annual Meeting. Chicago,
2015. 3. Mitchell ED, Pickwell-Smith B, Macleod U. Risk factors for emergency
presentation with lung and colorectal cancers: a systematic review. BMJ Open
2015;5(4):e006965. doi: 10.1136/bmjopen-2014-006965 4. NHS England. High
PA01: LUNG CANCER DIAGNOSIS AND CARE: IDENTIFYING AND IMPROVING COMMUNITY quality care for all, now and for future generations: Transforming urgent and
STANDARDS emergency care services in England - Urgent and Emergency Care Review End
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 of Phase 1 Report: NHS England Leeds, 2013. 5. Forbes L, Sarafraz-Shekary N,
Kaushal A, Ramirez A-J, Hughes C, Newsom-Davis T. What explains diagnosis
PA01.02 THE ROUTE TO DIAGNOSIS: IMPACTING SURVIVAL BY of lung or bowel cancer as an emergency? 10th NCRI Annual Conference; 2014;
Liverpool. 6. Cancer Research UK: ACE Programme: Cancer Research UK; 2016
CHANGING THE SYSTEM
[Available from: http://www.cancerresearchuk.org/health-professional/
Thomas Newsom-Davis early-diagnosisactivities/ace-programme accessed May 2016. 7. Expert Lung
Chelsea and Westminster NHS Foundation Trust, London/United Kingdom Cancer Working Group. Tackling emergency presentation of lung cancer: An
expert working group report and recommendations. London: British Lung
A significant proportion of lung cancer patients are first diagnosed with their
Foundation, 2015. 8. Ingeman ML, Christensen MB, Bro F, et al. The Danish
disease as part of an emergency presentation (EP) to acute medical services.
cancer pathway for patients with serious non-specific symptoms and signs
EP includes patients attending the emergency department (ED), primary care
of cancer-a cross-sectional study of patient characteristics and cancer
referrals to acute services, and emergency admissions to secondary care. This
probability. BMC Cancer 2015;15:421. doi: 10.1186/s12885-015-1424-5
route to diagnosis is more common in lung cancer than other malignancies1.
Initial studies focused on the United Kingdom, where 40% of lung cancer Keywords: Emergency, Presentation, Routes, diagnosis
patients were found to present in this fashion1, but it occurs in all European
countries, with rates up to 52%2. Lung cancer patients presenting via EP tend
to be older, have lower socio-economic status and greater social deprivation,
display worse overall health, and have a lower performance status3. They are PA01: LUNG CANCER DIAGNOSIS AND CARE: IDENTIFYING AND IMPROVING COMMUNITY
more likely to present with advanced stage disease, and are less likely to have STANDARDS
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
surgery or other treatments with curative intent2. The emergency route to
diagnosis is associated with poorer patient experience and is a significant
additional burden on acute medical services4. Most importantly, EP lung PA01.03 ESTABLISHING A PARADIGM FOR HIGH QUALITY LUNG
cancer patients have poorer survival1: the risk of dying in the first month CANCER TREATMENT
post-diagnosis is four times higher for EP compared to non-EP patients2.
For the majority of lung cancer patients, there are opportunities for earlier David Leduc
diagnosis and prevention of EP5. Most have a relatively long history of Addario Lung Cancer Foundation, San Carlos/CA/United States of America
symptoms, often more than 12 weeks, and three-quarters have been to their
Due to the complexities of diagnosing and treating lung cancer, and the high
general practitioner (GP) with their symptoms, usually on several occasions.
mortality rate of the disease, lung cancer specialty care is more important
There is also a group of patients who delay consulting a doctor, and they are
than ever. Proper and timely diagnosis and development of a patient-specific
more likely to report barriers to presenting to healthcare services5. Novel
treatment plan can impact patient outcome and quality of life with vulnerable
methods of lung cancer diagnosis, focusing on symptom recognition, early
populations, such as those who are uninsured or who live in rural and remote
involvement of primary care and prompt assessment in secondary care, have
places, often not having access to the quality of care and multi-disciplinary
the potential to address this important problem. In the UK, the issue of late
approach to treatment found at leading academic institutions. This dynamic
diagnosis and EP of cancer is increasingly recognised in cancer strategies. A
results in vulnerable populations being diagnosed in later stages, with limited
number of innovative approaches have been brought together by the ACE
treatment options and poorer outcomes than those patients with access
(Accelerate, Coordinate and Evaluate) program, which aims to improve early
to quality multi-disciplinary care. The Addario Lung Cancer Foundation
diagnosis of cancer across a range of tumour types by learning from current
(ALCF) Community Hospital Centers of Excellence Program (COE) directly
best-practice and trialling new projects, many of which focus on lung cancer6.
addresses this need by partnering with community hospitals, where 80% of
These are now informing health policy. Prominent independent reports
cancer patients are treated, to deliver standard of care lung cancer screening,
have also addressed the EP of lung cancer, and have produced a series of

diagnosis and treatment. The COE program currently includes 13 hospitals is rare, nationally and internationally. In response to the need to improve
and serves thousands of patients each year in regions of high unmet need. national lung cancer services, Lung Foundation Australia (LFA) successfully
The program aims to improve the standard of care, patient experience secured funding through the Cancer Australia grant initiative “Supporting
and patient outcome by offering patients and caregivers the same type of people with cancer”. LFA directed these funds toward addressing challenges
multi-disciplinary and comprehensive care provided at leading academic identified by Cancer Australia within the lung cancer community through
centers. ALCF also provides lung cancer education and services to patients, the appointment of a Lung Cancer Nurse to provide support and information
caregivers and the community. The COE program helps to bridge the health- across all stages of a lung cancer patient’s experience – not only at diagnosis,
equity disparity and lung cancer information gap by establishing a standard but also as a consistent point of contact throughout an extremely stressful
of care (SOC) to improve health outcomes and quality of life through an and uncertain time. The service is intended to be an extension of existing
approach that is personalized, multi-disciplinary/-institutional, considers the health services, supporting both patient and carer throughout their
totality of each individual’s cancer, and is coordinated by an onsite Patient journey. The role of the LFA Lung cancer nurse has evolved with the launch
Navigator (PN) cognizant of the unique medical, economic, emotional, and of the National Lung Multidisciplinary Team (MDT) directory in June 2016.
cultural needs of their unique population. The COE approach embodies a This directory, currently representing 64 Lung MDTs, provides a detailed
support and engagement strategy that targets the patient, caregiver, family, understanding of the services each hospital can provide for a patient,
healthcare team, and community. The goals of the program are to: Improve from diagnostics through to various treatment modalities. These two key
outcomes, survival and quality of life for patients. Implementation of SOC initiatives - the Lung Cancer Nurse Service and National Lung MDT Directory
best practices enable a comprehensive and fully integrated multidisciplinary - service have become intertwined, supporting the needs of patients and,
team (MDT) of doctors (oncologist, pulmonologist, radiologist, pathologist, importantly, navigating them towards achieving the best level of care whilst
immuno-oncologist, etc.) that personalizes treatment based on each ensuring the patient, their family and carers feel supported, informed and
patient’s specific disease state. SOC includes: tumor board review; timely respected. The most significant aspect of the Lung Cancer Nurse Service is
biopsy; molecular testing; consideration for targeted and immunotherapies that of patient advocate, reflecting and representing the needs of patients
and access to clinical trials. Successful implementation of COE standards of nationally and, where appropriate, linking patients back into the health
care helps to improve patient outcome and quality of life. Provide on-site care system. Lung cancer specialist nurse roles are pivotal in representing
Patient/Nurse Navigator (PN/NN) to manage each patient’s cancer journey. patient needs within Lung MDT meetings as well as referring them into
Navigators build a trusted relationship with patients, families/caregivers, and community support services. However, with the development of the National
physicians to better ensure patient retention, engagement, and utilization Lung MDT directory it has become evident there are significant variations
of comprehensive specialty care and support services. Patient oversight among Lung MDT operations: including representation of the different
includes guidance on molecular testing to identify unique genetic profile of professional disciplines involved in caring for patients with lung cancer;
the individual’s cancer to determine the best first-line treatment and develop formal communication channels to primary care providers; and providing
a treatment strategy. The PN also provides support by connecting patients to patients with access to a dedicated Lung Cancer Support Nurse. For example,
all ALCF programs and helps address non-clinical challenges. The PN oversees data from the commencement of the Lung Cancer Nurse Service in July 2015
MDT coordination, data tracking, patient surveys, and other monitoring tools confirms that not every patient has access to a specialist Lung Cancer Nurse
to measure patient satisfaction, outcomes, and program success. Educate – currently the National Lung MDT directory has highlighted the existence of
and empower patients/families/caregivers. Education empowers patients/ 30 dedicated Lung Cancer Nurses nationally, which currently equates to one
caregivers to self-advocate and communicate with their physician team to specialised nurse per 400 patients diagnosed with lung cancer. Overall the
ensure access to the full breadth of treatment and care options including National Lung MDT Directory and Lung Cancer Nurse Service have become
access to new diagnostic technologies and tests, clinical trials, symptom a vital link in delivering efficient, up-to-date information for patients and
management & palliative care among other resources. Patients and providers carers seeking support and guidance. Ultimately the objective of the Lung
have access to ALCF’s free support programs: Patient Education Handbook, Cancer Nurse Service is to continue to address the principles of best practice
“Navigating Cancer 360° of Hope” (in English, Spanish, Chinese and hard management in lung cancer ensuring: the patient and carer feel supported,
copy, downloadable, mobile App); Patient Web Portal; and monthly Living informed and respected; all patients receive timely access to all components
Room Education/Support & Speaker Series available 24/7 Video Library (with of their care regardless of location: and patients have access to all relevant
Spanish and Chinese subtitles to ensure access to diverse populations). The treatment and supportive options and, importantly, have well-coordinated
COE program also provides patient educational materials and outreach to lung cancer care. This Service complements the support structures that are
help promote the program in the local community and drive awareness. Track already in place, so clinicians can continue to strive to ensure the needs of
program progress & metrics through database tools. A key element of the lung cancer patients can be addressed and increase much-needed support and
program is the ability to collect and analyze COE data and provide COEs with resources. The experience in establishing this new role within LFA, forming
access to de-identified patient/population data and reports and insights collaborations with national Lung Cancer MDTs and the measurable impact
that drives interventions and improved patient outcomes. Participating COE of the role on outcomes for lung cancer patients, will be presented in both
hospitals provide metrics that demonstrate adherence to the COE SOC and qualitative and quantitative terms.
to patient care and outcome. Metrics include: survival rates; quality of life
as defined by NCCN guidelines; time from diagnosis to treatment; patient Keywords: Lung cancer support nurse,Telephone support, Multidisciplinary
referrals to ALCF education/support services; and patient-specific data such Team Directory
as percentages with: an early diagnosis; who complete molecular testing; are
referred to clinical trials; and reviewed by tumor board. Insights derived from
this data help demonstrate progress toward patient survival, and delineate
outcomes by care facility, geography, treatment approach, and ethnic group. PA01: LUNG CANCER DIAGNOSIS AND CARE: IDENTIFYING AND IMPROVING COMMUNITY
STANDARDS
Data is used to benchmark against other COE sites as well as compared to MONDAY, DECEMBER 5, 2016 - 11:00-12:30
national data/statistics. ALCF conducts an annual review, sharing all findings
with ALCF partners and community hospital COE sites. The COE model has
already demonstrated proof of concept and positive impact on patient care PA01.05 LUNG CANCER MANAGEMENT IN TURKEY
and outcomes. Several sites are already reporting servicing patients at levels Seda Kansu1, Beril Koparal1, Lutfi Kirdar2, Hasan Batirel3, Rıza Çetingöz4,
above community hospitals reported in the National Cancer Database. The Ahmet Özet5
1
COE data collection and analytics tools will enable ALCF to demonstrate Pembe Hanım, Istanbul/Turkey, 2Training and Research Hospital Department of
impact on the screening, diagnosis, treatment and survival of lung cancer Oncology, Istanbul/Turkey, 3Department of Thoracic Surgery, Marmara University
patients. Further, as the COE program adheres to SOC and produces data, it Medical Facult, Istanbul/Turkey, 4 Medicine Turkish Lung Cancer Society, Istanbul/
is anticipated that more patients will be diagnosed at earlier stages when Turkey, 5Turkish Medical Oncology Society, Istanbul/Turkey
survival rates are highest; more patients will receive molecular and genetic
The incidence of cancer in Turkey is 267 and 186 in a hundred thousand in
testing steering them towards targeted and immunotherapies that improve
men and women respectively. Lung cancer is the number one cause of cancer
outcome; and clinical trial participation rates will go up.
death in men in Turkey and its incidence is increasing in women in recent years
Keywords: community, lung cancer, Multi-disciplinary, standard of care as well. It is the fifth common cause cancer after breast, colon, thyroid and
gynecologic malignancies in women in Turkey.The number of cancer cases
directly related with smoking is expected to be 31.000. The incidence of lung
cancer in men and women is 21.9 and 5.3 in a hundred thousand respectively.
PA01: LUNG CANCER DIAGNOSIS AND CARE: IDENTIFYING AND IMPROVING COMMUNITY Namely there are 50.000 lung cancer patients in Turkey. And each year a new
STANDARDS 30.000 patients are added to this number. Between 2009-2013,the incidence
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 of lung cancer among men has decreased from 56 to 51 in a hundred thousand.
However the number has increased from 16 to 18 in a hundred thousand
PA01.04 NURSE-LED LUNG CANCER SUPPORT SERVICE among women. This decrease among men is the positive result of effective
smoking cessation campaigns as the main cause of lung cancer in Turkey is
Claire Mulvihill
smoking. The second reason is air pollution in workplaces. Lung cancer is
Lung Cancer Network, Lung Foundation Australia, Brisbne/QLD/Australia diagnosed generally at late stages in Turkey as well as in the west, and more
than 50% of the patients present with metastatic disease at diagnosis.
The presence of a Lung Cancer Nurse within a dedicated Lung Foundation
Only minority, less than 20% present with localized disease and these cases of lung cancer will be diagnosed the USA in 20163 resulting in 158,080
cases are generally detected incidentally for other health reasons. Curative deaths or about 27% of all cancer deaths 20164. Ready access to effective and
surgery can be offered to only 15% of the patients. There is no effective comprehensive medical care at a reasonable cost is the key to our well-being.
prevention other than smoking cessation and screening which is becoming This is especially true for lung cancer. For lung cancer patients, access takes
more popular for certain risk groups in the west but it is not a proposed many forms, to include diagnosis, treatment and financial support for care
method actually in Turkey. Treatment decisions in high volume centers are and treatment. Regardless, for lung cancer patients, time is of the essence,
taken by multidisciplinary way including radiologists, pathologists, nuclear making quick, effective and affordable access to care critical.
medicine specialists, surgeons, medical and radiation oncologists. Surgery
is the primary treatment modality in early stages of disease, and lung cancer This discussion will focus on four areas that affect access to care for lung
surgeons are well experienced throughout the country being able perform all cancer be it at the diagnostic stage or the treatment and care stage:
sort of surgical techniques including robotic one with high success. Cancer
(1) Stigma: At the outset, the negative bias against lung cancer may weigh
chemotherapy and radiotherapy are well developed in the country with the
against early access to treatment5. 68% of advanced cancer patients who
availability of recent FDA approved targeted drugs and immunotherapeutic
have never received cancer care are lung cancer patients6. Cancer patients,
agents as well. Certain centers in Turkey are also included in multinational
healthcare professionals, caregivers and the general public are all equally
studies involving new agents in treatment of this disease. Radiation oncology
likely to have a negative bias toward lung cancer 7.
centers are equipped with high technology radiotherapy machines being able
to perform image guided intensity modulated radiotherapies and stereotactic (2) Timely diagnosis: The good news is that thanks to advances in technology,
radiotherapies in treatment of lung cancer. For the last years prevention early detection screening using spiral CT has been shown to reduce lung
programs in Turkey has increased. Two main actions for this are smoking cancer deaths by 16% to 20% ( in a defined population), compared to standard
cessation and fight against air pollution. The effectiveness of early diagnosis chest x-rays among adults8 . Yet, only 16% of people will be diagnosed in the
programs in lung cancer has not been proved. There has been an initiation of earliest stage, when the disease is most treatable9 and at best, early diagnosis
screening programs by low dose BT in high-risk patients. The diagnosis and is usually the serendipitous result of some other unrelated procedure. Aside
treatment of lung cancer is in line with global standards considering surgery, from the lack of public awareness that anyone with a set of lungs may be at
radiotherapy and chemotherapy. The global improvements in lung cancer is risk for lung cancer, there remains no standard effective diagnostic tool for
closely followed by oncologists and scientists in Turkey and rapidly integrated lung cancer. The development of affordable diagnostic tools using biomarkers
into clinical practice by means of prevention, diagnosis, treatment and follow- in airway epithelial cells, sputum, blood, breath, and urine for early diagnosis
up. However the patient care in terminal stage should be improved. The set and prediction of high risk individuals is critical.
up of Turkish Cancer Institute has been initiated and targets for 2023 are the
determination of molecular genetic targets for diagnosis and the treatment (3) Current and evolving treatment options: Once again, the good news
of lung cancer, the identification of cellular therapies and immunotherapy and is that treatment options for lung cancer patients are rapidly improving.
other targeted therapy modalities. In Turkey it is not possible to talk about In the last two years more treatments have been approved by the United
early diagnosis. But we can talk about early stage diagnosis. The rate of early States Food and Drug Administration (FDA) for the treatment of lung cancer
stage lung cancer patients in Turkey is less than 1/5. Unfortunately population than had been approved in the prior ten years. Most of the discoveries and
based screening programs for lung cancer has not been approved by Ministry associated clinical trials are happening at academic centers yet 80% of lung
of Health yet. With a screening program a tumor of 1 cm can be diagnosed. cancer patients are treated at their local community hospital. New and life
However a patient with symptoms being diagnosed has a tumor of 3 cm and savings treatments along with clinical trials are happening so quickly that
the rate of cure between these patients is really different. 5 year survival for it is sometimes challenging for these advancements to reach the treating
a patient with a tumor of 1 cm is 100% and a patient with a tumor of 3cm is 65- physician thereby limiting ready access of these new treatments to the
70%. Under screening programs for high- risk patients, the risk of death from patient.
lung cancer decreases 20%. On the patient organization side Pembe Hanım
Association has made the first attempt in Turkey to raise awareness in the (4) Cost of treatment and care: The Patient Protection and Affordable Care
public for lung cancer. For four years a Project called “MegaLung” has reached Act (PPACA), commonly called the Affordable Care Act (ACA) or Obamacare,
many people talking about the prevention, diagnosis and treatment of lung is a United States federal statute signed into law by President Barack Obama
cancer. This was the first and only project about lung cancer. “MegaLung” on March 23, 2010. In April 2016, Gallup reported that the percentage of
had its place in many organizations open to public to reach as many people adults who were uninsured dropped from 18% in the third quarter of 2013
as possible as lung cancer is a wide range cancer and it has a preventable to 11% in the first quarter of 2016. Although individual insurance coverage
cause namely smoking. At the moment with the collaboration of members has improved, the rapid pace of discovery and FDA approval of treatments,
of Pembe Hanım Association, mainly Seda Kansu and Turkish Lung Cancer insurance payors and federal medical care assistance programs have
Society, a patient organization for lung cancer called “Nefes (Breath)” is not necessarily kept pace with these advancements in both testing and
being set up with the aim of raising awareness among public and lung cancer treatments by not providing insurance coverage, leaving lung cancer patients
patients about the all the issues related with lung cancer. * As Pembe Hanım without the financial ability to pay for needed care. Various organizations
Cancer Patients Society we would like to thank Turkish Society of Medical such as ESMO, ASCO, ICER and others are attempting to compare drug prices
Oncology,Turkish Lung Cancer Society, Dr Lutfi Kirdar Kartal Training and to overall patient benefit through programed algorithms in order to assist
Research Hospital Department of Oncology and Marmara University Medical payors and patients in treatment decision making. These are often long and
FacultyDepartment of Thoracic Surgery for their valuable support. Seda laborious projects which may be out of date by the time the recommendations
Kansu IASLC Patient Advocates Committee MemberReferences are published, and impede quick access to treatment and care Patients and
patient advocates are in a strategically advantageous position to affect
Pembe Hanım Cancer Patients Society change in these four areas in order to provide greater access to care for all
lung cancer patients. 1 http://www.medicalnewstoday.com/articles/282929.
Turkish Society of Medical Oncology php#top_10_leading_causes_of_death_in_more_detail
Turkish Lung Cancer Society 2 http://www.cancer.org/acs/groups/content/@editorial/documents/
document/acspc-044552.pdf
Dr Lutfi Kirdar Kartal Training and Research Hospital Department of Oncology
3 American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American
Marmara University Medical FacultyDepartment of Thoracic Surgery
Cancer Society; 2016.
4 http://www.cancer.org/acs/groups/content/@editorial/documents/
SESSION PA02: ACCESS TO CARE - 5 LoConte NK, Else-Quest NM, Eickhoff J, Hyde J, Schiller JH. Assessment of
EQUAL CHANCES IN THE WORLD? Guilt and Shame in Patients With Non-Small-Cell Lung Cancer Compared With
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 Patients With Breast and Prostate Cancer. Clinical Lung Cancer. 2008;9(3):171-
8.
6 http://thelungcancerproject.org/#need-for-change
PA02.01 ACCESS TO CARE: USA
Kim Norris 7 http://thelungcancerproject.org/#need-for-change
President, Lung Cancer Foundation of America, Marina Del Rey/CA/United States 8 http://www.cancer.org/acs/groups/content/@editorial/documents/
of America
In the United States of America (USA), the public is dangerously uninformed 9 http://seer.cancer.gov/statfacts/html/lungb.html
about lung cancer, our nation’s second leading cause of death behind heart
disease1. Lung cancer accounts for more deaths than any other cancer2; more Keywords: Early Detection, patient advocacy, Cost of Care, stigma
than breast, prostate and colon cancer combined! An estimated 220,000 new

PA02: ACCESS TO CARE - EQUAL CHANCES IN THE WORLD? clear and concise guide, the “Lung Cancer Patient Pathway”, for patients
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
with a confirmed lung cancer diagnosis. The guide is available as a printed
resource and online resource supported by a micro-site on Lung Foundation
PA02.03 ACCESS TO CARE: MALAYSIA Australia’s website and the Lung Cancer Network Australia website and has
been distributed to the majority of dedicated lung cancer treatment centers
Christina Van Tze Ng
around Australia. Project aims: The main aim of producing the Lung Cancer
The Cancer Advocacy Society of Malaysia, Petaling Jaya/Malaysia
Patient Pathway (LCPP) was to provide newly diagnosed patients with a “one
The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health stop” resource that outlines the clinical referral pathways and details the full
England reported the assessment of factors affecting 30-days mortality in range of treatment options and supportive care services available to them
national patient population. Although, the report was impressive, only 3% of throughout their lung cancer journey.
lung cancer patient treated with curative intent died within 30 days of The LCPP also aims to improve patient health literacy and empower patients
starting chemotherapy and 10% for palliative treatment. There was a vast with access to evidence based information to support informed decision
disparity among some hospitals. This concluded that clinical decision making making and treatment choices, self- management and ultimately, to improve
in can certainly impact on cancer mortality(Wallington et al., 2016). In the patient outcomes. Project Synergies: The LCPP was launched in conjunction
similar context, clinical decision making in Malaysia and the South East Asia with the launch of the Lung Foundation’s Australian Lung Cancer Multi-
(SEA) are hugely influenced by the affordability factor which can directly Disciplinary Team Directory http://lungfoundation.com.au/mdt/. This national
influence mortality rates. The clear evidence is seen in Globocan 2012 data. directory lists the current (64) dedicated lung cancer multidisciplinary (MDT)
SEA despite having the lowest prevalence for all cancers combined has a services around Australia. It is intended to facilitate referrals of patients
highest mortality to incidences ratio when compare with countries which to hospitals delivering MDT-based lung cancer management. The creation
have universal health coverage with better access to innovative care. of this national directory has forged closer relationships between the Lung
Foundation and dedicated lung cancer multidisciplinary (MDT) services and
provided a mechanism to be able to reach patients at time of diagnosis. Lung
Foundation has previously struggled to reach patients early in their cancer
journey. Strengthening these relationships with Lung MDT services has led
to a systematic distribution of Lung Foundation patient kits including the
LCPP info-graph. The Cancer Nurses Society of Australia Winter Congress in
May 2016 and Australian Lung Cancer Conference in August 2016 presented
opportunities to distribute the printed LCPP in conference delegate bags
and at trade exhibitions to more than 550 cancer clinicians and nurses.
Sustainability: The Lung Foundation will implement the following strategies
to ensure the sustainability of this project: · Info-graph will be trialed in
Lung Cancer MDTs around Australia · Info-graph will form part of the Lung
To understand why the clinical decision making in Malaysia or the SEA region
Cancer Consultative Groups activities · A minimum review period of two
is hugely influenced by the affordability factor we must first dive in the
years for info-graph and website content · Annual budget allocation for
health-care systems in southeast Asia (SEA). There is an enormous social,
ongoing promotion and dissemination Conclusion: The Lung Cancer Patient
economic and political diversity within and across the countries in SEA which
Pathway project has produced a patient centered resource to empower newly
is formed by its history, geography and position as a major trade route. All
diagnosed patients with current, evidence based information so that they can
these have had contributed not only to the diverse population but also to the
make informed decisions on treatment options and supportive care services
wide-ranging nature of its health systems which are at varying stages. This
and access the right treatment and care at the right time. This project was
highly diverse health-care system, range from dominant tax-based financing
managed by Glenda Colburn, Director, Lung Cancer National Program, Lung
to social insurance and high out-of-pocket payments across the regions. For
Foundation Australia. The Lung Cancer patient pathway was made possible
example, The World Health Report 2006 estimated that the total private
via unrestricted education grants. Principal sponsor: Bristol-Myers Squibb
finance sources account for 41.8% of total health expenditure in Malaysia
Supporting Sponsors: AstraZenea, Boehringer Ingelheim, Cancer Australia,
which is likely affect the equity of financing because private health payments
Pfizer, Maurice Blackburn Lawyers, MSD.
might impose disproportionate financial burden on households (“WHO | The
World Health Report 2006 - working together for health,” 2013). A subsequent Keywords: Pathway, patient, lung cancer, Access
analysis showed private health expenditure has dominant role in financing
healthcare in five of the seven countries in the SEA, contributing more than
70% of the total spending on health in Laos and Cambodia. This urge for
health-financing reform and there are multiple model which are considered by PA02: ACCESS TO CARE - EQUAL CHANCES IN THE WORLD?
varies government. Among them are financial protections through payroll- MONDAY, DECEMBER 5, 2016 - 16:00-17:30
financed social health insurance or tax-funded arrangements for formal
employment. However, this approach still challenges the informal and the rest
PA02.06 ACCESS TO CARE: ISRAEL
of the population with countries such as the Philippines and
Vietnam(Tangcharoensathien et al., 2011) A reformed health-financing with Shani Shilo
universal coverage will not only decrease the Lung cancer mortality as seen in The Israel Lung Cancer Foundation, Rehovot/Israel
the developed countries but also hugely impact daily clinical practice and
The defining characteristic of the health system in Israel is its governance by
increase quality of services provided to the patients. Bibliography. Globocan.
the National Health Insurance Law (1995). This law ensures health coverage to
(2012). Fact Sheets by Cancer. Retrieved October 14, 2016, from http://
every resident of Israel and defines the government’s responsibility to provide
globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Tangcharoensathien, V.,
health services to every person without discrimination. In other words, health
Patcharanarumol, W., Ir, P., Aljunid, S. M., Mukti, A. G., Akkhavong, K., …
insurance is mandatory, and all residents of Israel must be insured. Citizens
Wagstaff, A. (2011). Healthfinancing reforms in southeast Asia: challenges in
pay a healthcare tax – 4.8% of income. Private Health Services Patients have
achieving universal coverage. The Lancet, 377(9768), 863873. http://doi.
the option of seeking private medical care from a physician of their choice,
org/10.1016/S01406736(10)618909 Wallington, M., Saxon, E. B., Bomb, M.,
and at their own expense. There are four health funds, where each fund has
Smittenaar, R., Wickenden, M., McPhail, S., … Dodwell, D. (2016). 30-day
branches throughout the country and provide its members with all mandated
mortality after systemic anticancer treatment for breast and lung cancer in
services. The Basket of Health Services, consists of a range of essential
England: a population-based, observational study. The Lancet Oncology, 17(9),
medical services, including treatments, medications, and equipment which
1203–1216. http://doi.org/10.1016/S1470-2045(16)30383-7 WHO | The World
each health fund is obligated to provide to its members. Its contents are
Health Report 2006 - working together for health. (2013). WHO.
defined by law, but are subject to periodic revision. Therefore, a treatment
Keywords: Access, advocacy, patient, Malaysia or medication that was covered at one point may be discontinued, or new
items may be added. Every end of a year, new treatments and technologies
are submitted to be included to the new health basket. First the physicians
rate the proposed new treatments and technologies, then the top ones enter
PA02: ACCESS TO CARE - EQUAL CHANCES IN THE WORLD? the basket debate, where eventually only some every year enter the health
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 system. In the past years new treatments and technologies could be added
until the sum of 300 million NIS, that equals, 80 million dollars. This year the
basket fund was increased to 146 million dollars. The problem is that there are
PA02.05 ACCESS TO CARE: AUSTRALIA
many new treatments and that the oncology rating is among all oncological
Kerrie Callaghan1, Glenda Colburn2 diseases. Last year, four new lung cancer drugs were proposed to the health
1
National Lung Cancer Program, Lung Foundation Australia, Brisbane/Australia, basket. The Israel Lung Cancer Foundation, advocated in the Israeli Kneset
2
Lung Cancer National Program, Lung Foundation Australia, Brisbane/Australia (house of parliament), attended meetings, raised awerness in digital and
written media. Eventually 3 new lung cancer drugs were approved including
In June 2016, Lung Foundation Australia launched an evidence-based,
OPDIVO, TAGRISSO and ALECTINIB. This end of year, KYTRUDA and OPDIVO
for larger indications were submitted in addition to foundation 1 diagnosis 20 locations and peer-to-peer counselling in two Info centres. The lung cancer
test. This year, the foundation submitted to the health basket the lung cancer patients are entering the programme alongside the other cancer patients.
screening test, LDCT to be included for population at risk. Clinical studies take The peer-to-peer support programme has developed the system of regular
place in Israel, although as a very small country with only 8 million people, the supervisions, initial education, the study material aimed at volunteers and the
number of clinical trials is not large. Companionate programs exist as well. network of self-help groups spread over the Slovenia. The research analysing
Overall, Israel has a very good health system with good access to targeted peer-to-peer support showed clear benefits for the patients1,2. Since 2014,
therapy and immunotherapy. Drugs for mutations such as ALK and EGFR are the Lung Cancer Support Division is organised in the framework of CPAS. Its
approved including immunotherapy for NSCLC. main aim is the development of the programmes for lung cancer patients and
their relatives. In Slovenia, with roughly 2 million inhabitants, there are some
Keywords: Health system, Access, funds, services 1230 new lung cancer patients every year, and 1100 deaths due to lung cancer3.
Patients with lung cancer are treated in four oncological centres (Institute
of Oncology Ljubljana, University Clinic Golnik, University Medical Centres
Ljubljana and Maribor). Among the burdens, all cancer patients are carrying,
such as confronting its own vulnerability, mortality, coping with the hardships
SESSION PA03: PATIENT SUPPORT AND INVOLVEMENT of treatment, psychic distress often combined with the fear of recurrence,
IN RESEARCH lack of social support and changes in financial situation, some are disease
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 specific. The burdens lung cancer patients are experiencing are connected
with the poor prognosis, poorer quality of life and greater symptom
management needs. These are due to physical troubles, social presentation
PA03.01 ESTABLISHING A CENTRAL EUROPEAN LUNG CANCER of lung cancer as death sentence, sense of guilt and stigmatisation, but are
also due to the need of information regarding new treatments available4–6.
PATIENT NETWORK
To be able to react on the specific lung cancer patient’s needs, we have
Franz Buchberger within the Lung Cancer Support Division supplemented volunteer self-help
Lungenkrebsforum Austria, HImberg/Austria programme »On the way to recovery« with the programme »How to live with
lung cancer« 7. How to live with lung cancer is a one-day programme, which
Background: Patient Advocacy Groups (PAG) can improve the situation of lung
is being implemented in various also smaller places and medical institutions
cancer patients by participation as stake-holders in decision processes, by
throughout the Slovenia. It is aimed at lung cancer patients, their relatives
building awareness for the disease and by lobbying at politicians.
and also health providers. The programme is carried out through recognized
As a matter of fact there are existing European patient advocacy networks consultants working with lung cancer (surgeons, medical oncologists,
for different kinds of cancer, e. g. breast cancer, prostate cancer etc. working radiation oncologists, physiotherapists, nurses and clinical psychologists
strongly and successfully together in e. g. building awareness for these from the medical institutions treating lung cancer). Methods: All participants
diseases.Although lung cancer is one of the most common types of cancer in the programme were given a specific designed evaluation questionnaire.
worldwide there is a lack in patient advocacy groups created by a shorter live We present an evaluation from the program participants in the year 2016.
time of lung cancer patients compaired with other patients. We analysed the participants’ responses and the evaluation will be used in
further program development. Results: The participants are being highly
While there are national LC patient advocacy groups in almost every country satisfied by the programme as whole and also with the individual sets of
of Western Europe they are very rare in Eastern European countries and lectures. They are highly appraising the help our programme is providing
consequently need special attention. Methods:This project was motivated in understanding the health situation, communication with the health
by the break-out session during the “Central European Initiative Against professionals and in understanding coping processes. The programmes main
Lung Cancer” in 2014. The main requests resulting from the expert discussion goal is to inform participants on the lung cancer diagnostics, treatment and
included that lung cancer patients need to speak up and international PAGs the rehabilitation possibilities. This information is given by the relevant
should be connected with each other.The Austrian LC patient advocacy group, professional. There is a special emphasis on the new and more efficient
Lungenkrebsforum-Austria, initiated the Central European Lung Cancer treatment possibilities. The programme presents in depth the ways and the
Patient Network and started with the first steering committee meeting in means for the optimal coping with the disease and its treatment and also the
July 2014. Medical experts from Austria, Czech Republic, Hungary, Slovakia advices for the living with the disease. We are widening the importance of
and Slovenia determined the aims of CELCAPANET with promotion and comprehensive patient treatment, informing on psycho social considerations,
support of PAG establishment, providing a network for PAG within Central possibilities on entering the CPAS programmes (and also related programmes
Europe and empowering patients.Challenged by the fact that all potential that are offered locally), we are informing on benefits of early inclusion
patient organizations had to be contacted and encouraged to participate in the palliative care thus busting the myths regarding the palliative care.
in the newly formed project the first patient advocacy meeting was held Except for presenting information, the programme’s goal is also the social
in November 2014 with particpating general oncological PAG from Croatia, support for lung cancer patients, as a large amount of the time is set by
Hungary, Poland, Slovakia and Slovenia. One of the main outcomes of this for the talk and the exchange of experiences among the participants. The
meeting and discussion was that it is necessary to offer information online inclusion of different professions into the comprehensive care of cancer
not just in English but in different Eastern European languages in order to patients due to the patients’ needs is being represented on the symbolic
encourage patients to establish a PAG for lung cancer. As a consequence the level with the joint presentation, where the presenters are alternating thus
website is now available in 12 different languages.In order to find out what rounding up the “story” of treatment and rehabilitation. Incorporated in
PAG in Eastern Europe need most the participants were asked for topics they this programme is also a chance for the patients and their relatives to have
are interested in. Results: Till 2016 the number of paricipants is constantly an individual conversation with the medical professionals regarding their
growing with PAG from Israel, Latvia, Lithuania and Romania and expert treatment and dilemmas. While the programme is being primarily aimed
lectures about lobbying, social media for PAG, the system of patient advocacy at the patients and their relatives, the local medical professionals are also
in Austria, Biosimilars - what patient groups need to know were held. invited. This beside the information point of view gives them also a chance
to interact with the presenters and an opportunity to discuss with them
Conclusions: CELCAPANET offering lectures for patient groups and a forum to their questions and dilemmas. Through this we are trying to ensure the
work together and share national activities identfies the inequalities in access equal availability of treatment and to approach the people with medical and
to diagnosis and treatment and bridges PAG on an European level in order to psycho social support. Conclusions: With this programme we are following
improve the situation of every single lung cancer patient. all three fields where the peer support programmes have been found to be
beneficial to patient. Namely, their informational needs about the cancer
and its treatment, management of emotional distress and finally the
facilitation of empowerment 1,2. REFERENCE: 1. Meyer A, Coroiu A, Korner
PA03: PATIENT SUPPORT AND INVOLVEMENT IN RESEARCH A. One-to-one peer support in cancer care: a review of scholarship published
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 between 2007 and 2014. Eur J Cancer Care (Engl). 2015;24(3):299-312. 2.
Campbell HS, Phaneuf MR, Deane K. Cancer peer support programs-do they
work? Patient Educ Couns. 2004;55(1):3-15. 3. Studio N. Rak v Sloveniji 2012
PA03.03 HOW TO LIVE WITH LUNG CANCER? THE SLOVENIAN LUNG
Cancer in Slovenia EPIDEMIOLOGIJA IN REGISTER RAKA EPIDEMIOLOGY AND
CANCER PATIENT SUPPORT CANCER REGISTRY. 2016. 4. Missel M, Pedersen JH, Hendriksen C, Tewes M,
Andreja Cirila Škufca Smrdel Adamsen L. Diagnosis as the First Critical Point in the Treatment Trajectory:
1
Dept. of Psycho-Oncology, Institute of Oncology Ljubljana, 2Cancer Patients’ An Exploration of Operable Lung Cancer Patients’ Lived Experiences. Cancer
Association of Slovenia, Ljubljana/Slovenia Nurs. 2015;38(6):E12-21. 5. Pujol J-L, Mérel J-P, Roth C. How preconceptions
about lung cancer treatment interact with medical discourse for patients
Background: Cancer Patient’s Association of Slovenia (CPAS) is a non- who accept chemotherapy? Psychooncology. July 2016. [Epub ahead of print]
governmental organisation, connecting the patients with all cancer types as 6. Pozo CLP, Morgan MAA, Gray JE. Survivorship issues for patients with lung
well as their relatives and health professionals. The central programme that is cancer. Cancer Control. 2014;21(1):40-50. Available at: http://www.ncbi.nlm.
being offered to patients by CPAS for more than three decades is an organized nih.gov/pubmed/24357740. Accessed August 21, 2016. 7. Čufer T., Simonič A.,
self-help »On the way to recovery«, that offers support in self-help groups on

Koren P., Crnjac A, Računica K., Rajer M., Kovač V, Škufca Smrdel A. C. VPM. involvement all along the medicine’s evaluation lifecycle:
KAKO ZIVETI Z RAKOM_za splet-film. 2015. Available at: https://drive.google.
com/file/d/0ByMyk7OmgaDSVzR3ME1vZzltbVU/view. Accessed Sept 20, 2016
Keywords: patient support, non-governmental patient organization, lung

cancer
PA03: PATIENT SUPPORT AND INVOLVEMENT IN RESEARCH

PA03.04 PATIENT INVOLVEMENT IN THE EVALUATION OF CANCER

MEDICINES: THE EMA EXPERIENCE
Nathalie Bere
European Medicines Agency, London/United Kingdom
The European Medicines Agency (EMA) is the authority which evaluates and EMA continually looks to further enhance its methods for gathering patient
monitors medicines across all EU Member States. Pharmaceutical companies knowledge and preferences at each stage of the process and is investigating
wishing to market a new cancer medicine in Europe are obliged to apply for a the use of additional tools to complement those already in-house. Surveys are
licence through the EMA. With a remit to ensure that European citizens are regularly used to elicit feedback from both regulators and patients/
provided with safe and effective medicines, the EMA realised early on that consumers on their involvement, its added value to the process and identify
patients’ experience with their disease and its treatment is a fundamental areas for potential improvement. There are inevitably challenges to overcome,
parameter to include within the evaluation of medicines. The Agency’s for example finding suitable patients (e.g. language barrier, availability),
engagement with these stakeholders has been a progressive journey whereby ensuring tailored support to facilitate and enhance participation, providing a
a steady increase in the numbers involved (76 in 2007 to 740 during 2015) has clear definition of the patient role, addressing issues around confidentiality
been coupled with a diversification of methodologies ensuring opportunities and representation and also how to measure the impact/value of the input.
all along the medicines lifecycle. Learning from experience has also been Evidence, including testimonies and concrete examples, has demonstrated
paramount to ensure that the interaction is mutually beneficial and is carried that ultimately patient/consumer input:
out in the most optimal manner possible. Key milestones of EMA interaction
Brings the everyday aspects of living with a disease into the scientific
with patients and consumers:
discussions;
Improves the quality of patient information and communication on

medicines;
Increases the dissemination of EMA outcomes.
Today patients and consumers are a valued and integral part of the work
at the EMA and their perspectives are considered an essential element
for increasing transparency in the regulatory process and ensuring more
meaningful decisions for all concerned.
Keywords: patient engagement
The “framework of interaction” adopted by the EMA management board in SESSION PA04: FOCUS ON ADVOCACY AND COMMUNI-
2005 provides the formal basis for involving patients and consumers in CATION: JOINT IASLC/ GLOBAL LUNG CANCER COALITION
Agency activities and relies on five critical elements: SESSION (GLCC)
A network of European patients and consumers organisations
A forum of exchange: EMA Working Party with Patients and Consumers’

organisations PA04.01 A REALISTIC GOAL? ACHIEVING A TOBACCO FREE IRELAND
BY 2025
A pool of patients acting as experts in their disease and its management
Donal Buggy
Interaction with the EU Regulatory Network Head of Services & Advocacy, Irish Cancer Society, Dublin/Ireland
Capacity-building focusing on training and raising awareness about EU Introduction: Ireland has a proud record of leadership in the field of tobacco
regulatory system control. It was the first country in the world to introduce a Workplace
Smoking Ban in 2013 and the first country in Europe to announce its
Today patients and consumers are systematically involved in a wide range of intention to introduce plain packaging for cigarettes. In 2013 Ireland set a
EMA activities: target date to achieve a tobacco free society with a targeted adult tobacco
use prevalence of under 5%. Other countries to formally adopt a target for
Members of EMA Management Board and scientific committees
tobacco free societies include Finland 2040, New Zealand 2025, and Scotland
Members of the EMA ‘Patients and Consumers Working Party’ 2034. Tobacco Free Ireland1 is a new tobacco policy for Ireland coming more
than a decade after the publication of the previous national policy Towards
Scientific advice procedures during medicines development; a Tobacco Free Society 2. It is a timely successor because of the emerging
non-communicable disease burden which is caused by risk factors that can
Discussions on benefit/risk evaluations; be prevented. Tobacco is well known as a major contributor to ill-health and
Review of information (e.g. package leaflet, safety communication); premature mortality. It is responsible for more than a third of all cancers. For
the first time, we have a target date for Ireland to be tobacco free of 2025. The
Topic groups and workshops question is whether this target is in any way realistic.
The Agency works with a large network of organisations and individuals; Discussion: Tobacco Free Ireland addresses a range of tobacco control issues
organisations can register with the Agency and if they meet certain eligibility and initiatives and contains over 60 recommendations. A high level action
criteria they are then listed on the EMA website (EMA website). Individuals plan, was drawn up in consultation with those who will lead out on the
are also encouraged to register to be included in the EMA “individual experts’ recommendations which outlines the responsibilities, actions necessary
stakeholder database” (registration form); they then receive targeted and timelines for the implementation of the recommendations. The
information and can be contacted for involvement in EMA activities. Patients recommendations to support Ireland becoming a tobacco free Society are
usually participate in person or via written procedure and are involved as categorised under:
either representatives of their organisation or as individual experts,
depending on the nature of the activity. There are opportunities for Protection of children and denormalisation of tobacco use
Legislative compliance and regulating the retail environment programmes in lung cancer. The authors’ research institutes were used to
identify which country or countries had contributed to that paper. The study
Protect people from tobacco use also analysed whether research outputs had changed over time as well as the
focus of the research and how close the research is to patients. The
Offer help to quit tobacco use
methodology allows total number of papers, type, and research
Warn about the dangers of tobacco collaborations to be analysed over time. Results: The bibliometric review is a
comprehensive and powerful resource allowing lung cancer patients,
Enforcement of bans on tobacco advertising, promotion and sponsorship clinicians and policymakers to examine their national lung cancer research
output and compare it with that of other countries. The 24 countries
Raising taxation on tobacco products responsible for the majority of lung cancer research activity are: Australia,
Austria, Belgium, Brazil, Canada, China (People’s Republic of), Denmark,
National and International Partnerships
France, Germany, Greece, India, Italy, Japan, Netherlands, Norway, Poland,
For the first time in policy we see a commitment to substantially address Taiwan, Turkey, South Korea, Spain, Sweden, Switzerland, United Kingdom,
supply side issues through introduction of levies such as an environmental and the USA (figure 1).
waste levy and an industry profitability levy ring fencing income to
address health promotion, cessation supports and illegal trade initiatives.
The document fails to substantially address the inequality inherent in
smoking patterns. In Ireland the bottom decile, at 35% prevalence, is more
than twice as likely to smoke as the top decile at 16%. Specific deprived
population targeted programmes such as the Irish Cancer Societies ‘We Can
Quit’ programme, which challenges intergenerational smoking, have been
successful and need to be funded and enhanced if a Tobacco Free Society is
to be achieved. Conclusion: Current adult smoking rates of 19.5%3 suggest
Ireland has some significant way to go towards achieving its target. Recent
youth smoking rates of 13% 4 for 15-17 year olds and 8%5 for 10-17 year olds
suggests significant progress in reducing the uptake of smoking. Major
investment is required to support increased quit attempts and increased
success from quit attempts if the target of a Tobacco Free Ireland by 2025 is to
be achieved.
References: 1. http://health.gov.ie/wp-content/uploads/2014/03/
TobaccoFreeIreland.pdf
2. http://health.gov.ie/blog/publications/towards-a-tobacco-free-society-
report-of-the-tobacco-free-policy-review-group
3. http://health.gov.ie/wp-content/uploads/2015/10/Healthy-Ireland-Survey-
2015-Summary-of-Findings.pdf
4. http://health.gov.ie/blog/publications/irelands-report-on-the-european-
schools-project-on-alcohol-other-drugs-in-ireland-espad/
5. http://health.gov.ie/wp-content/uploads/2016/01/HBSC2014web3.pdf
Keywords: tobacco policy, smoking inequalities
PA04: FOCUS ON ADVOCACY AND COMMUNICATION: JOINT IASLC/ GLOBAL LUNG CANCER
Worldwide, the number of papers published on lung cancer has more than
COALITION SESSION (GLCC) doubled from 2,157 papers in 2004 to 4,845 in 2013. However, there has only
TUESDAY, DECEMBER 6, 2016 - 14:30-15:45 been a small increase in the proportion of global cancer research that is
dedicated to lung cancer – from 4.4% in 2004 to 5.6% in 2013. By comparison
(figure 2), both breast and colorectal cancer account for greater proportion of
PA04.02 THE GLOBAL STATE OF LUNG CANCER RESEARCH –
research activity, despite having a similar burden of disease.
COMMUNICATING THE MESSAGES
Sarah Winstone
Incisive Health, London/United Kingdom
Background: The Global Lung Cancer Coalition (GLCC) is a unique partnership,

dedicated to improving disease outcomes for all lung cancer patients
worldwide. Research is essential to drive improvements in cancer prevention,
screening, diagnosis and treatment.i However, it is clear that lung cancer
research is not being prioritised to a level that reflects its significant impact,
with 1.8 million new cases globally every year.ii Poor lung cancer survival
demonstrates that more can and should be done. The GLCC is calling for every
country across the globe to examine and increase its investment in lung
cancer research. Evidence of variations between countries in their approach
to lung cancer research can be a powerful tool to advocate for increased
investment and national policy that encourages a flourishing lung cancer
research community. The GLCC commissioned the Institute of Cancer Policy at
King’s College London to undertake a comprehensive examination of the state
of global lung cancer research. The findings, published in the Journal of
Thoracic Oncology, are intended to guide public policy and highlight where
improvements can and should be made.iii They have also been made available Colorectal cancer accounted for 6.2% of research activity in 2013 whereas
on the GLCC website with a range of campaigning materials for advocates to breast cancer, at 10%, had nearly double the percentage of research activity
use in sharing insights and recommendations. Methodology: The GLCC compared to lung cancer. The figures can be used to make a persuasive case
commissioned the Institute of Cancer Policy at King’s College London to for increased investment in lung cancer research. To support this, the project
undertake a bibliometric review of global lung cancer research efforts. The team produced a campaigning toolkit, giving headline figures and statistics,
team developed a complex validated mathematical algorithm to search tips for engagement and template briefings and press releases. Global and
articles and reviews in the Web of Science database for lung cancer research national-level briefing documents and infographics are also available on the
during 2004-13, looking to: · Identify the total number of papers in cancer GLCC’s website at: http://www.lungcancercoalition.org/en/state-global-
research for each year in 24 leading countries, compared to that of other lung-cancer-research. The GLCC is calling for every country across the globe to
common cancers (breast and colorectal) · Isolate the number of papers increase its investment in lung cancer research, to increase research efforts
referencing lung cancer or other relevant key words in their title The study in aspects of care that are currently under-researched, and to collaborate
identified the 24 countries globally with the most extensive research with international partners to share findings and improve patient care.

Conclusions: Feedback from GLCC members confirms that the bibliometric

review is a valuable campaigning resource. The GLCC is keen for the review’s
findings to be shared and for policymakers – nationally, regionally and globally
– to consider how lung cancer research can be further supported. i Yarden Y,
Carols C, on behalf of the European Association for Cancer Research, Basic
cancer research: why it is essential for the future of cancer therapy. European
Journal of Cancer 2013, 49 issue 12. Accessed June 2015 ii GLOBOCAN 2012, Lung
Cancer, available here: http://globocan.iarc.fr/Pages/fact_sheets_cancer.
aspx. Accessed June 2015 iii Aggarwal A, Lewison G, Idir S, et al. The State of
Lung Cancer Research: A Global Analysis; J Thorac Oncol. 2016 Jul;11(7):1040-50
Keywords: campaigning, bibliometric, global lung cancer research, advocacy
PA04: FOCUS ON ADVOCACY AND COMMUNICATION: JOINT IASLC/ GLOBAL LUNG CANCER
COALITION SESSION (GLCC)
PA04.03 HELPLINE: ADAPTING TO CHANGING NEEDS AND

EVOLVING SCIENCE
Jennifer King
Science & Research, Lung Cancer Alliance, Washington/DC/United States of America
The Lung Cancer Alliance HelpLine launched over 21 years ago and until
recently was the only lung cancer-specific toll-free line in the United
States. The reasons people call—for information, understanding, referral,
compassion and most of all, hope—remain the same over time. But to
keep pace with dramatic advances in the ways lung cancer is detected,
diagnosed and treated, the LCA HelpLine has adapted quickly to meet the
changing needs of our community. For many survivors and their loved ones,
understanding lung cancer and its treatment is a challenge. Those impacted
by the disease tend to be older, poorer and less educated, groups which also
prefer to get their initial cancer information from their treatment teams.
With competing time demands, treatment teams may not have enough time
to ensure information is understood or to be sensitive to providing it when
the survivor can absorb, process and remember. Some are hesitant to admit
they don’t understand all they have been told and are uncomfortable asking
questions. Over the past 3.5 years, there have been nearly equal numbers
of patients and caregivers calling the HelpLine. Roughly three-quarters
of callers were women. In 2016, LCA began tracking more call statistics.
Of those who told us the type of lung cancer, we see 83% NSLCC and 17%
SCLC – quite representative of the lung cancer population. More than half
(53%) were already in treatment. As the science has evolved and practice-
changing discoveries are made, professional HelpLine staff provide up-to-date
information, support and referrals to those in our community, no matter
their place in the journey. The HelpLine provides the opportunity for in-depth
conversations, problem solving and the development of questions to ask
the team—it serves not as a substitute for conversations with treatment
team but as support and complement to them. The LCA HelpLine also has
grown with the internet. For some, the internet is a wealth of knowledge,
psychosocial support and information. But sometimes even savvy users need
help interpreting the information they have found. For others, the internet
is a scary and overwhelming place, full of difficult statistics, conflicting
recommendations and hard to understand concepts. Additionally, many in
our community do not have access to the internet at all or lack broadband
speeds that make it an effective tool. While the internet can be helpful, it
does not take the place of contact with another caring person who can help.
The HelpLine also gives us daily contact with lung cancer community and
allows us to keep abreast of what lung cancer patients, their loved ones and
those at risk need most. And as we listen, we adapt our services and programs
to their needs. For example, we have recently started offering a new webinar
series on the top symptoms and side effects reported by those in treatment
and long-term survivors. Recently, the pace of scientific discovery and drug
development in lung cancer has been accelerating rapidly. With six new drugs
approved by the Food and Drug Administration in 2015 and countless new
clinical trials launching to test not only new drugs but novel combinations
of different classes of agents, patients and caregivers can be even more
confused about the best treatment options for them. To address this
changing environment, we have recently launched the LungMatch program
to help patients find and understand personalized treatment options that
they can discuss with their treatment team. LungMatch includes referrals to
a concierge service for molecular testing if patients have not had it, a new,
user-friendly online matching platform, and in-house personalized clinical
trial navigation for interested callers on the HelpLine. The program is still
in its infancy, but in the first month of tracking, we determined that 85% of
callers asked had never been on clinical trials and only 50% reported molecular
testing of the lung cancer. These early statistics indicate the widespread need
in the lung cancer community. Through adapting to the changing needs of our
community and helping them understand the evolving science, the HelpLine
has been a lifeline for the lung cancer community in the United States for over
21 years.
Keywords: patient support, lung cancer, clinical trials, psychosocial support
inherent part of those associations whereas in nonrandomized studies no

YOUNG INVESTIGATOR SESSION direct conclusion can be driven that any association not due to chance indicates
a causal relationship. Methods: Randomization is a process in which each of the
SESSION YI01a: CLINICAL TRIALS & SCIENTIFIC MENTO- patients has the same but not necessarily the equal chance to be assigned to
predefined treatment arms ensuring that the treatment arms are comparable
RING with respect to known or unknown risk factors. Hence, it is a method to remove
SUNDAY, DECEMBER 04, 2016 - 08:00-09:45 selection and accidental bias and to guarantee the validity of statistical tests.
Main design issues of studies are the formulation of the primary aim, the
question of blinding, and the boundary conditions of sample size calculations.
YI01A.01 HOW TO IMPLEMENT AN IDEA/HYPOTHESIS INTO A [2] Tables of baseline data and outcome events are part of most medical journal
CLINICAL TRIAL papers concerning treatments. Generally the first table displays the patients’
Carlos Silva characteristics including some demographic variables and variables related
to the primary aim. The main outcome events are forming the key table of
Department of Oncology, Hospital Britanico de Buenos Aires, Buenos Aires/
Argentina
every paper stratified by treatment groups. Categorical variables are shown as
number and percent by group. Continuous variables can either be presented
Last decades have shown an impressive advance in terms of biological by mean and the standard deviation or by median and the interquartile range.
knowledge in cancer. Traditional way to bring new ideas/hypotesis into clinical Latter is preferred if the data are scattered and far from normal distribution
trials was overcoming by this fact. New agents directed against specific with the implication that in the sequel non-parametric tests should be favored.
molecular targets have important impact in terms of response rate (RR), For composite events like severe toxicities, progression of disease, and death
response duration (RD), progression free survival and eventually overall survival the number of patients experiencing any of them plus the number in each
(OS) as well as quality of life (QoL). If you have an interesting idea/hypotesis, component should be given, since we have the effect of multiple events. In
today you have to take on account several points that can exclude it. Select focus are often variables displaying the time to the first event (e.g. progression
population becomes a very important issue. How to do this? Selecting a target, of disease which can happen more than once during treatment history). For
a tumor, both, other conditions? Following the tradition of research phases, time driven events in the sequel analysis of general survival times are applied
Phase I refers to measure safety and pharmacokinetics assesing maximum leading to special statistics and graphs. The Kaplan-Meier plot is the most used
tolerated dose (MTD) but a number of new agents have a non reachable MTD graph to show time-to-event outcomes as death, time to progression, disease
because they have a low toxicity. On the other hand, phase II refers to the free interval etc. In general the graph displays the steadily increasing difference
assesing of efficacy in a certain tumor as well as safety, but, in the case of new in incidence rates of the outcome for two or more treatment arms. To make the
agents you may select a tumor (as ussual), a specific target no matter wath process clearer, the numbers at risk in each group should be shown at regular
tumor carry it (basket), or other conditions. In this phase measurement of time intervals in the time axis. Individuals who did not reach the endpoint are
response is important as a precedent of next phase trials and the challenge is censored (e.g. still alive, lost to follow-up) and should be marked in the plot. The
the method you will use to do it. New inmunotherapeutic agents probably need conditional probabilities of Kaplan-Meier statistics indicate the probability
a different way to do this. Also, to have predictive biomarkers for most of these of experiencing the endpoint under consideration beyond a certain length of
agent will help to select the potential population that will achieve the more follow-up. Estimation of treatment effects is to measure the magnitude of the
benefit and avoid futile toxicity and a waste of time and resources. We have to difference between treatments on patient outcomes. Normally this is done by
remember that biological effects not always means clinical benefit. Breaking a point estimate showing the actual difference observed. Inherent in this kind
barriers, for phase III comparator selection, primary and secondary end points of statistics is that the bigger the trial, the more precise the point estimate
as well as inclusion and exclusion criteria become a very important point and will be. Such uncertainty is usually expressed by a 95% confidence interval in
are different in the traditional way and in a proposed new way. OS is the gold which this percentage of the sample will be found. The primary aim of the study
standard end point but there are many more very important like PFS, RR, DoR, determines the type of estimate required. Namely, there are three main types
QoL. Again, measurement methods are very important and may be different of outcomes: (a) Binary (dichotomous) response, e.g. dead or alive, progressive
related with biological mechanism and length of response for different agents or non-progressive, success or failure, respectively. (b) Time to event outcome
than chemotherapy. As phase III trials select (include and exclude) patients most measured in intervals, e.g. time from randomization to death, time of
troughout very strict criteria and there are some late toxicities that can be inclusion in the study to treatment failure. (c) Quantitative outcome as the
as important as the acute and subacute toxicities, phase IV trials are very reduction of a certain percentage of tumor loads at a given time point (e.g. a
important because they represent better the daily patient we see at office seen reduction of 30% after exactly 6 months). Estimates based in percentage
practice and is a powerfull pharmacovigilance mechanism. Sanctuaries have are indicated if a binary outcome has to be judged in terms of absence or
to be consider as far as the prevalent tumors have a very frequent involvement presence. Then a confidence interval of the proportion of interest can be given.
of Central Nervous System and these patient are mostly excluded from Relative risks are the ratio of two percentages and can be converted to relative
clinical trials at the beggining. Ethics is a fundamental point as far as the most risk reduction. Alternatively relative odds can be applied which is a cross-
important objective is the patient safety and treatment accesibility. If we went product relationship and shows the relation of chance. Relative risk and relative
troughout these restriction points and our idea/hypotesis has survive, we can odds are sometimes called risk ratio and odds ratio instead. The absolute
follow the development of trials around wasting less time and resources. difference in percentage is taken as a measure of absolute risk reduction.
Estimates for time-to-event outcomes are used in all survival statistics as time
Keywords: clinical trial, Targeted Therapies, idea/hypotesis, Response criteria to death, time to progression etc. The Kaplan-Meier plot depicts the first time
of the occurrence of the event but does not in itself provide a simple estimate
summarizing the treatment difference. The Kaplan-Meier estimate at the
end of plotted time or at any other time between can be taken as cumulative
YI01A: CLINICAL TRIALS & SCIENTIFIC MENTORING rate of the leading event. That is only a time point estimate. Instead, the most
SUNDAY, DECEMBER 04, 2016 - 08:00-09:45 common approach is to use a Cox proportional hazards model to obtain a
hazard ratio and its 95% confidence interval. The hazard ratio can be thought
of as the hazard rate in one group divided by the hazard rate in the other group
YI01A.02 BASIC STATISTICAL CONSIDERATIONS averaged over the whole follow-up period. Examples from medical trials will be
Lothar Pilz used to explain the statistical principles shown here.References [1] Pocock SJ,
Senior Statistical Consultant, Deanery, University of Heideberg, Medical Faculty McMurray JJV, and Collier TJ: Making sense of statistics in clinical trial reports.
Mannheim, Mannheim/Germany J Am Coll Cardiol 2015; 66(23):2648-2662. [2] Pilz LR, Manegold C: Endpoints in
lung cancer trials: Today’s challenges for clinical statistics. MEMO 2013; 6(2):
Introduction: Published and officially approved medical research is based on 92-97.
evidence and subsequently, statistical methods are an essential part in proving
the usefulness of results. The translation in statistical terms in most cases Keywords: statistical principles, randomized clinial trials, interpretation of
is to build hypotheses and their alternatives to be tested. Clearly, medical statistical terms, design of clinical trials
researchers need some sound understanding of statistical principles which can
be taken, however, not as a matter of course. The aim of the contribution is to
communicate among readers of medical journals and reports statistical matters
focusing on basic statistical considerations to enable a better understanding.
YI01A: CLINICAL TRIALS & SCIENTIFIC MENTORING
[1] Essentials of statistical analysis and reporting: (i) Making the information SUNDAY, DECEMBER 04, 2016 - 08:00-09:45
content of the research results visible in summarizing and prescinding them
in tables, graphs, and figures. (ii) Assessing and quantifying any associations
of reported measures like possible differences in the outcome of treatment YI01A.04 CRITICAL EYE ON PRACTICE CHANGING LITERATURE
actions etc., and using confidence intervals to express the uncertainty of Jin Soo Lee
those associations. (iii) Building hypotheses and their alternatives to prove Center for Lung Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do/Korea,
that these associations have a real biomedical basis which is performed by Republic of
statistical testing under a given level of significance (p-values). Important is
the design of the research project: In randomized trials comparisons are an Clinical trials in cancer have typically investigated agents or regimens

in selected groups of patients based primarily on histology and clinical Over the last two decades, research has pushed lung cancer investigations from
characteristics (e.g., tumor stage, performance status, prior treatment, etc). the shallows of cancer treatment to one of the most innovative positions in
The major goal of those trials was to demonstrate statistically significant oncology. The improvements in molecular diagnostics, in targeted therapy and
improvement in outcome with minimum p-value of 0.05, as compared with immunotherapy with the linked creeping decline of traditional chemotherapy
the control arm. In the majority of cases, this approach resulted in only small act as a model for many other tumor entities. Joined by this paradigm shift
incremental improvements in overall survival. In some cases, even without any is a demographic change to young investigators who start their career in the
improvement in survival, a certain regimen became the foundation for adding innovative fields of lung cancer research instead of thinking in the traditional
novel targeted agents only based on the favorable toxicity profile and has chemotherapy-based fashion. Nevertheless, in order to detect the needs and
been widely used in practice over the last two decades. More recently, targeted expectations from young investigators, even the definition of “young” is hard
therapies administered to patients with biologically relevant biomarkers, such to handle, and subjective expectations might be biased by the socioeconomic
as activating EGFR mutations and ALK alternation, have produced substantial background of the investigator. We therefore set out to find a way to present
improvements in outcomes and rapidly changed the treatment paradigm more robust and reliable data on the topic. We created an online questionnaire
of lung cancer. In addition, newer treatment modalities such as immune covering age, experiences, interests, and of course needs and expectations of
check-point inhibitors and antibody-drug conjugates are emerging as highly young investigators. The expectations focus on research topics, treatment
effective therapies that are providing improvements in patient outcome. options, mentorships and social networking. The questionnaire will be
In fact, between 2004 and 2015, 14 new drugs were approved by the FDA for forwarded to 20 investigators in the EU, Asia, South America and the US
NSCLC. However, the relevance of statistical significance has increasingly with link to the emerging fields of lung cancer research, in order to forward
been challenged when the treatment effect is small. [1,2] To resolve this issue, it to participants who they consider young in both clinical and preclinical
there has been growing consensus to raise the bar of efficacy for approving investigations. For subgroup analyses, we will include students with interest in
new cancer drugs.[3,4] The critical question is what is clinically meaningful this field, too. Results will be analyzed by the presenters. The poll will be open
and how can this outcome be measured. The FDA considered OS to be the until one week of the WCLCs Young Investigator’s Scientific Mentoring Session,
standard clinical benefit endpoint that should be used to establish efficacy and results of this interim analysis will be presented by this talk. Nevertheless,
of a treatment in patients with locally advanced or metastatic NSCLC.[5] The all participants of the WCLC 2016 are invited to answer the questionnaire during
FDA also has recognized that PFS may be appropriate as the primary endpoint the Conference, and a final data cut will be made at December 10th, 2016. We
to establish efficacy for drug approval if the trial is designed to demonstrate a are aware of the potential biases in online polls. A valid e-mail address and the
large magnitude for the treatment effect as measured by both the hazard ratio source of the online link (i. e., who was the “supervisor”) are necessary. As an
and absolute difference in median PFS and an acceptable risk-benefit profile incentive to participate properly, we offer all participants to be part of the
of the drug is demonstrated. The remaining question is, “What is clinically “WCLC young Investigator Expectations Network (WIEN)” which will coauthor
meaningful?” Modest benefits could be considered worthwhile if associated the final manuscript. As we question the expectations of how lung cancer
with moderate costs and toxicity, whereas a new drug with a very high cost research will work in five years, it is intended to repeat the poll in a regular
and/or substantial toxicity is worthwhile only if it produces sizeable clinical manner, maybe yearly. We expect a view on the expectations from young
benefits. To address this issue, the ASCO Cancer Research Committee convened investigators worldwide and a feeling of their needs for the future.
four disease-specific working groups, including the lung cancer working group.
The Committee generally agreed that relative improvements in median OS of Keywords: future, young investigators, lung cancer, expectations
at least 20% are necessary to define a clinically meaningful improvement in
outcome.[3] For lung cancer, it was recommended that one experimental agent
in non-squamous NSCLC should be considered practice changing if it increases
PFS by at least 4 months and OS by 3.5-4 months with a corresponding death YI01B: SCIENTIFIC MENTORING
SUNDAY, DECEMBER 04, 2016 - 09:45-11:45
risk reduction of 20-24%. Due to less favorable prognosis, the desired benefit
in squamous NSCLC was 3 months increase in PFS and 2.5-3 months increase in
OS with a death risk reduction of 20-23%.[3] Obviously, if a new treatment is to YI01B.03 SCIENTITIFIC MENTORING: THE REALITY
be introduced into clinical practice, it is not sufficient to demonstrate that it Mirjana Rajer
is “better than” or “non- interior to” the standard therapy. As cancer care costs
Institute of Oncology Ljubljana, Ljubljana/Slovenia
continue to increase at an unsustainable rate, oncology professionals need to
focus more on delivering value-based patient care rather than simply practicing All oncologists are part of the mentor-mentee relationship at some point of
evidence-based patient care. In addition, it has become increasingly clear that their career. Mentoring can be considered one of the critical factors in achieving
the traditional fee-for-service model will no longer serve the interest of all the a successful career. The importance of a good mentor is best described by the
parties involved, including the pharmaceutical company.[6] It seems to be a sentence of Robert S.Kerbel: “I have been extremely fortunate if not blessed,
matter of time that the fee-for-service system will be replaced with the value- with having series of outstanding mentors [1].” In spite of the importance of
based reimbursement system. Reference 1. Sobrero A, Bruzzi P. Incremental mentoring, what makes good mentors and mentoring is often not well defined
advance or seismic shift? the need to raise the bar of efficacy for drug approval. J [2]. According to Nature’s guide for mentors, one of the most important
Clin Oncol 2009;27:5868–73. 2. Ocana A, Tannock IF. When are “positive” clinical characteristics of a good mentor is his/her orientation towards mentee’s long-
trials in oncology truly positive? J Natl Cancer Inst 2011;103:16–20. 3. Ellis LM, term career development as a main focus of mentoring. In this way, the mentor
Bernstein DS, Voest EE, Berlin JD, Sargent DJ, Cortazar P, et al. American Society becomes a “mentor for life” and not only temporary supervisor [2]. According
of Clinical Oncology perspective: raising the bar for clinical trials by defining to mentees, a good mentor has some distinct personal characteristics like
clinically meaningful outcomes. J Clin Oncol 2014;32:1277–80. 4. Sobrero AF, enthusiasm, passion, positivity, compassion and understanding. Beside these,
Pastorino A, Sargent DJ, Bruzzi P. Raising the bar for antineoplastic agents: some others like appreciating individual differences, being respectful and
How to choose threshold values for superiority trials in advanced solid tumors. unselfish are also very important. To properly advise and guide mentees in
Clin Cancer Res. 2015;21:1036-43. 5. United States, Department of Health and their work, mentors should be able to see their individual characteristics and
Human Services, Food and Drug Administration (FDA). Clinical Trial Endpoints support their personal strengths. Showing respect means that the protégée
for the Approval of Non-Small Cell Lung Cancer Drugs and Biologics Guidance is not only seen as an workforce, but also as a genuine collaborator. Regarding
for Industry (published April 2015) : Available online: http://www.fda.gov/ unselfishness: letting the mentee be the first author of a common article,
downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ even if the mentor provided the initial idea is a good example [2]. Personal
UCM259421.pdf, 2015. 6. Eaton KD, Jagels B, Martins RG. Value-based care in characteristics aside, abilities to become a good mentor can be gained by
lung cancer. Oncologist. 2016;21:903-6. following some useful rules. Mentors should be generally available and have an
“open door” policy instead of restricted and limited dedicated time. Availability
Keywords: Targeted therapy, Value-based patient care, Clinical trial
should also be shown by quickly answering e-mails and phones calls. They
interpretation
should be inspirational and show optimism on every-day issues but – even more
importantly - when facing failure. Mentors should find a balance between doing
and letting do, should support mentees in analytical thinking and adapt to their
needs according to the progress of the protégée (e.g. different mentoring at the
beginning and the end of the PhD course). They should celebrate successes with
SESSION YI01b: SCIENTIFIC MENTORING the mentee [2, 3]. Scientific mentors have the obligation to teach, encourage
SUNDAY, DECEMBER 04, 2016 - 09:45-11:45 and support students in some specific activities in which skills are essential in
the world of science. Examples are writing and oral presentations. Supporting
writing with fast and accurate reviews, while resisting the temptation of
YI01B.02 EXPECTATIONS FROM A YOUNG INVESTIGATOR rewriting instead of the student is one of the main goals. Extensive mentoring
Matthias Scheffler 1, Sophia Koleczko1, Diana Abdulla1, Reinhard Büttner2, regarding oral presentations is also needed due to the fact, that not many
Jürgen Wolf 1 students have a natural gift for presenting. Mentors should also try to provide
1
Department I of Internal Medicine, Lung Cancer Group Cologne, University as many opportunities for oral presentations as possible. Involving students in
Hospital of Cologne, Cologne/Germany, 2Department of Pathology University mentors’ networking should also be a continuous process [2]. How to choose
Hospital of Cologne, Cologne/Germany a good mentor is a question that should be carefully addressed. In selecting
mentors, trainees should follow some recommendations. They should look for
possible mentors online, see which mentors possibly have the same interests, similar outcomes as SBRT (2); however, a recent systematic review of cost-
e-mail previous mentees inquiring about their experience with the mentor effectiveness analyses did not support the use of PT (3). To improve outcomes
and afterwards meet the potential mentor in person at work. Trainees should in locally-advanced lung cancer, IMRT and PT have been actively investigated.
carefully look for signs of poor mentorship, like no available time for one-to- Several in silico studies have suggested the superiority of IMRT over CRT,
one conversation, repressed and stressed co-workers that show no respect for and PT over IMRT, but this remains to be demonstrated clinically. Subgroup
their head, the potential mentor [2, 4]. Even if some trials report objective data, analyses of RTOG 0617, which compared a high dose (74 Gy) vs. a standard
evaluating mentorships can be challenging since it is a complex interpersonal dose (60 Gy) and allowed both CRT and IMRT, showed similar efficacy, less
interaction. In a trial reported by Badawi the majority (74%) of mentors and radiation pneumonitis, and better compliance of consolidative chemotherapy
mentees report the experience as rewarding, worth their time and effort, many favoring IMRT over CRT, despite there being more advanced cases in the IMRT
(58%) achieve their goals in a timely manner and plan to continue (89%) their group (4). The study authors generated a hypothesis that dose intensification
collaboration after the mentorship period is finished [5]. High satisfaction with by IMRT may result in better efficacy with less toxicity. However, we could
the mentorship experience is commonly reported in other surveys. DeCastro not determine the true difference between IMRT and CRT among patients
conducted a trial on 1708 clinicians-researchers and only 10% of them were who received the standard dose, which is our current practice, because their
not satisfied with the experience, without differences between male and analysis included both high- and standard-dose arms; the differences might
female mentees [6]. Some surveys, like the one reported by Dhami, show the be more prominent in the high-dose arm. These investigators also suggested
importance of formal mentorship. Satisfaction with the mentorship experience that increasing the radiation dose to the heart may worsen survival, so dose
was greater in mentees included in formal mentorship compared to those who constraints to the heart became stricter thereafter. Results of a Bayesian phase
had an informal one (72% vs. 36%, p<0.01) [7]. Formal mentoring influences II randomized trial of IMRT vs. PT were reported at the ASCO Annual Meeting
also on research productivity. In the survey of Riechelman, responders with earlier this year (5). The primary endpoint was incidence and time to protocol
mentors were more involved (more available time dedicated) in academic failure, defined as Grade 3 or higher pneumonitis or local failure. The observed
research compared to those without mentors [8]. A model mentor is involved local failure rates at 12 months were similar (13% vs. 12%). The investigators
in the fruitful career development of the mentee and broadly shares the assumed Grade 3 or higher pneumonitis of 15% in the IMRT arm and 5% in
knowledge, skills and expertise that the mentee needs. As the mentee advances the PT arm; however, they observed 6.5% in the IMRT arm, which was lower
and gains independence, a good mentor is able to guide him/her toward new than the assumed probability, and 10.5% in the PT arm, higher than expected.
opportunities and facilitates the mentee’s growth [9]. 1. Kerbel, R.S., Some Because this was a phase II trial with some limitations, firm conclusions could
guidelines for building a successful career in cancer research. Cancer Biol Ther, not be drawn. However, PT failed to suggest a clinical benefit over IMRT. A
2003. 2(1): p. 111-4. 2. Lee, A., C. Dennis, and P. Campbell, Nature’s guide for meta-analysis of the phase III trials conducted by the Radiation Therapy
mentors. Nature, 2007. 447(7146): p. 791-7. 3. Powers, P.J., Engaged mentors offer Oncology Group between 1968 and 2002 showed that new treatments were
inspiration and open doors. Am J Med, 2006. 119(1): p. 3. 4. Purcell, E.P., et al., demonstrated to be better than existing ones in only 6 of 59 comparisons.
Research to reality (R2R) mentorship program: building partnership, capacity, In addition, overall survival of all of the accrued patients did not differ
and evidence. Health Promot Pract, 2013. 14(3): p. 321-7. 5. Badawy, S.M., et al., between groups, while the odds ratio of 1.76 for treatment-related death was
Early career mentoring through the American Society of Pediatric Hematology/ significantly higher for the new treatments (6). These results clearly showed
Oncology: Lessons learned from a pilot program. Pediatr Blood Cancer, 2016. 6. that “New is not always better.” We need to identify the subpopulations for
DeCastro, R., et al., Mentoring and the career satisfaction of male and female whom new techniques are more effective and to demonstrate these have
academic medical faculty. Acad Med, 2014. 89(2): p. 301-11. 7. Dhami, G., et al., true value with scientifically strong evidence, instead of just believing in their
Mentorship Programs in Radiation Oncology Residency Training Programs: efficacy, complaining about the challenges associated with evaluating them, or
A Critical Unmet Need. Int J Radiat Oncol Biol Phys, 2016. 94(1): p. 27-30. 8. advertising them directly to patients.
Riechelmann, R.P., et al., The influence of mentorship on research productivity in
oncology. Am J Clin Oncol, 2007. 30(5): p. 549-55. 9. Gitlin, S.D. and M.L. Lypson,
For Residents and Fellows: What to Look for in a Laboratory Research Mentor. J
Cancer Educ, 2015.
Keywords: mentor, mentee, career development, scientific mentoring
SESSION YI02: BASICS OF RADIO-ONCOLOGY

References
1. Chen AB, Neville BA, Sher DJ, et al. Survival outcomes after radiation
therapy for stage III non-small-cell lung cancer after adoption of computed
YI02.02 MODERN TREATMENT TECHNIQUES IN LUNG CANCER: tomography-based simulation. J Clin Oncol 2011;29:2305-2311
THE ADVANTAGES OF CONFORMAL RADIOTHERAPY, IMRT AND
2. Grutters JP, Kessels AG, Pijls-Johannesma M, et al. Comparison of the
PROTON THERAPY
effectiveness of radiotherapy with photons, protons and carbon-ions for non-
Satoshi Ishikura small cell lung cancer: a meta-analysis. Radiother Oncol 2010;95:32-40
Department of Radiology, Koshigaya Municipal Hospital, Koshigaya/Japan
3. Verma V, Mishra MV, Mehta MP. A systematic review of the cost and cost-
As technology has advanced, modern radiotherapy (RT) techniques, such as effectiveness studies of proton radiotherapy. Cancer 2016;122:1483-1501
conformal radiotherapy (CRT), intensity-modulated radiation therapy (IMRT),
and proton therapy (PT), have become available. In this session, the advantages 4. Chun SG, Hu C, Choy H, et al. Outcomes of intensity modulated and
of these techniques in the treatment of early-stage and locally-advanced lung 3D-conformal radiotherapy for stage III non-small cell lung cancer in NRG
cancer will be presented, along with their uncertainties. Conformal RT uses CT Oncology/RTOG 0617. J Thorac Oncol 2015;10:S213
scans to create 3-dimensional images of the tumor and normal tissues, which
leads to more accurate treatment planning. It also uses multiple radiation 5. Liao ZX, Lee JJ, Komaki R, et al. Bayesian randomized trial comparing
beams from various angles to concentrate the radiation dose to the tumor intensity modulated radiation therapy versus passively scattered proton
while reducing the dose to normal tissues. Furthermore, conformal RT improves therapy for locally advanced non-small cell lung cancer. J Clin Oncol 2016;34
tumor control and reduces toxicity compared to 2-dimensional RT (1). IMRT (suppl; abstr 8500)
is a sophisticated form of CRT, which enables us to more exactly concentrate
6. Soares HP, Kumar A, Daniels S, et al. Evaluation of new treatments in
and shape the dose distribution to the tumor and spare normal tissues. It can
radiation oncology: are they better than standard treatments? JAMA
also partially intensify doses to individual areas deemed to be more aggressive
2005;293:970-978
or radioresistant. PT uses charged particles, which have a unique physical
characteristic called the Bragg peak. The Bragg peak describes a certain tissue Keywords: lung cancer, Proton therapy, Conformal Radiotherapy, Intensity
depth at which the protons stop just after transferring most of their energy. Modulated Radiation Therapy
This feature is particularly convenient for tumors located close to critical
normal tissues. PT is commonly adopted for pediatric, central nervous system,
and intraocular malignancies. Stereotactic body radiation therapy (SBRT),
also called stereotactic ablative radiation therapy (SABR), is characterized by
YI02: BASICS OF RADIO-ONCOLOGY
accurate target definition, precise tumor positioning, steep dose gradients WEDNESDAY, DECEMBER 7, 2016 - 14:30-15:45
outside targets, and very high dose per fraction. SBRT can be delivered using
either CRT or IMRT. In the treatment of peripheral early-stage lung cancer,
SBRT is widely adopted as a standard treatment and is considered better YI02.03 DOSE LIMITATIONS FOR RADIOTHERAPY OF LUNG CANCER
than conventional fractionated RT. PT can also be used in this setting, despite Antonio Juretic 1, Ana Frobe2, Jasmina Maric Brozic2, Lea Galunic Bilic3,

Martina Basic-Koretic3 to the normal tissues. Newer radiotherapy equipment, techniques and
1
Department of Oncology, School of Medicine, University of Zagreb and University treatment planning software can, due to a better delineation of tumor margins
Hospital Center “Zagreb”, Zagreb/Croatia, 2Department of Oncology and Nuclear and reduced rates of radiation-associated toxicity, allow tumor dose escalation
Medicine, University Hospital Center “Sestre Milosrdnice”, Zagreb/Croatia, to improve local control and possible tumor cure. Improvements in radiotherapy
3
Department of Oncology, University Hospital Center “Zagreb”, Zagreb/Croatia technique are achieved by using functional images for target definition (PET/
CT), 4D-computed tomography (4D-CT), intensity modulated radiation therapy
Lung cancer is the most frequent cancer and the leading cause of cancer (IMRT) and adaptive radiotherapy. (3,4) Several studies have shown a better
mortality. Lung cancer treatment results in terms of patients’ long-term response with dose escalation in NSCLC. Doses of up to 74 Gy can be delivered
survival and cure are far from ideal. Radiotherapy as one of the lung cancer when normal tissue constraints are considered. The phase I/II RTOG 9311 trial
standard treatment modalities can be applied with curative or palliative intent. reported the outcome of a dose-escalated 3D conformal radiotherapy in stage
Radiotherapy treatment intent depends on tumor extent (disease stage), I-III NSCLCs stratified at escalation dose level according to parameters V20 Gy
tumor location, patient’s performance status and comorbidities, availability of (percentage of the total lung volume that received > 20 Gy). The results of this
modern radiotherapy treatment machines and their technical and software trial showed that radiation dose escalation was considered safe when using 3D
capabilities (1-4). Radiotherapy with curative intent is indicated as an conformal techniques to 83.8 Gy in patients with a V20 < 25% and 77.4 Gy in
alternative to surgical treatment in patients having the early stage disease patients with V20 between 25 and 36% (7). In the RTOG 0617 trial two schedules
(generally stages I and II) or a locally more advanced disease (stage III). In early were compared: 60 Gy (in 6 weeks) versus 74 Gy (in 7.5 weeks) in a 2×2 design
stage disease patients, which are the group with the best prognosis, where patients were also randomized to receive or not receive cetuximab.
radiotherapy can be applied as, for example, the sole treatment modality in the Surprisingly, the higher dose arm was not associated with improved survival at 1
form of hypofractioned stereotactic ablative radiotherapy (SABR) for patients year but, rather, showed a contrary trend. The trial showed an OS of 28.7
with lymph node-negative peripheral non-small cell lung cancer (NSCLC). For months for patients who received standard dose radiotherapy compared with
patients having inoperable locally advanced lung cancer (stage III) the five-year 20.3 months for those who received high dose radiotherapy. Median survival in
overall survival rate is at around 15-20%. Therefore, the two remaining standard patients who received cetuximab was 21.3 months compared to 24.0 months in
treatment modalities, chemotherapy and radiotherapy with curative intent, are those who did not receive cetuximab (p = .29) (8). The use of IMRT allows
used and combined whenever possible. Concomitant chemoradiotherapy is the clinicians to obtain better radiotherapy planning parameters such as V20 and
treatment of choice since it gives better results, but in practice a significant mean lung dose and to reduce the probability of development of lung toxicity -
number of patients is not fit for this approach. Therefore, the alternative in radiation pneumonitis. As reported in literature, V20 values of 35–37% and the
unfit patients is sequential chemoradiotherapy or radiotherapy alone. In MLD value of 20–23 Gy have been considered safe but 10–15% of patients can
patients having concomitant chemoradiotherapy there are no results in favour still develop a severe radiation pneumonitis when lower doses are delivered (9).
of induction or consolidation chemotherapy. It might be that a novel The concomitant use of chemotherapy with radiotherapy can achieve a better
immunotherapy approach with anti-PD-1 or anti-PD-L1 inhibition will in the overall response, albeit with an increased number of treatment related
future improve the survival rate of this group of patients and patients with the toxicities – esophagitis and pneumonitis in 10 to 40% of patients (7-9). The use
metastatic disease (1-4). The effectiveness of radiotherapy depends on the total of radiotherapy after chemotherapy with delivered escalated doses of 74 Gy and
radiation dose being delivered accurately. For most tumors there is a 86 Gy is associated with a higher incidence of bronchial stenosis (4% and 25%,
dose-response effect, i.e. the higher the dose, the higher the chance of local respectively) and can increase when radiotherapy is used concurrently with
tumor control and cure. The first trial that in the case of lung cancer chemotherapy. For patients with a locally advanced NSCLC stereotactic
demonstrated this relationship was published by Perez et al (RTOG 71-01 trial) ablative radiation treatment (SABR) can be used as a boost to the primary
(5). In this dose escalation trial, the dose of 60 Gy in comparison with the dose of parenchymal lesion. SABR treatment was added after the conventional
50 and 40 Gy was found, evaluated clinically, to have a lower incidence of local chemo-radiation (60 Gy/ 30 fractions) treatment: the prescription dose varied
failures (33% versus 39% versus 44% to 49%). The survival of patients according from 10 Gy in 2 fractions in peripheral lesion to 6.5 Gy in 3 fractions in the central
to treatment regimen was not statistically significantly different. The one-year tumors. After a median follow-up of 13 months local control was 82.9% and
and two-year survival rates for all groups were, respectively, 45% and 25%. On there were no patients with a radiation pneumonitis grade 4 or 5 (10). Proton
the basis of this trial the dose of 60 Gy in 30 fractions (60 Gy/30x) or higher has therapy is a new potential therapeutic approach to the treatment of NSCLC.
since that time been the optimal standard radiotherapy treatment, although Protons have the potential role of reducing the dose to the normal tissue, in
patient outcomes were objectively very poor. It should be mentioned that from particular to the lung and the heart. Initial studies have demonstrated that in
today’s perspective the radiotherapy techniques that were then used (2D patients receiving a concomitant treatment of chemo-radiotherapy the overall
radiotherapy planning and relatively large tumor/target volumes) are not survival is influenced by the mean dose to the heart and the lung (3,4,11). As
recommendable nowadays in radiotherapy treatments with curative intent previously described, the univariate and multivariate analysis of RTOG 0617
(3,4). The objectively unsatisfactory clinical outcomes in terms of local tumor demonstrated that lung V5, heart V5 and heart V30 were considered predictors
control, progression free survival (PFS) and overall survival (OS) after of OS. Intraluminal (IL) high-dose rate (HDR) brachytherapy, as the exclusive
radiotherapy +/- chemotherapy treatments are probably the consequence of the conformal brachytherapy technique, avoids the previously mentioned dose
inadequate radiation dose to the tumor tissue. However, the usage of higher constraints and could be applied in highly selective cases with significant
doses is limited by the radiation tolerance of surrounding normal tissues and predominantly endobronchial or endotracheal tumors as a ¨boost” of 10-15 Gy
organs (3,4). In clinical radiotherapy, the radiation tolerance of normal tissues after external beam radiation therapy (EBRT) (60 Gy/30 fractions) or in a
and organs surrounding the tumor limits the radiotherapy dose that can be palliative setting in recurrent tumors after EBRT in various fractionation
given safely. As the dose is increased, the incidence and severity of normal schemes according to the American Brachytherapy Society (ABS): 10-15 Gy in
tissue damage rises. When severe, normal tissue damage can produce life one fraction or IL high-dose rate (HDR) alone 22,5 Gy/3 fractions, 24Gy/4
threatening morbidities. Multiple parameters such as total radiation dose, fractions, 30 Gy/6 fractions. Brachytherapy is recommended if there is a
fraction size, overall treatment time, volume and type of normal tissues to be collapsed lung at the first presentation because of improved re-expansion rates
irradiated, definition of target volume, and quality control of radiotherapy using IL HDR over EBRT (4,12,13). In conclusion, remarkable technological
techniques should be taken into account. A reduction of radiotherapy-related advances in the planning and delivery of radiotherapy allows us to do more,
toxicity is fundamental to the improvement of clinical results in lung cancer as which raises hopes that this will be translated into improved clinical outcomes
well as other types of cancers. Organs at risk of lung cancer radiotherapy include for patients having lung cancer.References: 1. Non-Small Cell Lung Cancer
the lungs, heart, spinal cord, and esophagus. Present knowledge of radiation Treatment (PDQ®) - Health Professional Version. Available from https://www.
toxicity is derived from conventional and newer 3D-conformal radiotherapy cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq 2. Small Cell Lung
(3D-CRT) data. The QUANTEC project (6) produced data that are currently used Cancer Treatment (PDQ®) - Health Professional Version. Available from https://
to predict the side effects of radiotherapy and the plausibility of evaluated www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq 3. Baker S et al.
treatment plans. Before being approved all radiotherapy treatment plans have Radiat Oncol. 2016;11:115. doi: 10.1186/s13014-016-0693-8. 4. Giaj-Levra N et al.
to be evaluated for the probability of organ-specific radiation toxicity (3,4). Cancer Invest. 2016;34:80-93. doi: 10.3109/07357907.2015.1114121. 5. Perez CA et
Thanks to the evolving radiation imaging and computer technology, a number al. Cancer. 1980;45:2744-53. 6. Marks LB et al. Int J Radiat Oncol Biol Phys.
of innovations in radiotherapy have been introduced in radiotherapy practice 2010;76(3 Suppl):S70-6. doi: 10.1016/j.ijrobp.2009.06.091. 7. Bradley J et al. Int J
within the several past decades. Conventional 2D treatment simulation has Radiat Oncol Biol Phys 2005;61:318–28. 8. Bradley JD et al. Lancet Oncol.
been replaced with computer tomography (CT) planning, with volumes 2015;16:187-99. doi: 10.1016/S1470-2045(14)71207-0. 9. Graham MV et al. Int J
delineated according to the International Commission on Radiation Units and Radiat Oncol Biol Phys 1999;45:323–9. 10. Feddock J et al. Int J Radiat Oncol Biol
Measurements (ICRU) report and ICRU supplements. This CT-based planning Phys 2013;8:1325–31. 11. Oshiro Y et al. J Radiat Res 2014;55:959–65. 12. Stewart
together with the possible implementation of other imaging methods such as A et al. Brachytherapy, 2016:15:1-11. 13. Langendijk H et al. Radiother Oncol 2001;
PET/CT and MRI have enabled more precise target borders and volume 58: 257–68.
determination with the consequence of radiotherapy treatment plans having
better tumor dose conformity and sparing the surrounding normal tissues (3,4). Keywords: Radiotherapy, Radiotherapy dose escalation, Radiation dosimetric
Due to a better delineation of tumor margins and reduced rates of radiation- parameters of toxicity, lung cancer
associated toxicity, the current standard radiation treatments based on the
implementation of these various technical and technological advances in
radiation planning and delivery have allowed the design of clinical studies with
radiotherapy dose escalations and modified fractionation schemes. The goal of
radiation treatment is to improve clinical outcomes while reducing the damage
(IRESSA). Br. J. Cancer. 2007;97(6):778-784. 3. Douillard JY, Ostoros G, Cobo M,

JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free
CHINESE ALLIANCE AGAINST LUNG CANCER SESSION tumor DNA as a surrogate for determination of EGFR status. J. Thorac. Oncol.
2014;9(9):1345-1353. 4. Couraud S, Vaca-Paniagua F, Villar S, et al. Noninvasive
diagnosis of actionable mutations by deep sequencing of circulating free DNA in
SESSION JCES01: JOINT IASLC - CHINESE SOCIETY FOR lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-
CLINICAL ONCOLOGY - CHINESE ALLIANCE AGAINST LUNG 1002. Clin. Cancer Res. 2014;20(17):4613-4624. 5. European Medicines Agency.
CANCER SESSION Summary of Product Characteristics 2014 [EB/OL], 10/14 update. http://www.
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45 ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/
human/001016/WC500036358.pdf. 6. Iressa 250mg Leaflet professional China.
CN52-086A. 20150203. . 7. Sacher AG, Oxnard GR, Mach SL, et al. Prediction
of lung cancer genotype noninvasively using droplet digital PCR (ddPCR)
JCES01.04 LIQUID BIOPSY IN MONITORING DYNAMIC CHANGES OF
analysis of cell-free plasma DNA (cfDNA). Paper presented at: Journal Of Clinical
DRIVER GENES IN ADVANCED NSCLC
Oncology 2014. 8. Marchetti A, Palma JF, Felicioni L, et al. Early Prediction of
Qing Zhou Response to Tyrosine Kinase Inhibitors by Quantification of EGFR Mutations
Guangdong Lung Cancer Institute; Guangdong General Hospital(GGH)& Guangdong in Plasma of NSCLC Patients. J. Thorac. Oncol. 2015;10(10):1437-1443. 9. Mok
Academy of Medical Sciences, Guangzhou/China T, Wu YL, Lee JS, et al. Detection and Dynamic Changes of EGFR Mutations
from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC
Epidermal growth factor receptor (EGFR) activating mutations in the tyrosine
Patients Treated with First-line Intercalated Erlotinib and Chemotherapy. Clin.
kinase domain serve as predictive biomarkers for EGFR-tyrosine kinase inhibitor
Cancer Res. 2015;21(14):3196-3203. 10. Zhou Q, Yang JJ, Chen ZH, et al. Serial
(EGFR-TKI) treatment outcome for patients with advanced non-small cell lung
cfDNA assessment of response and resistance to EGFR-TKI for patients with
cancer (NSCLC).1 However, due to the invasive procedures required to obtain
EGFR-L858R mutant lung cancer from a prospective clinical trial. Journal of
tumor tissues, not all patients can provide enough high-quality tissues for
Hematology&Oncology. 2016;9:86.
EGFR mutation analysis. Circulating free DNA (cfDNA) in plasma provides
a noninvasive substitute for tumor tissues. Several studies have reported Keywords: liquid biopsy, epidermal growth factor receptor (EGFR), non-small
a concordance rate between tumor and plasma > 90%, even reaching 97%, cell lung cancer (NSCLC)
demonstrating the feasibility of detecting EGFR mutations in cfDNA.2-4EGFR
mutation status detection in cfDNA has been approved by the European
Society for Medical Oncology and by China to be used with EGFR-TKI treatment
for NSCLC.5,6 In addition to providing pretreatment information, plasma-based JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
EGFR mutation detection makes it possible to monitor dynamic changes in AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
this mutation during treatment. Several studies have reported a quantitative
change in EGFR mutations during EGFR-TKI treatment by comparing pre- and
post-treatment plasma, in which various types of plasma EGFR mutations were JCES01.09 A COMPARISON OF DDPCR AND ARMS FOR DETECTING
found.7,8 The quantity of the plasma EGFR mutation sometimes decreases, or EGFR T790M STATUS FROM ADVANCED NSCLC PATIENTS WITH
sometimes decreases slowly or rapidly. Patients whose plasma EGFR mutations
ACQUIRED EGFR-TKI RESISTANCE
decrease rapidly usually exhibit a better response to EGFR-TKI treatment.8
However, these studies were not based on prospective clinical trials, therefore Wenxian Wang 1, Zhengbo Song2, Yiping Zhang 3, Ying Jin3
1
the number of patients who had serial plasma specimens tested during EGFR- Zhejiang Cancer Hospital, Zhejiang/China, 2Medical Oncology, Zhejiang Cancer
TKI treatments was limited, and very few plasma specimens were collected as Hospital, Hangzhou/China, 3 Zhejiang Cancer Hospital, Hangzhou/China
part of a pre-planned schedule. The only recent study on plasma EGFR mutation
Background: To assess the ability of droplet digital PCR and ARMS technology
changes based on a prospective clinical trial was reported by Mok et al.9 In
to detect epidermal growth factor receptor (EGFR) T790M mutations from
this phase III trial (FASTACT-2), patients received gemcitabine/platinum plus
circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC)
sequential erlotinib or placebo. EGFR mutation-specific cfDNA levels decreased
patients with acquired EGFR-TKI resistance. A sensitive and convenient
at cycle 3 and increased at the time of disease progression. Positive plasma
method for detecting T790M mutation would be desirable to direct patient
EGFR mutant DNA at cycle 3 predicted a worse clinical outcome. In this study,
sequential treatment strategy. Methods: To assess the ability of droplet
the treatment was chemotherapy plus EGFR-TKI or placebo, not EGFR-TKI,
digital PCR and ARMS technology to detect epidermal growth factor receptor
and there was no information on the plasma EGFR mutation at other time
(EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced
points except at baseline, cycle 3, and at disease progression. The dynamic
non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance.
changing types of plasma EGFR mutations during the whole course of EGFR-TKI
A sensitive and convenient method for detecting T790M mutation would be
treatment and its correlation with clinical outcomes were not determined. To
desirable to direct patient sequential treatment strategy.To assess the ability
measure changes of plasma EGFR L858R mutation during EGFR-TKI treatment,
of droplet digital PCR and ARMS technology to detect epidermal growth factor
and to determine its correlation with the response and resistance to EGFR-
receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in
TKI, we conducted a study. This study was a pre-planned exploratory analysis
advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI
of a randomized phase III trial conducted from 2009 to 2014 comparing
resistance. A sensitive and convenient method for detecting T790M mutation
erlotinib with gefitinib in advanced NSCLC harboring EGFR mutations in
would be desirable to direct patient sequential treatment strategy. Results:
tumor (CTONG0901). Serial plasma samples were collected as a pre-planned
A total of 108 patients were enrolled in this study. 108 patient plasma samples
schedule. This trial was conducted in Guangdong Lung Cancer Institute, China.
were detected by ddPCR and 75 were detected by ARMS. And 16 patients
Totally, 256 patients were enrolled in CTONG0901. One hundred and eight
experienced re-biopsy were detected T790M status by ARMS method. 43.7%
patients harbored L858R mutation in tumors and 80 patients provided serial
(47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma
blood samples as pre-planned scheduled. Patients were randomized to receive
samples, comparing ddPCR with ARMS, the rates of T790M mutation were
erlotinib or gefitinib. Serial plasma L858R in 80 patients was detected using
46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16
quantitative polymerase chain reaction. Changing types of plasma L858R
patients both had tumor and plasma samples, the T790M mutation rates were
were analyzed using Ward’s Hierarchical Clustering Method. Progression-free
56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA.
survival (PFS) and overall survival (OS) were compared between different types.
Among them, there were two ctDNA T790M mutations by ddPCR but T790M
As a whole, the quantity of L858R decreased and reached the lowest level at
gene negative in tumor tissue by ARMS method. For all patients, the median
the time of best response to EGFR-TKI. In 61 patients, L858R increased to its
PFS and OS were 12.3 months and 32.8 months, respectively. The patients
highest level when disease progressed (Ascend Type), while in 19 patients,
with T790M-positive tumors had a longer time to disease progression after
L858R maintained a stable level when disease progressed (Stable Type). Median
treatment with EGFR-TKIs (median, 13.1 months vs 10.8 months; P=0.010) and
PFS was 11.1 (95%CI, 6.6–15.6) and 7.5 months (95%CI, 1.4–13.6) in patients
overall survival (median, 35.3 months vs 30.3 months; P=0.214) compared with
with Ascend and Stable Types, respectively (P = .023). Median OS was 19.7
those with T790M-negative patients. Conclusion: Our study demonstrates
(95%CI, 16.5–22.9) and 16.0 months (95%CI, 13.4–18.5), respectively (P = .050).
dPCR assay provide feasibility and sensitive method in detecting EGFR T790M
This is the first report finding two different changing types of plasma L858R
status in plasma samples from NSCLC patients with acquired EGFR-TKI
mutation during EGFR-TKI treatment based on a prospective randomized
resistance.And T790M-positive patients have better clinical outcomes to
study. Different changing types were correlated with benefits from EGFR-
EGFR-TKIs than patients with T790M negative.
TKI. The impact of plasma L858R levels at disease progression on subsequent
treatment strategy needs further exploration. This study was recently
published in Journal of Hematology&Oncology.10 In summary, liquid biopsy
is very promising in monitoring dynamic changes of driver genes in advanced
NSCLC, which promotes the development of precision medicine.References JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
1. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
pulmonary adenocarcinoma. N. Engl. J. Med. 2009;361(10):947-957. 2. Kimura
H, Suminoe M, Kasahara K, et al. Evaluation of epidermal growth factor
receptor mutation status in serum DNA as a predictor of response to gefitinib JCES01.10 SERIAL QUANTITATIVE ASSESSMENT OF PLASMA

CIRCULATING TUMOR DNA BY DIGITAL NGS IN PATIENTS WITH PD-L1 expression was identified in 52.6% (40/76) of SCC patients while 61.8%
LUNG CANCER (47/76) were positive for PD-L1 expression after neoadjuvant chemotherapy .
Nine patients switched from negative to positive while another two patients’
Yue Zhao 1, Jay Gong2, Weijie Ma3, Kimberly Banks4, Huiyu Wen5, Elizabeth H
samples showed the reverse of the above result. Multivariate analysis
Moore6, Richard Lanman7, Tianhong Li8
1
demonstrated that postoperative expression of PD-L1 was an independent
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center,
prognostic factor for overall survival (HR=0.50, P=0.003), but not for PD-L1
Shanghai/China, 2University of California Davis Comprehensive Cancer Center,
Sacramento/United States of America, 3Division of Hematology & Oncology, expression prior to neoadjuvant chemotherapy. Conclusion: Neoadjuvant
University of California Davis Comprehensive Cancer Center, Sacramento/AL/ chemotherapy may up-regulate the expression of PD-L1. As compared with
United States of America, 4 Medical Affairs, Guardant Health, Inc, Redwood City/CA/ the status of PD-L1 expression prior to chemotherapy, the postoperative
United States of America, 5UC Davis Comprehensive Cancer Center, Sacramento/ expression of PD-L1 is a better prognostic factor for overall survival in SCC.
AL/United States of America, 6University of California Davis School of Medicine,
Sacramento/AL/United States of America, 7Guardant Health, Inc., Redwood City/
CA/United States of America, 8Division of Hematology & Oncology, University of
California Davis Comprehensive Cancer Center, Sacramento/CA/United States of
America JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
AGAINST LUNG CANCER SESSION
Background: Next generation sequencing (NGS) has been increasingly used SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
in oncology practice but proven practically difficult when serial tumor
specimens are needed. The objectives of this study were to determine
feasibility and explore clinical utility of serial NGS analyses of circulating
JCES01.14 MUTATIONAL PROFILING OF NON-SMALL-CELL LUNG
tumor DNA (ctDNA) in patients (pts) with advanced solid tumors undergoing CANCER PATIENTS RESISTANT TO FIRST-GENERATION EGFR
treatment. Methods: ctDNA digital NGS was performed by a CLIA-certified TYROSINE KINASE INHIBITORS USING NEXT GENERATION
lab (70-gene panel with mutant allele fraction (MAF) quantification). ctDNA SEQUENCING
results were retrospectively analyzed and decreases/increases/stability of Ying Jin1, Xinmin Yu2, Xun Shi2, Yiping Zhang2, Guangyuan Lou2
molecular tumor load (MTL) defined here as MAFs of truncal driver mutations 1
Zhejiang Cancer Hospital, Hangzhou/China, 2Medical Oncology, Zhejiang Cancer
were correlated with clinical and radiographic response to treatment Hospital, Hangzhou/China
(response, progression, or stable disease, respectively). Results: From Jan
2015 to July 2016, 38 consecutive pts with advanced lung tumors (84% LUAD, Background: Patients with advanced non-small-cell lung cancer (NSCLC)
5% LUSC, 5% SCLC, 5% NOS) receiving treatment (Table) had serial ctDNA harboring sensitive epithelial growth factor receptor (EGFR) mutations
analyses (median 2, range 2-7). ctDNA alterations were detected at least once invariably develop acquired resistance to EGFR tyrosine kinase inhibitors
in 37 (97.4%) pts. Changes in MTL correlated with or predicted all (95% CI, (TKIs). Although previous research have identified several mechanisms of
82.0-99.8%) radiological and/or clinical responses except for the patient with resistance, the systematic evaluation using next generation sequencing (NGS)
no genomic alteration detected. MTL results clarified response status when to establish the genomic mutation profiles at the time of acquired resistance
radiographic responses were difficult to assess in 9 (28%) of pts with either has not been conducted. Methods: In our single center, we performed NGS
complex pleural disease (n=6), pneumonitis during PD-1 inhibitor therapy (2). of a pre-defined set of 416 cancer-related genes in a cohort of 97 patients
Two MTL change patterns were observed: 1) clonal changes while receiving with NSCLC harboring TKI-sensitive EGFR mutations at the time of acquired
targeted therapy, including EGFR (12), ALK (3), MET (2), ERBB2 (2); 2) global resistance to first-generation EGFR-TKIs between January 2015 to December
changes to PD-1 inhibitors, chemotherapy or radiation. Representative tumor 2015. Results: In 97 samples we found total 345 gene alterations (mean 3.6
response maps will be presented. mutations per patient, range 1-10). Fifty-six patients (57.7%) still exhibit
EGFR-sensitive mutations as pretreatment, 93 patients (95.9%) exhibit at
Table. Summary of tumor types and cancer treatment. least one mutation except for previous existed EGFR-sensitive mutations. In
all the 97 patients, most frequently mutated genes were TP53 (59.8%), T790M
Targeted Immuno- Chemo- (28.9%), TET2 (11.3%), EGFR amplification (10.3%), PIK3CA (8.2%), BIM (8.2%),
Cancer Type Radiation TOTAL KRAS (7.2%), APC (7.2%), RB1 (7.2%), HER2 (6.2%), DNMT3A (6.2%) and MET
Therapy therapy therapy
(5.2%). Conclusion: NGS in this study uncovered many new genetic alterations
LUAD 14 8 7 3 32 potentially associated with EGFR TKI resistance and provided information
LUSC 1 1 0 0 2 for the further study of drug resistance and corresponding relevant tactics
against the challenge of disease progression.
SCLC 0 0 2 0 2
NOS 1 0 1 0 2
All 16 9 10 3 38
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
Conclusion: Serial liquid biopsies and ctDNA digital NGS are feasible and AGAINST LUNG CANCER SESSION
clinically useful in monitoring MTL and genomic alterations during cancer SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
treatment, especially in situations when radiographic responses are
equivocal. Prospective evaluation of impact on clinical decision making is JCES01.15 ANALYSIS OF GENOMIC ALTERATIONS AND
warranted.
HETEROGENEITY IN PULMONARY ADENOID CYSTIC CARCINOMA BY
NEXT-GENERATION SEQUENCING
Min Li, Bingrong Zhao, Pengbo Deng, Liming Cao, Huaping Yang, Qihua Gu,
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE Chengping Hu
AGAINST LUNG CANCER SESSION Department of Respiratory Medicine, Xiangya Hospital, Central South University,
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
Changsha/China
Background: Pulmonary adenoid cystic carcinoma (PACC) is one of the rare

JCES01.11 ALTERED EXPRESSION OF PROGRAMMED DEATH-
malignancies, that primary from glandular tissues of lung. Currently, the
LIGAND 1 AFTER NEO-ADJUVANT CHEMOTHERAPY IN PATIENTS treatment of PACC relies on surgery and local radiotherapy. However the
WITH LUNG SQUAMOUS CELL CARCINOMA therapy for advanced PACC patients is limited. A larger number of studies
Zhengbo Song 1, Yiping Zhang2, Xinmin Yu2 demonstrated that advanced PACC patients obtained little benefit from
1
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer chemotherapy. Moreover, only a few case reports revealed PACC patients were
Hospital, Hangzhou/China appropriate for target therapy. Using high-flux and high-resolution techniques
to detect the genomic alterations of PACC could provide theoretical
Background: Programmed death-ligand 1 (PD-L1) is known to be over-expressed foundation for the precision therapy of PACC. Methods: 8 PACC patients
in non-small cell lung cancer (NSCLC). However, the impact of chemotherapy who received surgical resection between January 2013 to December 2015
on the altered status of PD-L1 expression has not been examined for NSCLC. were enrolled. The tumor tissues from different locations and blood samples
The present study was intended to examine the impact of neoadjuvant were collected. The oncoscreenTM panel by Illumina platform, which utilizing
chemotherapy on PD-L1 expression and its prognostic significance in lung probe hybridization to gathering 287 exon regions and 22 intron regions,
squamous cell carcinoma (SCC). Methods: Matched tumor samples were were used to detect the gene mutation status of PACC. And the embryonal
obtained from SCC patients prior to and after neoadjuvant chemotherapy. The system mutations were filtered by contrasting the gene mutation status of
expression of PD-L1 was evaluated by immunohistochemistry. Survival analysis the leukocytes. The tumor heterogeneity was revealed by comparing the gene
was performed by the Kaplan-Meier method. mutation status in different areas of the same PACC, and the phylogenetic
relationships were analyzed to disclose the evolving and developing
Results: A total of 76 eligible SCC patients were recruited. There were 51 males
progression of PACC. Results: There were 69 gene mutations together among
and 25 females with a median age of 60 (39-72) years. The smoking status
8 patients including 29 samples. Each patient has 8.6 mutations averagely.
was former (n=46) and never (n=34). Prior to neoadjuvant chemotherapy,
The high-frequency mutations were PAK3-D219E, FBXW7-D112E, TET2-T418I, metastasis is limited due to poor drug penetration into the brain. Epitinib is
KAT6A-E796A, and MET-R1005Q. However, the common mutations in other an EGFR TKI designed to improve brain penetration. A Phase I dose escalation
NSCLC, like EGFR, KRAS, ALK, etc., weren’t happened in this group of PACC. In study on epitinib has been completed and the recommended Phase 2 dose
this study, the spatial heterogeneity was discovered in PACC, not only in the (RP2D) determined (Y-L Wu, 2016 ASCO). This Phase I dose expansion study
mutation site, but also in the mutant abundance. Moreover, the phylogenetic was designed to evaluate the efficacy and safety of epitinib in EGFR-mutant
relationships revealed that the clonal evolution and development existed in NSCLC patients with brain metastasis. Methods: This is an ongoing open
PACC. Conclusion: The status of genomic alterations in PACC was different label, multi-center Phase I dose expansion study. EGFR-mutant NSCLC
from the other non-small cell lung cancer (NSCLC). PACC showed obvious patients with confirmed brain metastasis, either prior EGFR TKI treated or
spatial heterogeneity and clonal evolution. EGFR TKI treatment naïve, were enrolled to receive oral epitinib 160 mg per
day. Patients with extra-cranial disease progression while on treatment
with an EGFR TKI were excluded. Tumor response was assessed per RECIST
1.1. Results: As of 31 May, 2016, 27 patients (13 EGFR TKI pretreated, 14 EGFR
TKI treatment naïve) have been enrolled and treated with epitinib. The most
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE frequent adverse events (AEs) were skin rash (89%), elevated ALT (41%)/AST
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45 (37%), hyper-pigmentation (41%) and diarrhea (30%). The most frequent
Grade 3/4 AEs were elevations in ALT (19%), gamma-GGT (11%), AST (7%),
hyperbilirubinemia (7%) and skin rash (4%). There have been no Grade 5 AEs
JCES01.16 A MET INHIBITOR IN THE TREATMENT OF METASTATIC to date. Among the 24 efficacy evaluable patients (11 TKI pretreated, 13 TKI
NON SMALL CELL LUNG CANCER WITH MET AMPLIFICATION naïve), 7 (7/24, 29%) achieved a partial response (PR), including 1 unconfirmed
Tongtong Zhang1, Junling Li2 PR. All PRs occurred in EGFR TKI treatment naïve patients (7/13, 53.8%). Of the
1
Department of Medical Oncology, Cancer Institute & Hospital, Peking Union 24 evaluable patients, 8 (5 EGFR TKI treatment naïve, 3 EGFR TKI pretreated)
Medical College/chinese Academy of Medical Science, Beijing/China, 2Cancer had measurable brain metastasis (lesion diameter>10 mm per RECIST 1.1)
Institute & Hospital, Peking Union Medical College/chinese Academy of Medical with 2 PRs (both EGFR TKI treatment naïve patients, 2/5, 40%). Conclusion:
Science, Beijing/China Epitinib 160mg per day treatment in EGFR-mutant NSCLC patients with
brain metastasis demonstrated clinical activity both extra- and intra-cranial.
Background: Amplification of the mesenchymal-epithelial transition Epitinib was well tolerated. The data to date appears encouraging and
factor (MET) gene plays a vital role in non-small cell lung cancer (NSCLC). warrants further development of epitinib.
The anti-MET therapeutic strategies are still unclear in epidermal growth
factor receptor (EGFR) mutant patients and EGFR-naive patients. Aims
of our study are to discuss role of MET amplification in Chinese NSCLC
patients, and evaluate the antitumor activity of crizotinib (MET inhibitor) JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
in Chinese NSCLC patients with MET gene amplification. Methods: From AGAINST LUNG CANCER SESSION
Jun 2015 to Jan 2016, we detected 11 metastatic NSCLC patients with MET SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
amplification by fluorescence in situ hybridization (FISH). MET amplification
was defined as gene focal amplification or high polysomy (at least 15% cells
JCES01.18 DUAL POSITIVE PD-L1 AND CD8+ TIL REPRESENTS A
with ≥5 copy numbers). Patients with MET de novo amplification received
PREDOMINANT SUBTYPE IN NSCLC AND CORRELATES WITH
crizotinib, patients with concomitant MET acquired amplification and EGFR
mutation received combined therapy of EGFR-tyrosine kinase inhibitors AUGMENTED IMMUNOGENICITY
(TKIs) (gefitinib, erlotinib, icotinib)and crizotinib. All enrolled subjects Si-Yang Liu1, Zhong-Yi Dong2, Wen-Zhao Zhong 3, Si-Pei Wu1, Zhi Xie2, Hai-Yan
received tumor measurement according to RECIST1.1 Results: The frequency Tu4, Yi Long Wu5
1
of MET de novo amplification was 54.5%(6/11), and that of concomitant MET Guangdong Lung Cancer Institute; Guangdong General Hospita & Guangdong
acquired amplification and EGFR mutation was 45.5%(5/11) respectively. 4 of Academy of Medical Sciences, Guangzhou/China, 2Guangdong Lung Cancer
6 patients with MET de novo amplification received crizotinib, 2 patients had Institute, Guangdong General Hospital, Guangzhou/China, 3Department of
partial response (PR), 1 patient had stable disease (SD), 1 patient died due to Pulmonary Oncology, Guangdong General Hospital & Guangdong Academy
of Medical Sciences, Guangzhou/China, 4 Guangdong Lung Cancer Institute,
heart disease. Response rate (RR) of crizotinib was 50%(2/4). Encouraging
Guangdong General Hospital & Guangdong Academy of Medical Sciences,
response was observed in one case, a CT scan performed 31 days after starting Guangzhou/China, 5 /
crizotinib revealed 42.2% decrease in tumor measurement, until now, a
7-month CT revealed 60.0% decrease. 3 of 5 patients with concomitant MET Background: Recent studies have identified that the degree of tumor
acquired amplification and EGFR mutation received the combined therapy infiltrating lymphocyte (TIL) infiltration and PD-L1 expression in the tumor
of EGFR-TKIs and crizotinib. 1 patient achieved PR, 2 patients had SD. RR microenvironment (TME) are significantly correlated with the clinical
of combined therapy was 33.3%(1/3). Dramatic response was observed in outcomes of anti-PD-1/PD-L1 therapies. Here we conducted this study to verify
one case with combined therapy, a 2-month CT revealed 31.0% decrease in the distribution of PD-L1/CD8+ TIL expression and its clinical significance in
tumor measurement. Conclusion: According to our study, patients with MET non-small cell carcinoma (NSCLC). Potential mechanism predicted for PD-1
amplification benefited from crizotinib, and RR was inspiring. Patients with blockade was explored in depth as well. Methods: Immunohistochemistry
concomitant MET acquired amplification and EGFR mutation need combined was performed to detect PD-L1 and CD8 expression in NSCLC. The Kaplan–
targeted therapy. Meier (KM) survival curve was used to estimate disease free survival (DFS)
and overall survival (OS). Gene Set Enrichment Analysis (GSEA) was used to
determine potentially relevant gene expression signatures.
Results: 288 cases with stage I-IIIA NSCLC were evaluated for PD-L1 and
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE CD8+ TIL staining. Dual positive PD-L1 and CD8 (PD-L1+/CD8+) represents a
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45 predominant subtype in NSCLC, accounting for 36.5% (105/288), followed by
PD-L1-/CD8- (24.3%, 70/288), PD-L1-/CD8+ (26.0%, 75/288) and PD-L1+/CD8-
(13.2%, 38/288). Survival analysis of DFS (p=0.031) and OS (p=0.002) showed
JCES01.17 A PHASE I DOSE EXPANSION STUDY OF EPITINIB TO a significant difference between four subgroups. Furthermore, we analyzed
EVALUATE EFFICACY AND SAFETY IN EGFR MUTATION POSITIVE the correlation between expression types of PDL1/CD8 and mutation burden
(EGFRM+) NSCLC PATIENTS WITH BRAIN METASTASIS and angtigen presentation. We can identified dual positive PD-L1 and CD8
was significant with increased mutation burden (p<0.001), high frequency
Qing Zhou1, Bin Gan2, Qunying Hong 3, Mengzhao Wang4, Xiaoqing Liu5, Liwei
of mismatch repair (MMR) related gene mutation. More interestingly, tumor
Yuan6, Ye Hua7, Hongcan Ren6, Weiguo Su7, Yi Long Wu8
1 with dual positive PD-L1 and CD8 manifested a remarkable activated angtigen
Guangdong Lung Cancer Institute; Guangdong General Hospital(GGH)&
presentation and T cell receptor signature compared with other subgroups.
Guangdong Academy of Medical Sciences, Guangzhou/China, 2Guangdong Lung
Cancer Institute, Guangdong General Hospital (GGH)and Guangdong Academy Conclusion: Dual positive PD-L1 and CD8 was identified as a predominant
of Medical Sciences, Guangzhou/China, 3 Zhongshan Hospital, Shanghai Fudan subtype in NSCLC and correlates with increased immunogenicity. These
University, Shanghai/China, 4Peking Union Medical College Hospital, Beijing/China, findings provide the evidence that combined analysis of PD-L1 and CD8 in
5
Department of Pulmonary Oncology, 307 Hospital of the Academy of Military NSCLC may be a promising way to predict PD-1 blockade immunotherapy.
Medical Sciences, Cancer Center, Beijing/China, 6Hutchison Medipharma Ltd,
Shanghai/China, 7Hutchison Medipharma Limited, Shanghai/China, 8 /
Background: A significant portion of patients with non-small cell lung cancer

(NSCLC) develop brain metastasis. Patients with brain metastasis suffer JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
from poor prognosis with a median survival of less than 6 months and low AGAINST LUNG CANCER SESSION
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
quality of life with limited treatment options. First generation EGFR tyrosine
kinase inhibitors (EGFR TKIs) have demonstrated significant clinical benefit
for patients with EGFR-mutant NSCLC. However, their effect on brain JCES01.19 CLINICOPATHOLOGIC CHARACTERISTICS,

GENETIC VARIABILITY AND THERAPEUTIC OPTIONS OF RET PULMONARY NEUROENDOCRINE CARCINOMA WITH COMPLETELY
REARRANGEMENT PATIENTS IN LUNG ADENOCARCINOMA RESECTION
Zhengbo Song 1, Xinmin Yu2, Yiping Zhang2 Guangyuan Lou1, Zhengbo Song 2, Yiping Zhang1
1
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer 1
Hospital, Hangzhou/China Hospital, Hangzhou/China
Background: RET fusion gene is identified as a novel oncogene in a subset of Background: According to the 2015 World Health Organization classification
non-small cell lung cancer (NSCLC). However, few data are available about of lung tumors, pulmonary Large cell neuroendocrine carcinoma (PLCNC) is
the prevalence, clinicopathologic characteristics, genetic variability and grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary
therapeutic options in RET-positive lung adenocarcinoma patients. Methods: neuroendocrine carcinoma(PNC) for the common features of neuroendocrine
For 615 patients with lung adenocarcinoma, RET status was detected by characteristics . Molecular profiles and prognosis of primary pulmonary
reverse transcription-polymerase chain reaction (RT-PCR). Next-generation neuroendocrine carcinoma(PNC) are not well investigated currently. We
sequencing (NGS) and FISH were performed in positive cases. Thymidylate conducted present study to evaluate genomic abnormality and survivals in
synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) patients with primary PNC. Methods: Tumor samples of PNC after completely
was evaluated by Kaplan-Meier method and compared with log-rank test. resection from Zhejiang Cancer Hospital were collected from 2008 to 2015.
Results: Twelve RET-positive patients were identified by RT-PCR. However, Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF,
one patient failed the detection of RET arrangement by FISH and NGS. Totally, HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival
11 patients (1.8%) confirmed with RET rearrangements by three methods analysis was evaluated using the Kaplan-Meier method. Results: Totally, 108
, including six females and five males with a median age of 54 years. The patients with pathologic confirmed PNC were enrolled. Samples included
presence of RET rearrangement was associated with lepidic predominant lung 52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients
adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised were found to harbor genomic aberrations (11.1%). The most frequent gene
of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent abnormality was PIK3CA (n=5,4.6%),followed with EGFR (n=3,2.8%), KRAS
gene variability by NGS detection,including EGFR(n=1),MAP2K1 (n=1), CTNNB1 (n=2,n=1.9%), ALK (n=1,0.9%), RET (n=1,0.9%). No ROS1,BRAF,NRAS and HER2
(n=1) and AKT1 (n=1) . No survival difference existed between RET-positive and mutations were observed. The frequencies of gene aberrations in PLCNC,
negative patients (58.1 vs. 52.0 months, P=0.504) . The median progression- SCLC and carcinoid were 15.4%,6.8% and 8.3%,respectively. Sixty-seven
free survival of first-line pemetrexed/platinum regimen was 7.5 months for patients were with recurrence or metastasis after surgery, including 32
four recurrent cases,and longer than RET-negative patients(7.5 vs.5.0 months, PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among
P=0.026). . The level of TS mRNA was lower in RET-positive patients than that the 32 patients with PLCNC,none received molecular targeted treatment,28
in those RET-negative counterparts (239±188×10 -4 vs. 394±457×10 -4,P=0.019) received first-line chemotherapy, including 18 of etoposide/platinum regimen
. Conclusion: The prevalence of RET fusion is approximately 1.8% in Chinese and 10 of other platinum-based treatment. The progression free survival in
patients with lung adenocarcinoma. RET arrangement is characterized by patients with etoposide/platinum regimen was longer than patients with
lepidic predominance and a lower TS level. RET-rearranged patients may non-etoposide/platinum treatment (4.8 vs.3.4 months,P=0.019) . Survival
benefit more from pemetrexed-based regimen. difference was observed among the PLCNC,SCLC and carcinoid group (37.0 vs.
34.0 vs.not reached, P=0.035), but no difference existed between the PLCNC
and SCLC group (P=0.606). Conclusion: Common genomic abnormality is
rare in PNC patients and most frequently observed in PLCNC. Patients with
carcinoid had a superior survival than PLCNC and SCLC.
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
JCES01.20 PATIENTS WITH ROS1 REARRANGEMENT POSITIVE NON- JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
SMALL CELL LUNG CANCER BENEFIT FROM PEMETREXED-BASED SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
CHEMOTHERAPY
Zhengbo Song 1, Yiping Zhang2, Xinmin Yu2
1
JCES01.22 COMPARISON OF FOUR LEADING TECHNOLOGIES FOR
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer
Hospital, Hangzhou/China
DETECTING EGFR MUTATIONS IN CIRCULATING TUMOR DNA FROM
PATIENTS WITH NON-SMALL CELL LUNG CARCINOMA
Background: ROS1 gene-rearrangement in non-small cell lung cancer (NSCLC) Xiaozheng Kang1, Ting Xu2, Guobin Xu3, Ke-Neng Chen4
patients has recently been identified as a driver gene and benefited from 1
Department of Thoracic Surgery I, Peking University Cancer Hospital and Institute,
crizotinib treatment. However, no data is available for ROS1-positivity NSCLC Beijing/China, 2Peking University Cancer Hospital and Institute, Beijing/China,
about chemotherapeutic options and prognostic data. We investigated 3
Department of Clinical Laboratory, Key Laboratory of Carcinogenesis and
pemetrexed-based treatment efficacy in ROS1 translocation NSCLC patients Translational Research (Ministry of Education), Peking University Cancer Hospital
and determined the expression of thymidylate synthetase (TS) to provide a and Institute, Beijing/China, 4The First Department of Thoracic Surgery, Beijing
rationale for the efficacy results. Methods: We determined the ROS1 status Cancer Hospital, Beijing/China
of 1750 patients with lung adenocarcinoma. Patients’ clinical and therapeutic
Background: This study aimed to assess the ability of different technology
profile were assessed. In positive cases, thymidylate synthetase (TS) mRNA
platforms to detect epidermal growth factor receptor (EGFR) mutations
level was performed by RT-PCR. For comparison, we evaluated the TS mRNA
including L858R, E19-dels, T790M, and G719X from circulating tumor DNA
status and pemetrexed-based treatment efficacy from 170 NSCLC patients
(ctDNA) in patients with non-small cell lung cancer (NSCLC). Methods: Plasma
with anaplastic lymphoma kinase (ALK) translocation(n=46), EGFR mutation
samples were collected from 20 patients with NSCLC including detailed
(n=50), KRAS mutation (n=32) and wild-type of EGFR/ALK/ROS1/KRAS (n
clinical information along with data regarding treatment response. ctDNA
= 42). Results: Thirty-four ROS1 translocation patients were identified at
was extracted from 10 mL plasma using the QIAamp Circulating Nucleic Acid
two institutions. Among the 34 patients, twelve with advanced stage or
Kit (Qiagen). Extracted ctDNA was analyzed using two real time-amplification
recurrence were treated with pemetrexed-based first-line chemotherapy.
refractory mutation system-quantitative PCR platforms (cobas® EGFR
The median progression-free survivals of pemetrexed-based first-line
Mutation Test: cobas; and AmoyDx® EGFR 29 Mutations Detection Kit:
chemotherapy in ROS1 translocation, ALK translocation, EGFR mutation,
ADx), one digital platform (Droplet DigitalTM PCR, ddPCR: Bio-rad), and one
KRAS mutation and EGFR/ALK/ROS1/KRAS wild-type patients were 6.8, 6.7,
next-generation sequencing platform (firefly NGS: Accuragen). Results: If a
5.2, 4.2 and 4.5 months, respectively (P=0.003). The TS mRNA level was lower
positive result was obtained from any one of the four platforms, the sample
in patients with ROS1-positive than ROS1-negative patients (264±469×10 -4 vs.
was categorized as positive. We identified 15 EGFR mutations in 20 patients
469 ± 615×10 -4 , P=0.03), but similar with ALK-positive patients (264±469×10-4
with NSCLC using the four platforms, for which 7, 11, 10, and 12 mutations
vs. 317±524×10 -4, P=0.64).
were detected by ADx, cobas, ddPCR, and firefly NGS, respectively. Among
Conclusion: Patients diagnosed with ROS1 translocation lung adenocarcinoma the 15 EGFR mutations, six and seven EGFRalterations demonstrated an
may benefit from pemetrexed-based chemotherapy. TS mRNA level enables allele frequency of more or less than 1% (group A or B, respectively), and two
the selection of therapeutic options for ROS1translocation patients. exhibited unknown allele frequency. In group A, 5, 5, 5, and 6 EGFR mutations
were detected by ADx ,cobas, ddPCR, and firefly NGS, respectively. The
positive coincidence rate of any two platforms ranged from 66.7% to 100%
and the kappa value varied from 0.787 to 1.000 in group A. In group B, 1, 5, 5,
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE and 6 EGFR mutations were detected and the positive coincidence rate of
AGAINST LUNG CANCER SESSION any two platforms ranged from 16.7% to 100% and the kappa value varied
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
from 0.270 to 1.000. The output of cobas, ddPCR, and firefly NGS were highly
correlated, whereas ADx displayed weak concordance with these three
JCES01.21 MOLECULAR PROFILING AND SURVIVAL OF PRIMARY platforms in group B. In addition, we identified 75 wild-type loci when EGFR
alleles identified as negative by one or more platforms were considered as
negative. ADx, cobas, ddPCR, and firefly NGS uncovered 73, 69, 70, and 68 JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE
EGFR wild-type loci, respectively. The concordance and negative coincidence SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
rates between any two platforms were over 90%. Conclusion: The detection
rate and concordance were probably affected by the abundance of EGFR
mutations and the sensitivity of different platforms. Three platforms, JCES01.24 MOLECULAR MECHANISM OF TRANSFORMATION FROM
including cobas, ddPCR, and firefly NGS, exhibited higher positive coincidence ADENOCARCINOMA TO SMALL-CELL LUNG CANCER AFTER EGFR-
and detection rates when the allele frequency was lower than 1%. TKI
Jiefei Han1, Qiuyi Zhang2, Binchao Wang 3, Qing Zhou2, Lixu Yan3, Zhou Zhang 3,
Huajun Chen3, Jian Su4, Zhi Xie5, Feiyu Niu3, Yi Long Wu6, Shannon Chuai7, Jinji
Yang8, Zhong-Yi Dong 5
1
JCES01: JOINT IASLC - CHINESE SOCIETY FOR CLINICAL ONCOLOGY - CHINESE ALLIANCE Guangdong Lung Cancer Institute, Guangzhou/China, 2Guangdong Lung Cancer
AGAINST LUNG CANCER SESSION Institute; Guangdong General Hospital(GGH)& Guangdong Academy of Medical
SUNDAY, DECEMBER 04, 2016 - 08:00-11:45
Sciences, Guangzhou/China, 3Guangdong Lung Cancer Institute, Guangdong
General Hospital & Guangdong Academy of Medical Sciences, Guangdong Key
Laboratory of Lung Cancer Translational Medicine, Guangzhou/China, 4 Guangdong
JCES01.23 EGFR MUTATION STATUS ANALYSIS IN CEREBROSPINAL
Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational
FLUID AND PLASMA OF ADVANCED LUNG ADENOCARCINOMA Medicine in Lung Cancer, Guangdong General Hospital & Guangdong Academy
WITH BRAIN METASTASES of Medical Sciences, Guangzhou/China, 5Guangdong Lung Cancer Institute,
Liang Shi1, Zhe Liu2, Jungfang Tang1, Hongbo Wu1, Lili Guo1, Mingzhi Li1, Li Guangdong General Hospital, Guangzhou/China, 6 /, 7Burning Rock Dx Ltd,
Guangzhou/China, 8 Guangdong Lung Cancer Institute, Institution: Guangdong
Tong1, Wei Wu3, Hong Tao1, Weihua Wu1, Hongxia Li3, Qiyi Meng1, Liyan Xu1,
General Hospital and Guangdong Academy of Medical Sciences, Guangzhou/China
Yunzhong Zhu1
1
Oncology, Beijing Chest HospitaL, Capital Medical University, Beijing/China, Background: In patients with advanced non–small-cell lung cancer (NSCLC)
2
Oncology, Beijing Chest Hospital, Capital Medical University, Beijing/China, harboring epidermal growth factor receptor (EGFR) activating mutations,
3
Beijing Chest Hospital, Beijing/China EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line
treatment due to favorable clinical efficacy. However, acquired resistance
Background: We aimed to investigate the feasibility of droplet digital PCR
inevitably develops after median progression-free survival (PFS) of 9-14
(ddPCR) for the detection of epidermal growth factor receptor (EGFR)
months. Among the mechanisms of acquired resistance, small-cell lung cancer
mutations in circulating free DNA (cfDNA) from cerebrospinal fluid (CSF) and
(SCLC) transformation was reported to account for nearly 5%. However,
plasma of advanced Lung Adenocarcinoma (ADC) with brain metastases (BM).
the molecular details underlying this histological change and resistance to
Methods: Fourteen advanced ADC patients with BM carrying activating EGFR
EGFR-TKI therapy remain unclear. Methods: 15 out of 233 (6.4%) patients
mutations in tumour tissues were enrolled in this study, and their matched
were confirmed to develop SCLC transformation after failure to EGFR-TKI.
CSF and plasma samples were collected. EGFR mutations were detected by
We analyzed the clinical parameters of these patients by using chi-square
the Amplification Refractory Mutation System (ARMS) in tumour tissues.
test and Kaplan-Meier analysis. To explore gene alterations that might
EGFR mutations, including 19del, L858R, and T790M were examined in cfDNA
contribute to SCLC transformation, next generation sequencing (NGS) was
isolated from 2milliliter CSF or plasma by ddPCR assay. The clinical response
performed on four pairs of matched pre- and post-transformation tumor
was assessed according to Response Evaluation Criteria in Solid Tumors
tissue samples. We further performed NGS on 11 matched circulating tumor
(RECIST) version 1.1 guidelines. Overall survival (OS) and progression free
DNA (ctDNA) to explore the potential mechanism of resistance to EGFR-TKI.
survival (PFS) after the diagnosis of BM were also evaluated. Results: Out of
Results: The median age of SCLC transformed patients was 53 years. 93.3%
14 patients, eleven were females and three males aged from 34 to 74 years
(14/15) patients harbored EGFR exon19 deletion. The median PFS and overall
old (median age of 55 years old). In all of cases, CSF cytology were negative.
survival (OS) of SCLC-transformed patients treated with EGFR-TKI compared
In ddPCR assays, EGFR mutations were detected in CSF of three patients
to those without transformation were 11.7 versus 11.9 months (P=0.473) and
(21.4%; one of 19del and two of L858R), and in plasma of six patients (42.9%;
29.4 versus 24.3 months (P=0.664), respectively. All 4 patients developed
one of 19del, one of L858R, one of T790M, two of L858R&T790M, and one of
loss of heterozygosity of TP53/RB1 after transformation. Besides, increased
19del&T790M). All EGFR T790M mutations were found during or after EGFR-
copy number of five proto-oncogenes were identified in post-transformation
TKIs treatments. The three patients with activating EGFR mutations in CSF
tissue samples. Three patients developed EGFR T790M mutation in the
achieved partial response (PR) of BM after treated with combination of WBRT
post-transformation ctDNA rather than their tissue samples. Conclusion:
and EGFR-TKIs. The median OS and PFS after the diagnosis of BM were 18.0
SCLC transformation was commonly seen in patients harboring EGFR exon 19
months and 9.0 months, respectively.
deletion. The clinical outcomes of TKI and OS in SCLC transformed patients
were similar to non-transformed patients. The loss of heterozygosity of TP53
Tissue CSF Plasma Systematic Treat- and RB1along with increased copy number of proto-oncogenes may lead to
Patient BM Treatment
EGFR EGFR EGFR ment the SCLC transformation. The mechanisms of acquired resistance to TKI
Erotinib WBRT during SCLC transformation might be the emergence of classic drug resistance
1 19del WT T790M
+Chemotherapy +Gamma knife mutations, which was undetectable due to the intra-tumor heterogeneity.
Erotinib
2 19del WT 19del WBRT
+Chemotherapy
Gefitinib
3 L858R L858R L858R WBRT
+Chemotherapy
Gefitinib
4 L858R WT WT WBRT
+Chemotherapy
Gefitinib
5 19del WT WT WBRT
+Chemotherapy
L858R/ Erotinib
6 L858R WT WBRT
T790M +Chemotherapy
7 L858R WT WT Gefitinib WBRT
19Del/
8 19del 19Del Gefitinib WBRT
T790M
Erotinib
9 L858R WT WT NONE
+Chemotherapy
Erotinib
10 19del WT WT WBRT
+Chemotherapy
Icotinib
11 19del WT WT WBRT
+Chemotherapy
L858R/
12 L858R WT Chemotherapy WBRT
T790M
13 L858R L858R WT Icotinib WBRT
Gefitinib
14 19del WT WT WBRT
+Chemotherapy
Conclusion: It was feasible to test EGFR mutation in CSF. CSF may serve as
liquid biopsy of advanced ADC with BM by enabling measurement of cfDNA
within CSF to characterize EGFR mutations.

(NSCLC). Methods: We used logistic regression to develop a risk-prediction

ORAL ABSTRACT SESSIONS – MONDAY, DECEMBER 5, 2016 model for 30-day mortality following surgical treatment for Stage I/II NSCLC
in patients age 65 to 79 using SEER-Medicare linked databases (2007-2012).
SESSION OA01: RISK ASSESSMENT AND FOLLOW UP IN Additionally, all patients had at least 1 year of Medicare enrollment prior to
NSCLC diagnosis and received initial surgical treatment within 6 months of
SURGICAL PATIENTS diagnosis. We developed the model with a training sample of 1,571 surgical
MONDAY, DECEMBER 5, 2016 cases and conducted internal validation exercises with a sample 4,632
independent surgical cases. Models included age, sex, race, country of birth,
urban-rural status, and comorbidities in the year prior to NSCLC diagnosis.
OA01.01 INSTITUTIONAL-BASED DIFFERENCES IN THE QUALITY The Hosmer-Lemeshow test (by decile) and area under the receiver-operating
AND OUTCOMES OF US LUNG CANCER RESECTIONS characteristic curve (AUC) were assessed as measures of model calibration
Raymond Osarogiagbon1, Matthew Smeltzer2, Chun Chieh Lin3, Ahmedin and discrimination, respectively. Results: Within the full sample of 6,203
Jemal3 cases, 201 deaths were identified within 30 days of surgical treatment (3.2%
1 of sample). In the training and internal validation sets, the AUC was 0.831 and
Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis/TN/
United States of America, 2Epidemiology and Biostatistics, University of Memphis
0.734, respectively. The observed risk of 30-day mortality was 9.3-fold greater
School of Public Health, Memphis/TN/United States of America, 3Surveillance and in the highest decile of predicted risk (8.3%) vs. the lowest decile (0.7%), and
Health Services Research, American Cancer Society, Atlanta/AL/United States of the Hosmer-Lemeshow test indicated satisfactory model fit (p=0.92). The
America model had similar performance in women, men, whites, and non-whites; and
also had similar calibration and discrimination for 60- and 90-day mortality.
Background: Institutional-level differences in NSCLC survival are associated Conclusion: Our risk-prediction model has good ability to identify patients
with differences in the quality of oncologic care. We examined stage- at increased risk of mortality following surgical treatment for early-stage
stratified and overall survival of patients in different categories of US NSCLC, and pending additional development and validation, can potentially
Commission-on-Cancer (CoC)-accredited institutions, to quantify inter- be applied in clinic to inform lung cancer screening shared decision-making
institutional differences in survival-impactful quality measures and estimate with minimal time or resource impacts.
their relative survival impact, in order to identify the most impactful targets
for improvement efforts. Methods: National Cancer Data Base (NCDB) Keywords: Risk prediction, Screening, surgical mortality
institutions were grouped according to CoC category into: Community
Cancer Program (CCP), Comprehensive Community Cancer Program (CCCP),
Teaching Research Program (TRP), and NCI Program/Network (NCIP).
Resections for stage I-IIIA NSCLC in the National Cancer Data Base from
2004-2013 performed within each category of institution were examined OA01: RISK ASSESSMENT AND FOLLOW UP IN SURGICAL PATIENTS
for specific quality parameters. Survival was estimated by the Kaplan-Meier MONDAY, DECEMBER 5, 2016 - 11:00-12:30
method and compared with the log-rank test. Results: Of 125,408 NSCLC
eligible patients, 8% received surgery at CCP, 52% at CCCP, 28% at TRP,
and 12% at NCIP. The pNX rate was 8%, 5.7%, 5.5%, and 3.2% respectively OA01.03 IMPACT OF INCREASING AGE ON CAUSE-SPECIFIC
(p<.0001); the median (IQR) nodal count for pN0/1 patients was 6 (7), 7 (7), MORTALITY AND MORBIDITY IN STAGE I NSCLC PATIENTS: A
8 (9), and 10 (10) respectively, and the CoC quality criterion attainment COMPETING RISK ANALYSIS
rate (examination of >10 nodes for stage I/II patents) was 25.5%, 30.2%, Takashi Eguchi1, Sarina Bains1, Kay See Tan2, Manjit Bains1, Robert Downey1,
38.7%, and 51.4% (p<.0001). The nodal upstaging rate from clinical (c) N0 to James Huang1, James Isbell1, Bernard Park1, Valerie Rusch1, David Jones1,
pathologic N-positive was 10.4%, 10.8%, 10.7% and 13.1% (p<.0001); for cN1, Prasad Adusumilli1
nodal upstaging rate was 9.4%, 10.5%, 10.4% and 15.5% (p<.0001). There was 1
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center,
no significant inter-institutional difference in 5-year OS for stage I/II patients New York/NY/United States of America, 2Epidemiology and Biostatistics, Memorial
with pNX resections: 0.47 v 0.50 v 0.51 v 0.54 (log-rank p=.27), whereas stage Sloan Kettering Cancer Center, New York/NY/United States of America
I/II patients with resections meeting or failing the CoC quality standard had
persistent inter-institutional survival differences. For those with <10 nodes, Background: At the time of diagnosis, two-thirds of patients with lung cancer
5-year survival was 0.59 v 0.63 v 0.65 v 0.69 (log-rank p<.0001) and for those are ≥65 years of age with significant comorbidities. We sought to determine
with >10 nodes, it was 0.62 v 0.64 v 0.67 v 0.69 (log-rank p<.0001). Conclusion: the short- and long-term cancer- and noncancer-specific mortality and
Striking differences in the quality and accuracy of NSCLC pathologic nodal morbidity in patients who underwent resection for stage I non-small cell lung
staging exist between the different categories of CoC-accredited facilities. cancer (NSCLC). Methods: Of 5371 consecutive patients who had undergone
Institutions with higher quality staging have significantly better stage- curative-intent resection of primary lung cancer (2000–2011), 2186 patients
stratified OS. This inter-institutional survival difference disappears in the with pStage I NSCLC were included in the analysis. All preoperative clinical
patients without examination of any lymph nodes, who arguably have variables known to affect outcomes were considered, including, Charlson
similarly bad quality pathologic nodal staging. However, adjustment for other comorbidity index, predicted postoperative (ppo) diffusion capacity of the
measures of pathologic nodal staging quality failed to eliminate the inter- lung for carbon monoxide (DLCO), and ppo–forced expiratory volume in 1
institutional survival disparity. Further investigation of inter-institutional second (FEV1). Association between factors and cause-specific mortality was
practice differences is needed to understand the institutional-level difference performed using competing risks approach. Results: Of 2186 patients, 1532
in survival after lung cancer surgery. patients (70.1%) were ≥65 years of age, including 638 patients (29.2%) ≥75
years of age. In patients ≥65 years of age, for up to 2.5 years after resection,
Keywords: Survival disparities, Quality of care, Surgical resection, Staging noncancer-specific CID was higher than lung cancer–specific CID, the higher
noncancer-specific early-phase mortality was enhanced in patients ≥75 years
of age compared with 65-74 years of age (Figure 1a). Multivariable analyses
adjusted by age, sex, smoking status, comorbidities, tumor size, and surgical
OA01: RISK ASSESSMENT AND FOLLOW UP IN SURGICAL PATIENTS procedures showed that low ppoDLCO was an independent predictor for
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 severe morbidity (p<0.001), 1-year mortality (p<0.001), and noncancer-specific
mortality (p<0.001), whereas low ppoFEV1 for lung cancer–specific mortality
OA01.02 A LUNG CANCER SURGICAL MORTALITY RISK-PREDICTION (p=0.002). PpoDLCO can be used for estimation of 5-year cumulative incidence
of noncancer death (Figure 1b, right, red curve) because of its linear relation,
ALGORITHM TO INFORM LUNG CANCER SCREENING SHARED
whereas ppoFEV1 for lung cancer-specific death (Figure 1b, left, black curve).
DECISION-MAKING
Conclusion: In patients undergoing curative-intent resection of stage I NSCLC,
Joshua Roth1, Scott Ramsey2 noncancer-specific mortality is a significant competing event, with increasing
1
Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer impact as patient age increases.
Research Center, Seattle/United States of America, 2Hutchinson Institute for
Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle/WA/
Background: Low-dose computed tomography lung cancer screening has been

demonstrated to increase detection of cases at an early-stage and reduce lung
cancer mortality (vs. x-ray or no screening). However, screening benefits are
greatly reduced in persons who are poor candidates for curative intent surgery
in the event of screen-detected early-stage disease. To date, no practical tools
have been developed to assess potential suitability for surgical treatment
at the time of screening shared decision-making. The objective of this study
was to use readily available socio-demographic and medical history variables
to develop a prediction model that estimates the risk of 30-day mortality
following surgical treatment for early-stage non-small cell lung cancer
complications in lung cancer patients with CPFE.
Keywords: lung age, postoperative complications, lung cancer, Combined

pulmonary fibrosis and emphysema
OA01: RISK ASSESSMENT AND FOLLOW UP IN SURGICAL PATIENTS

MONDAY, DECEMBER 5, 2016 - 11:00-12:30
OA01.06 EARLY POST-OPERATIVE AMBULATION AFTER THORACIC

SURGERY - THE WAVE EXPERIENCE
Sandeep Khandhar 1, Christiana Powers1, Christy Schatz2, Carolyn Rosner2,
Amit Mahajan3, Paul Kiernan4
1
Thoracic Surgery, Cvtsa, Falls Church/United States of America, 2Inova Fairfax,
Falls Church/VA/United States of America, 3Thoracic Surgery, Cvtsa, Falls Church/
VA/United States of America, 4 Cvtsa, Falls Church/VA/United States of America
Background: The occurrence of minimally invasive thoracic surgery

interventions has grown steadily since the early 1990s, yet practice patterns
for peri-operative management of these patients has lagged behind
technical progress. Our thoracic program has created WAVE (Walking After
VATS Experiment) which focuses on a multidisciplinary approach to early
ambulation after thoracic surgery. A report from our first 3 years of data
(July 2010 - July 2013) was presented at the 2013 IASLC meeting in Sydney,
Australia. In response to the positive comments, we have continued our
endeavor and in addition, investigated 30 day outcomes and length of stay
for the homogeneous subset of anatomic lobectomy. Methods: Data was
collected from a single surgeon at a single center and includes all consecutive
thoracic surgical patients recovered through the WAVE program from July
2010 - July 2016. We excluded patients undergoing tracheostomy, endoscopic
only procedures, and mediastinoscopy. Data was collected prospectively and
analyzed retrospectively. Results: From July 2010 - July 2016, 1152 patients
were included for analysis. Within the 6 year period, 798/1152 patients (69%)
walked any distance within one hour of extubation, 945/1152 patients (82%)
walked 250 feet at any time while in the PACU, 721/1152 patients (63%)
successfully walked the targeted distance of 250 feet within one hour of
extubation and only 37/1152 patients (3%) were unable to ambulate at all in
Keywords: competing risk, lung resection, Comorbidity, Pulmonary Function the PACU. There were no adverse events. The subset of anatomic lobectomies
included 290 patients of which 197/290 patients (68%) walked any distance
within one hour of extubation, 239/290 patients (82%) successfully walked
250 feet at any time while in the PACU, 175/290 patients (60%) achieved the
OA01: RISK ASSESSMENT AND FOLLOW UP IN SURGICAL PATIENTS target distance of 250 feet within one hour of extubation and only 5/290
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
patients (1.7%) were unable to ambulate at all in the PACU. The rate of 30 day
post-operative complications compares favorably with the literature and are
OA01.05 THE IMPACT OF LUNG AGE ON POSTOPERATIVE as follows: 4.1% atrial arrhythmia, 1.0% pneumonia, 6.6% air leak > 5 days,
COMPLICATIONS IN PATIENTS WITH LUNG CANCER COMBINED 0.7% DVT, 0.3% acute renal failure, 0.3% pulmonary embolism, 0% stroke,
0% myocardial infarction, 4.8% readmission and 0% mortality. Mean length
WITH PULMONARY FIBROSIS AND EMPHYSEMA
of hospital stay was 1.6 days with a median of 1 day. Conclusion: Our “WAVE”
Masahito Naito, Yasuto Kondo, Hirotsugu Yamazaki, Hiroyasu Nakashima, experience reveals that aggressive early ambulation is effective in reducing
Yoshio Matsui, Kazu Shiomi, Yukitoshi Satoh post-operative complications and shortening length of stay. The platform
Kitasato University School of Medicine, Sagamiharashi/Japan is simple, reproducible and feasible for any thoracic surgical program.
Key features for successful implementation include patient and family
Background: Postoperative complications after pulmonary resection may
engagement, a multi-disciplinary team and administrative support.
cause morbidities such as prolonged hospitalization. Recently, combined
pulmonary fibrosis and emphysema (CPFE) have reportedly been linked to Keywords: Thoracic Surgery, Lung cancer resection, Post-operative Recovery,
a high risk for postoperative complications following lung cancer surgery. Early Ambulation
Moreover, some studies have claimed that lung age (LA) is associated with
postoperative complications. Here we clarify the relationship between LA
and postoperative complications in lung cancer patients with CPFE. Methods:
Among a total of 1166 consecutive patients who underwent curative resection OA01: RISK ASSESSMENT AND FOLLOW UP IN SURGICAL PATIENTS
for lung cancer from January 2004 to April 2016 at the Kitasato University MONDAY, DECEMBER 5, 2016 - 11:00-12:30
Hospital, Japan, a dataset of 36 patients with CPFE was retrospectively
analyzed. Lungs with CPFE were defined based on preoperative chest
computed tomography (CT) findings. LA was determined using the methods
OA01.07 ALTERNATIVE FOLLOW-UP METHODS BASED ON
advocated by the Japanese Respiratory Society. The difference between “real RECURRENCE PATTERNS AFTER SURGERY FOR NON-SMALL CELL
age” (RA) and LA was calculated as “RA−LA,” and patients were classified LUNG CANCER
into three groups: group A, RA−LA > 0 (n = 10); group B, −15 ≤ RA−LA ≤ 0 (n = Katsuya Watanabe 1, Kentaro Sakamaki2, Teppei Nishii2, Atsuo Gorai1,
13); group C, RA−LA < −15 (n = 13). Results: The average age was 70 (males, 69.1; Taketsugu Yamamoto2, Takuya Nagashima2, Kohei Ando2, Yoshihiro Ishikawa2,
females, 73.2) years. Thirty two patients were male and four were female. Tetsukan Woo2, Hiroyuki Adachi2, Yutaka Kumakiri2, Takamitsu Maehara2,
Almost all patients were ex- or current smokers. The average postoperative Haruhiko Nakayama2, Munetaka Masuda2
hospital stay was 16 (range, 7–56) days. There were no significant differences 1
General Thoracic Surgery, Yokohama Medical Center, Yokohama/Japan, 2Yokohama
in age, gender, smoking history, and postoperative hospital stay among City University, Yokohama/Japan
the three groups. The surgical procedures were lobectomy (n = 29),
segmentectomy (n = 2), and wedge resection (n = 5). Histologically, the Background: There is no consensus for the appropriate follow-up of patients
tumors were squamous cell carcinoma (n = 22), adenocarcinoma (n = 9), and after complete resection of non-small cell lung cancer (NSCLC). Our study
other types (n = 4). Postoperative complications were arrhythmia (4 cases), was designed to visually represent postoperative recurrence patterns for
hypertension (4 cases), air leakage (3 cases), pneumonia (5 cases), hypoxemia NSCLC with the use of event dynamics and to optimize postoperative follow-
(3 cases), and others (5 cases). There were no significant differences up schedule based on risk factors for recurrence. Methods: A total of 829
in postoperative complications among the groups (p = 0.69). However, patients with NSCLC who underwent complete pulmonary resection were
cardiovascular complications in group C were significantly higher than those studied. There were 538 men and 291 women with a mean age of 69.2 at the
in the other groups (p = 0.008). There were 26 patients with postoperative time of operation. The majority of the patients had adenocarcinoma (62.5%),
acute exacerbation, but there were no significant differences among the underwent lobectomy (85.9%) and pathological stage IA (47.3%). Event
groups. Conclusion: LA accurately predicted postoperative cardiovascular dynamics, based on the hazard rate, were evaluated and only first events

(distant metastases or local recurrence) were considered. The effects of sex, of miR-15/16, resulted in enhanced activity. Treatment with recombinant
histological type and pathological stage were studied. Results: On non- FGF2 further reduced mature as well as pri-microRNA levels and also could
parametric kernel smoothing, the resulting hazard rate curves indicated that prevent/reduce growth inhibition by mimics, but only when added within 24
the recurrence risk pattern was definitely correlated to sex, with a sharp peak hours after transfection. TLDA screens after stimulation/inhibition of FGF
in the first year for men and broad peak during the 2 to 3 years for women. signals identified regulation of several other miRNAs involved in pathways
This finding was also confirmed by the analysis of histological type. Although relevant for tumour growth and aggressiveness. Conclusion: Our data shows
pathological stage IA patients lacked such a large peak in both sexes during that the post-transcriptional repression of FGF-mediated signals contributes
the follow-up period, gender difference was shown in pathological stage IB to the tumour-suppressor function of the microRNA-15/16 family. Impairing
and stage IIA to IIIB patients. hyperactivated FGF signals as well as the anti-apoptotic protein bcl-2 through
the restoration of this miRNA family might serve as a novel therapeutic
strategy in mesothelioma.
Keywords: Mesothelioma, MicroRNAs, Fibroblast Growth Factors
OA02: NOVEL TARGETS AND BIOMARKERS IN MALIGNANT PLEURAL MESOTHELIOMA

MONDAY, DECEMBER 5, 2016 - 11:00-12:30
OA02.02 GREMLIN-1 IS A KEY REGULATOR OF THE INVASIVE

PHENOTYPE IN MESOTHELIOMA
Miao Yin1, Mira Tissari1, Jenni Tamminen1, Irene Ylivinkka1, Mikko Ronty2, Kaisa
Lehti1, Marko Hyytiainen1, Marjukka Myllarniemi3, Katri Koli4
1
University of Helsinki, Helsinki/Finland, 2Huslab, Helsinki/Finland, 3Helsinki
University Hospital, Helsinki/Finland, 4Translational Cancer Biology/a503B,
University of Helsinki, Helsinki/Finland
Background: Malignant mesothelioma is an aggressive cancer that develops

from mesothelial cells, most often in the pleural lining of the lung. We have
previously shown that the BMP inhibitor protein gremlin-1 is highly expressed
in mesothelioma and induces a mesenchymal and chemoresistant phenotype
in mesothelioma cells. Since mesothelioma tumors are locally highly
invasive, we analyzed the role of gremlin-1 in mesothelioma cell migration
and invasive growth. Methods: Primary mesothelioma cells isolated from
Conclusion: The use of recurrence dynamics allows the times of peak patient pleural fluid as well as mesothelioma cell lines were used for in vitro
recurrence to be visualized. The hazard rate and the peak times of recurrence studies. Cells were transfected with siRNAs or transduced with lentiviral
differed considerably between genders in pathological stage IB or higher. expression vectors. Invasive growth was analyzed in 3D matrigel or collagen
Postoperative follow-up methods should be based on currently recommended I matrices. mRNA expression was analyzed using a commercial PCR array and
follow-up guidelines, give adequate consideration to the recurrence patterns, quantitative RT-PCR. Migration assays were performed using scratch wound
and be modified individually. assay or Transwell migration assay with fibronectin or collagen coating. TGF-β
and BMP signaling activity was measured with reporter-luciferase assays.
Keywords: Non-small-cell lung cancer, postoperative, follow-up, recurrence For in vivo mouse xenograft experiment cells were additionally transduced
dynamics to express a luciferase marker. Subcutaneous cell injection with matrigel
matrix was performed in the flank of nude mice. Results: Mesothelioma cells
expressing gremlin-1 showed invasive sprouting when tumor cell spheroids
were imbedded into 3D collagen matrix. Silencing of gremlin-1 expression
significantly reduced invasive growth. In addition, cells overexpressing
SESSION OA02: NOVEL TARGETS AND BIOMARKERS IN gremlin-1 gained invasive growth ability. This was associated with increased
MALIGNANT PLEURAL MESOTHELIOMA mRNA expression levels of Slug and matrix metalloproteinases (MMP) as
well as reduced expression of E-cadherin. The cells were more migratory
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
and exhibited increased expression of certain integrins, especially the αv
subunit. Gremlin-1 induced invasive growth was dependent on MMP activity
and associated with increased TGF-β activity. Intrapleural injection of
OA02.01 THE MICRORNA-15/16 FAMILY REGULATES TUMOUR gremlin-1 overexpressing mesothelioma cells isolated from a patient with
CELL GROWTH VIA FIBROBLAST GROWTH FACTOR SIGNALS IN epithelioid mesothelioma, produced tumors in 2/4 mice over 4 months after
MALIGNANT PLEURAL MESOTHELIOMA injection. Cells transduced with vector only did not produced tumors (0/4).
Karin Schelch1, Michaela Kirschner2, Marissa Williams1, Ruby Lin1, Yuen Yee When cells were injected subcutaneously together with matrigel gremlin-1
Cheng1, Michael Grusch3, Walter Berger3, Nico Van Zandwijk1, Glen Reid1 overexpressing tumors appeared more slowly, but exhibited comparable
1
Asbestos Diseases Research Institute, Sydney/NSW/Australia, 2Divison of Thoracic luciferase signal 2.5 months after injection. However, gremlin-1 tumors
Surgery, University Hospital Zurich, Zurich/Switzerland, 3Institute of Cancer showed more local spreading and in contrast to control tumors some also
Research, Medical University of Vienna, Vienna/Austria developed metastasis (2/6 mice). Conclusion: Mesothelioma invades locally
and has poor prognosis. We have identified gremlin-1 as an important
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive, regulator of mesothelioma chemoresistance and invasive growth behavior.
asbestos-related malignancy characterized by poor outcome and limited Blocking gremlin function may overcome drug resistance and reduce invasion
therapeutic options. Fibroblast growth factor (FGF) signals play important of mesothelioma.
roles in mesothelioma cell growth and malignant behavior and their
inhibition leads to reduced tumor growth. MicroRNAs (miRNAs) are conserved Keywords: invasive growth, Mesothelioma, gremlin
noncoding RNAs controlling gene expression via translational repression
of target mRNAs. The miR-15/16 family is downregulated in MPM and has
tumor suppressor functions. Several FGFs/FGFRs are predicted miR-15/16
targets. The aim of this study was to explore the link between the miR-15/16 OA02: NOVEL TARGETS AND BIOMARKERS IN MALIGNANT PLEURAL MESOTHELIOMA
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
and the FGF/R family in MPM. Methods: Gene and microRNA expression was
determined by RT-qPCR or Taqman Low Density Arrays (TLDAs). Mimics were
used for restoring microRNA expression. Stimulation or inhibition of FGF OA02.03 CIRCULATING FIBROBLAST GROWTH FACTOR 18 IS
signals or bcl-2 was achieved by recombinant FGF2, siRNAs, or small-molecule ELEVATED IN MALIGNANT PLEURAL MESOTHELIOMA PATIENTS -
inhibitors, respectively. A SYBR green-based proliferation assay and colony
A MULTI-INSTITUTIONAL STUDY
formation assays were used to monitor effects on cell growth. Results:
Expression analysis showed a consistent downregulation of target FGF/ Yawen Dong 1, Hao Zhang2, Karin Schelch3, Thomas Klikovits1, Paul
FGFR genes after transfection with miRNA mimics. Restoration of miR-15/16 Stockhammer 1, Marko Jakopovic4, Miroslav Samarzija4, Luka Brcic5, Glen
led to dose-dependent growth inhibition, which significantly correlated Reid6, Michaela Kirschner 7, Steven Kao8, Isabelle Opitz9, Walter Weder9,
with sensitivity to the specific FGFR1 inhibitor PD166866. Re-expression Thomas Frauenfelder 10, Thi Dan Linh Nguyen-Kim10, Walter Klepetko1, Nico
of microRNAs in combination with FGFR knock-down or pharmacological Van Zandwijk11, Balazs Hegedus1, Walter Berger 12, Balazs Dome1, Viktoria
inhibition resulted in reduced activity, indicating target competition. Laszlo1, Michael Grusch12, Mir Hoda13
1
Combined inhibition of the FGF-axis and bcl-2, another established target Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria,
2
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou pri-miR-223 than human pri-miR-223 (p < 0.001), with only minimal expression
Medicaluniversity, Xuzhou/China, 3 Asbestos Diseases Research Institute, Sydney/ levels of human tumour pri-miR-223 within xenograft tumours. Conclusion:
NSW/Australia, 4Department for Respiratory Diseases “Jordanovac”, University Mature miR-223 is significantly overexpressed in xenograft tumours
Hospital Centre Zagreb, Zagreb/Croatia, 5Institute of Pathology, Medical University
compared to corresponding in vitro mesothelioma cell lines suggesting
of Graz, Graz/Austria, 6 Asbestos Diseases Research Institute, Sydney/Australia,
7 stromal contribution. Species-specific pri-miRNA confirmed miR-223 is almost
Divison of Thoracic Surgery, University Hospital Zurich, Zurich/Switzerland,
8
Medical Oncology, Chris O’Brien Lifehouse, Sydney/Australia, 9Division of exclusively expressed by the mouse stromal cells in xenograft tumours.
Thoracic Surgery, University Hospital Zurich, Zurich/Switzerland, 10 Department Ultimately, localising the expression of miR-223 to specific cell types (such
of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich/ as myeloid derived cells) through in situ hybridisation should help identify a
Switzerland, 11 Asbestos Diseases Research Institute, University of Sydney, Concord/ more biologically relevant role for miR-223 in the tumour microenvironment.
Australia, 12Institute of Cancer Research, Medical University Vienna, Vienna/
Austria, 13Division of Thoracic Surgery, Medical University of Vienna, Vienna/Austria Keywords: Mesothelioma, microRNA
Background: Malignant pleural mesothelioma (MPM) is a rare but devastating

malignancy. Despite the search for new promising treatment approaches, the
outcome for most MPM patients remains dismal. Therefore, the identification OA02: NOVEL TARGETS AND BIOMARKERS IN MALIGNANT PLEURAL MESOTHELIOMA
of novel biomarkers is urgently needed in order to identify patients with a MONDAY, DECEMBER 5, 2016 - 11:00-12:30
better prognosis and to support personalized therapeutic decisions. In our
previously published study, we were able to show that fibroblast growth
factor 18 (FGF18) is overexpressed in MPM tissue specimens and cell models.
OA02.06 CONVERTING TUMOR-MEDIATED PD-L1 INHIBITION INTO
The objective of this study was the evaluation of FGF18 as a circulating CAR T-CELL COSTIMULATION TO POTENTIATE THORACIC CANCERS
biomarker in MPM. Methods: Plasma was collected from 107 MPM patients IMMUNOTHERAPY
at the time of diagnosis or before surgical resection. Samples were included Aurore Morello1, Nan Chen2, Leonid Cherkassky2, Michel Sadelain3, David
from the Medical University of Vienna, University Hospital Center in Zagreb Jones2, Prasad Adusumilli1
and from The Concord Repatriation General Hospital and Strathfield Private 1
Thoracic Service and Center for Cell Engineering, Memorial Sloan Kettering Cancer
Hospital in Sydney. Samples from 49 healthy volunteers and from 8 patients Center, New York/NY/United States of America, 2Thoracic Service, Department of
with non-malignant pleural diseases served as controls. Circulating FGF18 Surgery, Memorial Sloan Kettering Cancer Center, New York/NY/United States of
was measured by enzyme-linked immunosorbent assay and correlated to America, 3Center for Cell Engineering, Memorial Sloan Kettering Cancer Center,
clinical, pathologic and radiologic parameters. Results: Plasma FGF18 level New York/NY/United States of America
was significantly elevated in MPM patients vs. healthy controls (P<0.0001).
Background: To overcome tumor-mediated inhibition of chimeric antigen
A slight increase of circulating FGF18 level was also detected in patients with
receptor (CAR) T cells, we herein investigated the impact of tumor PD-L1
pleuritis or fibrosis (vs. control, P=0.0067). Sarcomatoid (n=7) morphology
upregulation on CAR T-cell exhaustion and anti-tumor efficacy, and further
was associated with high FGF18 levels when compared to the epithelioid
developed clinically translatable T-cell extrinsic as well as intrinsic strategies
(n=77) histology (P=0.0064). Importantly, MPM patients presenting with
to overcome PD-L1 inhibition in models of lung cancer (LC) and malignant
FGF18 levels below the median had a significantly longer overall survival
pleural mesothelioma (MPM). Methods: Human T cells were transduced with
when compared to those with high FGF18 levels (median survival 625 versus
MSLN-specific CAR with CD28 and CD3zeta domains (M28z) were tested in
382 d, P=0.0038). Data on multivariate analysis, disease-free survival,
vitro and in clinically-relevant LC and MPM mouse models by bioluminescence
correlation with other biomarkers and tumor volume will be presented at
imaging, BLI of tumor burden progression. To counteract PD-1/PD-L1 inhibition
the conference. Conclusion: Our findings reveal that FGF18 is a promising
in vivo, we evaluated the efficacy of PD-1 blocking antibody or cell-intrinsic
blood-derived candidate biomarker in MPM. Furthermore FGF18 may support
genetic-engineering strategies by cotranducing M28z CAR T cells with a PD-1
the histological classification of MPM and the identification of MPM patients
dominant negative receptor (PD1-DNR) or with PD-1/4-1BB fusion protein.
with poor prognosis.
Results: A single, low-dose of M28z CAR T cells is able to resist the progression
Keywords: mesothelioma, biomarker, fibroblast growth factors of established tumor for 40 days, but mice eventually died with progressing
tumor. Tumor harvest analysis demonstrated the PD-1 and PD-L1 upregulation
on CAR T cells and tumor cells (Figure panel A). We then confirmed in vitro
that PD-L1 inhibits M28z T-cell effector functions (proliferation, cytotoxicity
OA02: NOVEL TARGETS AND BIOMARKERS IN MALIGNANT PLEURAL MESOTHELIOMA and cytokine secretion). The addition of PD-1 blocking potentiates CAR
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 T-cell therapy in vivo but its efficacy requires multiple injections (Panel B). In
contrast, a single dose of M28z T cells coexpressing PD1-DNR restore effector
functions, enhance tumor burden control (Panel C) and prolong median
OA02.05 EXPRESSION OF MIR-223 IN MESOTHELIOMA survival (56 vs 82 days, p=0.001). Converting PD-L1 inhibition into a positive
XENOGRAFTS ORIGINATES FROM STROMAL CELLS IN THE TUMOUR costimulatory signal by PD-1/4-1BB construct cotransduction into M28z CAR T
MICROENVIRONMENT cells enhanced cytokine secretion and T-cell accumulation (Panel D).
Kadir Sarun1, Yuen Yee Cheng1, Michaela Kirschner2, Nico Van Zandwijk1, Ruby
Lin1, Glen Reid1
1
Asbestos Diseases Research Institute, Sydney/NSW/Australia, 2Divison of Thoracic (See Figures next page)
Surgery, University Hospital Zurich, Zurich/Switzerland
Background: Malignant pleural mesothelioma (MPM) is an aggressive

cancer caused by asbestos exposure with limited therapeutic options.
Dysregulated microRNAs play an important role in MPM biology and
candidate microRNAs have been investigated as diagnostic and prognostic
biomarkers or as a potential treatment targets. The role of miR-223 has
previously been investigated in MPM tumour cells and was shown to act as
a tumour suppressor by regulating cell mobility. Previous research indicated
miR-223 to be primarily expressed by myeloid progenitor derived cells during
differentiation of granulocytes and monocytes. This suggests miR-223
might have a more significant role in the inflammatory response during
tumourigenesis. In this study we aimed to investigate the origin of miR-223
using mesothelioma xenograft and syngraft models. Methods: Human and
mouse mesothelioma cell line-derived xenograft (MSTO-H211 and H226) and
syngraft (AB1) models were established. MicroRNA profiles of xenografts
were compared against profiles of their corresponding in vitro cultured cells
to determine candidates. RT-qPCR using TaqMan MicroRNA assays was used
to validate expression levels of miR-143-3p, miR-214-3p and miR-223-3p in
tumour xenografts and syngrafts with those in corresponding cell lines in
vitro. Species-specific ddPCR analysis was performed on RNA from xenograft
tumours to determine the expression of human and mouse pri-miR-223.
Results: MicroRNA profiles of xenograft tumours showed significant
upregulation (p < 0.05) of miR-143-3p, miR-214-3p and miR-223-3p compared
to corresponding in vitro mesothelioma cell lines. Only miR-223 showed
significant upregulation in both xenograft and syngraft tumours compared to
corresponding in vitro mesothelioma cell lines (>10000-fold increase). Other
microRNAs were not significantly different between cell lines and tumours.
RNA isolated from xenograft tumours contained significantly more mouse

Conclusion: Our results demonstrate the therapeutic benefit of providing

optimal costimulation and coinhibitory blockade to counteract PD-L1/PD-1
immunosuppression, thus potentiate CAR T-cell therapy for lung cancer and
mesothelioma.
Keywords: CAR T-cell immunotherapy, PD-1 and PD-L1, Mesothelioma, lung

cancer
OA02: NOVEL TARGETS AND BIOMARKERS IN MALIGNANT PLEURAL MESOTHELIOMA expression (p<0.001). Less than half of the samples showed positivity
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 for granzyme B. Both, untreated and pretreated patients had PD-1+ TILs,
while only 10% of the untreated patients also had PD-1+ tumor cells. PD-L1
positivity on lymphocytes and/or tumor cells was observed for more than
OA02.07 CHARACTERIZATION OF THE TUMOR
half of the patients, with significant differences according to the histological
MICROENVIRONMENT AND INVESTIGATION OF IMMUNE subtype (p<0.001). Patients with a sarcomatoid histology showed the most
CHECKPOINT EXPRESSION IN MALIGNANT PLEURAL PD-1 expression. TIM-3 was expressed in tumor cells, stromal lymphocytes
MESOTHELIOMA and plasma cells, less often in pretreated samples compared to untreated
Elly Marcq1, Vasiliki Siozopoulou2, Jorrit De Waele1, Jonas Van Audenaerde1, samples. All samples were negative for LAG-3. After multivariate analysis
Karen Zwaenepoel2, Eva Santermans3, Niel Hens3, Patrick Pauwels2, Jan Van stromal CD45RO expression was found to be an independent negative
Meerbeeck4, Evelien Smits1 predictive factor for response to chemotherapy (p=0.017) and expression
1
Center for Oncological Research (Core), University of Antwerp, Wilrijk/Belgium, of CD4 and TIM-3 in lymphoid aggregates were good prognostic factors
2
Departement of Pathology, Antwerp University Hospital, Edegem/Belgium, (p=0.008; p=0.001). Conclusion: Our data reveal the diversity of immune
3
Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt cells present in MPM and point to TIM-3 as a new target in mesothelioma.
University, Diepenbeek/Belgium, 4Thoracic Oncology, Antwerp University Hospital, Administering chemotherapy before or together with PD-1/PD-L1/TIM-3
Edegem/Belgium blocking agents may not be the best combination sequence and further
research on the predictive value of CD45RO in the stroma might guide patient
Background: Malignant pleural mesothelioma (MPM) is an aggressive
selection for chemotherapy.
cancer with a poor prognosis and an increasing incidence, for which novel
therapeutic strategies are urgently required. Since the immune system has Keywords: Immune checkpoints, tumor microenvironment, biomarkers
been described to play a role in protection against MPM, characterization of
its tumor immune microenvironment (TME) and immune checkpoints might
help to identify new immunotherapeutic targets and their predictive and/
or prognostic value. Methods: Immunohistochemistry (IHC) was performed
on tissue samples of untreated (n=40) and chemotherapy-pretreated (n=14) SESSION OA03: IMMUNOTHERAPY CHECKPOINT INHIBI-
MPM patients. Different subsets if immune cells were identified based on
TORS IN ADVANCED NSCLC
staining for CD4, CD8, FoxP3, CD68, CD45RO and granzyme B. The expression
of the immune checkpoints TIM-3, LAG-3, PD-1 and its ligand PD-L1 was also MONDAY, DECEMBER 5, 2016 - 11:00-12:30
investigated. The relationship between the immunological parameters
and survival, as well as response to chemotherapy was analyzed using the
R statistical software. Results: All patients had CD8+ tumor infiltrating OA03.01 FIRST-LINE NIVOLUMAB MONOTHERAPY AND
lymphocytes (TILs), CD68+ histiocytes and macrophages and CD45RO+ T NIVOLUMAB PLUS IPILIMUMAB IN PATIENTS WITH ADVANCED
cells in their stroma, with CD8+ TILs being the predominant cell type of the NSCLC: LONG-TERM OUTCOMES FROM CHECKMATE 012
immune infiltrate. Stromal CD4+ TILs were found in 75% of the untreated Scott Gettinger 1, Naiyer Rizvi2, Laura Chow3, Hossein Borghaei4, Julie
and 71% of the pretreated samples. A subset of those cells was also FoxP3+ Brahmer5, Frances Shepherd6, Neal Ready 7, David Gerber8, Scott Antonia9,
and these CD4+FoxP3+ cells were positively correlated with stromal CD4
Jonathan W. Goldman10, Rosalyn Juergens11, William Geese12, Tina Young12,

12-mo OS rate, % 61% (48.8–73.8) 66% (57.9–74.5)
Xuemei Li12, Matthew Hellmann2
1
Yale Cancer Center, New Haven/United States of America, 2Memorial Sloan mPFS, mo 7.3 (4.9–12.0) 7.3 (5.6–9.1)
Kettering Cancer Center, New York/NY/United States of America, 3University of
Washington, Seattle/WA/United States of America, 4Fox Chase Cancer Center, 12-mo PFS rate, % 36% (23.8–48.8) 32% (24.0–40.7)
Philadelphia/PA/United States of America, 5Johns Hopkins Kimmel Cancer Center,
Baltimore/MD/United States of America, 6Princess Margaret Cancer Centre, NE, not estimable.
Toronto/ON/Canada, 7Duke University Medical Center, Durham/NC/United States
a
of America, 8University of Texas Southwestern Medical Center, Dallas/TX/United TC ≥50% or IC ≥10% PD-L1–expressing cells.
States of America, 9H. Lee Moffitt Cancer Center and Research Institute, Tampa/
b
FL/United States of America, 10University of California, Los Angeles, Los Angeles/ TC or IC ≥5% PD-L1–expressing cells.
CA/United States of America, 11Juravinski Cancer Centre, Mcmaster University,
Hamilton/ON/Canada, 12Bristol-Myers Squibb, Princeton/NJ/United States of Keywords: Immunotherapy, NSCLC, atezolizumab
America
This abstract is under embargo until December 5, 2016 at 07:00 CET. OA03: IMMUNOTHERAPY CHECKPOINT INHIBITORS IN ADVANCED NSCLC
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
OA03: IMMUNOTHERAPY CHECKPOINT INHIBITORS IN ADVANCED NSCLC OA03.03 JAVELIN SOLID TUMOR: SAFETY AND CLINICAL ACTIVITY
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 OF AVELUMAB (ANTI-PD-L1) AS FIRST-LINE TREATMENT IN
PATIENTS WITH ADVANCED NSCLC
OA03.02 ATEZOLIZUMAB AS 1L THERAPY FOR ADVANCED NSCLC Guy Jerusalem1, Franklin Chen2, David Spigel3, Nicholas Iannotti4, Edward
IN PD-L1–SELECTED PATIENTS: UPDATED ORR, PFS AND OS DATA Mcclay5, Charles Redfern6, Jaafar Bennouna7, Matthew Taylor8, Howard
FROM THE BIRCH STUDY Kaufman9, Karen Kelly10, Vikram Chand11, Anja Von Heydebreck12, Claire
Verschraegen13
Marina Garassino 1, Naiyer Rizvi2, Benjamin Besse3, Pasi Jänne4, Daniel
1
Christoph5, Solange Peters6, Chee Keong Toh7, Takayasu Kurata8, Enric CHU Sart Tilman Liege and Liege University, Liege/Belgium, 2Novant Health
Oncology Specialists, Winston-Salem/NC/United States of America, 3Sarah Cannon
Carcereny Costa9, Marianna Koczywas10, Enriqueta Felip11, Jamie Chaft12,
Research Institute, North Nashville/TN/United States of America, 4Hematology
Jiaheng Qiu13, Marcin Kowanetz13, Shelley Coleman13, Simonetta Mocci13, Alan Oncology Associates of the Treasure Coast, Port St. Lucie/FL/United States of
Sandler 13, Scott Gettinger 14, Melissa Johnson15 America, 5California Cancer Associates for Research & Excellence, Encinitas/CA/
1
Thoracic Oncology Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan/ United States of America, 6Sharp Healthcare, San Diego/CA/United States of
Italy, 2New York-Presbyterian/columbia University Medical Center, New York/ America, 7Ico René Gauducheau Recruiting, St Herblain/France, 8 Oregon Health
NY/United States of America, 3Department of Cancer Medicine, Gustave Roussy, & Science University Knight Cancer Institute, Portland/OR/United States of
Villejuif/France, 4Dana-Farber Cancer Institute, Boston/MA/United States of America, 9Rutgers Cancer Institute of New Jersey, New Brunswick/NJ/United
America, 5West German Cancer Center, Universitätsklinikum Essen, and the States of America, 10University of California Davis Comprehensive Cancer Center,
Ruhrlandklinik, Universität Duisburg–Essen, Essen/Germany, 6Hfr Fribourg-Hôpital Sacramento/CA/United States of America, 11Emd Serono, Inc., Billerica/MA/United
Cantonal, Fribourg/Germany, 7National Cancer Centre, Singapore/Singapore, States of America, 12Merck KGaA, Darmstadt/Germany, 13University of Vermont
8
Kansai Medical University Hirakata Hospital, Osaka/Japan, 9 Catalan Institute of Cancer Center, Burlington/VT/United States of America
Oncology Badalona - Germans Trias I Pujol Hospital Badalona, Barcelona/Spain,
10
City of Hope Medical Center, Duarte/CA/United States of America, 11Vall D’Hebron
Institute of Oncology, Barcelona/Spain, 12Memorial Sloan Kettering Cancer Center, This abstract is under embargo until December 5, 2016 at 07:00 CET.
New York/NY/United States of America, 13Genentech, Inc., South San Francisco/
CA/United States of America, 14Yale Cancer Center, New Haven/CT/United States of
America, 15Sarah Cannon Research Institute, Nashville/TN/United States of America
OA03: IMMUNOTHERAPY CHECKPOINT INHIBITORS IN ADVANCED NSCLC
Background: Atezolizumab, a humanized anti-PDL1 mAb, inhibits the MONDAY, DECEMBER 5, 2016 - 11:00-12:30
PD-L1/PD-1 pathway to restore tumor-specific T-cell immunity, resulting in
durable anti-tumor effects. BIRCH (NCT02031458) is a single-arm Phase II
study of atezolizumab monotherapy in PD-L1–selected advanced NSCLC OA03.05 ANALYSIS OF EARLY SURVIVAL IN PATIENTS WITH
patients, across multiple therapy lines. Primary analyses (median follow- ADVANCED NON-SQUAMOUS NSCLC TREATED WITH NIVOLUMAB
up, 8.5 months) demonstrated a meaningful ORR with durable response in VS DOCETAXEL IN CHECKMATE 057
chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we report
Solange Peters 1, Frederico Cappuzzo2, Leora Horn3, Luis Paz-Ares4, Hossein
updated efficacy data in 1L patients. Methods: 1L eligibility criteria included
Borghaei5, Fabrice Barlesi6, Martin Steins7, Enriqueta Felip8, David Spigel9,
PD-L1–selected, advanced-stage NSCLC with no CNS metastases or prior
Cécile Dorange10, Haolan Lu10, Diane Healey10, Teresa Kong Sanchez10, Prabhu
chemotherapy. PD-L1 was centrally evaluated (VENTANA SP142 IHC assay).
Bhagavatheeswaran10, James Novotny Jr.10, Brian Lestini10, Julie Brahmer 11
Patients expressing PD-L1 on ≥5% of tumor cells (TC) or tumor-infiltrating 1
University of Lausanne, Lausanne/Switzerland, 2 Ausl Romagna, Ospedale Santa
immune cells (IC), ie, TC2/3 or IC2/3, were enrolled. Patients with EGFR
Maria Delle Croci, Department of Oncology and Hematology, Ravenna/Italy,
mutation or ALK rearrangement must have had prior TKI treatment. 3
Vanderbilt University Medical Center, Nashville/TN/United States of America,
Atezolizumab 1200mg was administered IV q3w until radiographic disease 4
Hospital Universitario Doce de Octubre & Cnio, Madrid/Spain, 5Medical Oncology,
progression or unacceptable toxicity. The primary endpoint was independent Fox Chase Cancer Center, Philadelphia/PA/United States of America, 6 Aix-
review facility(IRF)-assessed ORR. Secondary endpoints included Marseille Université, Assistance Publique Hôpitaux de Marseille, Marseille/France,
7
investigator(INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS. Results: With Thoraxklinik-Heidelberg Ggmbh, Heidelberg/Germany, 8Hospital Universitari Vall
a median follow-up of 14.6 months, median OS was not reached in TC3 or IC3 D’Hebron, Barcelona/Spain, 9Thoracic Oncology, Sarah Cannon Research Institute/
patients and was 20.1 months in TC2/3 or IC2/3 (ITT) patients; INV-assessed tennessee Oncology, Pllc, Nashville/TN/United States of America, 10 Bristol-Myers
Squibb, Princeton/NJ/United States of America, 11Johns Hopkins Kimmel Cancer
ORR was 32% and 24%, respectively (Table). Furthermore, ORR was 31% for
Center, Baltimore/MD/United States of America
mutant EGFR (n=13) vs 20% for wild-type EGFR patients (n=104), and 27%
for mutant KRAS (n=33) vs 21% for wild-type KRAS patients (n=67). No new
safety signals were observed. Updated efficacy (including IRF ORR), safety This abstract is under embargo until December 5, 2016 at 07:00 CET.
and exploratory biomarker analyses will be presented. Conclusion: With
longer follow-up, atezolizumab continued to demonstrate promising efficacy
in 1L NSCLC. These results indicate that atezolizumab has durable efficacy in
the 1L setting, in EGFR and KRAS mutant and wild-type tumors, and support OA03: IMMUNOTHERAPY CHECKPOINT INHIBITORS IN ADVANCED NSCLC
ongoing Phase III trials evaluating atezolizumab vs chemotherapy in 1L NSCLC. MONDAY, DECEMBER 5, 2016 - 11:00-12:30
Endpoint (95% CI)

TC2/3 or IC2/3b OA03.07 KEYNOTE-010: DURABLE CLINICAL BENEFIT IN PATIENTS
TC3 or IC3a (n=65)
(n=139) WITH PREVIOUSLY TREATED, PD-L1-EXPRESSING NSCLC WHO
INV ORR, % 32% (21.2–45.1) 24% (16.9–31.7) COMPLETED PEMBROLIZUMAB
Roy Herbst 1, Edward Garon2, Dong-Wan Kim3, Byoung Chul Cho4, Shirish
EGFR mutant/wild-type, % 25%/29% 31%/20% Gadgeel5, Hervé Léna6, Alfonso Gúrpide7, Ji-Youn Han8, Catherine Dubos
KRAS mutant/wild-type, % 38%/27% 27%/21% Arvis9, Margarita Majem10, Martin Forster 11, Isabelle Monnet12, Silvia
Novello13, Hideo Saka14, Zsuzsanna Szalai15, Matthew Gubens16, Wu-Chou Su17,
mDOR, mo 13.1 (8.5–NE) 13.1 (9.9–17.5) Gregory Lubiniecki18, Yue Shentu18, Geri Ferraro18, Paul Baas19
1
Yale School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New
mOS, mo NE (12.0–NE) 20.1 (20.1–NE)
Haven/CT/United States of America, 2David Geffen School of Medicine at UCLA/

Translational Research in Oncology- Us Network, Los Angeles/CA/United States of (70.3%) lowest in Sao Tome (7.4%); whereas female tobacco use highest in
America, 3Seoul National University Hospital, Seoul/Korea, Republic of, 4Division Madagascar (21%) and lowest in Tajikistan (0.22%). Among men educational
of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, inequalities varied widely between countries but aggregate RII and SII showed
Seoul/Korea, Republic of, 5Oncology, Karmanos Cancer Institute/wayne State an inverse trend by country wealth groups. RII was 3.61 (95% CI 2.83-4.61)
University, Detroit/MI/United States of America, 6Centre Hospitalier Universitaire in LICs, 1.99 (95% CI 1.66-2.38) in lMIC, and 1.82 (95% CI 1.24-2.67) in uMIC.
de Rennes, Rennes/France, 7Clínica Universidad de Navarra, Pamplona/Spain,
8 Wealth inequalities among men varied less between countries but both RII
Center for Lung Cancer, National Cancer Center, Goyang/Korea, Republic of,
9
Centre François Baclesse, Caen/France, 10 Medical Oncology, Hopital de La and SII showed an inverse pattern where RII was 2.43 (95% CI 2.05-2.88) in
Santa Creu I Sant Pau, Barcelona/Spain, 11University College Hospital, London/ LICs, 1.84 (95% CI 1.54-2.21) in lMICs, and 1.67 (95% CI 1.15-2.42) in uMIC. For
United Kingdom, 12Centre Hospitalier Intercommunal de Créteil, Créteil/France, educational inequalities among women, the RII varied much more than SII
13
University of Turin, Turin/Italy, 14Respiratory Medicine, National Hospital varied between the countries, and aggregate RII was 14.49 (95% CI 8.87-23.68)
Organization Nagoya Medical Center, Nagoya/Japan, 15Petz Aladár County Teaching in LICs, 3.05 (95% CI 1.44-6.47) in lMIC and 1.58 (95% CI 0.33-7.56) in uMIC.
Hospital, Győr/Hungary, 16Hematology and Oncology, University of California, Wealth inequalities among women showed a pattern similar to that of men:
San Francisco, San Francisco/CA/United States of America, 17National Cheng the RII was 5.88 (95% CI 3.91- 8.85) in LICs, 1.76 (95% CI 0.80 -3.85) in lMIC,
Kung University Hospital, Tainan/Taiwan, 18 Merck & Co., Inc., Kenilworth/NJ/
and 0.39 (95% CI 0.09 -1.64) in uMIC. In contrast to men, among women the
United States of America, 19Department of Thoracic Oncology, Netherlands Cancer
Institute, Amsterdam/Netherlands SII was pro-rich (higher smoking among the more advantaged) in 13 of the
52 countries (7 of 23 lMIC and 5 of 7 uMIC). Conclusion: Our results confirm
Background: Checkpoint inhibitors such as the anti–PD-1 monoclonal that socio-economic inequalities tobacco use exist in LMIC, varied widely
antibody pembrolizumab have demonstrated antitumor activity and a between the countries, and were much wider in the lowest income countries.
manageable safety profile in several advanced malignancies. Although These findings are important for better understanding and tackling of socio-
checkpoint inhibitors are rapidly becoming a standard-of-care therapy economic inequalities in health in LMIC.
in multiple tumor types, the optimal treatment duration has not been
established. We plan to assess outcomes in patients who completed the Keywords: Tobacco use; socio-economic status; health inequalities; low-and-
maximum 24 months of pembrolizumab in the phase 3 KEYNOTE-010 study middle-income countries
(NCT01905657), in which pembrolizumab provided superior OS over docetaxel
in patients with previously treated, PD-L1–expressing advanced NSCLC.
Methods: 1034 patients with advanced NSCLC that progressed after ≥2 cycles
of platinum-based chemotherapy (and an appropriate therapy for targetable OA04: EPIDEMIOLOGY AND PREVENTION OF LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
EGFR and ALK aberrations if present) and had a PD-L1 tumor proportion
score ≥1% were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg Q3W or to
docetaxel 75 mg/m2 until disease progression, intolerable toxicity, physician OA04.02 SMOKING BEHAVIOR IN PATIENTS WITH EARLY STAGE
or patient decision; the maximum duration of pembrolizumab was 24 months NON-SMALL CELL LUNG CANCER: A REPORT FROM ECOG-ACRIN
of uninterrupted treatment or 35 cycles, whichever was later. Response was 1505 TRIAL
assessed per RECIST v1.1 every 9 weeks. After completion of 24 months/35
Suresh Ramalingam1, Suzanne Dahlberg2, Heather Wakelee3, Steven Keller4,
cycles, patients continued to undergo imaging every 9 weeks; patients with
William Tester5, David R. Gandara6, Stephen Graziano7, Alex Adjei8, Charles
subsequent disease progression were eligible for a second treatment course if
Butts9, Joan Schiller 10
they did not receive other anticancer therapy after stopping pembrolizumab. 1
Winship Cancer Institute of Emory University, Atlanta/GA/United States of
Results: Reason late-breaking status required: As of the most recent analysis,
America, 2Dana Farber Cancer Institute, Boston/MA/United States of America,
which had a data cutoff date of March 31, 2016, and a median follow-up of 3
Stanford University, Palo Alto/CA/United States of America, 4 Montefiore Medical
19.2 months (range, 11.7-29.7), only 3 patients in each pembrolizumab arm Center, Bronx/NY/United States of America, 5 Albert Einstein Cancer Center,
completed 24 months/35 cycles of treatment. At the time of the next data Philadelphia/PA/United States of America, 6Division of Hem-Oncology, UC Davis
analysis, which is planned for September 2016, we expect ≥35 patients to have Comprehensive Cancer Center, Sacramento/CA/United States of America, 7Suny
reached the 24-month/35-cycle plateau, allowing for a more robust analysis. Upstate Medical Center, Syracuse/NY/United States of America, 8 Medical Oncology,
Conclusion: Anticipated data: We anticipate providing the following for Mayo Clinic, Rochester/MN/United States of America, 9Division of Oncology,
patients who completed 24 months/35 cycles of pembrolizumab: best overall Univeristy of Alberta, Edmonton/Canada, 10 Inova Schar Cancer Institute, Falls
Church/AL/United States of America
response, ORR, time to response, and duration of response to first-course
therapy; time since the last pembrolizumab dose; incidence of death and Background: Approximately 85% of lung cancer is related to cigarette
disease progression after stopping pembrolizumab; and frequency of second- smoking. Smoking cessation has been reported to benefit patients even after
course initiation. the diagnosis of lung cancer. We studied the smoking behavior of patients
Keywords: pembrolizumab, PD-L1, non-small cell lung cancer with lung cancer in a phase 3 study for early stage lung cancer. Methods: The
ECOG-ACRIN 1505 study enrolled patients with stages IB, II and IIIA non-small
cell lung cancer (NSCLC) after they had undergone surgical resection. It was
designed to evaluate whether the addition of bevacizumab would improve
survival relative to cisplatin-based chemotherapy alone. Studying the
SESSION OA04: EPIDEMIOLOGY AND PREVENTION OF correlation between smoking status and outcome was a secondary endpoint.
Patients completed a questionnaire about their smoking habits at baseline,
LUNG CANCER 3, 6, 9 and 12 months after study entry. Results: Out of 1501 patients enrolled,
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 99%, 90%, 85%, 82% and 80% responded to the questionnaire at baseline, 3,
6, 9 and 12 months respectively. Nearly 90% reported having smoking during
their lifetime. At study entry, 12% reported ongoing smoking. The median
OA04.01 EDUCATIONAL AND WEALTH INEQUALITIES IN TOBACCO age patients started smoking was 17 years and the median age at which
USE AMONG MEN AND WOMEN IN 54 LOW-AND-MIDDLE-INCOME they quit smoking was 55 years. The median number of cigarettes smoked
COUNTRIES per day was 20. Approximately 4% smoked cigars (median number 2/day).
Of the 40% that reported smoking after the diagnosis of lung cancer, only
Chandrashekhar Sreeramareddy 1, Sam Haprper2, Linda Ernstsen3
1
15% reported smoking at 12 months. At 12 months after study entry, among
Family Medicine and Population Health, International Medical University, Kuala
those who continued to smoke, 79% reported smoking fewer cigarettes/
Lumpur/Malaysia, 2Department of Epidemiology, Biostatistics and Occupational
day, whereas 11% smoked more cigarettes. When asked about the number of
Health, McGill University, Montreal/AB/Canada, 3Department of Nursing Science,
Faculty of Health and Social Sciences, Norwegian University of Science and cigarettes smoked at 12 mos, 63% reported smoking fewer than 10 cigarettes/
Technology, Trondheim/Norway day. The incidence of grades 3-5 toxicity was 76% in smokers versus 69%
in non-smokers (p=0.06). There were no differences in dose reductions for
Background: To support health policies and place monitoring systems to chemotherapy (P=0.55) or bevacizumab (P=0.90) between smokers and non-
tackle socio-economic inequalities in tobacco use in low-and-middle-income smokers. The median number of chemotherapy cycles were nearly identical
countries (LMIC) are seldom reported. We aimed to describe, sex-wise, for smokers and never-smokers. The disease-free survival (DFS) and OS for
educational and wealth-related inequalities in tobacco use in low-and-middle smokers relative to never-smokers were 0.97 (P=0.83) and 1.54 (P=0.01)
income countries. Methods: We analyzed DHS data on tobacco use collected respectively. Conclusion: This is the first comprehensive, prospective report of
in 54 countries. We calculated weighted prevalence estimates of current smoking habits of patients with lung cancer. There were a high rate of smoking
tobacco use (any type of tobacco) in each country for five wealth groups and cessation and reduction in number of cigarettes smoked, that was maintained
four educational groups. We calculated both absolute and relative measures at 12m after study entry. Toxicity and DFS did not differ significantly between
of inequality, i.e., the Slope Index of Inequality (SII) and Relative Index of smokers and never-smokers, though overall survival was more favorable with
Inequality (RII), which take into account the distribution of prevalence the never-smokers. Study was coordinated by ECOG-ACRIN (Robert L. Comis,
across all wealth and education groups and account for population size. We M.D., Chair) and supported in part by Public Health Service Grants CA180820,
also calculated the aggregate SII and RII for low-income (LIC), lower-middle CA180888, CA180821, & CA180863.
income (lMIC) and upper-middle-income (uMIC) countries as per World Bank
classification. Results: Male tobacco use among was highest in Bangladesh Keywords: lung cancer, smoking, tobacco control
OA04: EPIDEMIOLOGY AND PREVENTION OF LUNG CANCER influence the pathogenesis of both diseases. Despite the plausibility for shared
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
genetic predisposition, knowledge about pleiotropy between COPD and lung
cancer is limited. Methods: Using the Genetic Epidemiology Research on Adult
OA04.03 PRELIMINARY RESULTS OF A LOW COST INTERVENTION Health and Aging cohort established at Kaiser Permanente Northern California
TO IMPROVE TOBACCO CESSATION PRACTICES WITHIN A LARGE (KPNC), an integrated healthcare system, we examined non-Hispanic white
smokers aged ≥40 years diagnosed with lung cancer (n=489), including those
UNIVERSITY HEALTH SYSTEM
with COPD (n=243) or without COPD (n=174), and neither disease (n=26,553)
Mary Kay Hamby1, Allison Nix 2, Julie Tobi2, Kelly Rysso2, Douglas Arenberg 3 through January 31, 2014. Those with lung cancer were identified from KPNC
1
University of Michigan, Ann Arbor/MI/United States of America, 2University of Cancer Registry data. Those with COPD were identified from electronic health
Michigan, Ann Arbor/United States of America, 3Internal Medicine, University of record data, requiring at least one hospitalization with a principal discharge
Michigan, Ann Arbor/MI/United States of America
diagnosis or two outpatient visits with a diagnosis of chronic bronchitis,
Background: Tobacco cessation is critical for both population and individual emphysema, or COPD (ICD-9 codes: 491.*, 492.*, 496.*). We examined 16
health, and especially so in the context of a lung cancer screening program. single nucleotide polymorphisms (SNPs) in 10 risk loci identified previously
Our institution initiated formal lung caner screening in 2013. In preparation for COPD or airflow obstruction by genome-wide association studies (1q41,
for this we audited randomly selected clinic visits to assess adherence to 4q22.1, 4q31.21, 5q32, 6p21.32, 11q22, 14q32, 15q25.1, 16p11.2, 19q13) for their
published tobacco cessation guidelines. Our findings in that study prompted associations with lung cancer risk, overall and stratified by COPD. SNPs were
us to initiate a systematic multi-step program to improve tobacco practices examined individually and also jointly as an unweighted 16-SNP risk score.
from assessing tobacco use to presribing pharmacotherapy, and referral to Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using
tobacco cessation counselors. Methods: The project included four separate logistic regression, adjusted for age, sex, pack-years of smoking, and principal
but related interventions; 1) Inviting clinic directors to send a clinic staff components of genetic ancestry. Results: Only two SNPs at 15q25.1, a risk locus
member of their choice for formal training in a specialize Tobacco treatment also known for lung cancer and nicotine dependence, were associated with
Specialist (TTS) course. 2) Generating monthly reports showng completeless of overall lung cancer risk: rs8034191 (per-allele OR=1.22, 95% CI: 1.07-1.39, p=0.003)
tobacco history (Current/Former/Never), pack-years recording, and (for former and rs12914385 (per-allele OR=1.23; 95% CI: 1.08-1.40, p=0.002). In stratified
smokers) quit dates, use of pharmacotherapy for current smokers, and referrals analyses, associations were marginally stronger for lung cancer without COPD
for either tobacco cessation or formal lung cancer screening. 3) Providing (rs8034191: OR=1.36, 95% CI: 1.09-1.69; rs12914385: OR=1.24, 95% CI: 1.00-1.54)
monthly feedback to clinic directors comparing their performance to others than lung cancer with COPD (rs8034191: OR=1.09, 95% CI: 0.90-1.31; rs12914385:
in the project, and 4) Initiation of an electronic Best Practice Alert prompt for OR=1.17, 95% CI: 0.97-1.40). The 16-SNP risk score was suggestively associated
smokers including links to a Lung Cancer Screening Questionaire & decision aid with overall lung cancer risk (highest vs. lowest quintile: OR=1.31, 95% CI: 0.97-
and referral to Tobacco Counselor. Results: This University Health System is 1.76), with the magnitude of association somewhat stronger for lung cancer
affiliated with over 150 satellite clinical sites. 20 sites delivering mostly adult with COPD (OR=1.28, 95% CI: 0.84-1.97) than without COPD (OR=1.16, 95%
primary care were invited to participate. Individuals from 14 sites completed CI: 0.72-1.88). Conclusion: Our preliminary results provide minimal evidence
TTS training. Initial assessment of tobacco use (Current/Former/Never) was of pleiotropic associations of identified genetic variants for COPD with lung
excellent (>99%) across all clinical sites, including those who did not particpate cancer risk, although analyses are limited by the number of lung cancer patients
in TTS training. However, pack-years were recorded on average less that 40% examined.
of the time and quit dates for former smokers were recorded less than 30% of
the time at baseline. After training clinic staff in the TTS course, and regular Keywords: lung cancer, pleiotropy, Chronic obstructive pulmonary disease
ongoing feedback to clinical directors, we observed a significant initial increase
in accurate recording of pack-years and quit dates (two points of emphasis) for
all sites involved in the project, as well as referals to tobacco counselling. Over
OA04: EPIDEMIOLOGY AND PREVENTION OF LUNG CANCER
this time, unfortunately we did not detect an increase in the rate of prescription MONDAY, DECEMBER 5, 2016 - 11:00-12:30
of tobacco pharmacotherapy. The There was a gradual increase in the the
number of referrals for lung cancer screening Cts increased from an average of
30 per month to an average of over 70. Conclusion: This project to disseminate OA04.07 CLINICAL CHARACTERISTICS OF LUNG ADENOCARCINOMA
the skills of a TTS training course to clinics within a large University Health IN THE YOUNG: RESULTS FROM THE GENOMICS OF YOUNG LUNG
System has led to modest improvements in overall practices and demonstrated CANCER STUDY
areas where additional improvements are needed. Barbara Gitlitz 1, Anna Wu1, Marisa Bittoni2, Bonnie Addario3, Alicia Sable-
Hunt4, Mark Jennings1, Silvia Novello5, Tiziana Vavala6, Ruthia Chen7, Deborah
Keywords: tobacco cessation, quality improvement, screening
Morosini8, Geoffrey Oxnard7, S. Lani Park1
1
University of Southern California Keck School of Medicine, Los Angeles/CA/United
States of America, 2Ohio State University, Columbus/OH/United States of America,
3
Bonnie J. Addario Lung Cancer Foundation, San Carlos/United States of America,
OA04: EPIDEMIOLOGY AND PREVENTION OF LUNG CANCER 4
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 Addario Lung Cancer Medical Institute, San Carlos/United States of America,
5
Department of Oncology, University of Turin, Turin/Italy, 6University of Turin,
Turin/Italy, 7Dana-Farber Cancer Institute, Boston/MA/United States of America,
8
OA04.05 CHRONIC INFLAMMATION, NSAIDS AND THE RISK OF Foundation Medicine Inc., Cambridge/MA/United States of America
LUNG CANCER DEATH Background: Background: Lung cancer is increasingly recognized as a
Marisa Bittoni1, David Carbone2, Randall Harris3 heterogeneous disease comprised of genomically defined subtypes with
1
The Ohio State University, Columbus/United States of America, 2Medical Oncology, distinct targetable genomic alterations. However, it is unknown whether
The Ohio State University, Columbus/OH/United States of America, 3The Ohio State established lung cancer risk factors differ between these genomically
Unversity, Columbus/OH/United States of America distinct subtypes. In this study of the genomics of young lung cancer
(GoYLC), we present preliminary results of lifestyle risk factors by specific
genomic alteration to better characterize lung cancer in the young. Methods:
Methods: Beginning in July of 2014, patients diagnosed with a bronchogenic
lung cancer under the age of 40 were recruited to the GoYLC study. Informed
consent was obtained in-person and virtually (online), allowing patients to
OA04: EPIDEMIOLOGY AND PREVENTION OF LUNG CANCER participate globally, regardless of proximity to study sites (https://www.
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 openmednet.org/site/alcmi-goyl). To date, this study has accrued a total of
101 cases, of which 85 are adenocarcinoma (AC). Stage 4 AC is the focus of this
OA04.06 EXAMINING PLEIOTROPIC ASSOCIATIONS OF GENETIC analysis. Results: Results: Among the 63 stage 4 AC cases, the most common
genomic alterations were ALK rearrangements (n=28; 44% of stage 4 AC
RISK VARIANTS FOR CHRONIC OBSTRUCTIVE PULMONARY
cases) and EGFR mutations (n=17; 27%) while the other genomic alterations
DISEASE WITH LUNG CANCER RISK
(n=18; 29%) include ROS1, BRCA2, HER2, P53, RET and ATM. The prevalence
Lori Sakoda1, Khanh Thai1, Nareg Roubinian2, Carlos Iribarren1, Catherine of active smoking and/or exposure to passive smoking was highest among
Schaefer 1, Neil Risch3, Laurel Habel1, Charles Quesenberry Jr.1, Eric Jorgenson1 those with ALK (64%), intermediate for those with EGFR (47%) and lowest
1
Division of Research, Kaiser Permanente Northern California, Oakland/CA/United for those with other genomic alterations (39%). However, the prevalence of
States of America, 2Department of Pulmonary Medicine and Critical Care, Kaiser only active smoking was lowest among those with ALK (28%), followed by
Permanente Northern California, Oakland/CA/United States of America, 3Institute EGFR (35%) and highest for those with other genomic alterations (39%). The
for Human Genetics, University of California San Francisco, San Francisco/CA/
majority of patients with ALK rearrangements or EGFR mutations reported no
family history of lung cancer (82% and 88%, respectively), compared with 67%
Background: Tobacco smoke is the primary cause of chronic obstructive among those with other genomic alterations. Conclusion: Conclusion: These
pulmonary disease (COPD) and lung cancer, and among smokers, COPD is preliminary results suggest that lifestyle characteristics and family history in
associated with increased lung cancer risk. However, fewer than 30% of young lung cancer patients may differ by genomic alteration. Passive smoke
smokers are diagnosed with either disease, suggesting that genetic factors also exposure was more prevalent among those with ALK rearrangements or EGFR

mutations. Those with other genomic alterations, albeit, a heterogeneous OA05: TREATMENT ADVANCES IN SCLC
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
group, were least likely to be exposed to passive smoking and more likely to
be active smokers. We are continuing to enroll participants and are expanding
the epidemiologic characterization to all study patients to evaluate if risk OA05.03 SINGLE-AGENT ROVALPITUZUMAB TESIRINE, A DELTA-
factors also differ by tumor stage and histology (Data to be presented). LIKE PROTEIN 3 (DLL3)-TARGETED ANTIBODY-DRUG CONJUGATE
Importantly, this analysis lays the groundwork for the development of our
(ADC), IN SMALL-CELL LUNG CANCER (SCLC)
more comprehensive epidemiology of young lung cancer study that may
identify potential lifestyle and environmental risk factors related to specific David Spigel1, M Catherine Pietanza2, Todd Bauer 1, Neal Ready3, Daniel
genomic alterations. Morgensztern4, Bonnie S. Glisson5, Lauren Averett Byers5, Melissa Johnson1,
Howard Burris1, Francisco Robert6, Tae Han7, Sheila Bheddah7, Noah Theiss8,
Keywords: genomic alterations, Young Lung Cancer, clinical characteristics Sky Watson8, Deepan Mathur8, Bharathi Vennapusa8, Donald Strickland9,
Hany Zayed7, Scott Dylla7, Stanford Peng7, Ramaswamy Govindan4, Charles
Rudin10
1
Sarah Cannon Research Institute/tennessee Oncology, Nashville/TN/United States
of America, 2Memorial Sloan Kettering Cancer Center, New York/NY/United States
SESSION OA05: TREATMENT ADVANCES IN SCLC of America, 3Duke University Medical Center, Durham/NC/United States of America,
4
Washington University School of Medicine in St. Louis, St. Louis/MO/United
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 States of America, 5The University of Texas MD Anderson Cancer Center, Houston/
TX/United States of America, 6University of Alabama - Birmingham, Birmingham/
AL/United States of America, 7Abbvie Stemcentrx Llc, South San Francisco/CA/
OA05.01 PEMBROLIZUMAB IN PATIENTS WITH EXTENSIVE-STAGE United States of America, 8Roche Diagnostics, Tucson/AZ/United States of America,
9
SMALL CELL LUNG CANCER: UPDATED SURVIVAL RESULTS FROM Tennessee Oncology, Pllc, Sarah Cannon Research Institute, Nashville/TN/United
States of America, 10 Medicine, Memorial Sloan Kettering Cancer Center, New York/
KEYNOTE-028 NY/United States of America
Patrick Ott 1, Enriqueta Felip2, Sandrine Hiret3, Dong-Wan Kim4, Anne
Morosky5, Sanatan Saraf5, Bilal Piperdi5, Janice Mehnert6 Background: SCLC is one of the most deadly malignancies. Rovalpituzumab
1
Dana-Farber Cancer Institute, Boston/MA/United States of America, 2Vall tesirine (SC16LD6.5, Rova-T) is a first-in-class ADC directed against DLL3, a
D’Hebron Institute of Oncology, Barcelona/Spain, 3Ico Site René Gauducheau, novel target identified in tumor initiating cells and expressed in over 80%
Nantes/France, 4Seoul National University Hospital, Seoul/Korea, Republic of, of SCLC cases. Methods: Seventy-four patients with progressive SCLC after
5
Merck & Co., Inc., Kenilworth/NJ/United States of America, 6Rutgers Cancer at least one previous systemic therapy were enrolled in a first-in-human
Institute of New Jersey, New Brunswick/NJ/United States of America study (NCT01901653), irrespective of DLL3 expression, including 68 at active
doses of 0.2-0.4 mg/kg administered intravenously every 3 or 6 weeks.
Available archived tumor tissue (n=48) was assessed retrospectively by
This abstract is under embargo until December 5, 2016 at 07:00 CET. immunohistochemistry for DLL3. Results: Among 60 evaluable subjects,
active dose levels resulted in a confirmed objective response rate (ORR) of 18%
and a confirmed clinical benefit rate (CBR; stable disease or better) of 68%.
Among 26 evaluable subjects with DLL3 expression in at least 50% of tumor
OA05: TREATMENT ADVANCES IN SCLC cells (DLL3-high), confirmed ORR and CBR were 39% and 89%, respectively.
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
Median duration of response was 5.6 months. One-year survival rates among
all and DLL3-high subjects were 18% and 32%, respectively. Among primary
OA05.02 ANTI-TUMOR IMMUNITY IS A KEY DETERMINANT OF SCLC sensitive relapse patients, confirmed ORR and CBR among all subjects were
SURVIVORSHIP 24% (8/33) and 67% (22/33); and among DLL3-high subjects were 53% (8/15)
Farhad Kosari, Simone Terra, Aqsa Nasir, Prasuna Muppa, Marie Christine and 100% (15/15), with one-year survival rates of 17% and 33%, respectively.
Aubry, Joanne Yi, Nafiseh Janaki, Aaron Mansfield, Mariza De Andrade, Ping Among primary resistant/refractory relapse patients, confirmed ORR and CBR
Yang, George Vasmatzis, Virginia Van Keulen, Tobias Peikert among all subjects were 12% (3/25) and 72% (18/25); and among DLL3-high
subjects were 18% (2/11) and 73% (8/11), with one-year survival rates of 21%
Mayo Clinic, Rochester/United States of America
and 29%, respectively. The most common grade 3 or higher toxicities included
Background: While the majority of small cell lung cancer (SCLC) patients thrombocytopenia (12%), serosal effusions (11%), and skin reactions (8%).
succumb to their disease within a few months, there is a small group ADC pharmacokinetics were linear with a terminal half-life of 10 - 14 days and
of patients who survive for many years after their diagnosis. Factors anti-therapeutic antibodies did not develop Conclusion: Rovalpituzumab
contributing to the SCLC long-term survivorship remain largely unknown. tesirine demonstrates encouraging single-agent anti-tumor activity with a
Herein, we compared tumors from exceptional survivors (EXS) and patients manageable safety profile, including among patients with disease resistant or
with the expected outcome (EOP) to determine genomic and immunological refractory to primary chemotherapy. Further development of rovalpituzumab
determinant of SCLC survivorship. Methods: In the Mayo Clinic tissue registry, tesirine in SCLC is warranted.
we identified surgical blocks from 12 EXS who survived > 4 years after surgery
Keywords: clinical trial, Rovalpituzumab tesirine, Delta-like protein 3, SCLC
and 14 EOP who died < 2 years of surgery. These cohorts were created to
have no statistical differences in clinical TNM stage, curative versus non-
curative intent surgery, age, gender, and smoking status between EXS and
EOP. Tumor areas were macro-dissected for gene expression profiling by the
OA05: TREATMENT ADVANCES IN SCLC
Human Transcriptome Array (Affymetrix). Also, tissue sections were stained MONDAY, DECEMBER 5, 2016 - 14:15-15:45
for key immunological markers, including CD8, CD4, CD3, CD279, FoxP3,
CD138, CD20, CD21, CD14, CD68, and also LYZ. Concentrations of immune cells
in intra-tumor areas (IE), stroma (ST), and tumor/non-tumor interface (IF) OA05.05 RANDOMIZED PHASE 2 STUDY: ALISERTIB (MLN8237) OR
were assessed by an image processing program (Aperio). Staining patterns PLACEBO + PACLITAXEL AS SECOND-LINE THERAPY FOR SMALL-
in each of the three zones in EXS and EOP tumors were compared. Results: CELL LUNG CANCER (SCLC)
More than 90% of differentially expressed genes were over-expressed in EXS Taofeek Owonikoko 1, Kristiaan Nackaerts2, Tibor Csoszi3, Gyula Ostoros4,
compared with EOP. Furthermore, over 75% of the known over-expressed Christina Baik5, Claudio Dansky Ullmann6, Erin Zagadailov 7, Emily Sheldon-
genes were either immunoglobulin or MHC related and a majority of the Waniga7, Dirk Huebner8, E Jane Leonard9, David Spigel10
remaining genes were immune function related such as cytokines. We then 1
Hematology/medical Oncology, Emory University, Atlanta/GA/United States of
performed IHC for key immunological markers and found significantly higher America, 2KU Leuven, University Hospital of Leuven, Leuven/Belgium, 3Onkologiai
concentration of immune cells including CD8 and PD-1 positive cells in the Kozpont, Szolnok/Hungary, 4Viii, National Koranyi Institute of Pulmonology,
tumor microenvironment, especially at the tumor stromal interface in EXS Budapest/Hungary, 5Medical Oncology, University of Washington, Seattle Cancer
compared with EOP (p < 0.005 for both markers). Furthermore, the total Care Alliance, Seattle/WA/United States of America, 6Infinity Pharmaceuticals,
number of infiltrating immune cells (T-cells, B-cells, Plasma cells, monocytes Cambridge/MA/United States of America, 7Global Outcomes Research, Millennium
and macrophages was significantly higher in EXS in the interface region (p Pharmaceuticals Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical
Company Limited, Cambridge/MA/United States of America, 8 Millennium
< 0.0005). Conclusion: Gene expression profiling revealed that anti-tumor
Pharmaceuticals Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical
immunity is an important factor for SCLC survival. Further studies by IHC
Company Limited, Cambridge/United States of America, 9 Oncology Clinical
suggested the presence of immune cells especially cytotoxic T-cells in the Science, Millennium Pharmaceuticals Inc., A Wholly Owned Subsidiary of Takeda
tumor microenvironment and particularly at the tumor-stromal interface Pharmaceutical Company Limited, Cambridge/MA/United States of America,
to be major contributors to long term survivorship in SCLC. These findings 10
Sarah Cannon Research Institute | Tennessee Oncology, Nashville/AL/United
suggest that immunotherapeutic strategies may be effective for patients States of America
with SCLC.
Background: Alisertib, an investigational selective Aurora A kinase inhibitor,
Keywords: exceptional survivors, anti-tumor immunity, expression profiling, showed single-agent antitumor activity in preclinical in vivo SCLC models
tumor microenvironment and was synergistic with paclitaxel in this setting. We report the efficacy,
quality of life (QoL), and safety from this study. Methods: Patients ≥18 Background: A significant proportion of limited-stage small cell lung cancer
years with SCLC relapsed <180 days after standard first-line platinum-based are elderly. However, there is paucity of data on the efficacy and safety of
chemotherapy were randomized 1:1 to alisertib 40 mg orally twice-daily concurrent chemo-radiotherapy in the elderly to guide treatment decision-
on days 1–3, 8–10, 15–17 + paclitaxel 60 mg/m2 IV on days 1, 8, 15 (Arm A) or making. Methods: Data from the CONVERT trial was retrospectively analysed
matched placebo + paclitaxel 80 mg/m2 (Arm B) in 28-day cycles. Patients were to compare the outcome of patients 70 years or older to patients younger
stratified using an interactive voice response system (IVRS) by type of relapse than 70 years. Patients were randomised 1:1 to receive 45Gy in 30 twice-daily
post-frontline platinum (sensitive vs resistant/refractory) and presence/ fractions over 3 weeks or 66Gy in 33 once-daily fractions over 6.5 weeks
absence of brain metastases at baseline. Protocol Amendment 2 corrected starting on day 22 of cycle 1 chemotherapy (4 to 6 cycles of Cisplatin 25mg/
the definition for relapse per standard guidance; stratification factors were m2 days 1-3 or 75mg/m2 day 1 with Etoposide 100mg/m2 days 1-3), followed
corrected accordingly. Primary endpoint was progression-free survival (PFS) by Prophylactic Cranial Irradiation if indicated. Radiotherapy planning
per stratified log-rank test. QoL outcomes were assessed per EORTC QLQ-C30 was with a 3D conformal technique or intensity modulated radiotherapy.
and -LC13. Results: 178 patients were randomized, 89/89 to Arm A/B (median Results: Of 547 patients randomised between April 2008 and November
age 62/62 years). Survival, response, QoL, and safety results are presented in 2013, 57 patients were excluded for the purposes of this analysis as they did
the Table. The analysis of PFS using IVRS stratification favored Arm A, as did not receive concurrent chemo-radiotherapy. Of the 490 included patients,
the analysis per corrected stratification factors. Mean EORTC QLQ-C30 QoL 67 (13.7%) were age 70 years or older with median age of 73 years (70-82).
scores were similar between arms, as were mean change-from-baseline values Patients’ characteristics were well balanced apart from more male in the
at end of treatment (-5.7 in Arm A vs -4 in Arm B). elderly group (p=0.02). There was no significant difference in the number
of chemotherapy cycles administered in the two groups (p=0.24). A higher
proportion of patients received 30 or 33 fractions of radiotherapy as per
protocol in the younger group (85% vs. 73%; p=0.03). Neutropenia grade 3/4
occurred more frequently in the elderly group (84% vs. 70%; p=0.02) but there
was no statistically significant difference in neutropenic sepsis (4% vs. 7%;
p=0.07) and non-haematological acute/late toxicities. There were two vs.
six treatment-related deaths in the elderly and younger group respectively
(p=0.67). At median follow up of 46 months for those alive; two-year survival
was 53% (95% CI 41-64) vs. 57% (95% CI 52-61), median survival was 29 months
vs. 30 months in the elderly vs. younger group respectively. Hazard ratios for
overall survival and progression free survival were 1.15 (95% CI 0.84-1.59; log-
rank p=0.38) and 1.04 (95% CI 0.76-1.41; log-rank p=0.81) respectively. In the
elderly group median survival was not significantly different in patients who
received once vs. twice daily radiotherapy (p=0.91). Conclusion: Radiotherapy
treatment delivery was higher in the younger group but toxicity and survival
rates were similar in elderly compared to younger patients. Concurrent
chemo-radiotherapy with modern radiotherapy techniques is a treatment
option for elderly patients with good performance status.
Keywords: Radiotherapy, small cell lung cancer, elderly

MONDAY, DECEMBER 5, 2016 - 14:15-15:45
OA05.07 PROGNOSTIC VALUE OF CIRCULATING TUMOUR CELLS IN

LIMITED-DISEASE SMALL CELL LUNG CANCER PATIENTS TREATED
ON THE CONVERT TRIAL
Fabiola Fernandez-Gutierrez 1, Victoria Foy2, Katy Burns3, Jackie Pierce1,
Karen Morris1, Lynsey Priest1, Jonathan Tugwood1, Linda Ashcroft4, Corinne
Faivre-Finn5, Caroline Dive1, Fiona Blackhall6
Conclusion: Alisertib + paclitaxel shows favorable PFS over placebo + 1
Clinical & Experimental Pharmacology Group, CRUK Manchester Institute,
paclitaxel with both initial and updated IVRS stratification. A similar Manchester/United Kingdom, 2The Christie NHS Foundation Trust, Manchester/
favorable trend was also observed for OS and ORR although not statistically United Kingdom, 3Institute of Cancer Sciences, University of Manchester,
significant. Comparable changes in QoL scores were observed from baseline Manchester/United Kingdom, 4 Manchester Academic Health Science Centre-
in both arms. The alisertib + paclitaxel arm showed higher rates of AEs and Trials Coordination Unit, Manchester/United Kingdom, 5Department of Clinical
discontinuation due to AEs. Updated survival analyses are pending. Oncology, Univ. of Manchester and the Christie NHS Foundation Trust, Manchester/
United Kingdom, 6Univ. of Manchester and the Christie NHS Foundation Trust,
Keywords: Aurora A Kinase inhibitor, MLN8237, small cell lung cancer, alisertib Manchester/United Kingdom
Background: Circulating tumour cells (CTCs) are prevalent in patients with

small cell lung cancer (SCLC) (Hou et al. JCO 2012) but their clinical utility is
not known for patients with limited disease (LD) who receive concurrent
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 chemoradiation. Here we report on a patient subgroup who underwent CTC
analysis and treatment on the Concurrent ONce-daily (OD) VErsus Twice-
daily (BD) RadioTherapy (CONVERT) trial (Faivre-Finn Proc. ASCO 2016) that
OA05.06 COMPLIANCE AND OUTCOME OF ELDERLY PATIENTS demonstrated a non-significant difference in the primary endpoint of two-year
TREATED IN THE CONCURRENT ONCE-DAILY VERSUS TWICE-DAILY survival for the OD (51%) and BD (56%) arms. Methods: Blood samples (7.5mls)
RADIOTHERAPY (CONVERT) TRIAL were collected at baseline, prior to any treatment from patients who were
Marianna Christodoulou1, Fiona Blackhall2, Linda Ashcroft3, Ahmet Leylek4, enrolled to the CONVERT trial at The Christie Hospital site, Manchester, UK.
Joost Knegjens5, Vincent Remouchamps6, Isabelle Martel-Lafay 7, Núria Farré8, CTCs were enumerated prospectively using the Cellsearch platform. Patients
Matjaz Zwitter9, Delphine Lerouge10, Nicolas Pourel11, Henri Janicot12, Arnaud were randomised 1:1 to receive 45Gy in 30 twice-daily fractions over 3 weeks
Scherpereel13, Caroline Tissing-Tan14, Karine Peignaux15, Xavier Geets16, (Arm 1) or 66Gy in 33 once-daily fractions over 6.5 weeks (Arm 2) starting on
Krzysztof Konopa17, Corinne Faivre-Finn2 day 22 of cycle 1 chemotherapy (4 to 6 cycles of Cisplatin 25mg/m2 days 1-3 or
1 75mg/m2 day 1 with Etoposide 100mg/m2 days 1-3), followed by prophylactic
The Christie NHS Foundation Trust, Manchester/United Kingdom, 2University of
Manchester, Manchester/United Kingdom, 3Manchester Academic Health Science cranial irradiation if indicated. Radiotherapy planning was with a 3D conformal
Centre- Trials Coordination Unit, Manchester/United Kingdom, 4 Cancercare technique or intensity modulated radiotherapy. Staging by Positron Emission
Manitoba, Winnipeg/Canada, 5The Netherlands Cancer Institute – Antoni Van Tomography (PET) was permitted. Standard statistical methods were used
Leeuwenhoek Hospital, Amsterdam/Netherlands, 6CHU UCL Namur, Site Ste to examine associations between CTC number (CTC#), clinical factors and
Elisabeth, Namur/Belgium, 7Centre Léon Bérard, Lyon/France, 8Hospital de outcomes. Results: Of 547 patients randomised between April 2008 and
La Santa Creu I Sant Pau, Barcelona/Spain, 9Institute of Oncology, Ljubljana/ November 2013, 79 patients (41 in Arm1 and 38 in Arm 2) underwent CTC
Slovenia, 10 Centre François Baclesse, Caen/France, 11Institut Sainte-Catherine,
enumeration (CTC subgroup). The clinical demographics and median overall
Avignon/France, 12CHU Gabriel Montpied, Clermont-Ferrand/France, 13Hospital
survival (OS) of the CTC subgroup did not differ significantly from the overall
of the University (CHRU) of Lille, Lille/France, 14Radiotherapiegroep, Arnhem/
Netherlands, 15Georges Francois Leclerc Center, Dijon/France, 16Cliniques study population. The median number (range) of CTCs per 7.5mls blood for all
Universitaires Saint-Luc, Miro-Irec-Ucl, Brussels/Belgium, 17Medical University of 79 patients was 1 (0-3750) and for arm 1 and arm 2 patients respectively, 12
Gdansk, Gdansk/Poland (0-164) and 158 (0-3750) (p=0.495). There was a trend for association of CTC#

with higher TNM stage. CTC# was significant for survival in univariate and and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano/
multivariate analysis. The median (95% CI) OS for ≥15 CTCs (n=18) was 6.01 Italy, 4Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan/
(4.2-11.5) months compared to 30.77 (19.7-39.3) months for < 15 CTCs (n=61), p Italy
<0.001. The positive predictive value of CTC# ≥15 for survival ≤ 2 years is 100%,
Background: The issue of overdiagnosis in low-dose computed tomography
and ≤ 1 year is 72%. CTC# also predicted for worse outcome in patients who had
(LDCT) screening trials for lung cancer has to be addressed by the
undergone PET staging. Conclusion: CTC# is highly prognostic for poor survival
development of complementary biomarkers able to improve detection of
in patients with LD-SCLC, treated with concurrent chemoradiotherapy, and
aggressive disease. We previously identified a 24 plasma miRNA signature
could aid treatment decision making for this disease.
endowed with good performance in terms of sensitivity and specificity
Keywords: SCLC, Circulating Tumour Cells, chemoradiation, biomarker in subjects enrolled in independent LDCT screening trials. However, the
relationship between circulating miRNAs in plasma and the molecular
heterogeneity of the patients’ tumors needs to be considered. Linking tumor
genomics to circulating miRNA profiles represent an attractive approach. In
fact a plasma miRNA assay able to classify molecular subclasses of tumors
SESSION OA06: PROGNOSTIC & PREDICTIVE BIOMARKERS could constitute a sort of “liquid biopsy” endowed with not only diagnostic
but also prognostic and, potentially, therapeutic value. Methods: We
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
evaluated the mutation profile by targeted Next-Generation Sequencing
(NGS) analysis (Cancer Hotspot Panel v.2) in 94 Low Dose Computed
Tomography (LDCT) screening-detected lung tumors resected from subjects
OA06.01 CLINICAL UTILITY OF CIRCULATING TUMOR DNA (CTDNA) participating in 3 screening trials for lung cancer. Mutation profile was
ANALYSIS BY DIGITAL NEXT GENERATION SEQUENCING OF OVER associated with clinicopathologic, survival features and with a plasma MSC
5,000 ADVANCED NSCLC PATIENTS risk level of patients. The mutational profile obtained was compared with the
Philipp Mack 1, Kimberly Banks2, Jonathan Riess1, Oliver Zill2, Stefanie mutations of a selected dataset of clinically detected lung tumors through
Mortimer2, Darya Chudova2, Justin Odegaard2, Christine Lee2, Rebecca Nagy2, The Cancer Genome Atlas (TCGA). Results: We showed alterations in the
Helmy Eltoukhy2, Amirali Talasaz2, Richard Lanman2, David R. Gandara1 main genetic drivers in 79% of screening lung tumors whereas 21% of tumor
1
Internal Med, UC Davis Cancer Center, Sacramento/CA/United States of America, samples had no alteration within these amplicons. Significant associations
2
Guardant Health, Redwood City/CA/United States of America between TP53, squamous histology and smoking intensity as well as KRAS
mutations with worse OS were detected. EGFR alterations were present in
Background: Detection of actionable genomic alterations is now required 4 tumors from heavy smokers. The 5-year overall survival (OS) of screening
for NCCN guideline-compliant work-up of NSCLC adenocarcinoma. Next- patients with and without mutations in the tumors was 64% and 100%,
generation sequencing (NGS) of ctDNA, if sufficiently sensitive and specific, respectively (p=0.019). By combining the mutational status with the MSC risk
could provide a non-invasive, comprehensive genotyping platform relevant to profile, patients were stratified into 3 groups with 5-year OS ranging from
clinical decision-making when tissue is insufficient or at time of progression 41% to 96% (p<0.0001) and the prognostic value was significant even when
on targeted therapies. Methods: A highly accurate, deep-coverage (15,000x) controlling for stage (p=0.017). A similar mutational profile and mutation
ctDNA plasma NGS test targeting 54-70 genes (Guardant360) was used to frequency was observed in screening- and in clinical (TCGA) tumors, whereas
genotype 5,206 advanced-stage NSCLC patients accrued between 6/2014 difference in 5-year OS between subjects with and without mutations was
– 4/2016. The frequency and distribution of somatic alterations in key exclusively detected in screening patients. Conclusion: The mutation profile
genes were compared to those described in TCGA (Pearson and Spearman of screening-detected tumors, while similar to that of clinically-detected
correlations). The clinical impact of ctDNA testing was evaluated by tumors, was a strong predictor of OS. The combination of tumor mutational
identification of resistance mechanisms emergent at progression on targeted status with a circulating miRNA-based risk classifier predicts tumor
therapies, and through analysis of additional driver mutations detected by aggressiveness and clinical outcome and may find rapid application in LDCT
ctDNA at baseline in 362 consecutive NSCLC patients with tissue mutation screening programs by reducing the number of unnecessary interventions and
data available. The positive predictive value (PPV) of ctDNA sequencing was helping plan targeted treatment
assessed in 229 patients with known tumor driver alterations. Results: ctDNA
alterations were detected in 86% of cases; EGFR mutations in 25%, KRAS Keywords: low-dose computed tomography, lung cancer screening,
mutations in 17%, MET amplification in 4%, BRAF mutations in 3% and other Mutational profiles, MicroRNA-based liquid biopsy
rare but potentially actionable alterations in 9%. Mutation patterns among
driver oncogenes were highly consistent with those from TCGA (Pearson
r=0.92, 0.99, 0.99 for EGFR, KRAS, and fusion breakpoint location). PPV of
ctDNA-detected variants was 100% for EGFRL858R , 98% for EGFRE19del, 96% OA06: PROGNOSTIC & PREDICTIVE BIOMARKERS
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
for ALK, RET, or ROS1 fusions, and 100% for KRASG12/G13/Q61 mutations. In 362
cases with tissue information available, 63% (229/362) were tissue quantity-
insufficient or undergenotyped (QNS/UG). ctDNA analysis identified driver OA06.03 TRANSCRIPTOME ANALYSIS OF ATM-DEFICIENT NSCLC
mutations in 51 of the 229 QNS/UG cases, a 38% increase in detection rate
Lars Petersen1, Emeka Enwere1, Mie Konno1, Olga Kovalchuk2, D. Gwyn Bebb1
over tissue alone. Among 1,111 EGFR-mutant cases, resistance mutations were 1
Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary/AB/Canada,
identified at progression at frequencies consistent with published literature: 2
University of Lethbridge, Lethbridge/AB/Canada
EGFRT790M 47%, MET amp 5%, ERBB2 amp 5%, FGFR3 fusions 0.4%, ALK/other
fusions 1%, BRAF mutations 1.8%, PTEN inactivation 2.5%, NF1 inactivation Background: Current targeted therapy options in lung cancer, such as EGFR
3%, RB1 inactivation 3%, KRAS mutations 1.9%. In 143 consecutive NSCLC and ALK inhibitors, are effective, though limited in use by the low percentage
patients with detailed follow-up and serial analysis seen at the UC Davis of patients that carry targetable mutations for these biomarkers. Targeting
Cancer Center, informative driver mutations were observed in 48 (34%). a broader biological process like DNA damage response (DDR), as with recent
Conclusion: This series represents the largest NSCLC ctDNA study to date. synthetic lethality exploits in BRCA-deficient tumours, may offer a form of
Genotypic patterns of truncal mutations were highly consistent with TCGA precision therapy for a larger number of patients. We have shown that NSCLC
in terms of frequency and distribution. At baseline, ctDNA augmented cells deficient in the DDR protein ATM, exhibit similar synthetic lethality when
tissue analysis by identifying additional, actionable mutations when tissue treated with a PARP1 inhibitor, and that NSCLC patients lacking detectable
was QNS/UG. ctDNA NGS conducted at progression identified emergent ATM have poorer overall survival. In vitro, ATM deficient, or “ATMic” cells
resistance mutations that could inform subsequent courses of therapy. show increased sensitivity to chemotherapeutics at much lower levels when
given in combination with PARP inhibitor. This data suggests that ATM
Keywords: liquid biopsy, ctDNA, NSCLC
status may be an important determinant for treatment modalities including
low dose radiation or platin therapy, or novel synthetic lethality therapies.
Here, we seek to determine the cause of ATM loss in NSCLC patients through
targeted sequencing, and thorough transcriptomic and epigenetic analysis.
OA06: PROGNOSTIC & PREDICTIVE BIOMARKERS
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 Methods: We perform whole-transcriptome analysis on NSCLC patient
samples previously characterized as normal or ATMic, to detect differences in
intracellular pathway activation in these tumours. Additional analysis using
OA06.02 MUTATIONAL LOAD PREDICTS SURVIVAL IN LDCT OncoFinder software identifies possible effective therapies based on which
SCREENING-DETECTED LUNG CANCERS signalling pathways are most active in the normal or ATMic patients. We also
Gabriella Sozzi1, Carla Verri1, Cristina Borzi1, Todd Holscher2, Matteo Dugo3, perform targeted NGS on these samples. To our knowledge, no sequencing
Andrea Devecchi3, Katherine Drake2, Stefano Sestini4, Paola Suatoni4, Elisa of ATM has been performed on samples that have also been characterized
Romeo2, Mattia Boeri1, Ugo Pastorino4 through other methods (i.e. quantitative IHC) to be ATM deficient. Results:
1
Tumor Genomics Unit, Department of Experimental Oncology and Molecular
We have generated a substantial body of evidence showing that ATM loss has
Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori Int, Milano/Italy, significant impact on the cell sensitivity to several therapeutic modalites. As
2
Gensignia Life Sciences, Inc, San Diego/CA/United States of America, 3Unit of such ATMic tumours may be treated more effectively using specific treatment
Functional Genomics and Bioinformatics, Department of Experimental Oncology strategies than their ATM competent counterparts. Initial analysis of
NSCLC cell lines using the outlined methodologies distinguishes ATM status CARCINOGENESIS PATHWAYS DRIVE THE PROGNOSIS OF
and identifies different therapeutic agents based on inherent molecular SQUAMOUS CELL LUNG CARCINOMA (SQCLC)
differences. A complete analysis of the transcriptome profiles of ATMic NSCLC
Sara Pilotto 1, Michele Simbolo2, Isabella Sperduti3, Silvia Novello4, Caterina
patients will be presented and discussed. Conclusion: This research helps
Vicentini2, Umberto Peretti1, Serena Pedron5, Roberto Ferrara1, Mario
complete the overall picture of what the therapeutic implications of ATM
Caccese1, Michele Milella3, Andrea Mafficini5, Paolo Visca3, Marco Volante4,
loss in NSCLC actually are and how ATMic tumours can best be identified in
Francesco Facciolo3, Antonio Santo1, Luisa Carbognin1, Matteo Brunelli5,
the clinic. Together, these analyses will give us a stronger understanding of
Marco Chilosi5, Aldo Scarpa5, Giampaolo Tortora1, Emilio Bria1
the mechanism for ATM loss in NSCLC, as well as allow us to develop an ATMic 1
Medical Oncology, University of Verona, Verona/Italy, 2 Arc-Net Applied Research
“signature” for reliably determining ATM status in patients for directing their
on Cancer Center, University of Verona, Verona/Italy, 3Regina Elena National Cancer
treatment options. Institute, Rome/Italy, 4Department of Oncology, University of Turin, Aou San Luigi,
Orbassano/Italy, 5Department of Pathology and Diagnostics, University of Verona,
Keywords: Personalized therapy, ATM, transcriptome Verona/Italy
Background: We previously built and validated a risk classification model for

resected SqCLC by combining clinicopathological predictors to discriminate
OA06: PROGNOSTIC & PREDICTIVE BIOMARKERS patients’ (pts) prognosis (Pilotto JTO 2015). Here we (AIRCMFAG project no.
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
14282) investigate the molecular portrait of prognostic outliers to identify
differentially expressed, potentially druggable alterations. Methods: Based
OA06.05 PROTEOMIC ANALYSIS OF ERCC1 PREDICTS BENEFIT OF on the published 3-class model, 176 and 46 pts with good and bad prognosis,
PLATINUM THERAPY IN NSCLC: A REEVALUATION OF SAMPLES respectively, were identified. Somatic Mutations (SM) and Copy Number
Alterations (CNA) were evaluated with Next Generation Sequencing (NGS)
FROM THE TASTE TRIAL
for 59 genes (Ion Proton system, Ion Ampliseq custom panel). Moreover, RNA
Jean-Charles Soria1, Ken Olaussen1, Fabiola Cecchi2, Eunkyung An2, Christina expression assays, immunohistochemistry (IHC) and immunofluorescence
Yau3, Marie Wislez4, Gérard Zalcman5, Denis Moro-Sibilot6, David Perol7, (FISH) were performed. Descriptive statistic was adopted and continuous
Franck Morin8, Benjamin Besse9, Todd Hembrough2 variables were dichotomized according to AUC or medians. Results: Herein,
1
Gustave Roussy Cancer Campus and University Paris-Sud, Paris/France, the analysis of 60 pts (good/poor 27/33) is reported. In the overall population,
2
Nantomics, Rockville/MD/United States of America, 3UCSF School of Medicine, the median rate of SM (3.3%) is lower compared to the median rate of CNA
San Francisco/CA/United States of America, 4Service de Pneumologie, Aphp Hôpital
(28.3%), without significant differences between the two prognostic groups.
Tenon, Paris/France, 5University Hospital Bichat, Paris/France, 6Pôle Thorax Et
Vaisseaux, Unité D’Oncologie Thoracique, Service de Pneumologie, Grenoble/ The most frequent SM resulted to be missense (66.7%) and nonsense (20.3%)
France, 7Centre Léon Bérard · Clinical Research & Biostatistics, Lyon/France, mutations, whereas the copy number gain is the most common CNA (76.7%),
8
French Cooperative Thoracic Intergroup (IFCT), Paris/France, 9Department of The distribution of relevant alterations in the main carcinogenesis pathways
Cancer Medicine, Gustave Roussy, Paris/France in term of SM, CNA and expression (by RNA, IHC and FISH), according to the
prognostic subgroups, are reported in the table.
Background: It is hypothesized that low or absent expression of the excision
repair cross-complementation group 1 (ERCC1) protein predicts improved Pathway Gene [method] Good [%] Poor [%] p-value
survival in NSCLC patients treated with platinum-based therapy. However,
the International Adjuvant Lung Cancer Trial Collaborative Group concluded Squamous dif-
SOX [CNA] 74.1 51.5 0.11
that current ERCC1 assessment methods are inadequate for clinical decision- ferentiation
making. Due to the unreliability of ERCC1 immunohistochemistry (IHC), the TP63 [CNA] 37.0 21.2 0.25
IFCT-0801 TASTE (Tailored Postsurgical Therapy in Early-Stage NSCLC) trial
Epithelial to
of adjuvant therapy for NSCLC was discontinued. We reevaluated a subset
mesenchymal SNAI1 [RNA] 59.2 90.9 0.006
of samples from the TASTE trial using mass spectrometry-based proteomics
transition
to quantitate ERCC1 protein. We correlated ERCC1 proteomic status with
survival after chemotherapy with cisplatin/pemetrexed and compared it to Vimentin [RNA] 44.4 69.7 0.07
ERCC1 IHC ranking. Methods: Formalin-fixed, paraffin-embedded NSCLC tumor mTOR PI3KCA [SM] 0 9.0 0.24
tissues were laser microdissected, solubilized, digested, and proteomically
analyzed. A multiplexed, selected reaction monitoring mass spectrometric RICTOR [CNA] 3.7 27.3 0.017
assay was used to quantitate levels of multiple proteins including ERCC1. The p-mTOR [IHC] 11.1 18.1 0.5
Kaplan-Meier method and univariate Cox analysis assessed overall survival
(OS) and relapse-free survival (RFS). A chi-squared test compared binary Tyrosine kinase
DDR2 [SM] 11.1 0 0.085
proteomic levels of ERCC1 (detectable vs. undetectable) with the IHC status receptors
assessed using an anti-ERCC1 antibody (8F1) during the TASTE trial. Results: FSR2 [CNA] 3.7 18.1 0.12
Of 146 evaluable patients, 33 (22.6%) had undetectable ERCC1 by quantitative
proteomics. Proteomics found no detectable ERCC1 protein in 8/36 (22.2%) MET [FISH] 11.1 24.2 0.32
IHC-positive patients nor in 8/22 (19.3%) IHC-indeterminate patients. ERCC1
FGFR3 [FISH] 25.9 42.4 0.28
was detected in 71/88 (80.7%) IHC-negative patients (range: 36-137 amol/µg
total tumor protein). Undetectable ERCC1 by proteomics was prognostic of Cell cycle
CDKN2A [CNA] 22.2 3.0 0.38
OS (hazard ratio [HR]: 5.45; p=0.031). In survival analyses of cisplatin-treated regulators
patients (n=122), only one of the 15 deaths occurred among the patients with SMAD4 [CNA] 33.3 57.6 0.074
undetectable ERCC1 protein. These patients had better OS than cisplatin-
treated patients with detectable ERCC1, although the difference statistically Immune check-
PD-L1 [IHC] 18.5 6.1 0.23
nonsignificant (HR: 3.98; p=0.102). RFS was similar between patients with points
and without detectable ERCC1. GARFT protein (predictive of response to PD-1 [RNA] 51.8 93.9 <0.0001
pemetrexed) was quantified in 100% of patients (range: 492-4006 amol/µg).
The 10 cisplatin/pemetrexed-treated patients with GARFT levels >900 amol/ Conclusion: Although performed on a limited number of pts, such
µg had nonsignificantly worse OS than their counterparts with lower GARFT comprehensive analysis of DNA, RNA and proteins, using different
levels (p=0.08). Conclusion: Although underpowered to detect statistically methodologies, is feasible and allow identifying potentially druggable
significant survival differences, this study clearly demonstrates that prognostic modulators, such as RICTOR/PI3K/mTOR signaling pathway. The
quantitative proteomics can increase accuracy in identifying NSCLC patients possibility to inhibit this pathway with selective agents is currently under
who will respond to platinum-based therapy because they do not express investigation in in vitro preclinical models.
ERCC1. Approximately 28% of such patients were misclassified by ERCC1 IHC
in the TASTE trial. Clinicians should be aware that multiplexed quantitative Keywords: squamous lung cancer, Prognosis, NGS
proteomics can quantitate ERCC1 simultaneously with multiple clinically
relevant proteins in lung tumors and small biopsies.
Keywords: Biomarkers, Quantitative-proteomics, Cisplatin-based- OA06: PROGNOSTIC & PREDICTIVE BIOMARKERS

chemotherapy, TASTE-trial MONDAY, DECEMBER 5, 2016 - 14:15-15:45
OA06.07 EVALUATING GENOMIC SIGNATURES PREDICTING

OA06: PROGNOSTIC & PREDICTIVE BIOMARKERS VELIPARIB SENSITIVITY IN NON-SMALL CELL LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 (NSCLC)
Lei He, Xin Huang, Yan Sun, Vasudha Sehgal, Xin Lu, Fang Jiang, Paul Jung,
OA06.06 DRUGGABLE ALTERATIONS INVOLVING CRUCIAL Youping Deng, Joann Palma, Anahita Bhathena, Peter Ansell, Mark Mckee

Abbvie Inc., North Chicago/IL/United States of America Keywords: non small cell lung cancer, N2 skip metastasis
Background: Veliparib is a potent poly(ADP-ribose) polymerase (PARP)-1

and PARP-2 inhibitor that has synthetic lethality interaction with cancers
harboring homologous recombination deficiency. In preclinical models, OA07: LYMPH NODE METASTASES AND OTHER PROGNOSTIC FACTORS FOR LOCAL
it has also been shown to delay the repair of DNA damage induced by SPREAD
chemotherapeutics (platinum, alkylators, topoisomerase inhibitors). MONDAY, DECEMBER 5, 2016 - 14:15-15:45
Clinically meaningful improvements in progression-free survival and overall
survival were observed in a phase 2 trial of veliparib with carboplatin/ OA07.02 OMITTING INTRAPULMONARY LYMPH NODE RETRIEVAL
paclitaxel in previously untreated metastatic or advanced NSCLC (M10-
MAY AFFECT THE ONCOLOGICAL OUTCOME OF PN0 LUNG CANCER
898 study). Intriguingly, smoking history had a major impact on veliparib
effect—smokers benefited most from veliparib addition. The underlying
PATIENTS: A PROPENSITY SCORE MATCH ANALYSIS
mechanism for this observation remains unclear. The efficacy benefit of Xing Wang1, Nan Wu2, Shi Yang2, Chao Lv2, Shaolei Li2, Yuzhao Wang2, Jia
veliparib in smokers is not dependent on tobacco exposure during study Wang2, Lijian Zhang2, Yue Yang2
1
treatment, but correlates with the duration of smoking history, suggesting Department of Thoracic Surgery Ii, Peking University Cancer Hospital & Institute,
a genetic basis. Methods: Genomic signatures in NSCLC associated with Key Laboratory of Carcinogenesis and Translational Research (Ministry of
smoking status have been identified by The Cancer Genome Atlas (TCGA) Education), Beijing/China, 2Department of Thoracic Surgery Ii, Key Laboratory of
Carcinogenesis and Translational Research (Ministry of Education), Beijing/China
Lung Cancer Project. Relevant observations were leveraged in the reported
analysis. To comprehensively identify genes or genomic features that are Background: Clinical practice involving segmental nodes (No.13) and
associated with smoking status and veliparib response, patient tumor subsegmental nodes (No.14) retrieval for pathological examination varies
samples from the M10-898 trial were subjected to whole-exome (N = 38) and during lung cancer surgery. This study aims to evaluate whether omitting
RNA sequencing (N = 75) analysis. Alexandrov somatic mutational signature No.13 and No.14 node retrieval could lead to an inferior oncological outcome
was calculated from exome sequencing data. Results: Data from TCGA show for pN0 non-small cell lung cancer (NSCLC) patients. Methods: This
that cancer genomes in smokers harbor significantly more genetic alterations retrospective study analyzed 442 cases of NSCLC, both treating with R0
than those in non-smokers. These alterations include high mutational resection and systematic mediastinal lymphadenectomy and confirming
burden, high C>A transversion, high mutation frequency of key cancer genes as pN0 on postoperative pathology. Study group defined cases whose N1
(particularly TP53), and high homologous recombination defect signature. nodes investigation involving from No.10 to No.14 in pathological report.
Similar observations were confirmed in the M10-898 study. Of the 38 patients In Control group, N1 nodes investigation only include No.10 to No.12.
with exome data, 26 were determined to be positive for a smoking-related Clinical and pathological parameters of above two groups were balanced
signature—signature 4. Elevated mutational burden was observed among by propensity score matching based on surgical quality and the oncological
current and former smokers, with a mean of 199 somatic mutations in current outcomes between two groups were assessed by log-rank test. Results:
or former smokers vs 60 in never-smokers (p = 0.004). The small sample size of Seven cases were lost during follow up and 435 cases entered final analysis
our genomic cohort nevertheless precludes conclusive association of genomic (Study group, n=170 vs. Control group, n=265). A total of 5.0±3.0 nodes per
signatures and veliparib benefits. Conclusion: Cancer genomes in smokers case were collected from No. 13 and No. 14 in Study group, which included
are enriched with genetic alterations associated with poor outcome using 3.1±1.9 nodes of No. 13 and 2.0±2.2 of No. 14. Tumor-located segments
standard chemotherapy, as well as with vulnerability factors that can prime harbored 2.8±2.2 lymph nodes, compared to 2.2±2.3 from non-tumor
tumors to respond to veliparib. For further validation, a targeted sequencing located segments (p=0.006). After propensity score matching, 143 cases
assay to detect key DNA damage and repair genes as well as key genomic remained in each group. Overall survival (OS) and disease-free survival (DFS)
signatures has been established and will be used in all phase 3 veliparib trials. were improved in Study group compared with Control group (the 5-year OS
Keywords: smoking status, veliparib, whole-exome sequencing, non-small cell rates, 89±3% vs. 77±4%, p=0.027; the 5-year DFS rates, 81±4% vs. 67±4%,
lung cancer (NSCLC) p=0.021, Figure1A,1B). In multivariate analysis, T staging and performing
intrapulmonary nodes collection were the prognostic factors for pN0 cases.
For the whole cohort, patients with two intrapulmonary stations collected
showed better survival than those with zero intrapulmonary station retrieved
SESSION OA07: LYMPH NODE METASTASES AND OTHER (Figure1C, 1D). Conclusion: Inferior oncological outcomes of pN0 cases without
PROGNOSTIC FACTORS FOR LOCAL SPREAD intrapulmonary node retrieval suggests this procedure may play a role in
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 outcome evaluation for pN0 NSCLC patients.
Keywords: intrapulmonary lymph node, lung cancer, propensity score

matching, outcome
OA07.01 INCIDENCE, LOCAL DISTRIBUTION AND IMPACT OF
PN2 SKIP METASTASIS IN PATIENTS UNDERGOING CURATIVE
RESECTION FOR NSCLC
Ariane Steindl, Sabrina Tahon, Mai Nguyen, Balazs Dome, Viktoria Laszlo, OA07: LYMPH NODE METASTASES AND OTHER PROGNOSTIC FACTORS FOR LOCAL
SPREAD
Walter Klepetko, Mir Hoda, Thomas Klikovits MONDAY, DECEMBER 5, 2016 - 14:15-15:45
Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria
Background: Background: The presence of N2 lymph node (LN) involvement OA07.03 PROGNOSTIC SIGNIFICANCE OF MICROMETASTASES
has strong impact on therapy and prognosis in non-small cell lung cancer IN MEDIASTINAL LYMPH NODES OF PATIENTS WITH RADICALLY
(NSCLC). N2 LN metastasis may occur by skipping N1 LN stations (N2skip- RESECTED NON-SMALL CELL LUNG CANCER
met). We aim to analyze incidence, local distribution and impact of N2skip-
Paweł Gwóźdź1, Monika Pasieka-Lis2, Katarzyna Kołodziej2, Juliusz
mets in a large cohort of patients undergoing curative resection for NSCLC.
Pankowski2, Marcin Zieliński3
Methods: Methods: A retrospective non-interventional singe-center cohort 1
study was conducted, assessing all patients undergoing curative resection for Thoracic Surgery, Pulmonary Hospital, Zakopane/Poland, 2Pathology Department,
Pulmonary Hospital, Zakopane/Poland, 3Thoracic Surgery Department, Pulmonary
NSCLC between 2006 and 2013 at our institution by reviewing medical charts.
Hospital, Zakopane/Poland
Incidence of N2skip-mets among these patients was the primary endpoint.
Subsequent secondary correlation of clinical parameters was performed using Background: Recurrence occurs in 30-50 % of patients operated for early
uni- and multivariate logistic and cox regression models. Results: Results: In stage non-small cell lung cancer (NSCLC), what suggests the existence of
total, 1110 patients were enrolled, with the following pathological LN status: occult metastases at the time of surgery. Preoperative detection of occult
789 (71%) pN0, 211 (19%) pN1, 105 (9.5%) pN2, 5 (0.5%) pN3. Histological micrometastases in mediastinal lymph nodes could contribute to better
subtype was: adenocarcinoma, n=675 (61%); squamous cell carcinoma, n=309 selection of patients apropriate for surgery. This retrospective study was
(28%); other, n=126 (11%). Incidence of N2skip was 55% (47/105). N2skip-mets undertaken to determine the prognostic significance of preoperatively
occurred more frequently in right sided tumors (odds ratio (OR) 2.14, p=0.058) detected mediastinal lymph node (LN) micrometastases in patients treated
and patients with adenocarcinoma (vs. other, OR 1.54, p=0.19). Presence with radical surgical resection for stage I and II NSCLC. Methods: From
of N2skip-mets did not correlate with tumor size (ROC, area under curve January 2007 to December 2010, 82 patients with stage I and 67 patients
(AUC) 0.44, p=0.32). Strikingly, presence of N2skip-mets was significantly with stage II NSCLC underwent transcervical extended mediastinal
increased in smokers (OR 3.5, 95% CI 1.38-8.83, p=0.006). Moreover, patients lymphadenectomy (TEMLA) and subsequent radical pulmonary resection.
with N2skip-mets were more likely to develop subsequent brain mets (OR A total of 4841 mediastinal lymph nodes resected during TEMLA procedure
4.13, p=0.06). Overall- and recurrence free survival will be presented at the and determined as metastases-free by hematoxylin and eosin staining were
conference. Conclusion: Conclusion: N2skip-mets occur in a high number labelled to detect occult micrometastases (dual immunohistochemical
of patients with N2 disease, with distinct differences in clinicopathologic staining with AE1/AE3 and BerEP4 antibodies). Results: Micrometastases
features. Considering the results of this study, subclassification of N2 disease were detected in mediastinal LN of 16 patients (9,7%). 11 patients had only one
as recently proposed by the IASLC may have clinical impact in patients with LN station affected (68,8%). Subcarinal LN were most frequently affected
resectable NSCLC.
station (11 patients, 68,8%). There was significant correlation between (STAS) further stratifies survival beyond tumor size, T-descriptor independent
the presence of micrometastases and tumor size. 5-year total survival was of resection type (lobectomy or limited resection) and surgical margin.
significantly better for stage I (64,1%, p=0.0001) and stage II (44,4%, p<0.05) Methods: In patients with pT1a-T2bN0M0 lung adenocarcinomas (LADC,
patients without micrometastases comparing to those with micrometastases n=1399), tumor size, distance of STAS from the tumor, type of resection,
(18,8%). By multivariate analysis, only the presence of micrometastases was surgical margin were evaluated. The patients with small (≤2cm) tumors were
demonstrated to be a significant prognostic factor for 5-year total survival. divided into STAS(-) (n=561) and STAS(+) (n=307) and their cumulative
Conclusion: Presence of micrometastases in mediastinal LN of patients incidence of recurrence (CIR), and lung cancer-specific death (CID) were
with radically resected stage I and II NSCL is associated with significantly compared with patients with larger tumors (2-3cm, n=299) by use of
reduced 5-year total survival. Preoprative detection of micrometastases with competing risk analysis. Results: Of 1399 tumors, 521 (37%) were STAS(+).
immunohistochemical staining of mediastinal LN resected during TEMLA Compared to STAS(-), recurrence rates were higher with STAS(+) tumors even
procedure improves staging and may contribute to better patient selection when the margin is ≥tumor size (Figure 1). In patients with ≤2cm STAS(+)
for curative surgery. tumors, CIR and CID are higher than in patients with larger (2-3cm) tumors
(Figure 2). The poor prognostic influence of STAS(+) was evident even when
Keywords: lung cancer, mediastinal lymph nodes, Staging, micrometastases analyzed by the procedure or recurrence pattern (Figure 2 table). Conclusion:
STAS further stratifies survival beyond tumor size, T-descriptor in early-stage
(pT1a-2b) lung adenocarcinoma based on the higher prognostic potential for
recurrence and lung cancer-specific death independent of the type of
OA07: LYMPH NODE METASTASES AND OTHER PROGNOSTIC FACTORS FOR LOCAL resection or margin.
SPREAD
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
OA07.05 PROGNOSTIC IMPACT OF PLEURAL LAVAGE CYTOLOGY

(PLC): SIGNIFICANCE OF PLC AFTER LUNG RESECTION
Shinya Katsumata1, Junji Yoshida1, Genichiro Ishii2, Keigo Sekihara1, Tomohiro
Miyoshi1, Keiju Aokage1, Tomoyuki Hishida1, Masahiro Tsuboi1
1
Division of Thoracic Surgery, Department of Thoracic Oncology, National Cancer
Center Hospital East, Kashiwa/Japan, 2Department of Pathology, Exploratory
Oncology Research & Clinical Trial Center, National Cancer Center Hospital East,
Kashiwa/Japan
Background: We previously reported the prognostic significance of pleural

lavage cytology (PLC) in patients undergoing surgery for non-small-cell lung
cancer (NSCLC). Based on a larger cohort of more than 3500 NSCLC patients,
which is the largest ever reported from a single institution in the literature, we
evaluated the prognostic impact of PLC on survival and recurrence. Methods:
From January 1993 to July 2015, 3671 patients underwent R0 surgical resection
for NSCLC at our institution and PLC results before (pre-) and after (post-)
lung resection were both available. The cytological evaluation was classified
into 3 categories: negative (-), suggestive (±), positive (+). We excluded 77
patients whose PLC results were suggestive, and 3594 patients were analyzed.
The impact of PLC results on survival and recurrence was evaluated with
conventional clinicopathological factors. Results: The overall survival (OS) of
pre-PLC (+) patients was significantly inferior to that of pre-PLC (-) patients.
However, the 5-year OS rate of pre-PLC (+) patients was 43%, which was
significantly better than that of patients with pleural dissemination (11%). In
the following analyses, we divided the patients into 3 groups according to pre/
post- PLC results as follows: Pre (-)/ post (-), Group A (n=3461); pre (+)/ post (-),
Group B (n=43); and post (+), Group C (n=87). Statistically significant difference
was not observed between Groups A and B in OS or in recurrence-free survival
(RFS) (p=1.00, 0.28, respectively). However, there were significant differences
in OS and RFS between Groups B and C (p=0.01 and p=0.02), and between
Groups A and C (p<0.01 and p<0.01), respectively. In univariate and multivariate
analyses of clinicopathological factors including post-PLC results to identify
prognosticators for OS, post-PLC(+) (hazard ratio (HR) =2.20, p<0.01), older
age (≥65 years; HR=1.95, p<0.01), smoking history (+) (HR=1.48, p<0.01),
elevated serum CEA level (>5.0 mg/dL; HR=1.28, p<0.01), pathological(p)T≥2
(HR=1.28, p<0.01), pN≥1 (HR=1.48, p<0.01), pStage≥II (HR=1.51, p<0.01), pl(+)
(HR=1.43, p<0.01), ly(+) (HR=1.32, p<0.01), and v(+) (HR=1.53, p<0.01) were
found to be significant independent unfavorable prognosticators. Conclusion:
The prognostic impact of pre-PLC was moderate and not prohibiting lung
resection. Post-PLC was shown to be a strong independent prognostic factor.
Its impact on survival of NSCLC patients was very strong, and therefore should
be incorporated in the future TNM classification.
Keywords: PLC, Surgery, prognostic factor, NSCLC
Keywords: surgical margin, sublobar resection, upgrading, T-factor
OA07: LYMPH NODE METASTASES AND OTHER PROGNOSTIC FACTORS FOR LOCAL
SPREAD
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
SESSION OA08: TARGETED THERAPIES IN BRAIN METAS-

OA07.06 IN EARLY-STAGE LUNG ADENOCARCINOMAS, SURVIVAL
TASES
BY TUMOR SIZE (T) IS FURTHER STRATIFIED BY TUMOR SPREAD
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
THROUGH AIR SPACES
Takashi Eguchi1, Koji Kameda1, Shaohua Lu2, Matthew Bott1, Kay See Tan3,
David Jones1, William Travis2, Prasad Adusumilli1
1
OA08.01 EXPLORATION OF THE UNDERLYING MECHANISMS OF
LEPTOMENINGEAL METASTASIS IN NSCLC PATIENTS THROUGH
New York/NY/United States of America, 2Department of Pathology, Memorial Sloan
Kettering Cancer Center, New York/NY/United States of America, 3Epidemiology NGS OF CEREBROSPINAL FLUID
and Biostatistics, Memorial Sloan Kettering Cancer Center, New York/NY/United Yun Fan1, Min Hu2, Xuehua Zhu3, Mengzhao Wang4, Yanjun Xu1, Xuesong Lv2,
States of America Haiyan Xu2, Jingyan Ding2, Xin Ye2, Luo Fang5, Zhiyu Huang5, Lulu Miao5, Lei
Gong5, Weimin Mao5, Hongyang Lu5
Background: We investigated whether tumor spread through air spaces

1
Chemotherapy, Zhejiang Cancer Hospital, Hangzhou/China, 2 Asia & Emerging pts. CSF penetration in LM patients is equivalent to those in previous reports.
Markets Imed, astrazeneca Innovative Medicine and Early Development, Shanghai/ Table1. Summary of ORR, TPP and OS
China, 3 Asia & Emerging Markets Imed, Astrazeneca Innovative Medicine and Early
Development, Shanghai/China, 4Department of Respiratory Medicine, Peking Union
Medical College Hospital, Chinese Academy of Medical Sciences, Beijing/China, ORR (%) mTTP (M) mOS (M)
5
Zhejiang Cancer Hospital,key Laboratory Diagnosis and Treatment Technology on
Thoracic Oncology , Hangzhou, China, Hangzhou/China
All (N=20) 30 2.3 3.1
EGFR mutant (N=17) 35 2.7 4.0
Background: About 10% of non-small cell lung cancer (NSCLC) patients with
EGFR mutations will develop leptomeningeal metastasis (LM) either at initial EGFR wild (N=3) 0 0.7 0.8
diagnosis or during treatment. LM is a devastating complication of NSCLC P value (mt vs. wt) - 0.0054 <0.0001
associated with poor prognosis. The median overall survival is 4.5-11 months,
with ~60% death due to LM or LM together with systemic lesions. However, Keywords: Erlotinib, CSF concentration, NSCLC, Leptomeningeal Metastasis
the underlying mechanisms of the metastasis process are still poorly
understood. Methods: we performed next-generation panel sequencing of
primary tumor tissue, cerebrospinal fluid (CSF) and matched normal controls
from 11 EGFRm+ NSCLC patients with LM. Among them, 2 patients had LM at OA08: TARGETED THERAPIES IN BRAIN METASTASES
initial diagnosis, and 8 patients developed LM during 1st generation EGFR-TKI MONDAY, DECEMBER 5, 2016 - 16:00-17:30
treatment, while such clinical information was missing for 1 patient. Results:
The status of EGFR active mutations was the same in the primary tumor and
OA08.03 MET COPY NUMBER GAIN ASSOCIATES WITH GEFITINIB
CSF of all the patients, except one whose EGFR mutation was undetectable
in the primary site probably due to low sequence coverage. In total, there
RESISTANCE IN LEPTOMENINGEAL CARCINOMATOSIS OF EGFR
were 8 patients with EGFR L858R, 1 with 19Del, and 2 with L858R & 19Del dual MUTANT LUNG CANCER
mutation. One patient also had de novo EGFR T790M in the primary site. None Seiji Yano 1, Shigeki Nanjo1, Sachiko Arai1, Shinji Takeuchi1, Tadaaki Yamada1,
of the CSF samples showed EGFR T790M mutation, suggesting that it was Yasunori Okada2, Akito Hata3, Nobuyuki Katakami3
not the resistance mechanism for the 8 patients who developed LM during 1
Cancer Research Institute, Division of Medical Oncology, Kanazawa University,
TKI treatment. PIK3CA E545K and H1047L, and PTEN R130Q were identified Kanazawa/Japan, 2Juntendo University, Tokyo/Japan, 3Institute of Biomedical
in primary site and/or CSF of 6 patients. Although with small sample size, this Research and Innovation, Kobe/Japan
ratio is much higher than what was reported in general EGFR L858R or 19Del
Background: Central nervous system (CNS) metastasis, such as brain
positive lung adenocarcinoma patient population (~2% from 4 datasets),
metastasis and leptomeningeal carcinomatosis (LMC), occurs frequently in
implicating that alternations in PI3K pathway may associate with LM risk.
EGFR mutant lung cancer. EGFR-TKIs are generally effective to CNS metastasis
Interestingly, in 9 of the 11 patients, only 0.9%-7.8% of variants in CSF samples
in EGFR mutant lung cancer patients who are naïve to TKI treatment.
overlapped with those in primary site, suggesting tumor heterogeneity,
Nevertheless, progression of CNS lesions are frequently observed during
divergence and clonal evolution during LM development. Moreover, when we
EGFR-TKI treatment. Brain metastases are manageable by concomitant use
cataloged the recurrent CSF-unique somatic genomic alterations existing in
of EGFR-TKI and local intervention, including whole brain irradiation and
>5 patients, we identified genes involved in DNA repair pathway, cell cycle
stereotactic radiotherapy. There is, however, no established therapy for LMC,
regulation and epigenetic reprogramming (NPM1, RAD50, MRE11A, POLE,
which is resistant to first and second generation EGFR-TKIs. Therefore, novel
CHEK1, XPC, KMT2B, KMT2C, KMT2D, and ATRX). Conclusion: In summary, our
and effective therapies need to be developed for managing LMC in EGFR
study has shed light on the genomic variations of LM and paved the way for
mutant lung cancer patients who become refractory to these EGFR-TKIs.
potential therapeutic approaches to this unmet medical need.
The purpose of this study is to clarify the mechanism of EGFR-TKI resistance
in LMC and establish novel therapeutic strategy. Methods: We examined
EGFR mutations, including T790M gatekeeper mutation, in 32 re-biopsy
specimens from 12 LMC and 20 extracranial lesions (e.c., lung metastasis
OA08: TARGETED THERAPIES IN BRAIN METASTASES
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 and malignant pleural effusions) of EGFR mutant lung cancer patients who
became refractory to EGFR-TKI treatment. To clarify molecular mechanisms
of acquired EGFR-TKI resistance in LMC, we utilized in vivo imaging model of
OA08.02 PHASE II STUDY OF ERLOTINIB IN ADVANCED NON- LMC with EGFR mutant lung cancer cell line PC-9/ffluc and induced acquired
SMALL CELL LUNG CANCER PATIENTS WITH LEPTOMENINGEAL resistance to gefitinib by continuous oral treatment. Results: We found that
METASTASIS (LOGIK1101) all 32 re-biopsy specimens had the same baseline EGFR mutations and that
Keiichi Ota1, Yoshimasa Shiraishi2, Taishi Harada1, Daisuke Himeji3, Takeshi T790M was less frequent in LMC specimens than extracranial specimens (8%
Kitazaki4, Noriyuki Ebi5, Akinobu Hamada6, Takeharu Yamanaka7, Kaname vs 55%). Compared with subcutaneous tumors, T790M was less frequent
Nosaki2, Mitsuhiro Takenoyama2, Kenji Sugio8 in LMC which acquired resistance to gefitnib. We further established PC-9/
1
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, LMC-GR cells from the gefitinib-resistant LMC model and found that PC-9/
Kyushu University, Fukuoka/Japan, 2Department of Thoracic Oncology, National LMC-GR cells were intermediately resistant to gefitinib and osimertinib (3rd
Kyusyu Cancer Center, Fukuoka/Japan, 3Department of Internal Medicine, generation EGFR-TKI). While EGFR-T790M was negative, MET copy number
Miyazaki Prefectural Miyazaki Hospital, Miyazaki/Japan, 4Department of gain associated MET activation was involved in the gefitinib resistance in
Respiratory Disease, Japan Red Cross Nagasaki Genbaku Hospital, Nagasaki/Japan, PC-9/LMC-GR cells. Moreover, combined use of EGFR-TKI and crizotinib, having
5
Department of Respiratory Oncology, Iizuka Hospital, Fukuoka/Japan, 6Division of inhibitory activity against MET, dramatically regressed LMC which already
Molecular Pharmacology and Pharmacokinetics, National Cancer Center Research acquired resistance to gefitinib or osimertinib. Conclusion: These findings
Institute, Tokyo/Japan, 7Department of Biostatistics, Yokohama City Univaesity,
suggest that combined use of MET inhibitors may be promising for controlling
Yokohama/Japan, 8Department of Thoracic and Breast Surgery, Oita University,
Oita/Japan LMC which acquires resistance to EGFR-TKIs including osimertinib.
Background: Leptomeningeal metastases (LM) occur in almost 5% of non- Keywords: CNS Metastasis, osimertinib, MET copy number gain, EGFR-TKI
small cell lung cancer (NSCLC) patients (pts) and are associated with a poor resistance
prognosis. To date, no prospective study has identified active chemotherapy
for NSCLC pts with LM. In retrospective studies, EGFR-TKI treatment is
reported to be effective in the treatment of LM. We conducted a multi-center,
single-arm phase II trial to evaluate the efficacy of erlotinib in pts with LM. OA08: TARGETED THERAPIES IN BRAIN METASTASES
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
Methods: NSCLC pts with cytologically confirmed LM were eligible and
received erlotinib 150mg daily. Overall cytological response rate (ORR; defined
“number of pts who achieves complete remission in CSF / number of all pts”), OA08.05 EFFICACY AND CEREBROSPINAL FLUID CONCENTRATION
time to LM progression (TTP), overall survival (OS) and pharmacokinetics OF AFATINIB IN NSCLC PATIENTS WITH EGFR MUTATION
were analyzed. Under the null hypothesis, the regimen would be rejected if DEVELOPING LEPTOMENINGEAL CARCINOMATOSIS
confirmed ORR was 5% or less. This study was closed because of low accrual
Akihiro Tamiya1, Motohiro Tamiya2, Takashi Nishihara2, Takayuki Shiroyama3,
with only 21 of required 32 pts (66 %) accrued. Results: From Dec 2011 to May
Keiko Nakao1, Taisuke Tsuji1, Naoko Takeuchi1, Shun-Ichi Isa1, Naoki Omachi1,
2015, 21 pts (17 pts with EGFR mutation) were enrolled. CSFs available for
Norio Okamoto2, Hidekazu Suzuki2, Ayano Iwazaki4, Kimie Imai4, Tomonori
EGFR mutation analysis (N=17) were all EGFR T790M negative. ORR was 30
Hirashima2, Shinji Atagi1
% (95%CI 12 -54 %). Median TTP was 2.3 months. Median OS was 3.1 months. 1
Kinki-Chuo Chest Medical Center, Sakai/Japan, 2Department of Thoracic
Significantly longer TTP and OS were observed in EGFR-mutant than in EGFR-
Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic
wild type (P=0.0054 and P<0.0001, respectively). Seven pts survived longer Diseases, Habikino/Japan, 3Thoracic Oncology, Osaka Prefectural Medical Center
than 6 months. CSF penetration rate (Mean + SD) was 3.3 + 0.8 %. There was for Respiratory and Allergic Diseases, Habikino/Japan, 4Pharmaceutical Sciences,
no correlation between CSF concentration and clinical efficacy. Conclusion: Setsunan University, Hirakata/Japan
Erlotinib treatment for LM is active, especially in EGFR-mutant. Our findings
suggest that erlotinib could represent a treatment option for EGFR mutated Background: Afatinib (AFA) is an effective treatment in advanced non-
small-cell lung cancer (NSCLC) patients harboring epidermal growth factor emergent adverse events in ALTA in patients with baseline brain metastases
receptor (EGFR) mutation. However, there were few reports about the (n=151 treated): nausea (A/B, 32%/43%), headache (30%/30%), diarrhea
cerebrospinal fluid (CSF) penetration rate and the efficacy for central (18%/36%), cough (21%/30%), vomiting (25%/26%); grade ≥3 (excluding
nervous system (CNS) metastasis. Therefore, we conducted the study to neoplasm progression): increased blood CPK (1%/11%), hypertension (4%/7%),
evaluate the CSF penetration rate and efficacy of AFA in NSCLC patients increased lipase (3%/3%), pneumonia (1%/4%). Conclusion: Brigatinib has
harboring EGFR mutation with leptomeningeal carcinomatosis (LC). Methods: demonstrated substantial clinical activity in ALK+ NSCLC patients with brain
Eligibility criteria included performance status (PS) 0-3, aged 20 years or metastases in both Ph1/2 and ALTA.
older, pathologically proven NSCLC, harboring EGFR mutation, with LC,
adequate organ function, and written informed consent. Patients received IRC-Assessed Confirmed Intracranial Response Rates for Patients With Mea-
AFA (40mg/body every day). We analyzed the blood and CSF level of AFA surable Brain Metastases at Baseline
before administrating AFA on the eighth day. The primary endpoint was the Any No rad/activea
CSF penetration rate. Secondary endpoints included objective response
Ph1/2 b n=15 n=9
rate (ORR), progression free survival (PFS), overall survival (OS), and safety
profile. Results: A total of 11 patients were enrolled. And we could analyze the iORR 8(53) 6(67)
blood level in10 patients and the CSF level in 8 patients. Median patients- iDCR 13(87) 8(89)
age was 66 years old. All patients were adenocarcinoma. In EGFR mutation
status, 5 patients had exon 19 deletion, 3 had L858R and 3 had minor (exon18) ALTAc
mutation. The patients with PS 2 were 3 patients and PS 3 were 4 patients. Arm A n=26 n=19
Almost all patients received AFA after third-line or more line chemotherapy. iORR 11(42) 8(42)
The blood level was the Median 88.2 ng/ml (range: 30.4-373), the CSF level was
Median 1.4 ng/ml (range: 0.39-2.85) and the CSF penetration rate was Median iDCR 22(85) 16(84)
1.65% (range: 0.1-9.25). The ORR is 27.3%, and two of three petients with exon Arm B n=18 n=15
18 mutation showed the partial response. Median OS was 3.8 months (95%CI:
iORR 12(67) 11(73)
1.1-13.1) and median PFS was 2.0 months (95%CI: 0.6-5.8). Hematological
toxicity was mild, however we have to take care of severe diarrhea and skin iDCR 15(83) 14(93)
toxicities, especially in patients with poor PS. Conclusion: The median CSF Data are n(%) iDCR=intracranial
penetration rate (1.65%) of AFA were higher than the penetration rate in disease control rate iORR=intracranial
previous case report. Although the efficacy for EGFR mutation positive objective response rate
patients with LC was moderate, the promising efficacy for the patient with IRC=independent review committee
a
LC harboring EGFR exon 18 mutation was demonstrated. And we have to take No prior brain radiotherapy (Ph1/2);
care of diarrhea and skin toxicities, especially in the patients with poor PS. active (untreated or treated and
progressed) brain lesions (ALTA)
Keywords: leptomeningeal carcinomatosis, cerebrospinal fluid penetration b
NCT01449461; last scan date: October
rate, EGFR mutation, afatinib 8, 2015 cNCT02094573; last scan date:
April 14, 2016
Keywords: NSCLC, TKI, ALK, brigatinib
MONDAY, DECEMBER 5, 2016 - 16:00-17:30

OA08.06 BRIGATINIB ACTIVITY IN PATIENTS WITH ALK+ NSCLC AND MONDAY, DECEMBER 5, 2016 - 16:00-17:30
INTRACRANIAL CNS METASTASES IN TWO CLINICAL TRIALS
Scott Gettinger 1, Dong-Wan Kim2, Marcello Tiseo3, Corey Langer4, Myung-
OA08.07 BRAF-V600E ADVANCED LUNG ADENOCARCINOMA WITH
Ju Ahn5, Alice Shaw6, Rudolf Huber 7, Maximilian Hochmair8, Sang-We Kim9,
LEPTOMENINGEAL (LM) DISEASE TREATED WITH VEMURAFENIB
Lyudmila Bazhenova10, Kathryn Gold10, Sai-Hong Ou11, Howard West12, William
Reichmann13, Jeff Haney14, Tim Clackson13, Frank Haluska14, David Kerstein14, Maria Gabriela Fernandes 1, José Costa2, Joana Reis2, Maria Jacob1, ConceiçÃo
D. Ross Camidge15 Moura3, José Machado2, Venceslau Hespanhol1
1
1
Yale Cancer Center, New Haven/CT/United States of America, 2Department of Pneumology, Centro Hospitalar SÃo JoÃo, Porto/Portugal, 2Is3/ipatimup - Institute
Internal Medicine, Seoul National University Hospital, Seoul/Korea, Republic of Pathology and Molecular Immunology of the University of Porto, Portugal,
of, 3Medical Oncology, University Hospital of Parma, Parma/Italy, 4University of Porto/Portugal, 3Pathology, Centro Hospitalar SÃo JoÃo, Porto/Portugal
Pennsylvania Abramson Cancer Center, Philadelphia/PA/United States of America,
5
Samsung Medical Center, Seoul/Korea, Republic of, 6Massachusetts General Background: BRAF mutations occur in around 3% of non-small cell lung
Hospital, Boston/United States of America, 7Thoracic Oncology Centre Munich, cancers (NSCLC) and V600E accounts for 50%. BRAF V600E is an attractive
University Hospital of Munich, Munich/Germany, 8Department of Respiratory molecular target for cancer tyrosine kinase treatment, but ideal treatment
and Critical Care Medicine, Otto Wagner Hospital, Vienna/Austria, 9 Asan Medical is still not defined. Methods: A case of a patient with BRAF-mutated non–
Center, Seoul/Korea, Republic of, 10 Moores Cancer Center, University of California small cell lung cancer (NSCLC) detected by NGS Ion torrent technology
San Diego, La Jolla/United States of America, 11Health Chao Family Comprehensive who presented with LM disease and was treated with the selective BRAF
Cancer Center, University of California at Irvine, Orange/CA/United States of
inhibitor vemurafenib is described. Results: 58 years old, female, non-smoker,
America, 12 Swedish Cancer Institute, Seattle/WA/United States of America,
13
Ariad Pharmaceuticals Inc., Cambridge/MA/United States of America, 14 Ariad
who presented in the emergency department with pericardial effusion.
Pharmaceuticals Inc., Cambridge/United States of America, 15University of Colorado Pericardial fluid cytology confirmed adenocarcinoma TTF1 positive. Multi-
Cancer Center, Denver/United States of America organ metastatic disease was diagnosed (bone, lung and thyroid) without
EGFR mutation or ALK-EML4 translocation. Four cycles of chemotherapy
Background: Patients treated with crizotinib often experience disease with pemetrexed and carboplatin were done. She started with refractory
progression in the brain. Brigatinib, an investigational next-generation headache and vomiting, brain CT and MRI showed no evidence of metastasis,
ALK inhibitor, is being evaluated in an ongoing phase 1/2 trial (Ph1/2) and a lumbar puncture confirmed malignant cells in the cerebrospinal fluid. A
an ongoing pivotal phase 2 trial (ALTA). Methods: In Ph1/2, patients with BRAF V600E was detected by NGS, Ion Torrence PGM technology in the
advanced malignancies, including ALK+ NSCLC, received 30–300 mg brigatinib initial tumour sample and in plasma circulating free DNA. An off-label
per day. In ALTA, patients with crizotinib-resistant advanced ALK+ NSCLC treatment with vemurafenib 960 mg q12hr was offered to the patient, with
received 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B). clinical improvement and radiologic lung stability. At month 2 of treatment,
Efficacy (in both trials) and safety (in ALTA) are reported for ALK+ NSCLC the patient developed respiratory insufficiency with lung infiltrates and
patients with brain metastases at baseline. Results: In Ph1/2 and ALTA, Influenza A virus was identified in a nasal swab. Vemurafenib was temporary
50/79 (63%; IRC-assessed) and 154/222 (69%; investigator-assessed) of ALK+ suspended and re-introduced until 720 mg q12h and maintained until disease
NSCLC patients, respectively, had baseline brain metastases. In Ph1/2 (n=50), progression (large volume pleural effusion with positive cytology), at month 6
median age was 53 years, 76% received prior chemotherapy, and 8% were of vemurafenib tretament. Third line treatment is being planned. Conclusion:
crizotinib-naive. In ALTA (n=154), median age was 52 years; 75% received prior The authors highlight the importance of using a multiplex screening
chemotherapy. As of November 16, 2015, 25/50 (50%) patients were receiving strategy to detect targetable mutations in advanced lung cancer patients.
brigatinib in Ph1/2; as of February 29, 2016, 101/154 (66%) patients were The application of next generation sequencing to the tumour and plasma
receiving brigatinib in ALTA. For patients with measurable lesions, confirmed cfDNA allowed the detection of a BRAF-V600E mutation. The improvement
iORR was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). Among patients of neurologic symptoms and disease control achieved with vemurafenib
with only nonmeasurable lesions (Ph1/2, n=31; ALTA A/B, n=54/n=55), 35% had supports vemurafenib´s efficacy. Care should be taken to the possibility of
confirmed complete resolution of lesions in Ph1/2; 7%/18% had confirmed occurring lung toxicity.
complete resolution in ALTA A/B. For all evaluable patients with baseline
brain metastases, median intracranial PFS was 15.6 months in Ph1/2 (n=46) Keywords: Vemurafenib, BRAF-V600E mutation, next generation sequencing,
and 15.6/12.8 months in ALTA A/B (n=80/n=73). Most common treatment- leptomeningeal (LM) disease

from the date of surgery until last follow-up. Univariate and multivariate
ORAL ABSTRACT SESSIONS - TUESDAY, DECEMBER 6, 2016 analysis were performed to identify prognostic factors. Results: From 2000
to 2015, 5416 patients underwent lung resection for NSCLC in our center. Sixty
SESSION OA09: LOCALLY ADVANCED NSCLC: patients (1%) underwent surgery for stage IIIB NSCLC. Forty-three were males
(72%). Median age was 58 years (from 22 to 79). Thirty-two patients had T4N2
INNOVATIVE TREATMENT STRATEGIES NSCLC involving the carina (n=16, 50%), superior vena cava (n=4, 12%), carina
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 and superior vena cava (n=5, 16%), left atrium (n=5, 16%), pulmonary artery
(n=1, 3%) and spine (n=1, 3%). Twenty-eight patients had N3-disease, involving
supraclavicular (n=14, 50%) or contralateral mediastinal lymph nodes (n=14,
OA09.01 THE NUMBER OR THE POSITION IS THE MAIN PROGNOSTIC 50%). Pneumonectomy was performed in 27 patients (45%). Twenty-nine
FACTOR FOR N2 NSCLC? A VALIDATION OF NEW IASLC N STAGING patients (48%) had induction therapy, consisting in chemotherapy alone for
PROPOSAL all patients. Adjuvant therapy was administered to 52 patients (87%) and
consisted mostly of chemoradiation (n=35, 67%). Complete resection (R0) was
Sara Ricciardi, Pietro Bertoglio, Marco Lucchi, Vittorio Aprile, Carmelina
performed in 55 patients (92%). Post-operative mortality was 3% (n=2). Three-
Zirafa, Alfredo Mussi
and 5-year overall survivals were 51% and 39%, respectively. Median survival
Department of Surgical Medical Molecular Pathology and Critical Care, Divison of
was 40 months. Median follow-up was 17 months. Results of the multivariate
Thoracic Surgery, University Hospital of Pisa, Pisa/Italy
analysis identified incomplete resection (p=0.008) and absence of adjuvant
Background: The eighth edition of lung TNM does not change any N descriptors, treatment (p=0.032) as prognostic factors for poor survival. Conclusion: An
but it suggests some potential changes that might be used in the next edition. excellent 5-year survival of 39% was achieved in highly selected patients with
In fact, N2 would be divided into three groups: pN2a1 (skip lymph-node stage IIIB NSCLC and treated with multimodality including surgery. Patients
involvement), pN2a2 (single mediastinal station with hilar involvement) with stage IIIB NSCLC should therefore be discussed in a multidisciplinary
and pN2b (multiple mediastinal involvement). The aim of this study was to setting, including thoracic surgeons.
verify the value of this classification proposal analyzing our recent surgical
Keywords: stage IIIB, NSCLC, Surgery
experience. Methods: We retrospectively selected all patients treated with
lobectomy, bilobectomy or pneumonectomy for T1/T2 N2 NSCLC (VII TNM
edition) in the period between 2006 and 2010. We excluded all patients who
underwent any kind of extended resection and who had another active tumor
OA09: LOCALLY ADVANCED NSCLC: INNOVATIVE TREATMENT STRATEGIES
at the time of operation. A systematic lymph-node dissection was always TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
carried out according to the IASLC guidelines. All patients were then restaged
according to the new IASLC proposal. Overall Survival (OS), Disease Free
Interval (DFI) and most important variables were analyzed. Results: Among 248 OA09.03 RANDOMIZED CONTROLLED STUDY COMPARING
surgically treated pN2 patients, 108 entered our inclusion criteria. Pathology ADJUVANT VERSUS NEO-ADJUVANT CHEMOTHERAPY IN
report showed a majority of T2 tumors (67,6%) and in almost half of cases an RESECTABLE STAGE IB TO IIIA NSCLC
adenocarcinoma (50,9%); a mean number of 16,4 (DS 7,8) lymph-nodes were Xue-Ning Yang1, Wen-Zhao Zhong1, Xiao-Song Ben2, Hong-He Luo3, Changli
resected (5,8 (DS 2,9) from the hilum and 10,6 (DS 5,9) from the mediastinum). Wang4, Qun Wang5, Guibin Qiao6, Hong-Hong Yan1, Yi Long Wu1
After restaging all cases with the new IASLC proposal we observed: 30 (27,8%) 1
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of
pN2a1; 57 (52,8%) pN2a2 and 21 (19,4%) pN2b. With a median follow up of Translational Medicine in Lung Cancer, Guangdong General Hospital & Guangdong
93 months, the median overall survival of the entire cohort was 27 months. Academy of Medical Sciences, Guangzhou/China, 2Department of Thoracic Surgery,
pN2a1 had a significant better overall survival compared with the other two Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of
groups (p=0,020); conversely no statistically significant difference was found Translational Medicine in Lung Cancer, Guangdong General Hospital & Guangdong
in OS between pN2a2 and pN2b. 1, 3 and 5-year survival for pN2a1, pN2a2 Academy of Medical Sciences, Guangzhou/China, 3Department of Thoracic
and pN2b were 90%, 81% and 71%; 53%, 37% and 24%; 45%, 26% and 19% Surgery, The First Affiliated Hospital; Sun Yat-Sen University, Guangzhou/China,
4
respectively. Concurrently DFI was significantly better for pN2a1 (p=0,025). At Department of Thoracic Oncology, Tianjin Medical University Cancer Institute &
Hospital, Tianjin/China, 5Department of Thoracic Surgery, Zhongshan Hospital,
univariate survival analysis age>65 years, more than 4 positive lymph nodes
Shanghai/China, 6Department of Thoracic Surgery, General Hospital of Guangzhou
and postoperative complications were statistically significant variables. At the Military Command of P.L.A, Guangzhou/China
multivariate analysis only age and the number of positive lymphnodes were
independent prognostic factors of a worse survival. Conclusion: Our experience Background: Adjuvant chemotherapy is the standard of care for completely
partially validate the new proposal of IASLC of N2 staging. Patients with skip resected stage II-IIIa non-small cell lung cancer (NSCLC). A few trials suggest
lymph-node metastasis (pN2a1) have a statistically significant better prognosis. that neoadjuvant chemotherapy is a promising strategy for resectable NSCLC.
Concurrently we observed and confirmed the important prognostic value of the Indirect comparison meta-analysis of adjuvant versus neoadjuvant therapy
number of the involved lymph-node, which should be considered as well in the showed no difference in survival. This study was conducted to determine the
next editions of the lung cancer staging system. difference of disease-free survival(DFS) between adjuvant chemotherapy and
neoadjuvant chemotherapy among patients with resectable NSCLC. Methods:
Keywords: n2 lung cancer, staging system, skip metastasis, NSCLC Patients with clinical stage IB-IIIA NSCLC were eligible. Patients were randomly
assigned to 3 cycles adjuvant DC (Docetaxel: 75mg/m2, Carboplatin:AUC=5 on
day 1, every 3wk) after completely resection (lobectomy or pneomonectomy
with mediastinal lymphnode dissection, or 3 cycles neoadjuvant DC at the
OA09: LOCALLY ADVANCED NSCLC: INNOVATIVE TREATMENT STRATEGIES same schedule followed by surgery 3-6 wk after chemotherapy. The primary
end point was 3 years DFS; secondary end points were 3ys and 5ys Overall
Survival(OS) and Safety. Planned sample size is 410. The trail was early closed
OA09.02 SHOULD SURGERY BE PART OF THE MULTIMODALITY because slowly accrued. Results: Between March 2006 and May 2011,198
TREATMENT FOR STAGE IIIB NON-SMALL CELL LUNG CANCER patients from 8 Institute were randomized to neoadjuvant arm (97 cases) or
Stephane Collaud1, Bastien Provost1, Dominique Fabre1, Sacha Mussot1, adjuvant arm (101 cases). The median age was 58, male accounted for 80.3%,
Benjamin Besse2, Olaf Mercier 1, Elie Fadel1 Adenocarcinoma 48.5%, stage Ib, II a, II b and IIIa were 32.5%, 12.2%, 28.4% and
1 26.9% respectively. Two arms were balanced. 100% cases received neoadjuvant
Marie Lannelongue Hospital, Le Plessis Robinson/France, 2Department of Cancer
Medicine, Gustave Roussy, Villejuif/France
chemotherapy and 87.4% finished the planned adjuvant chemotherapy. No
unexpected toxicities were seen and 41.2% of patients experienced grade 3-4
Background: Stage IIIB non-small cell lung cancer (NSCLC) is a heterogeneous neutropenia. In neoadjuvant arm, the ORR was 34% and 12.4% patients
patient group, including T4N2 and T1-4N3 NSCLC. Traditionally, treatment developed PD. No difference in postoperative complication was found
for stage IIIB consists in definitive chemoradiation. Surgical treatment between two arms. Survival analysis show in Table 1
for stage IIIB NSCLC is used anecdotally in highly selected patients. Here,
we studied patient outcome who underwent surgical resection as part of
multimodality treatment for stage IIIB NSCLC. Methods: All patients from a
single institution who underwent surgery for stage IIIB between 2000 and
2015 were included. Surgical candidates were selected on a case-by-case
basis during multidisciplinary tumorboard conference. In general, N2-N3
diseases are not considered an absolute contraindication to surgery if
lymph node involvement is limited to a non-bulky single site, the tumor is
deemed completely resectable without major morbidity and the patient will
tolerate multimodality treatment. Mediastinal staging comprised cervical
mediastinoscopy, positron emission tomography coupled with CT from 2005
and endobronchial ultrasound guided fine-needle aspiration from 2011. Charts
were retrospectively reviewed and data analyzed. Survival was calculated
Conclusion: Adjuvant or neo-adjuvant chemotherapy with docetaxel plus OA09: LOCALLY ADVANCED NSCLC: INNOVATIVE TREATMENT STRATEGIES
carboplatin in resectable clinical stage IB-IIIA NSCLC are feasible and safe. The
final results showed no difference in 3ys DFS and OS between two arms. Long
term survival in Adjuvant arm show the tendency of superior to neoadjuvant OA09.07 INDIVIDUAL ISOTOXIC RT DOSE ESCALATION BASED ON
arm. V20 AND ADVANCED  TECHNOLOGIES BENEFIT STAGE III NSCLC
Keywords: ADJUVANT, non-small cell lung cancer, neoadjuvant, chemotherapy TREATED WITH CCRT
Baosheng Li, Zhongtang Wang, Ming Liu
Radiation Oncology, Shandong Cancer Hospital, Jinan/China
OA09: LOCALLY ADVANCED NSCLC: INNOVATIVE TREATMENT STRATEGIES Background: RTOG 0617 recommended 60Gy as the standard dose for
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 unresectable stage III non-small cell lung cancer (NSCLC) treated with
concurrent chemoradiotherapy (CCRT) Is the conclusion true? The phase
I/II trial to determine the feasibility and effects of individual isotoxic
OA09.05 POSITRON EMISSION TOMOGRAPHY (PET) WITH
radiation dose escalation in unresectable stage III NSCLC treated with
18F-FLUOROAZOMYCIN ARABINOSIDE (FAZA) TO ASSESS TUMOR CCRT based on bilateral lung V20 and advanced technologies was studied.
HYPOXIA IN NON-SMALL CELL LUNG CANCER (NSCLC) Methods: Consecutive patients with unresectable stage III NSCLC were
Angela Lin1, Douglass Vines1, Brandon Driscoll2, Lisa Le1, Stephen Breen1, entered in cohorts of eight from March 2006 to May 2009. Patients were
Alexander Sun1 assigned to receive concurrent administration of late course accelerated
1
Department of Radiation Oncology, University of Toronto, Toronto/ON/Canada, hyperfrationation (LCAHF) intensity modulated radiotherapy (IMRT) and
2
University Health Network, Toronto/ON/Canada chemotherapy. Isotoxic dose escalation was based on V20 and advanced 
technologies including PET-CT, single-photon emission computed tomography
Background: Tumor hypoxia is an adverse prognostic factor in many cancers. (SPECT) and LCAHF IMRT. PET-CT was used to delineate the gross tumor
Hypoxia tracer 18F-FAZA provides a non-invasive method of hypoxia imaging. volume. SPECT lung perfusion was applied to define different functional
This study aims to evaluate the feasibility and potential benefits of using lung regions, which was used to optimize the IMRT plans. Patients with a V20
FAZA-PET scans to assess NSCLC tumor hypoxia. Methods: The initial 17 of 27% as a base level were enrolled into the first cohort. From the second
patients of an ongoing study with stage II–III NSCLC have been analyzed cohort, the V20 further increased to 30%, 33%, 35%, 37%, and so on. The
prospectively by imaging with FAZA-PET before initiation of a radical course criteria for cessation of dose escalation was defined as more than 25% of
of radiotherapy. The hypoxic volume (HV) was defined as all voxels within patients in the cohort experienced dose limiting toxicity (DLT). To test the
the tumor with standard uptake value (SUV) more than 1.2 times the aorta power of escalation dose, patients with total radiation dose over 66Gy would
SUVmean. The Tmax/Bmean ratio (T/B) was defined as maximum tumor be assigned to the higher dose group (HD), while the other patients would be
SUV divided by aorta SUVmean. The hypoxic fraction (HF) was determined assigned to the standard dose one (SD). Results: Forty patients were enrolled.
by dividing the HV by the entire gross tumor volume. Spearman correlation The maximum tolerated value of V20 was 37% in this study. Nineteen patients
and Fisher’s test were used to explore potential correlations among several entered SD group, while twenty-one in HD. The overall response rate was
variables. Results: Median primary and nodal FAZA SUVmax were 1.7 (range: as high as 80%. Follow-up for all patients ranged from 1 to 112 months with
1.0-3.8) and 1.7 (range: 1.0–3.3). Median primary and nodal T/B ratios were survival patients from 101 to 112 months. The median overall and progression
1.4 (range: 1.0–2.5) and 1.3 (range: 1.0–2.2). Median primary and nodal HF free survivals were 25.0 and 13.0 months, respectively. 1-, 3-, 5- and 8-year
were 3.9% (range: 0.0-38.2%) and 0.6% (range: 0.0-50.7%). The median time overall survival (OS) rates were 72.5%, 22.5%, 17.5%, and 10.0%, respectively.
from diagnostic FDG PET to study FAZA PET scans was 28 days (range: 1–63). Patients with stage IIIa achieved a longer median OS than those of stage IIIb
Median primary and nodal FDG SUVmax were 13.5 (range: 5.1–32.2) and 8.3 (31 vs. 21 months, P=0.029). Especially, patients received HD radiotherapy
(range: 2.3–15.7). Larger primary tumor volume is correlated with higher FAZA- got a significant better OS and local recurrence free survival than those in SD
T/B (p=0.01) and higher HF (p=0.01). Primary tumors with higher T/B also had (27, 23 vs. 16, 19 months, P = 0.053, 0.037) without increasing severe toxicity.
higher HF (p<0.0001). The same correlations also apply to nodal disease. Nodal Conclusion: The protocol is feasible and effective. In the future, the radiation
FAZA SUVmax is correlated with primary FAZA SUVmax (p<0.0001). When dose escalation for unresectable stage III NSCLC treated with CCRT should be
comparing FAZA-PET with FDG-PET, nodal FDG SUVmax is correlated with focused on toxicity control and advanced technology application.
nodal FAZA T/B (p=0.01) and nodal FAZA HF (p=0.01), which was not observed
for primary disease. For each patient, the nodal station with the highest Keywords: Individual isotoxic dose escalation,
FAZA SUVmax correlates with the highest FDG SUVmax (p=0.02). Conclusion: Advanced radiotherapy technologies, Non-small-cell lung cancer, concurrent
Imaging intra-lesional hypoxia in NSCLC primary and nodal tumors is feasible chemoradiotherapy
and can be achieved with FAZA-PET. Larger tumor volume is correlated with
higher T/B and HF in both primary and nodal masses. In the nodal volume only,
higher FDG activity is correlated with higher FAZA T/B and higher HF. Ongoing
trial accrual and follow-up of our patient cohort will provide more information
SESSION OA10: EGFR MUTATIONS
with regards to the imaging and clinical value of FAZA-PET. This study may TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
eventually lead to using FAZA-PET as a guiding tool to escalate dose to the
hypoxic region of the tumor.
OA10.01 COMPREHENSIVE GENOMIC PROFILING AND PDX
Keywords: Hypoxia, FAZA, lung cancer, imaging MODELING OF EGFR EXON 20 INSERTIONS: EVIDENCE FOR
OSIMERTINIB BASED DUAL EGFR BLOCKADE
Jonathan Riess 1, David R. Gandara1, Garrett Frampton2, Mingshan Cheng 3,
Primo Lara1, Karen Kelly1, Chunting Ye3, Russell Madison2, Nir Peled4, Jose
OA09: LOCALLY ADVANCED NSCLC: INNOVATIVE TREATMENT STRATEGIES
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 Bufill5, Grace Dy6, Sai-Hong Ou7, Darren Cross8, Carol Bult9, Susan Airhart9,
Philip Stephens2, Jeffrey Ross2, Vincent Miller2, Siraj Ali2, James Keck 3, Philipp
Mack10, Alexa Schrock2
OA09.06 METFORMIN USE DURING CONCURRENT 1
UC Davis Comprehensive Cancer Center, Sacramento/CA/United States of America,
CHEMORADIOTHERAPY FOR LOCALLY ADVANCED NON-SMALL 2
Foundation Medicine, Cambridge/MA/United States of America, 3The Jackson
CELL LUNG CANCER (NSCLC) Laboratory West, Sacramento/CA/United States of America, 4Thoracic Cancer Unit,
Davidoff Cancer Center, Petach Tiqwa/Israel, 5Michiana Hematology-Oncology, Pc,
Krista Wink 1, José Belderbos2, Edith Dieleman3, Maddalena Rossi2, Coen
Mishawaka/IN/United States of America, 6Medicine, Roswell Park Cancer Institute,
Rasch3, Ronald Damhuis4, Ruud Houben1, Esther Troost5 Buffalo/NY/United States of America, 7Health Chao Family Comprehensive
1
Radiation Oncology, Maastro Clinic, Maastricht/Netherlands, 2Department of Cancer Center, University of California at Irvine, Orange/CA/United States of
Radiation Oncology, The Netherlands Cancer Institute – Antoni Van Leeuwenhoek America, 8 Astrazeneca, Cambridge/United Kingdom, 9The Jackson Laboratory, Bar
Hospital, Amsterdam/Netherlands, 3Department of Radiation Oncology, Harbor/ME/United States of America, 10UC Davis Comprehensive Cancer Center,
Amsterdam Medical Centre, Amsterdam/Netherlands, 4Department of Research, Sacramento/United States of America
Netherlands Comprehensive Cancer Organization, Utrecht/Netherlands,
5
Department of Radiation Oncology, Medical Faculty and University Hospital Carl Background: EGFR exon 20 insertion mutations (EGFRex20ins) comprise
Gustav Carus, Dresden/Germany a subset of EGFR activating alterations relatively insensitive to 1st and 2nd
generation EGFR-TKIs. Comprehensive genomic profiling (CGP) integrated
with PDX modeling may identify new EGFR-inhibition strategies for
EGFRex20ins. Methods: EGFRex20ins and co-occurring genomic alterations
were identified by hybrid-capture based CGP performed on 14,483 consecutive
FFPE lung cancer specimens to a mean coverage depth of >650X for 236 or
315 cancer-related genes plus 47 introns from 19 genes frequently rearranged
in cancer. An EGFRex20ins(N771_P772>SVDNP)/EGFR-amplified tumor (24
copies) from this cohort was implanted subcutaneously into the flank of NOD.

Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice for tumor growth inhibition studies (TGI) associated with EGFR mutation-positive lung adenocarcinoma (Shiraishi et
with vehicle, erlotinib (50 mg/kg PO daily), osimertinib (25 mg/kg PO daily), al., Nature Communications, 2016, in press). Conclusion: This study indicates
and osimertinib (25 mg/kg PO daily) plus cetuximab (10 mg/kg IV, 2x/week) that multiple genetic factors, including an immunologic one, underlie the risk
administered for 21 days. Results: CGP identified 263/14,483 cases (1.8%) with of lung adenocarcinomas with EGFR mutations.
EGFRex20ins, which represent 12% (263/2,251) of EGFR activating mutations
in this series. 90% (237/263) were NSCLC-adenocarcinoma, 9% (23/263) were Keywords: HLA class II, EGFR, lung adenocarcinoma, SNP
NSCLC-NOS, and 1% (2/263) were sarcomatoid carcinoma. Over 60 unique
EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and
N771_P772>SVDNP (20%); 6% (15/263) harbored EGFR A763_Y764insFQEA,
an EGFRex20ins typically sensitive to erlotinib. Among EGFRex20ins cases, OA10: EGFR MUTATIONS
EGFR-amplification occurred in 22% (57/263). Putative co-occurring driver
alterations including EGFR (ex19del and L858R), Her2, MET and KRAS tended
to be mutually exclusive, occurring only in 5% (12/263) of cases. The most OA10.03 YAP-NOTCH AND STAT3 SIGNALING REBOUND AS A
common co-occurring alterations affected TP53 (56%), CDKN2A (22%), COMPENSATORY RESPONSE TO GEFITINIB OR OSIMERTINIB
CDKN2B (16%), NKX2-1 (14%) and RB1 (11%). Average tumor mutation burden TREATMENT IN EGFR MUTANT LUNG CANCER
was low (mean 4.3 mutations/Mb, range 0-40.3 mutations/Mb). Clinical
Rafael Rosell1, Imane Chaib2, Niki Karachaliou3, Peng Cao4, Miguel Angel
outcomes to 1st and 2nd generation EGFR-TKIs were obtained for a subset of
Molina Vila5, Xueting Cai4, Ana Drozdowskyj6, Jie Yang4, Chunping Hu4, Andrés
cases with various EGFRex20ins, and 0/6 patients had responses. However,
Cardona7, Alex Frías2, Chiara Lazzari8, Alberto Verlicchi9, Jordi Codony Servat5,
robust TGI was observed with combination osimertinib and cetuximab in
Carles Codony Servat5, José Luis Ramírez Serrano10, Alain Vergnenegre11,
a highly EGFR-amplified PDX model with a conserved EGFRex20ins (N771_
Patrick Ma12, Trever Bivona13
P772>SVDNP) not associated with response to earlier generation EGFR- 1
TKI, and was superior to vehicle, erlotinib or osimertinib alone (D21 mean Hospital Germans Trias I Pujol, Catalan Institute of Oncology, Badalona/Spain,
2
Laboratory of Cellular and Molecular Biology, Institut D’Investigació En Ciències
tumor size 70 mm3 vs. 1000, 800, 225 mm3 respectively; p-values all <0.001).
Germans Trias I Pujol, Badalona/Spain, 3Instituto Oncológico Dr Rosell (Ior),
Conclusion: Diverse EGFRex20ins were detected in 12% of EGFR-mut NSCLC. Hospital Universitario Quirón-Dexeus, Barcelona/Spain, 4Laboratory of Cellular
Available clinical outcomes data demonstrated lack of response to 1st and 2nd and Molecular Biology, Hospital of Integrated Traditional Chinese and Western
generation EGFR-TKIs. Identification of co-occurring EGFR-amplification in Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu/China,
5
22% of cases led to testing of a dual EGFR blockade strategy with an EGFR Laboratory of Cellular and Molecular Biology, Pangaea Biotech Sl, Ior Quirón-
monoclonal antibody and osimertinib, which demonstrated exceptional Dexeus University Institute, Barcelona/Spain, 6Statistics, Pivotal, Sl, Madrid/
tumor growth inhibition in an EGFRex20ins PDX minimally responsive to Spain, 7Clinical and Translational Oncology Group, Clinica Del Country, Bogotá/
erlotinib. These findings can rapidly be translated into an ongoing clinical trial Colombia, 8Divisione Di Oncologica Toracica, Istituto Europeo Di Oncologia -
Ieo, Milano/Italy, 9 Oncology, Ospedale Santa Maria Delle Croci, Ravenna/Italy,
of osimertinib and necitumumab. 10
Laboratory of Cellular and Molecular Biology, Catalan Institute of Oncology and
Institut D’Investigació En Ciències Germans Trias I Pujol, Badalona/Spain, 11CHU
Keywords: PDX, EGFR Exon 20 Insertion, Genomic Profiling
de Limoges, Limoges/France, 12Wvu Cancer Institute, West Virginia, Morgantown/
WV/United States of America, 13Medicine, UCSF Helen Diller Family Comprehensive
Cancer Center, San Francisco/CA/United States of America
OA10: EGFR MUTATIONS Background: Preclinical studies provide insights to therapy mechanisms of
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 resistance that are not feasible with clinical studies. We investigated the
signaling pathways that could be involved in adaptive resistance to gefitinib
OA10.02 ASSOCIATION OF VARIATIONS IN HLA-CLASS II AND and/or osimertinib in EGFR mutant cells. Methods: We performed several
laboratory methods to examine the signaling pathways involved in EGFR
OTHER LOCI WITH SUSCEPTIBILITY TO EGFR-MUTATED LUNG
mutations. Signal transduction pathway analysis was designed using the
ADENOCARCINOMA Ingenuity Pathway Analysis (IPA) software (https://www.ingenuity.com/)
Kouya Shiraishi1, Yukinori Okada2, Atsushi Takahashi3, Yoichiro Kamatani3,
Kyota Ashikawa3, Yukihide Momozawa3, Hideo Kunitoh4, Shingo Matsumoto5,
Atsushi Takano6, Kimihiro Shimizu7, Akiteru Goto8, Koji Tsuta9, Shun-Ichi
Watanabe10, Yuichiro Ohe11, Yukio Watanabe10, Yasishi Goto11, Hiroshi (See Figure next page)
Nokihara11, Koh Furuta12, Akihiko Yoshida13, Koichi Goto14, Tomoyuki Hishida15,
Masahiro Tsuboi15, Katsuya Tsuchihara5, Yohei Miyagi16, Haruhiko Nakamura17,
Tomoyuki Yokose18, Katsuya Tanaka7, Toshiteru Nagashima7, Yoichi Ohtaki7,
Daichi Maeda8, Kazuhiro Imai8, Yoshihiro Minamiya8, Yoko Shimada19, Kuniko
Sunami19, Motonobu Saito19, Jun Yokota20, Fumihiko Matsuda21, Keitaro
Matsuo22, Yataro Daigo6, Michiaki Kubo3, Takashi Kohno 19
1
National Cancer Center Research Institute, Tokyo/Japan, 2Osaka University
Graduate School of Medicine, Osaka/Japan, 3Riken, Yokohama/Japan, 4Japanese Red
Cross Medical Center, Tokyo/Japan, 5National Cancer Center Epoc, Kashiwa/Japan,
6
The University of Tokyo-Ims, Tokyo/Japan, 7Department of Integrative Center
of General Surgery, Gunma University Graduate School of Medicine, Maebashi/
Japan, 8 Akita University Graduate School of Medicine, Akita/Japan, 9National
Cancer Center Hospital, Tokyo/Japan, 10 Division of Thoracic Surgery, National
Cancer Center Hospital, Tokyo/Japan, 11Department of Thoracic Oncology, National
Cancer Center Hospital, Tokyo/Japan, 12Division of Clinical Laboratory, Kanagawa
Cancer Center, Kanagawa/Japan, 13Department of Pathology, National Cancer
Center Hospital, Tokyo/Japan, 14Department of Thoracic Oncology, National Cancer
Center Hospital East, Kashiwa/Japan, 15Department of Thoracic Surgery, National
Cancer Center Hospital East, Kashiwa/Japan, 16Kanagawa Cancer Center Research
Institute, Kanagawa/Japan, 17Department of Thoracic Oncology, Kanagawa Cancer
Center, Kanagawa/Japan, 18Department of Pathology, Kanagawa Cancer Center,
Kanagawa/Japan, 19 Genome Biology, National Cancer Center Research Institute,
Tokyo/Japan, 20 Institute of Predictive and Personalized Medicine of Cancer,
Badalona/Spain, 21Kyoto University Graduate School of Medicine, Kyoto/Japan,
22
Aichi Cancer Center Research Institute, Nagoya/Japan
Background: Lung adenocarcinoma (LADC) driven by somatic EGFR mutations

is more prevalent in East Asians (30-50%) than in European/Americans
(10-20%). Understanding the genetic factors underlying such LADC is
required to elucidate disease etiology and to identify effective methods of
prevention. Methods: We investigate genetic factors underlying the risk of
this disease by conducting a genome-wide association study, followed by two
validation studies, in 3,173 Japanese patients with EGFR mutation-positive
lung adenocarcinoma and 15,158 controls. Results: Four loci, 5p15.33 (TERT),
6p21.3 (BTNL2, HLA-class II), 3q28 (TP63) and 17q24.2 (BPTF), previously
shown to be strongly associated with overall lung adenocarcinoma risk in East
Asians, were re-discovered as loci associated with a higher susceptibility to
EGFR mutation-positive lung adenocarcinoma. In addition, two additional
loci, HLA-class II at 6p21.32 and 6p21.1 (FOXP4) were newly identified as loci
Results: Pathways mediating EGFR mutations are: i) ERK1/2 via Ras and
MEK1/2 ii) AKT via PI3K and iii) STAT3 via JAK (Figure). By Western blot
analysis, phosphorylation of Tyr705 on STAT3 was noted after 2 hours of
gefitinib or osimertinib treatment in PC9 and H1975 EGFR mutant cells.
Unexpectedly, YAP1 phosphorylation on Tyr357 and Notch activation was
detected. Co-targeting STAT3 and Src with gefitinib or osimertinib ablates
activation of STAT3 and YAP1-NOTCH3 signaling pathways (Figure). In vitro
and in vivo, the combinatory therapy of gefitinib or osimertinib plus TPCA-1 (a
dual inhibitor of IKKs and STAT3) plus saracatinib (a SFK inhibitor) leads to
significant tumor shrinkage in PC9 and H1975 cells.
In tumor samples of 64 EGFR mutant NSCLC patients treated with gefitinib,

the median progression free survival (PFS) was significantly shorter in those
with high levels of HES1, ALDH1A1, ALDH1A3, Bmi1, AXL, CDCP1, SHP2 and
ILK (Figure). However, the mRNA levels of STAT3 and YAP1 stand out in the
prediction of shorter PFS with a hazard ratio of 3.02 and 2.57, respectively
(P<0.001)
Conclusion: For the first time ever, we reported gefitinib induced activation
of theYAP1-NOTCH signaling pathway, in addition to activation of STAT3, in
EGFR mutant cells. Secondly, co-targeting STAT3 and Src, together with EGFR,
causes significant tumor growth inhibition, in comparison with gefitinib or
osimertinib single therapy.
Keywords: YAP-NOTCH, STAT3 signaling, EGFR mutant lung cancer,

osimertinib
OA10: EGFR MUTATIONS the number of stromal macrophages positive for CD163 or CD204, markers
for tumor-associated macrophages (TAMs), was significantly decreased
within tumors with EGFR mutations compared to within those with wild-type
OA10.05 EGFR GENE MUTATIONS AFFECT TUMOR-INFILTRATING EGFR, whereas the number of CD3+ T cells or FOXP3+ regulatory T cells was
STROMAL CELL COMPONENTS IN EARLY-STAGE LUNG comparable between these groups. Both tumors with missense mutations in
ADENOCARCINOMA exon 21 and deletions in exon 19 had a similar trend toward decreased TAMs in
the tumor stroma. Conclusion: Our data suggest that EGFR mutations in early-
Toshiyuki Shima1, Takao Shigenobu1, Masayuki Shimoda2, Takashi Ohtsuka1,
stage lung adenocarcinoma are associated with decreased TAMs in the tumor
Hisao Asamura1, Yae Kanai2
1
stroma. EGFR mutation status might act on not only cancer cell behavior but
Division of Thoracic Surgery, Keio University School of Medicine, Tokyo/Japan,
2 tumor microenvironment.
Department of Pathology, Keio University School of Medicine, Tokyo/Japan
Keywords: EGFR gene mutations, tumor-infiltrating stromal cell, early-stage
Background: Tumors are complex structures consisting of cancer cells
lung adenocarcinoma
surrounded by a tumor stroma that is now recognized to be critical for cancer
progression. Although epidermal growth factor receptor (EGFR) mutations
are frequently observed in non-small cell lung carcinoma, it remains poorly
understood whether EGFR mutations in cancer cells affect the tumor stroma. OA10: EGFR MUTATIONS
In this study, we studied the status of EGFR mutations in early-stage lung TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
adenocarcinoma and analyzed the relations of EGFR mutations to tumor-
infiltrating stromal cell components. Methods: A total of 152 consecutive
OA10.06 CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH
patients with clinical stage IA lung adenocarcinoma who underwent complete
tumor resection in Keio University Hospital between 2010 and 2014 were LUNG CANCER HARBORING MULTIPLE MOLECULAR ALTERATIONS
studied. Genomic DNA was isolated from formalin-fixed, paraffin-embedded (BIOMARKER IFCT STUDY)
tumor sections and mutational analyses of EGFR gene exons 19, 20 and 21 were Nicolas Guibert1, Fabrice Barlesi2, Renaud Descourt3, Hervé Léna4, Benjamin
performed by a polymerase chain reaction-based method. Paraffin sections Besse5, Michèle Beau-Faller6, Jean Mosser 7, Eric Pichon8, Jean-Philippe Merlio9,
were also subjected to immunohistochemistry for CD3, FOXP3, CD163 or L’Houcine Ouafik10, François Guichard11, Bénédicte Mastroianni12, Lionel
CD204. Numbers of CD3-, FOXP3-, CD163- or CD204-immunostained cells were Moreau13, Annie Wdowik14, Jean-Christophe Sabourin15, Antoinette Lemoine16,
counted by observing 5 different fields at x200 magnification. Results: EGFR Pascale Missy17, Alexandra Langlais18, Denis Moro-Sibilot19, Julien Mazieres 1
mutations were detected in 71 (47%) of the 152 patients with clinical stage 1
Centre Hospitalier Universitaire, Toulouse/France, 2 Assistance Publique Hôpitaux
IA lung adenocarcinoma and were found more frequently in women and non- de Marseille, Aix-Marseille University, Marseille/France, 3Centre Hospitalier
smokers. These contained 38 patients with missense mutations in exon 21 Universitaire de Brest, Brest/France, 4 CHU Rennes - Hôpital Pontchaillou, Rennes/
(L858R) and 30 patients with deletions in exon 19. By immunohistochemistry, France, 5Department of Cancer Medicine, Gustave Roussy, Villejuif/France,
6
Laboratoire de Biochimie Et de Biologie Moléculaire Et Plate-Forme de Génomique

Des Cancers, Centre Hospitalier Universitaire de Hautepierre, Strasbourg/ sequencing of amplified target genes. TMPRs from each subject was obtained
France, 7Service de Génétique Moléculaire Et Génomique, Centre Hospitalier or recovered for comparison with their LBx counterparts. TMPRs from this
Universitaire de Rennes, Rennes/France, 8Service de Pneumologie, CHU Tours, cohort was developed in different CLIA laboratories Results: 69 pts were
Hôpital Bretonneau, Tours/France, 9Pôle Biologie Et Anatomie Pathologique,
females; median age 72 (range, 27-99). 84/100 pts had at least 1 genomic
Centre Hospitalier Universitaire de Bordeaux, Pessac/France, 10Service de Transfert
alteration by LBx (range, 1-10). Most common abnormalities found in LBx were:
D’Oncologie Biologique, Aix Marseille University, Marseille/France, 11Polyclinique
Bordeaux Nord Aquitaine, Bordeaux/France, 12 Service de Pneumologie, HCL TP53 (37 pts), EGFR (35 pts), NF1 (20 pts), KRAS (12 pts), MET (14 pts). From
de Lyon, Hôpital Louis Pradel, Bron/France, 13Service de Pneumologie, Centre this 84 pts with + LBx results, 67 pts (80%) had TMPRs for comparison. Main
Hospitalier Général de Colmar, Hôpital Louis Pasteur, Colmar/France, 14Service reason for lack of TMPRs: insufficient tumor (19/100; 19%). For comparison
D’ Oncologie, Centre Hospitalier Bretagne Atlantique Site de Vannes, Vannes/ between the 2 modalities, we considered all pts with available results in both
France, 15Département D’Anatomie Et de Cytologie Pathologiques, Centre tests; hence, 81 pts were used to compare tumor biopsy (TBx) vs. LBx. 37
Hospitalier Universitaire de Rouen, Rouen/France, 16Service D’Oncogénétique – pts out of 81 (46%) had at least 1 similar genomic abnormality found in both
Oncomolpath, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Des
TBx and LBx, respectively. Most of the concordance was in EGFR alterations
Hôpitaux Universitaires Paris-Sud, Villejuif/France, 17Clinical Research Unit, French
(19/28; 68%). LBx caught 16 additional EGFR genomic aberrations not being
Cooperative Thoracic Intergroup (IFCT), Paris/France, 18Biostatistics Unit, French
Cooperative Thoracic Intergroup (IFCT), Paris/France, 19Thoracic Oncology Unit, identified by TBx. A total of 35 EGFR genomics aberrations were identified
Chest Department, CHU de Grenoble, Grenoble/France in LBx; 16/35 EGFR mutations found in LBx were actionable and 5 of these 16
actionable EGFR mutant cases were only found in LBx not in TBx. Conclusion:
Background: Carcinogenesis of non-small cell lung cancer (NSCLC) can be LBx offers an alternative to identify genomic alterations. Still, insufficient
driven by oncogenic addiction that can be targeted by specific inhibitors. tumor is the major reason for lacking of TMPRs. EGFR mutations are the most
It is commonly accepted that these molecular alterations are mutually common actionable mutations found in LBx; also, it has a high correlation
exclusive. Nevertheless, limited series suggest that concomitant molecular with TBx (68%). LBx identified more gene abnormalities than TBx, and in some
alteration can occur in lung cancer and little is known about their sensitivity cases, the actionable EGFR mutations were found only in LBx sample.
to treatment. Based on a nationwide screening program conducted during
one year, we aimed to analyze the largest molecular database to date for Keywords: molecular profile, Driver Mutations, lung adenocarcinoma, liquid
concomitant mutations in order to determine the prevalence of multiple biopsy
genomic alterations in NSCLC and their impact on both prognosis and
response to treatment. Methods: The database of Biomarker France
IFCT study collecting the molecular profile of 17 664 NSCLC has been
used. The prevalence of multiple alterations and of each association was
calculated. Impact on prognosis (overall survival, OS), response to targeted SESSION OA11: ANGIOGENESIS IN ADVANCED LUNG
or conventional treatments (progression free survival, PFS and objective CANCER
response rate, ORR) were established and compared with the population TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
of patients harboring single mutations and full wild-type. Results: We
identified 162 (0.9%) patients with double genetic alterations and 3 with
triple alterations. Multiple mutations involved preferentially KRAS (67.3%),
OA11.01 PROLONGED OS OF PATIENTS EXPOSED TO WEEKLY
PI3K (53.3%) and EGFR (42.4%). Patients with multiple alterations were male
(56.4%) with a median age of 66.7 and essentially adenocarcinoma (83.6%).
PACLITAXEL AND BEVACIZUMAB: IMPACT OF THE CROSS-OVER IN
More never-smokers were observed in comparison with patient with singles THE IFCT-1103 ULTIMATE STUDY
alterations (34.7 vs. 25.8 %, p<0.001). OS was not significantly different Alexis Cortot 1, Clarisse Audigier Valette2, Olivier Molinier3, Sylvestre Le
between single and multiple alterations whatever the type of mutations. Moulec4, Fabrice Barlesi5, Gérard Zalcman6, Patrick Dumont7, Damien
Patients with EGFR/KRAS and EGFR/PI3K mutated tumors had worse PFS Pouessel8, Claire Poulet9, Sandrine Hiret10, Pierre Jean Souquet11, Adrien
after biomarker analysis than patients with EGFR single mutation (7.1 and Dixmier 12, Patrick-Aldo Renault13, Alexandra Langlais14, Marie-Paule
7.1 months vs. 14.9 months, p=0.02 and 0.002, respectively). Concomitant Lebitasy14, Franck Morin15, Denis Moro-Sibilot16, Benjamin Besse17
mutations in patients harboring ALK rearrangement had little impact on OS 1
Thoracic Oncology, Lille University Hospital, Lille/France, 2Centre Hospitalier
(17.7 months vs. 20.3 months, p=0.57) or PFS (10.3 months vs. 12.1 months, Sainte Musse, Toulon/France, 3Hospital Center, Le Mans/France, 4Institut Bergonié,
p=0.93). Patients harboring KRAS mutations with another alteration had Bordeaux/France, 5Centre Essais Précoces En Cancérologie de Marseille Clip,
similar OS (13.4 vs. 11.2 months, p=0.28), PFS (6.4 months vs. 7.2 months, Marseille/France, 6University Hospital Bichat, Paris/France, 7Pneumology, Centre
Hospitalier de Chauny, Chauny/France, 8Hôpital Saint-Louis, Ap-Hp, Paris/France,
p=0.78) and ORR to first-line chemotherapy (41.7% vs. 37.2%) to those only 9
Amiens University Hospital, Amiens/France, 10 Ico, Nantes/France, 11CHU Lyon-Sud,
harboring KRAS mutations. Conclusion: With almost 1% of patients harboring Lyon/France, 12Chr D’Orléans, Orléans/France, 13Chr de Pau, Pau/France, 14Ifct,
multiple genomic alterations, the dogma of mutually exclusive mutations Paris/France, 15French Cooperative Thoracic Intergroup (IFCT), Paris/France, 16Pôle
should be reconsidered. Double mutations do not significantly decrease OS Thorax Et Vaisseaux, Unité D’Oncologie Thoracique, Service de Pneumologie,
but alter PFS under first line treatment for EGFR mutated patients. Therapies Grenoble/France, 17Department of Cancer Medicine, Gustave Roussy, Villejuif/
targeting the dominant oncogene remain generally active in this setting. France
Keywords: lung cancer, targeted therapy, mutation, prognosis Background: Overall survival (OS) is considered as the gold standard for
evaluating efficacy of antineoplastic treatments, including chemotherapy
and targeted therapies. In randomized trials, allowing patients to cross-
over to the other arm usually prevents demonstration of a survival benefit.
OA10: EGFR MUTATIONS However, it may provide important information with clinical relevance.
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 Methods: The phase III IFCT-1503 ULTIMATE study compared weekly paclitaxel
and bevacizumab (wPB) vs. docetaxel (DOC) as second- or third-line therapy
OA10.07 REPORT ON LIQUID BIOPSIES FROM ADVANCED LUNG in non-squamous NSCLC. At progression, patients were allowed to cross over
to the other arm. Date of progression was collected for patients who crossed
ADENOCARCINOMA PATIENTS AND CORRELATION WITH THEIR
over to the other arm and for those who did not cross over but received a
TUMOR BIOPSY PROFILES post-discontinuation treatment within 60 days following progression. Post-
Edgardo Santos 1, Luis Raez2, Lilibeth Castillero3, Camila Marana2, Brian discontinuation progression-free survival (PFS2) and OS2 were calculated
Hunis2 from day 1 of post-discontinuation treatment. Results: The study met its
1
Department of Oncology, Lynn Cancer Institute/florida Atlantic University, primary endpoint, PFS, which was significantly improved in the wPB arm
Boca Raton/FL/United States of America, 2Florida International University, (medians 5.4 vs. 3.9 mo, hazard ratio (HR) 0.62, p=0.006). No overall survival
Memorial Cancer Institute, Pembroke Pines/FL/United States of America, 3Human was observed (medians 9.9 vs. 11.4 mo, HR 1.18, p=0.4). Out of patients treated
Physiology, University of Panama, Panama/Panama with DOC (n=55), those who crossed over to wPB (n=21, 38.2%) had a median
Background: Liquid biopsy (LBx) has emerged as an alternative tool for PFS2 of 4.9 mo [3.1-6.2] and a median OS2 of 12.5 mo (7.0-NR), whereas those
the management of advanced lung cancer patients (pts) identifying who did not cross over but received a post-discontinuation treatment (n=13,
driver mutations, and hence, improving personalized medicine. There are 23.7%) had a median PFS2 of 1.7 mo [1.1-2.2] and a median OS2 of 4.1 mo
still controversial issues such as standardization, validation of different [2.1-5.9]. Out of patients treated with wPB (n=111), median PFS2 was 1.9 mo
technologies, concordance with tissue molecular profile results (TMPR), and [1.2-2.2] for those who crossed over to DOC (n=9, 8.3%) and median PFS2 and
others. LBx offers many advantages including non-invasive, bypass tumor OS2 were 1.9 mo [1.7-2.6] and 5.0 m [3.4-9.0] for those who did not cross over
heterogeneity, an opportunity for serial measurements to evaluate response but received a post-discontinuation treatment (n=57, 52.3%). Conclusion:
or early recurrence, and others. Methods: Guardant 360 was analyzed in Allowing patients to cross over to the other arm demonstrated benefit of wPB
100 consecutive stage IV or recurrent lung adenocarcinoma (adeno) pts. following progression on docetaxel and explains the absence of OS benefit.
Guardant 360 is a panel of 70 genes including single nucleotide variations, Keywords: paclitaxel, Second-line, non-small cell lung cancer (NSCLC),
amplifications, translocations, and short insertions/duplications/deletions bevacizumab
in exons 19 and 20 of the EGFR, and others. Cell-free DNA (cfDNA) is extracted
from plasma and genomic alterations are analyzed by massively parallel
OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER non-small cell lung cancer (NSCLC) patients. Fruquintinib is a potent and
highly selective oral kinase inhibitor targeting vascular endothelial growth
factor receptors and is currently in late stage development for multiple
OA11.02 RANDOMIZED PHASE 1B/3 STUDY OF ERLOTINIB PLUS cancers. This Phase II study was designed to evaluate the efficacy and safety
RAMUCIRUMAB IN FIRST-LINE EGFR MUT + STAGE IV NSCLC: PHASE of fruquintinib in third-line NSCLC patients (NCT02590965). Methods: A
total of 91 patients were randomized to receive best supportive care (BSC)
1B SAFETY RESULTS
plus fruquintinib or BSC plus placebo in a 2:1 ratio from 12 Chinese clinical
Kazuhiko Nakagawa1, Luis Paz-Ares2, Santiago Ponce2, Jesus Corral3, Oscar centers. Fruquintinib initial dose was 5 mg once daily and treatment was
Vidal4, Ernest Nadal5, Katsuyuki Kiura6, Jingyi Liu7, Shuang He7, Joseph Treat7, given in every 4-week cycle (3 weeks treatment followed by 1 week off). The
Rita Dalal8, Pablo Lee9, Martin Reck10 primary objective was to compare progression free survival (PFS) between
1
Kindai University Faculty of Medicine, Osaka-Sayama/Japan, 2Hospital Doce the two treatment groups. Secondary efficacy parameters included objective
de Octubre, Madrid/Spain, 3Hospital Virgen Del Rocío, Sevilla/Spain, 4Hospital response rate (ORR), disease control rate (DCR), overall survival (OS). Tumor
Universitario La Fe, Valencia/Spain, 5Institut Català D’Oncologia, L’Hospitalet,
response was assessed per RECIST 1.1. Results: As of August 7, 2015, median
Barcelona/Spain, 6Okayama University Hospital, Kitaku, Okayama/Japan, 7Eli
PFS was 3.8 months for the fruquintinib group comparing with 1.2 months
Lilly and Company, Indianapolis/IN/United States of America, 8Formerly Eli Lilly
and Company, Bridgewtaer/NJ/United States of America, 9Eli Lilly and Company, for the placebo group (hazard ratio=0.27, p<0.001). The ORR was 16.4% for
Bridgewtaer/NJ/United States of America, 10 Lungen Clinic Grosshansdorf, the fruquintinib group comparing with 0% for the placebo group (p=0.02).
Airway Research Center North (Arcn), German Center for Lung Research (Dzl), The DCR of the fruquintinib group was significantly higher than that of the
Grosshansdorf/Germany placebo group with a difference of 53.8% (36.3, 71.4; 95% CI, p<0.001). OS was
not mature and initial analysis revealed 3- and 6-month OS rates of 90.2%
Background: Ramucirumab, an antiangiogenic IgG1 VEGFR2-targeted and 68.3% for the fruquintinib group, and 73.3% and 58.2% for the placebo
monoclonal antibody, and erlotinib, an EGFR tyrosine kinase inhibitor, are group, respectively. Adverse event was reported in 68.9% and 60.0% patients
both active in advanced NSCLC. This global phase 1b/3 study (NCT02411448) in fruquintinib and placebo group, respectively. The incidence of serious
will assess safety, tolerability and efficacy of the combination of ramucirumab adverse events was 3.3% in the fruquintinib group and 6.7% in the placebo
with erlotinib in previously untreated patients with EGFR mutation-positive group. Conclusion: Fruquintinib in third-line NSCLC met the primary efficacy
stage IV NSCLC. Here we report phase 1b safety results. Methods: Eligible endpoint of PFS and demonstrated superiority in the secondary endpoints of
patients with ECOG PS 0-1, an activating EGFR mutation, and previously ORR and DCR as compared with placebo. OS has yet to mature. Fruquintinib
untreated stage IV NSCLC received ramucirumab 10 mg/kg intravenously was generally well tolerated and safety profile consistent with previously
on day 1 of repeating 14-day (± 3 days) cycle and erlotinib 150 mg orally daily. reported. These results support further development of fruquintinib in
Treatment continued until disease progression or unacceptable toxicity. third-line NSCLC patients. A randomized, double-blind, multi-center Phase
The primary objective of part A was to assess the safety and tolerability, in III registration study was initiated in December 2015 (NCT02691299). Clinical
terms of dose limiting toxicities (DLT), of adding the recommended dose trial information: NCT02590965.
of ramucirumab for phase 3 (part B) to standard dose erlotinib. Data were
analyzed separately for Japan (JP) (cohort 1) and US/EU (cohort 2). The DLT Keywords: non-small cell lung cancer, PROGRESSION FREE SURVIVAL,
assessment occurred during the first 2 cycles (approximately 28 days). vascular endothelial growth factor receptor, third-line treatment
Results: As of Dec 16th, 2015, 14 patients were treated in the phase 1b part
of this trial and 12 were DLT evaluable (6 JP; 6 US/EU). Overall, 6 grade (Gr) 3
treatment-emergent adverse events (TEAE) were noted, with at least one
TEAE in 5 patients; no serious adverse events or Gr 4-5 TEAEs occurred. In OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER
the JP cohort the median age was 73 (64-79), 57% had ECOG PS 1 and 29% TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
had a history of smoking. Four patients (57%) experienced a Gr 3 TEAE, of
which one was a DLT (elevation of alanine aminotransferase) while the others OA11.05 A PHASE 2 STUDY OF CABOZANTINIB FOR PATIENTS WITH
(hypertension [n=2], dermatitis acneiform, and diarrhea) were not DLTs. In
ADVANCED RET-REARRANGED LUNG CANCERS
the US/EU cohort the median age was 71 (31-83), 86% had ECOG PS 1, and no
patients had a history of smoking. One patient experienced Gr 3 TEAE of rash; Alexander Drilon, Romel Somwar, Roger Smith, Lukas Delasos, Melanie
no DLTs were observed in this cohort. Conclusion: Enrollment on the phase 1b Albano, Martine Van Voorthuyson, Lu Wang, Natasha Rekhtman, Andy Ni,
portion of this trial is complete and the safety results were consistent with Andrew Plodkowski, Michelle Ginsberg, Gregory Riely, Charles Rudin, Marc
previous combinations of antiangiogenic/erlotinib in this patient population. Ladanyi, Mark Kris
No unexpected toxicities were identified. Phase 3 enrollment has been Department of Medicine, Memorial Sloan Kettering Cancer Center, New York/
initiated maintaining the dose of ramucirumab at 10 mg/kg Q2W. United States of America
Keywords: Erlotinib, EGFR, VEGF, ramucirumab Background: RET rearrangements are actionable drivers found in 1-2% of
non-small cell lung cancers. We previously reported the efficacy and safety of
the multikinase RET inhibitor cabozantinib in 16 patients with RET-rearranged
lung cancers in the first stage of our Simon two-stage phase 2 clinical trial
OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER (overall response rate 38%; Drilon, ASCO 2015). This study has since completed
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 accrual of both stages, now with 26 patients treated with cabozantinib.
Methods: This was an open-label, single center, phase 2 trial (NCT01639508).
Eligibility criteria: stage IV pathologically-confirmed lung cancers,
OA11.03 A RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND PHASE presence of a RET rearrangement, KPS >70%, and measurable disease. RET
II STUDY OF FRUQUINTINIB IN PATIENTS WITH ADVANCED NON- rearrangements were detected by FISH or next-generation sequencing.
SMALL CELL LUNG CANCER Cabozantinib was administered in tablet form at 60 mg daily until progression
Shun Lu1, Jianhua Chang2, Xiaoqing Liu3, Jianhua Shi4, You Lu5, Wei Li6, Jinji of disease or unacceptable toxicity. The primary objective was to determine
Yang7, Jianying Zhou8, Jie Wang9, Lei Yang10, Zhiwei Chen11, Xiangdong Zhou12, the overall response rate (ORR, RECIST v1.1). Secondary objectives included
Zhe Liu13, Ye Hua14, Weiguo Su14 determining progression-free survival (PFS), overall survival (OS), and toxicity.
1
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong 5 responses in 25 response-evaluable patients were required to meet the
University, Shanghai/China, 2Department of Medical Oncology, Fudan University primary endpoint (Simon two-stage minimax design: H0 10% vs HA 30% ORR).
Shanghai Cancer Center, Shanghai/China, 3Department of Pulmonary Oncology, All patients who received at least one dose of cabozantinib were evaluable
307 Hospital of the Academy of Military Medical Sciences, Cancer Center, Beijing/ for toxicity. Results: 26 patients with RET-rearranged lung adenocarcinomas
China, 4 2Nd Chest Onocology Department, Linyi Tumor Hospital, Linyi/China, were treated with cabozantinib. KIF5B-RET was the predominant fusion type
5
Chest Cancer Department of Cancer Center, West China Hospital, Chengdu/China
6 identified in 16 (62%) patients. The median number of prior chemotherapy
Cancer Center, The First Hospital of Jilin University, Changchun/China, 7Guangdong
lines was 1 (0-5). One patient who discontinued therapy in cycle 1 and did not
Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of
Medical Sciences, Guangzhou/China, 8Respiratory Diseases, The First Affiliated undergo a response assessment was not response-evaluable as per protocol.
Hospital, College of Medicine, Zhejiang University, Hangzhou/China, 9Deparmtne The study met its primary endpoint with confirmed partial responses
of Thoracic Medical Oncology, Peking University, School of Oncology, Beijing Cancer observed in 7 (ORR 28% [95% CI 12-49%]) of 25 response-evaluable patients.
Hospital and Institute, Beijing/China, 10 Oncology Department, Nantong Tumor The median PFS was 5.5 months (95% CI 3.8-8.4). The median OS was 9.9
Hospital, Nangtong/China, 11Department of Shanghai Lung Cancer Center, Shanghai months (95% CI 8.1-not reached). Response by RET fusion partner: Unknown
Chest Hospital, Shanghai Jiao Tong University, Shanghai/China, 12Respiratory (FISH+) 2/6 (33%), KIF5B 3/15 (20%), CLIP1 1/1, TRIM33 1/1, CCDC6 0/1, ERC1 0/1.
Department, Xi Nan Hospital, Third Military Medical University, Chongqing/China,
13 In 26 patients evaluable for toxicity, the most common all-grade treatment-
Oncology, Beijing Chest Hospital, Capital Medical University, Beijing/China,
14 related adverse events were increased alanine aminotransferase in 25
Hutchison Medipharma Limited, Shanghai/China
(96%) patients, increased aspartate aminotransferase in 19 (73%) patients,
Background: Targeting the tumor microenvironment, such as tumor hypothyroidism in 18 (69%) patients, diarrhea in 16 (62%) patients, and palmar
angiogenesis, has led to the successful development and approval of a plantar erythrodysesthesia in 15 (58%) patients. Nineteen (73%) patients
number of targeted therapies thereby changing the standard of care for required dose reduction. Conclusion: This study met its primary endpoint.
many types of cancer. However, treatment options are limited in third-line Cabozantinib is an active agent in patients with RET-rearranged lung

cancers. An improved understanding of tumor biology and novel therapeutic PD-L1 expression, resulting in impairing antitumor immunity. Therefore,
approaches will be required to improve outcomes with RET-directed therapy. the current study aimed to investigate whether combining anti-angiogenic
and anti-PD-L1 treatments can induce synergistic antitumor effect by
Keywords: RET rearrangement, RET fusion, cabozantinib enhancing antitumor immune response in murine lung cancer. Methods:
We evaluated the antitumor effects of anti-VEGFR2 agent (apatinib) as
monotherapy or in combination with anti-PD-L1 monoclonal antibody in a
murine lung cancer model using Lewis lung cancer cells (LLCs). The changes
OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER of immune components in tumor and spleen were dynamically tested
in different treatment groups and time points by flow cytometry and
immunohistochemistry. Results: The results showed that VEGF/VEGFR2
OA11.06 ROLE OF FIBROBLASTS IN THE SUBTYPE-SPECIFIC blockade could retard tumor growth and inhibit tumor neovascularization
THERAPEUTIC EFFECTS OF NINTEDANIB IN NON-SMALL CELL LUNG via eradicating Foxp3+ regulatory T cells (Tregs) and myeloid derived
CANCER (NSCLC) suppressive cells (MDSCs) and reducing the density of microvessels in the
first two weeks of treatment. On the third week of apatinib monotherapy,
Marta Gabasa1, Rafael Ikemori1, Flavio Solca2, Frank Hilberg2, Noemi Reguart3,
the number of Foxp3+ Tregs and MDSCs had increased again. Although VEGF/
Jordi Alcaraz 1
1
VEGFR2 blockade induced more tumor infiltrating lymphocytes (TILs),
Dept of Biomedicine, Facultat de Medicina, Universitat de Barcelona, Barcelona/ especially CD8+ T cells, infiltrating into the tumor mass than control group (P
Spain, 2Boehringer Ingelheim Rcv Gmbh & Co Kg, Vienna/Austria, 3Hospital Clinic
< 0.01), the expression of PD-1 and PD-L1was also significantly upregulated
Barcelona, Barcelona/Spain
than that control group (P < 0.01). Compared to apatinib monotherapy,
Background: There is growing evidence that tumor-associated fibroblasts combining treatment demonstrated that anti-VEGFR2 plus anti-PD-L1
(TAFs) play a major role in critical steps of tumor progression in solid tumors therapy could significantly inhibit tumor growth (P < 0.01) by persistently
including NSCLC. However the role of TAFs in regulating the response to eliminating Foxp3+ Tregs and MDSCs. Furthermore, combining anti-VEGFR2
targeted therapies is poorly understood. One of such targeted therapies is and anti-PD-L1 therapy could not only dramatically increase TILs infiltration,
nintedanib (NTD), a multi-kinase inhibitor of VEGF, FGF and PDGF receptors especially CD8+ T cells, but also significantly reduce the expression of PD-1 and
that has been recently approved to treat advanced lung adenocarcinoma PD-L1. Conclusion: Simultaneous blockade of VEGF/VEGFR2 and PD-1/PD-L1
(ADC) patients. Although the therapeutic effects of NTD in lung cancer have pathways induced a synergistic anti-tumor effect in-vivo, possibly through
been associated with its anti-angiogenic functions, NTD has also been shown eliminating immunosuppressive components including Tregs and MDSCs and
to exhibit anti-fibrotic effects in patients with idiopathic pulmonary fibrosis. enhance antitumor immune response.
Since lung fibrosis is largely driven by activated fibroblasts/myofibroblasts,
Keywords: programmed death ligand-1, lung cancer, Immunotherapy,
and TAFs are positive for myofibroblasts markers, it is conceivable that NTD
angiogenesis
anti-tumor effects may be additionally driven through its direct action on
lung TAFs. The main goal of this study was to analyze the latter hypothesis.
Methods: Patient derived lung TAFs from ADC and SCC patients as well
as paired control fibroblasts from non-malignant pulmonary tissue were
exposed to increasing concentrations of NTD and analyzed for growth and
activation upon stimulation with growth factors and TGF- β1, respectively.
SESSION OA12: SBRT AND OTHER ISSUES IN EARLY
Activation markers included alpha-smooth muscle actin and collagen-I. STAGE NSCLC
Results: We found that NTD exhibited a dual inhibitory role in TAFs in terms TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
of growth and TGF-β1-induced activation in a subtype-specific fashion.
Specifically, NTD-mediated growth inhibition was larger in SCC-TAFs than in
ADC-TAFs, which correlated with the larger Erk signaling previously reported OA12.01 PHASE II RANDOMIZED STUDY OF 2 SBRT REGIMENS
by our group in SCC-TAFs in the absence of mitogenic stimuli. Conversely, FOR MEDICALLY INOPERABLE PATIENTS WITH NODE NEGATIVE
inhibition by NTD of TGF-β1-mediated activation was larger in ADC-TAFs than
PERIPHERAL NSCLC
SCC-TAFs. Likewise, NTD inhibited the growth and invasive advantages of ADC
cancer cells in vitro elicited by the conditioned medium of ADC-TAFs treated Jorge A. Gomez Suescun1, Gregory Videtic2, Kevin Stephans2, Jeffrey Bogart3,
with TGF-β1 compared to those advantages elicited in the absence of NTD. Lili Tian4, Adrienne Groman1, Anurag K Singh1
1
These results reveal for the first time that the pro-tumorigenic effects of ADC- Radiation Medicine, Roswell Park Cancer Institute, Buffalo/NY/United States of
TAFs in vitro are markedly reduced in the presence of NTD. Conclusion: TAFs America, 2Radiation Oncology, Cleveland Clinic, Cleveland/OH/United States of
America, 3Suny-Upstate Medical Center, Syracuse/AL/United States of America,
in vivo are largely activated and quiescent, and TGF-β1 is a potent fibroblast 4
Biostatistics, Roswell Park Cancer Institute, Buffalo/NY/United States of America
activator that is frequently upregulated in lung cancer and associated with
poor prognosis. Based on these previous observations, we argue that our new Background: This phase II, multi-institutional (Roswell Park Cancer Institute,
findings strongly suggest that the selective therapeutic advantage observed Cleveland Clinic, and Upstate Medical Center) randomized study was
for NTD in ADC patients may be in part related to its selective inhibition of conducted to compare incidence of RTOG grade 3 or higher adverse events
TGF-β1-dependent activation of ADC-TAFs. These findings provide novel (AEs) associated with 2 different, established SBRT regimens for NSCLC
mechanistic insights on the subtype-specific therapeutic effects of NTD in Methods: Patients with documented baseline medical conditions precluding
NSCLC. lobectomy and biopsy-proven peripheral (greater than 2 cm from the central
bronchial tree) T1/T2, N0 (clinically node negative by PET), M0 tumors were
Keywords: nintedanib, TGF-β, tumor microenvironment, cancer associated
eligible. Patients were randomized to receive either 30 Gy in one fraction
fibroblasts
(arm 1) or 60 Gy in 3 fractions (arm 2) over at least 8 days. Heterogeneity
corrections were not used. Randomization was stratified by treatment
center and Karnofsky performance status (100, 90, 80 and below.) The study
was designed to detect whether psAEs rate > 17% at a 5% significance level
OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 (1-sided) and 81% power. Secondary endpoints included: local control, greater
than 1 year toxicity, overall survival (OS) and progression-free survival (PFS).
Results: The study opened in September 2008, was suspended between April
OA11.07 COMBINING ANTI-ANGIOGENESIS AND IMMUNOTHERAPY 2010 to June 2010 as well as October 2010 to April 2011 while RTOG 0915 was
ENHANCES ANTITUMOR EFFECT BY PROMOTING IMMUNE open, and closed on April 15, 2015 after accruing a total of 98 patients. All
RESPONSE IN LUNG CANCER patients received planned SBRT treatment. Median follow-up was 27 months.
Sha Zhao 1, Tao Jiang2, Xuefei Li3, Caicun Zhou4 In follow-up, 10 patients were lost to follow-up; 1 was in arm 1 and 9 in arm 2.
1 Baseline patient and tumor characteristics were balanced between both arms.
Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer
Institute, Tongji University School of Medicine, Shanghai/China, 2Department On arm 1, 13 (27%) patients and 16 (33%) patients on arm 2 experienced RTOG
of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of grade 3 AEs, there were no grade 4 AEs. Thoracic grade 3 AEs were experienced
Medicine, Shanghai/China, 3Lung Cancer and Immunity Laboratory, Shanghai by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no
Pulmonary Hospital, Tongji University; Tongji University Medical School Pulmonary differences in OS or PFS survival, logrank p= 0.44 and 0.99 respectively. OS at
Cancer Institute, Shanghai/China, 4 Oncology, Shanghai Pulmonary Hospital, Tongji 2 years was 71% (95% CI, 55-82%) for arm 1 and 61% (95% CI, 44-78%) for arm 2.
University School of Medicine, Tongji University Cancer Institute, Shanghai/China PFS at 1 year was 63% (95% CI, 46-75%) for arm 1 and 51% (95% CI, 34-65%) for
arm 2. Conclusion: This randomized phase II study demonstrated that 30 Gy
Background: Increasing studies have shown that anti-angiogenic therapy
in one fraction was equivalent to 60 Gy in three fractions in terms of toxicity,
targeting VEGF/VEGFR2 axis are furnishing demonstrable therapeutic
progression free survival and overall survival. Acknowledgment: Supported by
effect on lung cancer，but the treatment benefit is transitory in clinic,
Roswell Park Alliance Foundation grant
generally followed by restoration of tumor growth and disease progression.
Blockade of VEGF/VEGFR2 pathway can not only induce anti-vascular
effect, but also remodel the immunosuppressive tumor microenvironment
probably due to promoting suppressive cells infiltration and enhancing
OA12: SBRT AND OTHER ISSUES IN EARLY STAGE NSCLC The median follow-up time was 20 months (range: 6 to 55 months). The mean
Krebs von den Lungen-6 (KL-6) level was 1608 ±1025 U/mL. The mean tumor
size was 24 ± 7mm. The mean percentage of predicted diffusing capacity
OA12.02 EXCELLENT SURVIVAL ACHIEVED BY STEREOTACTIC BODY for carbon monoxide (DLCO) was 37±27%. Thirty and 90-day mortality
RADIOTHERAPY FOR MEDICALLY OPERABLE AND YOUNG (< 75 was 0 and 18%, respectively. Two patients required chest tube drainage
because of severe pneumothorax. Acute exacerbation of IPF occurred in two
YEARS) PATIENTS WITH STAGE I LUNG CANCER
patients (18%). The use of oral steroids and need for chest tube drainage
Hiroshi Onishi1, Yoshiyuki Shioyama2, Yasuo Matsumoto3, Kenji Takayama4, were predictors of higher mortality (p < 0.05) and higher incidence of
Yukinori Matsuo5, Akifumi Miyakawa6, Hideomi Yamashita7, Haruo acute exacerbation of IPF (p < 0.05). However, higher level of KL-6 and low
Matsushita8, Masahiko Aoki9, Keiji Nihei10 percentage of DLCO were not significant risk factors of mortality or acute
1
Radiology, University of Yamanashi, Yamanashi/Japan, 2Heavy Particle Therapy exacerbation of IPF. Local progression-free survival at 1, 2 and 3 year was 51, 41
and Radiation Oncology, Kyushu University, Fukuoka/Japan, 3Niigata Cancer and 31%, respectively. Conclusion: Percutaneous cryoablation for lung cancer
Center Hospital, Niigata/Japan, 4Radiation Oncology, Kyoto University, Kyoto/
patients with IPF provoked acute exacerbation of IPF in 18% of patients. The
Japan, 5Kyoto University, Kyoto/Japan, 6Nagoya Municipal Hospital, Nagoya/
use of oral steroids and need for chest tube drainage were predictors of higher
Japan, 7Department of Radiology, University of Tokyo Hospital, Tokyo/Japan,
8
Tohoku University, Sendai/Japan, 9Hirosaki University, Hirosaki/Japan, 10Tokyo mortality and higher incidence of acute exacerbation of IPF.
Metropolitan Cancer and Infectious Diseases Center, Tokyo/Japan
Keywords: lung cancer, complications, cryoablation
Background: Stereotactic body radiotherapy (SBRT) has been sometimes
used as a curative treatment for both of medically operable patients with
stage I non-small cell lung cancer (NSCLC). However, most of these patients
are comparatively high-aged and not similar to the patients cohort generally OA12: SBRT AND OTHER ISSUES IN EARLY STAGE NSCLC
operated with surgery. So, the purpose of this study was to collect results
of SBRT for operable and young (70 years old or younger) patients with
stage I NSCLC from multiple Japanese institutions. Methods: We organized OA12.05 NONINVASIVE CT-BASED IMAGE BIOPSY SYSTEM
a multi-institutional SBRT study group in Japanese Radiological Society (IBIOPSY) FOR EARLY STAGE LUNG ADENOCARCINOMA
(JRS-SBRTSG) and conducted a study for SBRT for stage I non-small cell lung
Dawei Yang 1, Yu Zhu2, Charles Powell3, Ningfang Wang1, Vanbang Le2,
cancer (NSCLC). This is a retrospective analysis to review 252 patients (male
Bingbing Zheng2, Hongcheng Shi4, Changwen Zhai5, Shaohua Lu5, Yingyong
168, female 84) who were medically operable and 70 years old or younger
Hou5, Di Ge6, Xinwei Zhang7, Jian Zhou1, Ming Li8, Guozhen Zhang8, Chunxue
(range,40-74; median, 67 years) with stage I (IA 211, IB 41) NSCLC treated with
Bai1
curative intent by SBRT in 20 institutions of JRS-SBRTSG. Histology was 1
proven in 177 patients (adenocarcinoma 121, squamous cell carcinoma 41, Department of Pulmonary Medicine, Zhongshan Hospital Fudan University,
Shanghai/China, 2 School of Information Science and Engineering, East China
others 15), and the others were diagnosed clinically. Median tumor size was
University of Science and Technology, Shanghai/China, 3Division of Pulmonary,
22mm (range, 5-49mm). A total dose of 40 -70 Gy mainly was prescribed in Critical Care, and Sleep Medicine, Mount Sinai Hospital, New York/NY/United
4-10fractions. Median calculated biological effective dose (BED) was 107 Gy States of America, 4Department of Nuclear Medicine, Zhongshan Hospital Fudan
(range, 75-134 Gy) based on alpha/beta = 10Gy). Results: The median follow-up University, Shanghai/China, 5Department of Pathology Medicine, Zhongshan
period for all patients was 37 months. Overall survival rate (OS) at three and Hospital Fudan University, Shanghai/China, 6Department of Thoracic Surgery,
five year was 83.3% and 76.6%, respectively. Radiation pneumonitis of grade Zhongshan Hospital Fudan University, Shanghai/China, 7Department of Radiology,
3 or more was noted in 0.8% of the total patients. In the total patients, local Zhongshan Hospital Fudan University, Shanghai/China, 8Department of Radiology,
Huadong Hospital Fudan University, Shanghai/China
control rate (LC) at three year was 89.5%, and LC was significantly better
in the subgroup of adenocarcinoma than that of squamous cell carcinoma. Background: CT screening programs frequently detect early stage lung
According to univariate analysis, female, adenocarcinoma, no emphysema, adenocarcinoma. Recent studies show that distinct subtypes of lung
and no pulmonary interstitial change were better prognostic factors for adenocarcinoma are associated with different prognosis and suggest that
OS. According to multivariate analysis, pulmonary interstitial change was treatment should be tailored to histological subtypes as identified in the
only a worse survival factor for OS. OS at three and five year in the subgroup new WHO Lung Tumor Classification. To develop this personalized approach,
of patients without pulmonary interstitial change was 89.7% and 84.0%, it is important to have reliable tools to diagnose tumors before treatment,
respectively. Conclusion: The outcomes of SBRT for the medically operable preferably non-invasively through image analysis. We have developed a
and young (75 years or younger) patients with stage I NSCLC in the Japanese CT-image analysis system (iBiopsy) that uses computerized deep learning
large database of practice level was excellent and the overall survival rate and artificial intelligence. To validate the accuracy of a noninvasive CT-
would be comparable to that of surgery. The results will support a rationale of based image biopsy system (iBiopsy) in differentiating early stage lung
applying SBRT for younger and operable patients with operable stage I NSCLC. adenocarcinoma subtypes of atypical adenomatous hyperplasia (AAH),
Keywords: stereotactic body radiotherapy, stage I, non-small cell lung cancer, adenocaricnoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and
operable invasive adenocarcinoma (IAC). Methods: We retrospectively identified 365
eligible patients from Zhongshan Hopsital Fudan University, diagnosed
with AAH, AIS, MIA or IAC by surgical pathological diagnosis. The last high
definition CT scan prior to the surgery of the lesion was analyzed using the
OA12: SBRT AND OTHER ISSUES IN EARLY STAGE NSCLC
iBiopsy system, blinded to pathological result. Based on a pulmonary nodule
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 image feature set (PNIFS) in combination with classified pattern models,
such as R-SVM, all the pulmonary nodules were classified into four groups.
For diagnosis efficacy, area under the curve (AUC) of Precision-Recall score
OA12.03 PERCUTANEOUS CRYOABLATION FOR LUNG CANCER (PRS), receiver operating characteristic (ROC) of a classification model were
PATIENTS FOR WHOM SURGERY OR RADIOTHERAPY IS calculated in each group. Results: 365 patients were included in the analysis.
CONTRAINDICATED DUE TO IDIOPATHIC PULMONARY FIBROSIS The classification recognition rate of the PNIFS was 80.03%. The average
Takashi Ohtsuka1, Keisuke Asakura2, Kyohei Masai1, Kaoru Kaseda1, Ikuo value of PRS is 0.92, the mean of ROC is 0.95, and it is more than 0.80 for the
Kamiyama1, Masanori Inoue3, Seishi Nakatsuka3, Hisao Asamura1 cross validation value. Conclusion: iBiopsy system allows the non-invasive
1
Department of Thoracic Surgery, Keio University, School of Medicine, Tokyo/Japan, imaged based stratification of pulmonary adenocarcinoma nodules into
2
Thoracic Surgery, National Cancer Center Hospital, Tokyo/Japan, 3Department of four groups, from AAH to IAC. Our result suggest that iBiopsy system could
Diagnostic Radiology, Keio Univeristy, Tokyo/Japan ultimate facilitate the diagnosis and precision management of pulmonary
nodules.
Background: Interstitial lung disease, such as idiopathic pulmonary fibrosis
(IPF), have been widely known to be associated with lung cancer. Lung cancer Keywords: CT scan, lung adenocarcinoma, pulmonary nodule, image analysis
patients concomitant with IPF sometimes develop a life-threatening acute
exacerbation after surgery or radiotherapy. Percutaneous cryoablation
is evolving as a potentially less invasive local treatment for lung cancer.
The purpose of this study is to retrospectively analyze the outcomes of OA12: SBRT AND OTHER ISSUES IN EARLY STAGE NSCLC
cryoablation for clinical T1N0M0 non-small cell lung cancer (NSCLC) patients
for whom surgery or radiotherapy is contraindicated because of IPF. Methods:
Between December 2003 to March 2016, 210 patients underwent computer OA12.06 A RETROSPECTIVE ANALYSIS OF PATIENTS WITH SMALL
tomography guided percutaneous cryoablation for lung tumors at our LUNG ADENOCARCINOMA (≤2CM) BY NEW WORLD HEALTH
institution. Of these, 11 histologically proven clinical T1N0M0 NSCLC patients,
ORGANIZATION CLASSIFICATION
for whom surgery or radiotherapy was considered contraindicated because of
severe IPF, were retrospectively reviewed. Complications, local progression- Keita Nakao 1, Jun-Ichi Nitadori1, Shigeki Morita2, Hideki Kuwano1, Kazuhiro
free survival and clinicopathological factors were evaluated. Results: The Nagayama1, Masaki Anraku3, Aya Shinozaki-Ushiku2, Masaaki Sato1, Masashi
cohort was composed of 11 men with a mean age of 74 years (range: 68 to 82). Fukayama2, Jun Nakajima1

1
Thoracic Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo/
Japan, 2Department of Pathology, Graduate School of Medicine, the University of
Tokyo, Tokyo/Japan, 3The Study of the Safety of Healthcare, Graduate School of
Medicine, the University of Tokyo, Tokyo/Japan
Background: We have recently demonstrated that the presence of the

Spread Through Air Spaces (STAS) and the variety of histologic subtypes
increase the risk of recurrence after resection for small lung adenocarcinoma
(ADC). Currently, the new World Health Organization classification of lung
cancers was revised and newly prescribed to describe the presence of each
histologic subtypes and STAS. The purpose of this study is to examine the risk
factor for recurrence other than TNM staging analyzing clinical information
retrospectively. Methods: All available tumor slides from patients with
clinical stage I, therapy-naive, surgically resected solitary lung ADC ≤2 cm in
size (1998-2015) were reviewed. Each tumor was evaluated by comprehensive
histologic subtyping, and the percentage of each histologic component was
recorded in 5% increments. STAS was defined as the spread of tumor cells
into air spaces in the lung parenchyma adjacent to the main tumor according
to the WHO classification. Recurrence-free probability (RFP) was estimated
using the Kaplan-Meier method. Results: 354 patients met inclusion criteria
(52.3% men; median age: 67yrs; median tumor size: 1.3cm; 325 stage IA/
29 stage IB; 91 partial resection/ 22 segmentectomy / 241 lobectomy or
pneumonectomy). The prognosis didn’t differ significantly between sublobar
resection group and lobectomy or pneumonectomy group (5-year RFP: 88.4%
(N=113) vs. 91.9% (N=241), P=.162). Presence of STAS was identified in 74 cases
(20.9%) (36 Micropapillary pattern / 55 Solid pattern / 15 Single cells). STAS
was significantly associated with recurrence (5-year RFP: 94.3% vs. 76.2%,
P < .0001). Histologic subtypes were 62 adenocarcinoma in situ (18%), 110
minimally invasive adenocarcinoma (31%) and 182 invasive adenocarcinoma
(51%). The recurrence after sublobar resection was seen in 13 cases (1 partial Conclusion: Adjuvant chemotherapy was related with reduced recurrence
resection (4.5%) / 12 segmentectomy (13%), 5 STAS (+)/ 8 STAS (-), 6 solid and improved survival in patients with T2a tumors exceeding 4 cm. In
predominant / 5 acinar predominant / 2 lepedic predominant, 5 pulmonary considering the next upcoming 8th edition of the TNM classification, adjuvant
recurrence / 4 lymph node recurrence / 2 local recurrence / 2 others). chemotherapy is a worthwhile and justified treatment for tumors greater
Patients with solid component had significantly worse prognosis (5-year than 4 cm with early stage disease.
RFP: 71.7% (N=83) vs. 96.3% (N=271), P<.0001). Among them, patients with
sublobar resection had significantly more recurrence than with lobectomy Keywords: lung cancer, Surgery, adjuvant chemotherapy, Prognosis
or pneumonectomy (5-year RFP: 51.4% (N=19) vs. 77.7% (N=64), P=.0021).
Conclusion: The patients of small ADC with STAS or solid component had
worse prognosis. The patients after sublobar resection with solid component
should be made follow-up closely. We propose that the presence of those
features should be considered a factor to upgrade the pathologically defined SESSION OA13: IMMUNOTHERAPY IN MALIGNANT
T stage. PLEURAL MESOTHELIOMA: CURRENT STATUS OF TRIALS
Keywords: solid component, Adenocarcinoma, Spread Through Air Spaces, AND NEW APPROACHES
histologic subtypes TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
OA13.01 A PHASE II STUDY OF NIVOLUMAB IN MALIGNANT

OA12: SBRT AND OTHER ISSUES IN EARLY STAGE NSCLC PLEURAL MESOTHELIOMA (NIVOMES): WITH
TRANSLATIONAL RESEARCH (TR) BIOPIES
Josine Quispel-Janssen1, Giulia Zago2, Robert Schouten2, Wieneke Buikhuisen2,
OA12.07 SELECTION FOR ADJUVANT CHEMOTHERAPY IN STAGE IB Kim Monkhorst1, Eric Thunissen3, Paul Baas2
NON-SMALL CELL LUNG CANCER: A PROPENSITY SCORE-MATCHED 1
Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam/Netherlands,
ANALYSIS 2
Thoracic Oncology, The Netherlands Cancer Institue, Amsterdam/Netherlands,
3
Jae Hyun Jeon, Duk Hwan Moon, Hee Chul Yang, Moon Soo Kim, Jong Mog Lee Pathology, Free University, Amsterdam/Netherlands
Center for Lung Cancer, National Cancer Center, Goyang, Gyeonggi/Korea, Republic
of
Background: The newly proposed International Association for the Study of
Lung Cancer (IASLC) staging system reclassified T2aN0M0 tumors greater
than 4 cm as stage IIA instead of stage IB. This study investigated the role
of adjuvant chemotherapy in pathologic stage IB non-small cell lung cancer OA13: IMMUNOTHERAPY IN MALIGNANT PLEURAL MESOTHELIOMA: CURRENT STATUS
(NSCLC). Methods: The patients with pathologic T2aN0M0 NSCLC who OF TRIALS AND NEW APPROACHES
underwent complete resection between 2001 and 2013 were identified from
prospectively maintained databases, and classified into three groups based
on tumor size: A (≤3.0 cm, n = 205), B (3.1-4.0 cm, n = 264), and C (>4.0 cm, n OA13.02 PHASE II TRIAL OF PEMBROLIZUMAB IN PATIENTS WITH
= 254). After propensity score matching, overall survival (OS) and freedom MALIGNANT MESOTHELIOMA (MM): INTERIM ANALYSIS
from recurrence (FFR) were compared between each group of paired patients
Hedy Kindler 1, Theodore Karrison2, Yi-Hung Carol Tan1, Buerkley Rose1,
who received platinum-based adjuvant chemotherapy and those who did
Mehwish Ahmad1, Christopher Straus3, Robert Sargis4, Tanguy Seiwert1
not. Results: Among the 723 patients, 134 patients (18.5%) received adjuvant 1
chemotherapy: Group A, 38 (18.5%) patients; Group B, 47 (17.8%); and Group Section of Hematology/oncology, University of Chicago, Chicago/IL/United States
of America, 2Department of Public Health Sciences, University of Chicago, Chicago/
C, 49 (19.3%). Matching based on propensity scored produced 38, 47, and 49
IL/United States of America, 3Department of Radiology, University of Chicago,
paired patients in Group A, B, and C, respectively. In Group A and B, there Chicago/IL/United States of America, 4Department of Medicine, University of
was no significant difference in OS and FFR between patients who received Chicago, Chicago/IL/United States of America
adjuvant chemotherapy and those who did not. In Group C, patients who
received adjuvant chemotherapy experienced less recurrence and higher Background: Pembrolizumab showed significant activity in PD-L1+ MM in a
survival than those who did not. The 5-year FFR was 79.0% in in patients phase IB study (Alley, 2015). We are conducting a phase II trial (NCT02399371)
who received adjuvant chemotherapy and 66.1% in patients with surgery of pembrolizumab in previously-treated MM patients to further characterize
alone (p = 0.090). The 5-year OS was 95.8% in patients who received adjuvant its activity in a larger, non-selected population, determine a PD-L1 expression
chemotherapy and 68.9% in patients with surgery alone (p < 0.001). threshold, and interrogate the microenvironment. Methods: Eligible
patients have histologically-confirmed pleural or peritoneal MM, measurable
disease, PS 0-1, disease progression on/after pemetrexed/platinum, 1-2 prior
regimens, normal organ function, and available tissue. Patients receive 200
mg pembrolizumab IV Q21 days and CT scans Q9 weeks. Primary objectives:
1) determine the objective response rate in: A] an unselected population pembrolizumab is feasible in patients with MPM, and no new safety signals
and, B] a PD-L1 positive population; 2) determine the optimal threshold were identified.
for PD-L1 expression using the 22C3 antibody-based IHC assay (Qualtek).
Exploratory correlatives profile the inflammatory microenvironment via: a) Keywords: Mesothelioma, pembrolizumab, Immunotherapy, anti–PD-1
multi-color immunofluorescence of tumor infiltrating lymphocytes (TILs) and
macrophages, b) RNA-based inflammation signatures/pathway activation, c)
characterizing underlying mutations/copy number changes. Proceeding to a
2nd stage requires ≥3 responses in 35 patients. If an optimal threshold for PD- OA13: IMMUNOTHERAPY IN MALIGNANT PLEURAL MESOTHELIOMA: CURRENT STATUS
OF TRIALS AND NEW APPROACHES
L1 expression is determined, the 2nd stage only enrolls above that threshold. TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
Results: 35 patients enrolled 5/15-2/16. 1 withdrew. Male 82%; median age
63 (range 26-85); PS 0/1 63%/37%; epithelial/sarcomatoid/biphasic/NOS:
69%/26%/3%/3%; pleural/peritoneal 86%/14%; 1 prior regimen: 60%. Mean OA13.05 SOMATIC GENETIC ALTERATIONS AND IMMUNE
cycles: 8.5 (range 1-18). Median progression-free survival: 6.2 months (95% MICROENVIRONMENT IN MALIGNANT PLEURAL MESOTHELIOMA
CI: 3.2, 8.2). Median overall survival has not been reached. Partial response: 7 Wickii Vigneswaran1, Hiroyuki Inoue2, Jae-Hyun Park2, Sope Olugbile3, Yusuke
(21%), stable disease (SD): 19 (56%); progression: 6 (18%); early death: 2 (6%). Nakamura4
Ten patients received treatment beyond progression; 20% subsequently 1
Thoracic and Cardiovascular Surgery, Loyola University Health System, Maywood/
achieved SD. Grade 3/4 toxicity: pneumonitis 6%, fatigue 6%, adrenal IL/United States of America, 2University of Chicago, Chicago/IL/United States of
insufficiency 6%, colitis 3%, confusion 3%, hyponatremia 3%, neutropenia America, 3Medicine, University of Chicago, Chicago/IL/United States of America,
4
3%. Grade 1/2 immune-related toxicities: hypothyroidism 17%, rash 14%, Medicine, University of Chicago, Chicago/United States of America
pruritus 11%, diarrhea 9%, uveitis 6%, arthralgia 6%, hepatitis 3%, infusion
reaction 3%, mucositis 3%. Grade 5 toxicities: autoimmune hepatitis 3%, Background: The genomic landscape of malignant pleural mesothelioma
unknown 3%. PD-L1 expression by tumor proportion score (N=31): none (< 1%): (MPM) is not well understood. Advanced high-throughput sequencing
55%; low (1%-49%): 19%; high (≥ 50%): 26%. PD-L1 expression did not correlate technologies allow comprehensive characterization of genetic alterations.
with response (ROC area 0.62; 95% CI: 0.32, 0.94). Conclusion: Pembrolizumab Knowledge of the somatic mutations and the immune microenvironment
has robust activity in PD-L1 unselected, previously-treated MM patients, in patients with MPM will help to develop effective targeted therapies.
with a response rate of 21% and a disease control rate of 76%. An optimal Methods: We examined biopsy specimens from 12 MPM patients (8 epithelioid
PD-L1 threshold could not be established in this small sample. The 2nd stage and 4 biphasic) that were removed during maximal cyto-reductive surgery.
is enrolling an additional 30 patients without PD-L1 pre-selection. Correlative Specimens from 3 different sites (anterior, posterior and diaphragm, a total
studies including CD8 TILs, macrophage characterization, and presence of of 36 tissue samples) were studied through whole exome sequencing, T
T-regulatory cells will be presented. Funded by a grant from the Mesothelioma cell receptor (TCR) repertoire analysis of tumor-infiltrating T cells (TILs),
Applied Research Foundation. and expression levels of immune-related genes. We also performed in silico
prediction of potent neoantigens derived from non-synonymous somatic
Keywords: Mesothelioma, PD-1, phase 2 trial, pembrolizumab mutations in each specimen. For the comparison of tumor tissues from 3
different sites, we performed hierarchical clustering to assess the tumor
heterogeneity and differences in immune environment. Results: High
mutation/neoantigen load was significantly correlated with higher clonal
OA13: IMMUNOTHERAPY IN MALIGNANT PLEURAL MESOTHELIOMA: CURRENT STATUS expansion of TILs (R=0.46) and high expression levels of immune-associated
OF TRIALS AND NEW APPROACHES cytolytic factors, granzyme A (R=0.25) and perforin 1 (R=0.48), in tumor
tissues. In the clustering analysis, heterogeneous MPM cases revealed unique
neoantigens and clonotypes of TILs that were restricted to each of tumor
OA13.03 LONG-TERM OVERALL SURVIVAL FOR PATIENTS WITH site, suggesting infiltration of the neoantigen-specific T cells. Further sub-
MALIGNANT PLEURAL MESOTHELIOMA ON PEMBROLIZUMAB analysis according to histologic types showed that biphasic tumors had higher
ENROLLED IN KEYNOTE-028 mutation/neoantigen load and stronger oligo-clonal T cell expansion (p=0.01)
than epithelioid tumors. Conclusion: Our analysis demonstrated a significant
Evan Alley 1, Juanita Lopez2, Armando Santoro3, Anne Morosky4, Sanatan
correlation between somatic mutation/neoantigen load, clonality of TILs, and
Saraf4, Bilal Piperdi4, Jan H.M. Schellens5
the immune-related tumor microenvironment in MPM. Our findings suggest
1
University of Pennsylvania, Philadelphia/PA/United States of America, 2Drug that high mutation/neoantigen load in tumor cells might promote effective
Development Unit, Institute of Cancer Research, Sutton/United Kingdom, 3Istituto
expansion and infiltration of functional (tumorocidal) T cells into the tumor
Clinico Humanitas, Milan/Italy, 4 Merck & Co., Inc., Kenilworth/NJ/United States of
America, 5Netherlands Cancer Institute, Plesmanlaan/Netherlands
bed. These findings provide a rationale for selecting MPM patients who
can benefit from treatment with immune checkpoint blockades. This may
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive accelerate development of the neoantigen targeting TCR-engineered T cell
cancer with poor prognosis and limited treatment options after progression therapy for MPM.
on platinum-containing chemotherapy. Pembrolizumab, a humanized
anti–programmed death 1 (PD-1) antibody, has demonstrated robust Keywords: T cell receptor, Somatic mutation, malignant pleural
antitumor activity and a favorable safety profile in multiple tumor mesothelioma, sequencing
types. Here, we present long-term overall survival (OS) data for patients
with malignant pleural mesothelioma enrolled in the KEYNOTE-028
(ClinicalTrials.gov, NCT02054806) study. Methods: KEYNOTE-028 is a
OA13: IMMUNOTHERAPY IN MALIGNANT PLEURAL MESOTHELIOMA: CURRENT STATUS
nonrandomized, multicohort phase 1b trial of pembrolizumab in patients OF TRIALS AND NEW APPROACHES
with PD-L1–positive advanced solid tumors. 25 patients with MPM were TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
treated with pembrolizumab in the mesothelioma cohort. Patients received
pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed
progression or intolerable toxicity, death, withdrawal of consent, or OA13.06 AUTOLOGOUS DENDRITIC CELLS LOADED WITH
physician decision. Response was assessed per RECIST v1.1 by investigators ALLOGENEIC TUMOR CELL LYSATE (PHERALYS®) IN PATIENTS WITH
every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary MESOTHELIOMA: FINAL RESULTS OF A PHASE I STUDY
end point was objective response rate (ORR; per RECIST v1.1, investigator Joachim Aerts 1, Robin Cornelissen1, Cor Van Der Leest1, Joost Hegmans1,
assessed). Secondary end points included safety, tolerability, progression- Koen Bezemer 1, Margaretha Kaijen-Lambers1, Ferry Eskens2, Eric Braakman3,
free survival (PFS), and OS. Results: As of June 9, 2016, median duration of Bronno Van Der Holt4, Rudi Hendriks1, Henk Hoogsteden1
follow-up was 18.7 months (range, 1.5-24.6 months), and 4 patients (16%) are 1
Pulmonary Diseases, Erasmus MC Cancer Centre, Rotterdam/Netherlands,
still on treatment. ORR was 28% (n = 7); 12 (48%) patients had stable disease, 2
Medical Oncology, Erasmus MC Cancer Centre, Rotterdam/Netherlands,
resulting in a disease control rate of 76%; median duration of response was 3
Hematology, Erasmus MC Cancer Centre, Rotterdam/Netherlands, 4 Clinical Trial
9.2 months (range, 2.4-20.5+ months); median PFS was 5.8 months (95% CI, Centre, Erasmus MC Cancer Centre, Rotterdam/Netherlands
3.4-8.2 months), with 6- and 12-month PFS rates of 50% and 25%, respectively.
Median OS was 18.0 months (95% CI, 9.4 months-not reached) with 6- and Background: Mesothelioma is an aggressive malignancy without curative
12-month OS rates of 83.5% and 62.6%, respectively. No new safety signals treatment options. We have previously shown promising activity of dendritic
have been identified. Sixteen (64%) patients experienced a drug-related cell (DC) immunotherapy loaded with autologous tumor cell lysate (Hegmans
adverse event (DRAE), and 5 (20%) experienced grade 3/4 DRAEs. Three 2013, Cornelissen 2016). Because of quality and quantity issues (availability,
patients required dose interruption because of immune-related adverse standardization etc) with the autologous lysate, we have developed an
events (1 each, ALT increased, iridocyclitis, and pyrexia/arthralgia]). There was off-the-shelf allogenic tumor cell lysate from human mesothelioma cell lines
no treatment-related mortality or discontinuation due to DRAE. Conclusion: (Pheralys.®). Methods: Patients (pts) with advanced mesothelioma, either
Single-agent pembrolizumab has significant clinical activity in patients with treatment naive, or non-progressing after chemotherapy, were included.
PD-L1–positive MPM. Responses from pembrolizumab in patients with MPM Leucapheresis was performed to obtain an enriched monocyte fraction from
are durable; the 62.6% 12-month OS rate in this mostly pretreated patient which immature DC were generated which were loaded with the allogenic
population warrants further investigation. Long-term administration of lysate. The DC were matured, frozen and stored. In subsequent cohorts of

3 pts 10, 25, or 50 × 106 DC were administered IV and intradermally, 3 times SESSION OA14: NURSES IN CARE FOR LUNG CANCER
at a bi-weekly interval and after 3 and 6 months. Primary endpoint was
AND IN RESEARCH
toxicity occurring within 8 weeks after the first vaccination. Secondary
endpoints were response rate (RR), progression free survival (PFS) and TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
overall survival (OS). PFS and OS were determined from time of registration
in the trial. Immunological read-outs were performed (DTH skin testing,
peripheral blood testing). Results: Nine pts (median age 69yrs, 8 male, 1 OA14.01 ACCEPTABILITY OF AN ADVANCED PRACTICE NURSE IN
female) were included. All patients developed transient grade 1-fever and a LUNG CANCER BY HEALTH PROFESSIONALS AND PATIENTS: A
grade 1-2 injection site reaction. No dose limiting toxicities or autoimmunity QUALITATIVE EXPLORATION
signs were observed. In 2 pts (22%), both treated with 25 ×106 cells, a partial Andrea Serena, Andrew Dwyer, Manuela Eicher
response (PR) was observed, the other 7 pts had stable disease as best overall
Institute of Higher Education and Research in Healthcare, Faculty of Biology and
response. All patients are alive with a median follow up of 11.9 months after Medicine, University of Lausanne, Lausanne/Switzerland
trial inclusion(range 7.6-16.5 months). Median PFS was 8.3 months (95%
confidence interval (CI) 3.7-not yet reached), PFS at 12 months was 33% (95% Background: The advanced practice nurse in lung cancer (APNLC) has shown
CI 8%-62%). Data on immunological read outs are pending. Conclusion: DC to play a key role in meeting the complex supportive care needs of patients
immunotherapy with allogenic tumor cell lysate is safe and clinically active. with lung cancer. Nurses working in novel advanced practice nursing (APN)
Data on PFS and OS are promising and still maturing. The recommended dose roles encounter a range of barriers to effective practice particularly in
for future studies will be 25 * 106 cells based on the responses and logistic countries without an existing regulation of these novel roles. Being accepted
reasons (the number of monocytes obtained during leucapheresis to generate by patients and healthcare professionals (HCPs) is fundamental for successful
5 vaccinations). A randomized trial comparing DC therapy with Pheralys role implementation. The University Hospital of Lausanne (CHUV) was the
versus best supportive care as maintenance treatment after chemotherapy is first comprehensive cancer center in Switzerland to integrate an APNLC
planned to start in Q1 2017. into the specialized multidisciplinary team (MDT) of the thoracic cancer
center. To overcome barriers to implementing the APNLC role and promote
Keywords: vaccination, Mesothelioma, Immunotherapy, dendritic cell its long-term viability, we aimed to explore the acceptability of this novel
APNLC role from the perspective of the MDT and the patients cared for by the
APNLC. Methods: This qualitative study was part of a larger implementation
study (ClinicalTrials.gov, Number: NCT02362204). During summer 2015,
OA13: IMMUNOTHERAPY IN MALIGNANT PLEURAL MESOTHELIOMA: CURRENT STATUS we conducted focus groups and semi-structured interviews in the thoracic
OF TRIALS AND NEW APPROACHES
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 cancer center of CHUV. Participants were purposefully sampled and included
patients with lung cancer (n=4) and HCPs from the MDT [physicians (n=6),
nurses (n=5)], a social worker and the APNLC. Semi-structured individual
OA13.07 INTRAPLEURAL MODIFIED VACCINE STRAIN MEASLES interviews were conducted to examine the perspectives of patients and the
VIRUS THERAPY FOR PATIENTS WITH MALIGNANT PLEURAL APNLC alike. Focus groups were employed to gather perspectives from the
MESOTHELIOMA MDT. Data were analyzed using thematic content analysis. Results: Three
Tobias Peikert 1, Sumithra Mandrekar 1, Aaron Mansfield1, Virginia Van main themes emerged describing the acceptability of the APNLC: “role
Keulen1, Steven Albelda2, Sandra Aderca1, Stephanie Carlson1, Allen Dietz1, identification”, “role-specific contribution” and “flexible service provision”.
Mike Gustafson1, Robert Kratzke3, Val Lowe1, Fabien Maldonado4, Julian Physicians and patients identified the specific APNLC role within the MDT.
Molina5, Manish Patel3, Anja Roden1, Jin Sun2, Angelina Tan1, Maja Tippmann- In particular, they valued specific contributions to continuity of care,
Peikert1, Evanthia Galanis1 psychosocial support and self-management of symptoms. Nurses perceived
1
Mayo Clinic, Rochester/MN/United States of America, 2Medicine, University of the APNLC role as overlapping with the traditional oncology nurse role.
Pennsylvania, Philadelphia/PA/United States of America, 3University of Minnesota, They were concerned about losing part of their traditional role. Flexibility
Minneapolis/MN/United States of America, 4Pulmonary and Critical Care Medicine, in service provision was seen as strength of the APNLC role yet also posed
Vanderbilt University, Nashville, Tn/MN/United States of America, 5Mayo Clinic, organizational challenges related to the work-load. Conclusion: The new
Rochester/United States of America APNLC role appears to be well-accepted by patients and physicians. Barriers
identified during the implementation of the APNLC role were primarily related
Background: Malignant pleural mesothelioma (MM) remains an almost to intra-professional and organizational challenges. The intra-professional
universally fatal disease with limited treatment options. Preclinical models role tension could challenge effective role implementation. To maximize the
indicate the preferential oncolytic activity of the modified vaccine strain acceptability of a new APNLC role - particularly in countries that are in an
measles virus carrying the gene for the human sodium-iodine symporter (NIS) early stage of APN role development - we recommend formalizing nursing
– MV-NIS. Intraperitoneal and intravenous administration of MV-NIS was role expectations, providing appropriate support/resources and promoting a
recently found to be potentially effective in patients with refractory ovarian national plan for APN accreditation and certification.
cancer and multiple myeloma. However, whether MV-NIS is directly oncolytic
or triggers an anti-tumor immune response remains unclear. Methods: We Keywords: Lung cancer nurse, Advanced practice nursing, Multidisciplinary
conducted a phase I dose escalation study with 3+3 design and ongoing team
maximal tolerated dose (MTD) expansion cohort. MV-NIS was administered
as first or second line therapy via a tunneled intrapleural catheter to patients
with MM. MV-NIS dose ranged from 108 TICID50 to 9 x 109 TICID50. In the
absence of dose limiting toxicity and disease progression, patients received OA14: NURSES IN CARE FOR LUNG CANCER AND IN RESEARCH
up to 6 cycles of MV-NIS therapy (Phase I). Currently additional patients are TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
being randomized between a single and multiple cycles. MV-NIS infection
and replication are monitored by Iodine123 SPECT/CT (Phase I only) as well
OA14.02 NURSING AND ALLIED HEALTHCARE PRACTITIONER
as by RT-PCR and/or plaque-assay. Anti-tumor immunity is monitored in the
blood and pleural fluid and patients are followed clinically by chest CT using
DRIVEN INITIATIVE TO DEVELOP AN INTEGRATED EDUCATIONAL
the modified RECIST criteria. Results: Twelve patients (3/dose level) received AND ASSESSMENT PROGRAM FOR IMMUNOTHERAPY
MV-NIS therapy. There were no dose limiting adverse events and therapy Marianne Davies 1, Lisa Barbarotta2, Rebecca Abramovitz2, Lauren Cardone2,
was well tolerated. The best therapeutic response was stable disease, which Felicia Corolla2, Michelle Randall-Doran2, Monica Fradkin2, Stephanie
was achieved at 1 month by 8/12 evaluable patients (67%). Median overall Kulakowski2, Kelly Guttmann2, Susan Okon2, Laura Tuttle2, Emily Duffield1
survival was 449 days (95%CI: 221, 484) (~15 months) (4/12 patients remain 1
Medical Oncology, Yale Cancer Center, New Haven/CT/United States of America,
2
alive), and median progression free survival was 63 days (95% CI: 33, 174) (~2 Education, Yale New Haven Hospital, New Haven/United States of America
months). MV infection and replication were detectable by RT-PCR and plaque
assay in the pleural fluid between 24-72 hours after treatment. I123 SPECT-CT Background: Immunotherapy is rapidly becoming recognized as the fourth
demonstrated only marginal viral gene expression in a single patient treated pillar of treatment for lung cancer. As an academic center of excellence, our
with the highest dose level. MV-NIS therapy effectively boosted pre-existing staff have developed expertise with immune-oncology (I-O) agents though
anti-MV neutralizing antibody responses in the plasma and pleural fluid of clinical trials. Currently two agents (Nivolumab and Pembrolizumab) have
most patients. We observed a transient inflammatory response in the pleural been FDA-approved for the treatment of lung cancer. Variability existed in
space after MV-NIS administration. In addition, induction or boosting of patient assessment, patient education and staff education regarding how to
anti-tumor antibody responses was observed. Conclusion: The intrapleural identify and manage immune-related adverse events (IrAEs). Methods: Initial
administration of MV-NIS is safe, resulted in stable disease for 67% of evaluation consisted of an online staff survey and interviews to assess the
patients and may be associated with favorable overall survival in MM. While educational materials available for instruction of both patients and staff.
there was only transient infection and viral replication, we observed the A review of existing educational materials was conducted to determine the
induction of anti-tumor immune responses supportive of potential long-term breadth of information available as well as knowledge gaps. The evaluation
therapeutic impact. The study continues with the MTD expansion cohort. revealed a lack of standardization, with inconsistency in the educational
messages being delivered. A focused working group including CNS, APRNs,
Keywords: Measles Virus, Intrapleural therapy, Virotherapy, Mesothelioma Pharmacists and RNs from the academic hub and broader community care
center network was convened with the goal of developing educational Sarah Morgan1, Sharon Savory 2, Jeanette Draffan3, Vanessa Beattie4, Josie
platforms for nursing staff as well as patients. Bringing stakeholders together Roberts5, Diana Borthwick6, June Morley 7, Simon Bolton8, Jackie Fenemore9,
was felt to be important to increase buy-in across the spectrum of care Sarah Field10, Christine Thomas11, Patricia Rees1, Kelly Davies12, Suzanne
locations, as well as to ensure that the program was effective and appropriate Vizor 13
for all sites. Program components included the following:-Education for 1
Lung Cancer Service, Hywel Dda University Health Board, Carmarthenshire, Wales/
staff to better identify and manage IrAEs -Development of an electronic United Kingdom, 2Lung Cancer Service, University Hospitals of Leicester, Leicester/
nursing flow-sheet to standardize patient assessment and document IrAEs United Kingdom, 3Lung Cancer Service, North Tees & Hartlepool NHS Trust,
in the lung cancer population. -Automatic notification through the EMR to Hartlepool/United Kingdom, 4Lung Cancer Service, Aintree University Hospital,
alert staff in non-oncology settings regarding I-O patients. -Development Aintree/United Kingdom, 5Lung Cancer Service, Rotherham NHS Trust, Rotherham/
United Kingdom, 6Edinburgh Cancer Centre, Edinburgh/United Kingdom, 7Lung
of a forum for patient education to better understand I-O therapy and
Cancer Service, King’S Mill Hospital Nottinghamshire, Nottinghamshire/United
how to identify and manage IrAEs. - Development of lung cancer specific Kingdom, 8Harrogate & District NHS Trust, Harrogate/United Kingdom, 9 Christie
telephone triage guidelines. Results: The outcomes of implementing the I-O NHS Trust, Manchester/United Kingdom, 10 Northern General Hospital Sheffield,
program include increased patient participation in educational forums and Sheffield/United Kingdom, 11Leeds Teaching Hospitals NHS Trust, Leeds/United
improved patient satisfaction metrics. Incorporation of the I-O assessment Kingdom, 12Mid Yorkshire Hospital NHS Trust, Yorkshire/United Kingdom, 13Imperial
flow-sheet and telephone triage guidelines will improve staff competency, College Healthcare NHS Trust, London/United Kingdom
as well as standardize documentation and monitoring of IrAEs. These
metrics will allow for more accurate tracking of IrAes throughout the course Background: The United Kingdom National Lung Cancer Forum for Nurses
of treatment. Conclusion: The I-O Integrated Education and Assessment Workshop 2015 produced guidance to support Lung Cancer nurse Specialists
Program standardizes practice across all oncology care delivery sites within in developing and evaluating nurse-led clinics. Nurse-led clinics have been in
our network. This program allows patients to receive the highest level of care existence for years with little guidance on structure and evaluation. They are
at convenient regional locations closer to home, with the goal of maintaining safe and effective. Nurses provide individual care that makes a difference to
patient safety while maximizing the benefit they may receive from I-O patient outcomes. There is vast evidence available for nurse-led services but
therapies. significantly less on lung cancer specific services despite a growing body of
evidence to support this.
Keywords: Education, Allied Health, nursing, Immunotherapy
Methods: A literature search was performed. This included developing a
lung cancer nurse-led clinic, evaluation, audit tool and measurement. The
initial search found limited number of relevant documents. Therefore the
OA14: NURSES IN CARE FOR LUNG CANCER AND IN RESEARCH
search was widened to include developing general nurse-led services. The
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 NLCFN members were surveyed to evaluate current nurse-led clinics. The
questionnaire comprised of eighteen questions incorporating all aspects of
nurse-led follow up. Results: 60% responded, suggesting a high interest in
OA14.03 INTEGRATING THERAPIES INTO A SPECIALIST LUNG the area. Over half of the respondents ran nurse-led clinics. These included
CANCER NURSING TEAM: AN EVALUATION telephone, results, post-surgery, Health & Well being, TKI and breathlessness
Carol Brimacombe 1, Hannah Ball2 clinic. However 67% had not evaluated or audited these, 74% didn’t have
1
Respiratory Medicine, Churchill Hospital, Oxford/United Kingdom, 2Respiratory patient information leaflets and 96% had access to medical cover. The seven
Medicine, Churchill Hospital, Le/United Kingdom most important steps in developing a lung cancer nurse-led clinic are: Aims
and Objectives, Planning and Consultation, Multidisciplinary Support,
Background: A diagnosis of advanced lung cancer inevitably results in Infrastructure, promoting the nurse-led service, Professional Development
deterioration in both health and functional status. This threatens a person’s and Audit and Evaluation. These formed the basis of this framework.
independence and dignity and can be a burden to their family and carers. Conclusion: NICE (2011), suggests that patients should be offered a “follow-up
The lung cancer nursing team at Oxford identified a lack of timely therapy led by a LCNS” . However, nurse-led clinics are challenging and there are many
provision for their patient group and sought to improve this, concluding that practical and emotional hurdles to be overcome. This framework supports
having an occupational therapist (OT) in the team would significantly expand/ LCNS’s in developing and evaluating nurse-led clinics . It gives clear guidance
diversify the service that could be offered to patients. Lung cancer therapy to be considered when developing and new service as well as advising on
goals were identified as a) working with patients and carers to anticipate audit/evaluation tools and developing patient information leaflets.
functional need rather than waiting for a crisis to occur b) providing a rapid,
flexible and responsive service to those with existing needs and c) working Keywords: Nurse-Led Clinic Framework Evaluation
in a keyworker role outside of traditional therapy expertise supporting
patients at diagnosis, making treatment decisions and providing information
. Methods: Funding was obtained from Macmillan Cancer Support for a
three year project looking at delivering a new model of care. An Advanced OA14: NURSES IN CARE FOR LUNG CANCER AND IN RESEARCH
Therapist Practitioner (ATP) with an OT background was recruited and
embedded into the nursing team full time. Referrals were received from all
members of the lung cancer MDT, the inpatient team, primary and palliative OA14.06 THE ROLE OF A MULTI-DISCIPLINARY TEAM APPROACH
care. Interventions included home assessment, outpatient clinic review, TO EARLY REHABILITATION AND SYMPTOM MANAGEMENT IN
breathlessness and anxiety management, provision of aids, support,
THORACIC ONCOLOGY
education and advice. Results: Data was gathered from a one year period
when there were 305 new lung cancer diagnoses. 165 (54%) patients had Pippa Labuc 1, Tom Fynmore2
1
identified therapy needs. A further 40 (13%) patients were seen by the ATP Oncology, Guy’s & St Thomas’ NHS Foundation Trust, London/United Kingdom,
2
as part of her generic keyworker role. 205 referrals resulted in a total of Physiotherapy Department, Guy’s & St Thomas’ NHS Foundation Trust, London/
1005 interventions averaging 5 per person. Interventions were allocated to United Kingdom
three levels ranging from simple telephone calls and liaison to complex case Background: In the United Kingdom thoracic cancer is mainly diagnosed
management. Average time from referral to first contact with the patient was in an older population, who generally have significant co-morbidities, and
half a day. The value of the role was measured in three ways: User Feedback advanced stage disease. Due to this, they experiences high levels of disease
Event, Satisfaction Questionnaire and a Stakeholder Questionnaire. burden, both physical and psychological, impacting on individuals’ functional
Outcomes were overwhelmingly positive. Conclusion: Lung cancer patients independence and quality of life (QoL). The national governing bodies, such as
have high functional needs. An ATP can become an integral part of traditional NICE and LCA, recommend that all patients should have access to an Holistic
specialist nursing teams, is able to work in a keyworker capacity and is well Needs Assessment (HNA) and rehabilitation services. At Guy’s And St Thomas’
accepted and used by the lung cancer MDT. The ATP role provides a strong NHS Foundation Trust (GSTFT) we have developed a multi-disciplinary team
bridge between primary and secondary care environments and preserves (MDT), consisting of Dietetics, Occupational Therapy (OT) and Physiotherapy
independence and dignity for longer. Evidence from users and stakeholders (PT), who are present within the outpatient thoracic oncology clinics and
demonstrated high levels of satisfaction and quality of care. aim to address the rehabilitation and supportive care needs of all patients.
Keywords: Independence, Dignity, Occupational Therapy, Function Methods: All new thoracic oncology patients attending outpatient
consultant lead clinics at GSTFT were offered an HNA, in order to identify
their individual concerns/needs. The assessments are completed by the
MDT and individual intervention plans created. Over a three-month period,
January to March 2015, data was collected on patient’s diagnosis, treatment
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 offered, treatment intent, symptom concerns, QoL indicators, onward MDT
referrals and mortality. Results: 82 patients completed the assessments, of
these 85% reported unmet needs/concerns. The main tumour types seen were
OA14.05 A FRAMEWORK TO SUPPORT THE LUNG CANCER NURSE Adenocarcinoma, Squamous cell carcinoma, mesothelioma and small cell lung
SPECIALIST IN THE DEVELOPMENT AND EVALUATION OF NURSE- cancer. Of those reporting symptoms the most common were; breathlessness
LED CLINICS (55%), fatigue (52%), reduced appetite (43%), weight loss (41%), pain (37%),

emotions/mood (33%). sleep concerns (33%), and reduced mobility (32%). Kouzo Yamada5
69 patients had onward referrals to supportive care services. The most 1
Division of Thoracic Surgery, Department of Thoracic Oncology, National Cancer
common referrals were; OT (65%), PT (60%), Dietitian (43%), and patient Center Hospital East, Kashiwa/Japan, 2Division of Pathology, National Cancer
information (38%). 66% of patients were provided with on the spot MDT Center Hospital East, Kashiwa/Japan, 3Department of Thoracic Surgery, Kanagawa
intervention. Conclusion: Providing thoracic oncology patients access to an Cancer Center, Yokohama/Japan, 4Division of Pathology, Kanagawa Cancer Center,
MDT service on their initial oncology visit, has enabled early identification of Yokohama/Japan, 5Department of Thoracic Oncology, Kanagawa Cancer Center,
the key symptoms this patient group experience, as well as the need for allied Yokohama/Japan
health services. This has supported the role of early rehabilitation as being
Background: The objective of this study is to confirm limited resection
integral to improving patient’s level of symptom burden and QoL. Moving
efficacy as radical surgery in patients with minimally invasive lung cancer
forward it would be beneficial to do a comparative study of the symptoms
as indicated by high-resolution (HR) computed tomography (CT), and to
and intervention needs of this patient group over a longitudinal analysis,
confirm intraoperative cytology as a negative margin indicator and reliable
with the aim of showing the impact of early rehabilitation on patient’s QoL,
margin non-recurrence predictor. Methods: Enrollment required patients
survivorship, and life expectancy.
with a tumor ≤ 2 cm in diameter, diagnosed or suspected as a clinical T1N0M0
Keywords: Rehabilitation, Multi-disciplinary, symptom, supportive carcinoma in the lung periphery based on a CT scan. They had to have a HRCT
scan indicating a sub-solid nodule with tumor disappearance ratio; TDR ≥ 0.5.
(TDR = 1- DM/DL; DM: maximum tumor diameter on mediastinal settings, DL:
maximum tumor diameter on lung settings). Patients unfit for lobectomy
and systematic lymph node dissection were excluded. We performed a wedge
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 or segmental resection. The used stapling cartridges were washed with
saline, which was cytologically evaluated. If cytology was cancer positive,
additional margin was resected, and cytologic examination repeated. If
OA14.07 THE RELATIONSHIP BETWEEN LUNG CANCER STIGMA AND the second exam was positive, a routine lobectomy and systematic lymph
PATIENT REPORTED OUTCOMES node dissection was performed. We aimed at enrolling 100 patients. The
Roma Maguire1, Liane Lewis 1, John Mcphelim2, Janine Cataldo3, Robert primary endpoint is 10-year local recurrence free survival rate. Results: This
Milroy4, Kirstie Woods2, Maureen Perham4 prospective study started in November 2003, and 101 patients were enrolled
1
School of Health Sciences, University of Surrey, Glasgow/United Kingdom, in 6 years. Of them, 99 were eligible for analysis. The mean age was 62 years
2
Hairmyres Hospital, Glasgow/United Kingdom, 3Physiological Nursing, University (range: 30-75), and 60 were women. There were 11 Noguchi type A tumors, 54
of California, San Francisco, San Francisco/CA/United States of America, 4NHS type B tumors, 26 type C tumors, one type D tumor, one malignant lymphoma,
Greater Glasgow & Clyde, Glasgow/United Kingdom 3 hyperplastic lesions, and 3 inflammatory fibroses. None of the 93 malignant
nodules showed any vessel invasion. Although no positive cytology results
Background: Patients with lung cancer (LC) report lower quality of life
were obtained, pathologically positive margin was reported after surgery in
(QoL) and higher levels of psychological distress compared to other cancer
one type C patient. He later underwent a routine lobectomy and systematic
populations (Hewitt et al, 2013). Lung cancer stigma (LCS) may in part
lymph node dissection. There was no clear correlation between tumor size,
explain these findings. Evidence from studies in the Unites States has
TDR, and Noguchi subtype. No mortality occurred, but one patient developed
shown associations between LCS and lower QoL, higher symptom burden
postoperative pneumothorax and pneumonia, and another hemorrhagic
and higher levels of anxiety and depression (Cataldo et al, 2013). Whether
gastric ulcer. With a median follow-up period of 105 months (range: 72−129)
these associations exist in people diagnosed with LC in the United Kingdom
as of June 2016, there have been no recurrences, but one patient died for
is unknown. Therefore this study explored the prevalence of LCS and its
unspecified cause. Conclusion: We have repeatedly warned that delayed
relationship with patient outcomes as well as QoL in a Scottish population.
cut-end recurrence is possible following limited resection even for small
Methods: This study was a cross-sectional study. Patients (n=201) diagnosed
sub-solid lung cancers. So far, however, HRCT scans appear to predict non- or
with LC were recruited by health care professionals at follow-up clinics at
minimally invasive sub-solid lung cancers with high reliability, warranting
four hospitals in Scotland. Participants completed questionnaires to collect
limited resection as curative surgery in this cohort. Intraoperative cytology
demographic data and assess perceived LCS, QoL, symptom severity and
reliably indicated negative margins and seems to predict freedom from local
level of depression. Clinical data was collected by casenote review. Bivariate
recurrence.
correlations were performed to investigate the relationships between stigma,
demographics, and patient outcomes. Multiple regression further explored Keywords: small sub-solid lung cancer, tumor disappearance ratio, stapling
the individual contributions of LCS on symptom burden and quality of life. cartridge lavage cytology, limited resection
Results: Participants had a mean age of 69 years (range 41-89 years), 46.8%
were males, 92.0% were ever smokers, 17.9% current smokers. The mean LCS
score was 53.1 (SD=14.1, range 31-124,). There were significant correlations
between higher LCS and age (r= -0.28, p<0.001), being a current smoker (r= OA15: SUBLOBAR RESECTIONS FOR EARLY STAGE NSCLC
0.17, p<0.05), deprivation index (r=0.15, p<0.05) depression (r=0.40, p<0.001), TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
symptom burden (r=2.60, p<0.001), and QoL (r= - 0.52, p<0.001). Multiple
regression revealed an overall model that explained 30.6% of the total
OA15.02 SURVIVAL OUTCOMES IN SUBLOBAR RESECTION FOR
variance of stigma (F=14.82, p<0.001). Perceived stigma also accounted for
significant unique variance in QoL (4.3%, p<0.001) and depression (3.6%, CLINICAL T1N0M0 NON-SMALL CELL LUNG CANCER: WEDGE
p<0.001) above and beyond that accounted for by relevant variables. No RESECTION OR SEGMENTECTOMY
contribution of stigma on symptom burden was found. Conclusion: Stigma Aki Kobayashi, Renta Ishikawa, Motoshi Takao, Akira Shimamoto, Atsushi Ito,
was correlated with depression, and QoL. Therefore, it is expected that Hideto Shimpo
depression and stigma share some of the explanation of variance of QoL. Department of Thoracic & Cardiovascular Surgery, Mie University Graduate School
Nevertheless, stigma was found to have a unique contribution on QoL, and of Medicine, Tsu, Mie/Japan
on depression. With this in mind, management of patients with LC could
determine the patients’ experience of stigma to tailor treatment plans to Background: Lobectomy remains the standard treatment for early-stage
improve QoL and psychosocial outcomes. Being younger was correlated with non-small cell lung cancer (NSCLC).In practice, however, sublobar resection
higher LCS. This might reflect changed attitudes toward smoking due to has been selectively offered for patients with clinical Stage IA NSCLC as
changed marketing strategies in the 1960s. curative treatment. To seek optimal surgical procedure for early stage lung
cancer, we carried out retrospective analyses of 2122 patients who had
Keywords: Lung Cancer Stigma, patient reported outcomes, quality of life, undergone limited resection for c-T1N0M0 NSCLC from 26 institutions of
supportive care Japanese association for chest surgery. Methods: A total of 1963 patients with
lobectomy tolerance were eligible for survival analysis. We retrospectively
categorized patients of these nodules on numbers of criteria for CT findings;
scores were added according to the dominance of ground glass appearance
(GGA); >75% = 0, <75% =1, and size of tumor; T1a =0, T1b =1. Statistical analyses
SESSION OA15: SUBLOBAR RESECTIONS FOR EARLY were carried out using propensity-matching and Kaplan-Myer with log-rank
STAGE NSCLC testing. Results: We analyzed 1:1 matched 731 patients for segmentectomy
and wedge resection with propensity matching.The overall survival (OS) for
score 0 group was 90.2% in segmentectomy (n=419) and 94.7% in wedge
resection (n=451) (p=0.0351). The disease free survival (DFS) for score 0 group
was 90.2% in segmentectomy and 92.7% in wedge resection (p=0.0645). The
OA15.01 LIMITED RESECTION TRIAL FOR PULMONARY SUB-SOLID OS for score 1 group was 93.6% in segmentectomy (n=278) and 80.4% in wedge
NODULES: CASE SELECTION BASED ON HIGH RESOLUTION CT: resection (n=246)(P<0.001)(Fig. 1). The DFS for score 1 group is 94.1% in
OUTCOME AT MEDIAN FOLLOW-UP OF 105 MONTHS segmentectomy and 75.3% in wedge resection (P<0.001). The OS for scores 2
Junji Yoshida1, Genichiro Ishii2, Kanji Nagai1, Tomoyuki Hishida1, Keiju Aokage1, was 79.1% in segmentectomy (n=34) and 69.2% in wedge resection (n=34)
Masahiro Tsuboi1, Hiroyuki Ito3, Tomoyuki Yokose4, Haruhiko Nakayama3, (p=0.109). The DFS for score 2 group was 87.0% in segmentectomy and 58.1%
in wedge resection (p=0.581). 3

Kanazawa University, Kanazawa/Japan
Background: The identification of an accurate segment is essential for

successful anatomic pulmonary segmentectomy. We have previously developed
a new fluorescence technique using a PDD endoscope systemTM and vitamin
B2 for identification of pulmonary segments in animal experiments. In this
study, we applied this technique clinically to examine the efficacy and safety in
anatomical pulmonary segmentectomy and sub-segmentectomy for pulmonary
malignancies. Methods: Our technique requires two key instruments, a PDD
endoscope systemTM(KARL STORZ GmbH and Co., Tuttlingen, Germany)
as a fluorescence sensing device and vitamin B2 solution as a fluorescent
substance. 17 patients with small lung nodules were enrolled in this study.
Regarding our surgical technique, after identification of the target segmental
or sub-segmental bronchus, vitaminB2 solution is injected via the bronchus.
The target segment is identified as a fluorescent segment with the PDD
endoscope systemTM. The identified segment is resected with an electric
cautery, stapling devices, or combination of them. In case patient’s lung has
severe abnormal change such as emphysema or fibrosis, another technique
is indicated. After ligation of the target segmental or sub-segmental artery,
vitaminB2 solution is systemically administrated with intravenous injection.
The target segment is identified as a defect of fluorescence with the PDD
endoscope systemTM. Following outcomes were collected; success rate of
identifying the pulmonary segments, pathological evaluation of dissection
Conclusion: This study showed that GGA dominant T1a may be treated by margin, duration of chest drainage, and perioperative complications. Results:
wedge resection where possible. The consolidation dominant T1b did not A total of 18 procedures were performed using this technique. Performed
benefit from sublobar resection. In patients with GGA dominant T1b or segmentectomy or sub-segmentectomy were as follows; Right S1, S2, S3,
consolidation dominant T1a, anatomical segmentectomy with curative S2a+3b, S6, S9, Left S1+2, S3, S4+5, S6, S8a+9b, S9+10. Resected nodules were
intension may provide better prognosis. 14 primary lung cancers, 1 MALT-lymphoma, 1 metastatic lung cancer, and 2
benign lung nodules. Histology of primary lung cancer was adenocarcinoma
Keywords: segmentectomy, Ground Glass Appearance, sublobar resection in all 14 cases. Pathological stage of lung cancer was 12 stageIA (pT1a; 10, pT1b;
2), 1 stageIIA (pT1aN1), and 1 stageIIIA (pT1aN2). The success rate of identifying
pulmonary segments was 100%. Dissection of segmental border was performed
with only electric cautery in 12 procedures, and with both of electric cautery
OA15: SUBLOBAR RESECTIONS FOR EARLY STAGE NSCLCTUESDAY, DECEMBER 6, 2016 - and stapling device in 6 procedures. In all cases, no cancer cells were found on
16:00-17:30
the resection margin pathologically. Mean drainage time was 1.7 days (1-4 days).
Regarding perioperative complications, veno-vagal reflex was occurred after
OA15.03 COMPARISON OF PROGNOSIS BETWEEN LOBECTOMY AND systemic injection of vitaminB2 in one case, and 1 delayed pneumothorax was
SUBLOBAR RESECTION FOR CLINICAL STAGE I NON-SMALL CELL found in one case. Conclusion: Our novel fluorescence technique involving a
LUNG CANCER WITH INTERSTITIAL LUNG DISEASE PDD endoscope systemTM and vitaminB2 allowed performing accurate and safe
pulmonary segmentectomy and sub-segmentectomy.
Yasuhiro Tsutani, Takeshi Mimura, Yuichiro Kai, Masaoki Ito, Yoshinori
Handa, Norifumi Tsubokawa, Keizo Misumi, Hideaki Hanaki, Yoshihiro Miyata, Keywords: Surgery for lung cancer, Pulmonary segmentectomy, New
Morihito Okada technique
Hiroshima University, Hiroshima/Japan
Background: The prognosis after standard lobectomy for non-small cell lung
cancer (NSCLC) with interstitial lung disease (ILD) is poor. This study aimed OA15: SUBLOBAR RESECTIONS FOR EARLY STAGE NSCLC
to compare the prognosis after lobectomy and sublobar resection for early TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
NSCLC with ILD. Methods: Among 794 consecutive patients with clinical
stage I NSCLC who underwent complete resection, 107 patients with ILD on
high-resolution computed tomography (HRCT), which was defined according
OA15.06 THE EFFICACY OF LUNG VOLUME ANALYZER
to the American Thoracic Society, European Respiratory Society, Japanese FOR MEASURING RESECTION MARGIN IN PULMONARY
Respiratory Society, and Latin American Thoracic Association classification, SEGMENTECTOMY FOR MALIGNANT DISEASES
were identified. Results: Overall survival (OS) was significantly worse for Yasuo Sekine 1, Takamasa Yun2, Takahide Toyoda2, Daisuke Kaiho2, Eitetsu
patients with possible usual interstitial pneumonia (UIP) or UIP pattern Koh1, Toshiko Kamata1
than those with inconsistent with UIP pattern (3-year OS, 64.5% vs. 82.1%, 1
Department of General Thoracic Surgery, Tokyo Women’s Medical University
respectively; P = 0.031). No significant difference existed in OS between Yachiyo Medical Center, Yachiyo/Japan, 2Department of General Thoracic Surgery,
lobectomy and sublobar resection for all patients with ILD (3-year OS, 67.1% Kimitsu Central Hospital, Kisarazu/Japan
vs. 81.9%, respectively; P = 0.14). Although in patients with inconsistent
with UIP pattern, OS was similar between lobectomy and sublobar resection Background: Although the confirmation of an appropriate resection
groups (3-year OS, 81.1% vs. 83.6%, respectively; P = 0.87), OS was better for margin from the tumor is crucial for reducing the risk of local recurrence
patients who underwent sublobar resection than lobectomy in patients after lung segmentectomy for pulmonary malignancies, there has been no
with possible UIP or UIP patterns (3-year OS, 81.0% vs. 50.5%, respectively; method of measurement. We established a novel approach for performing
P = 0.069). Multivariate Cox analysis demonstrated that preoperative segmentectomy by using an infrared thoracoscopy with transbronchial
diffusing capacity of the lung for carbon monoxide (P = 0.018), not the surgical instillation of indocianine green (ICG), and improved this method by adding
procedure (P = 0.14), was an independent prognostic factor for OS. Conclusion: an advanced computer technology via lung volume analyzer for obtaining
Sublobar resection can be an alternative choice for clinical stage I NSCLC with an appropriate resection margin. Methods: Preoperatively, each patient
ILD especially for UIP or possible UIP patterns on HRCT. underwent multislice enhanced computed tomography (CT) using 320-slice
scanners for pulmonary angiography and virtual bronchoscopy, and to create
Keywords: non-small cell lung cancer, interstitial lung disease, sublobar several virtual segmentectomies by using Volume Analyzer Synapse VINCENT
resection (Fujifilm co., Tokyo, Japan). We measured the shortest distance from the
tumor to the resection margin in each simulated segmentectomy and selected
the most appropriate area of sublobar resection based on the adequate
resection margin of approximately 2 cm from the tumor. We prospectively
OA15: SUBLOBAR RESECTIONS FOR EARLY STAGE NSCLC performed segmentectomy in 17 patients and compared between simulated
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 distance and actual distance measured from the specimen. Results: The
average number of created patterns of virtual segmentectomy in each
OA15.05 ANATOMICAL PULMONARY SEGMENTECTOMY AND case was 4.1 ± 1.0. The mean distance of resection margin in selected virtual
segmentectomy was 19.3 ± 9.7 mm. On the other hand, actual shortest
SUB-SEBMENTECTOMY FOR LUNG CANCER USING THE NOVEL
distance in resected specimen was 25.4 ± 8.1 mm, which was significantly
FLUORESCENCE TECHNIQUE WITH VITAMIN B2 longer than simulated distance (p=0.027). There was no tumor recurrence
Ryuichi Waseda1, Yasuhiko Tatsuzawa2, Isao Matsumoto3, Hirofumi in all patients. Conclusion: Lung volume analyzer was an excellent tool for
Takemura3 selecting an ideal area of sublobar resection with an appropriate resection
1
Department of General Thoracic, Breast, and Pediatric Surgery, Fukuoka margin.
University, Fukuoka/Japan, 2 Saiseikai Kanazawa Hospital, Kanazawa/Japan,

Keywords: infrared thoracoscopy, indocianine green, lung cancer, virtual Patients were identified through LCC’s Medical Advisory Committee and their
segmentectomy networks, clinical trial investigators, outreach to other patient groups and
scans of LC patient/caregiver discussion boards. Results: Since 2014, LCC has
made five pCODR submissions. 91 patients and 72 caregivers participated in
the FOLC survey. The insights of an additional 62 patients and 38 caregivers
OA15: SUBLOBAR RESECTIONS FOR EARLY STAGE NSCLC with experience on the drugs under consideration were gathered qualitatively.
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 LCC’s submissions describe the emotional, practical and logistical challenges of
living with LC, and illustrate the “life impact” of the drug under consideration.
OA15.07 IS NECESSARY COMPLETION LOBECTOMY IN NSCLC (≤ - factors not traditionally included in clinical trial design. Conclusion: pCODR’s
deliberative process, partnered with LCC’s methodology, may be an effective
2CM) WITH VISCERAL PLEURAL INVASION OR LYMPHOVASCULAR
model to aid public funding discussions of new cancer drugs. pCODR and the
INVASION AFTER SUBLOBAR RESECTION?
reviewers have found patient group submissions valuable in providing lived-
Youngkyu Moon, Mi Hyoung Moon, Young Kyoon Kim, Kyo-Young Lee, Jae Kil experience insight, at times changing perspectives. LCC’s contribution has been
Park, Sook Whan Sung strongly reflected in the funding guidance reports. To supplement its process,
The Catholic University of Korea, Seoul St. Mary’S Hospital, College of Medicine, pCODR recently launched a pilot project to include clinician input in the review
Seoul/Korea, Democratic People’s Republic of process. The impact of the pilot will be assessed as data becomes available.
Background: The standard surgical treatment of stage I non-small cell lung Keywords: Regulatory-bodies, Patient-group, Public-funding, Patient-input
cancer is anatomical lobectomy. However, in some cases, small peripheral
lung cancer (≤2cm) is treated by sublobar resection. The purpose of this study
was to define the necessity of completion lobectomy when the tumor was
revealed as non-small cell lung cancer with pleural invasion or lymphovascular OA16: IMPROVING THE QUALITY OF LUNG CANCER CARE - PATIENTS PERSPECTIVE
invasion after sublobar resection. Methods: We retrospectively reviewed 271 TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
consecutive patients who underwent curative resection for stage I non–small
cell lung cancer of 2 cm or less. We analyzed clinicopathological findings and
OA16.02 SHARED DECISION MAKING (SDM) AND PATIENT
survival between two groups with either invasion-positive tumor (tumor with
visceral pleural invasion or lymphovascular invasion) or invasion-negative DECISION AIDS (PDAS) IN LUNG CANCER: SURVEY OF PATIENTS,
tumor (tumor without visceral pleural invasion and lymphovascular invasion): SIGNIFICANT OTHERS OR CAREGIVERS
sublobar resection group and lobectomy group. Results: Except for age Laurie Gaspar 1, Howard West2, Bonnie Addario3, D. Ross Camidge4
and pulmonary function, there were no differences in clinocopathological 1
Radiation Oncology, University of Colorado, Aurora/CO/United States of America,
2
characteristics between sublobar resection group and lobectomy group with Swedish Cancer Institute, Seattle/WA/United States of America, 3Founder/
invasion-positive tumor or invasion-negative tumor. There was no difference chair, Bonnie J. Addario Lung Cancer Foundation, San Carlos/CA/United States of
in the 5-year recurrence-free survival rate between two groups in the invasion- America, 4 Medical Oncology, Univ Colorado, Aurora/CO/United States of America
positive tumor and invasion-negative tumor (78.9% vs 79.8%; p=0.928, 80.2%
vs 85.4%; p=0.505). In the multivariate analysis, only number of dissected
lymph nodes was a significant recurrence-related factor of stage I invasive- This abstract is under embargo until December 4, 2016 at 07:00 CET.
positive non-small cell lung cancer (hazard ratio 0.914, 95% confidence
interval 0.845-0.988, p=0.023). Sublobar resection was not a risk factor for
recurrence. Conclusion: The survival between sublobar resection group and
lobectomy group in small (≤2cm) non-small cell lung cancer with visceral OA16: IMPROVING THE QUALITY OF LUNG CANCER CARE - PATIENTS PERSPECTIVE
pleural invasion or lymphovascular invasion were not different. Completion TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
lobectomy is not necessary in small lung cancer after sublobar resection
whether the tumor has visceral pleural invasion or lymphovascular invasion. OA16.03 THE ALCF CENTERS OF EXCELLENCE MODEL DELIVERS A
Keywords: visceral pleural invasion, lymphovascular invasion, non-small cell STANDARD OF CARE TO THE COMMUNITY SIMILAR TO ACADEMIC
lung cancer, sublobar resection AND RESEARCH CENTERS
Leah Fine1, Guneet Walia1, Raymond Osarogiagbon2
1
Addario Lung Cancer Foundation, San Carlos/United States of America,
2
Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis/
TN/United States of America
SESSION OA16: IMPROVING THE QUALITY OF LUNG
CANCER CARE - PATIENTS PERSPECTIVE This abstract is under embargo until December 4, 2016 at 07:00 CET.
OA16.01 THE ROLE OF PATIENT GROUPS IN INTEGRATING THE OA16: IMPROVING THE QUALITY OF LUNG CANCER CARE - PATIENTS PERSPECTIVE
PATIENT VOICE INTO DRUG FUNDING DECISIONS
Christina Sit 1, Helen Mai2, Alexandra Chambers3, Paul Wheatley-Price4
1
Lung Cancer Canada, Toronto/ON/Canada, 2CADTH – Pan-Canadian Oncology OA16.05 SOCIOECONOMIC DETERMINANTS OF LATE DIAGNOSIS OF
Drug Review (Pcodr), Toronto/ON/Canada, 3CADTH – Pan-Canadian Oncology Drug LUNG CANCER IN FRANCE: A NATIONWIDE STUDY (THE TERRITOIRE
Review (Pcodr), Toronto/Canada, 4 Medical Oncology, The Ottawa Hospital Cancer STUDY)
Centre, University of Ottawa, Ottawa/ON/Canada
Pierre Jean Souquet 1, Isabelle Durand-Zaleski2, Christos Chouaid3, Didier
Background: The recent emergence of multiple new targeted therapies and Debieuvre4, Arnaud Scherpereel5, Jérôme Fernandes6, Virginie Westeel7, Cécile
immunotherapy drugs has significantly increased options in the systemic Blein8, Anne-Françoise Gaudin9, Soline Leblanc8, Hervé Lemasson10, Nicolas
treatment of lung cancer (LC). While great news for patients, in the current Ozan10, François-Emery Cotté9, Pierre Chauvin11
1
environment of scarce health care resources, government agencies deliberating Department of Chest Medicine, Lyon Sud Hospital - Civils Hospices, Lyon/France,
2
on public funding of cancer drugs struggle with ensuring sustainability Department of Public Health, Henri-Mondor Hospital, Urceco Île-De-France,
of the public health system due to increasingly expensive drug costs. In Hôtel-Dieu Hospital, Paris - Créteil/France, 3Department of Chest Medicine, Créteil
Hospital (Chi), Créteil/France, 4Department of Chest Medicine, Emile Muller
Canada, the Pan-Canadian Oncology Drug Review (pCODR), a program
Hospital, Mulhouse/France, 5Pulmonary and Thoracic Oncology, Albert Calmette
of the Canadian Agency for Drugs and Technologies in Health (CADTH),
Hospital, Lille/France, 6Oc Santé Group, Montpellier/France, 7Department of Chest
provides recommendations that informs public funding decisions for cancer Medicine, Jean-Minjoz Hospital, Besançon/France, 8Heva, Lyon/France, 9Heor,
drugs. pCODR’s recommendations apply an evidence-based deliberative Bristol-Myers Squibb, Rueil-Malmaison/France, 10 Bristol-Myers Squibb, Rueil-
framework which considers the drugs clinical benefit, patient-based values, Malmaison/France, 11Department of Social Epidemiology, Sorbonne University,
cost-effectiveness and adoption feasibility. As part of the pCODR review, UPMC University Paris 06, Inserm, Institut Pierre Louis D’Epidémiologie Et de Santé
patient input is integrated into the clinical and economic reports and Publique (Iplesp Umrs 1136), Paris/France
recommendations. Patient groups, such as Lung Cancer Canada (LCC), can
Background: Socioeconomic disparities in survival of patients with lung cancer
play a pivotal role by synthesizing the evidence gathered from patients and
have been identified in many countries. The aim of this study was to examine
caregivers to inform the pCODR process. Methods: Both quantitative and
determinants of late diagnosis of lung cancer in France. Methods: All patients
qualitative techniques were used to gather data for LCC’s pCODR submissions.
with a first diagnosis of lung cancer in 2011 in the National hospitals databases
A national survey – the Faces of Lung Cancer (FOLC) - illustrated the perceptions
were included. Information on gender, age, presence of metastasis at diagnosis
and general unmet needs of those living with LC. Focus groups, one-on-one
and any significant chronic comorbidities (hypertension, diabetes mellitus,
interviews and audits of patient discussion boards gathered the insights of
renal insufficiency, and other chronic lung diseases) was retrieved. Based on
patients and caregivers with experience on the drug under consideration.
municipality of residence, patients were classified by population density, social Keywords: biopsy, advocacy, patient preference, Targeted therapy
deprivation, access to general practitioners and pulmonologists. Results: We
identified 41,015 patients newly diagnosed for lung cancer in French hospitals.
Mean age at diagnosis was 66.4 (±11.9) years and 72% patients were men. 53%
(N=21,613) patients were metastatic at the time of diagnosis. This rate was OA16: IMPROVING THE QUALITY OF LUNG CANCER CARE - PATIENTS PERSPECTIVE
higher for patients in public compared to private hospitals (56.1% vs 42.9%, TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
p<0.0001) and in community compared to university hospitals (60.2% vs
49.6%, p<0.0001). Multivariate analysis found that metastases at the time OA16.07 PATIENT-DRIVEN EPIDEMIOLOGIC ASSESSMENT OF ROS1-
of diagnosis were significantly associated with a younger age (55 years or
FUSION DRIVEN CANCERS
less, OR: 1.22 [95%CI:1.16–1.29]; p<0.0001), a low access to pulmonologists
(OR: 1.13 [95%CI:1.04–1.23]; p=0.004), a rural or semi-rural dwelling (OR: 1.07 Guneet Walia1, Ros1 Patients1, Bonnie Addario2, Manali Patel3
1
[95%CI:1.02–1.13]; p=0.004) and deprived areas (OR: 1.06 [95%CI:1.01–1.11]; Research and Medical Affairs, Bonnie J. Addario Lung Cancer Foundation, San
p=0.01). Of the 8,413 patients (20%) who were initially admitted through Carlos/CA/United States of America, 2Founder/chair, Bonnie J. Addario Lung
Cancer Foundation, San Carlos/CA/United States of America, 3School of Medicine,
emergency room (ER) 68.1% had metastatic tumors. Multivariate analysis
Stanford University, Stanford/CA/United States of America
showed significantly higher rate of admission through ER at diagnosis in
patients from most deprived areas (OR: 1.44 [95%CI:1.37–1.52]; p0.0001), Background: There are limited data on factors that contribute to the
rural or semi-rural (OR: 1.25 [95%CI:1.19–1.32]; p<0.0001), with a low access to development of ROS1-fusion positive cancers. A group of ROS1+ patients
pulmonologists and general practitioners (OR: 1.24 [95%CI:1.17–1.30]; p<0.0001 approached the Bonnie J. Addario Lung Cancer Foundation (ALCF) for support
and 1.15 [95%CI:1.08–1.23]; p<0.0001, respectively). Gender (male) and presence of ROS1 research. As a first step in this unique, patient-driven effort, we
of comorbidities were also significant determinants of metastatic disease and designed a survey to understand epidemiologic/clinical factors that may
admission through ER at diagnosis. Conclusion: A majority of French patients contribute to the development and progression of ROS1 cancers. We aim
with lung cancer were initially metastatic at the time of diagnosis and 1 out of to collect data with biospecimens and make these available through an
5 were diagnosed following admission through ER. Residential socioeconomic open-access data-sharing platform to accelerate ROS1 research. Methods:
indicators and access to general practitioners and pulmonologists were With guidance from ROS1 patients, we designed a 204-question survey,
significantly associated with these indicators of poor outcome. obtained Stanford University IRB approval. The survey on the ALCF website
from May 18, 2016, was widely publicized through conferences, patient
Keywords: diagnosis, inequality, epidemiology, deprivation
support networks, social media and community-based outreach. The survey
questions address demographic-, clinical-, diagnostic and treatment- factors,
family and reproductive history, dietary, exercise, environmental exposure
and hormone and substance use. We used Z-proportions test for statistical
OA16: IMPROVING THE QUALITY OF LUNG CANCER CARE - PATIENTS PERSPECTIVE
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 significance defined as p<0.05. Results: In 53 days, 95 global patients with
ROS1-fusion+ cancer responded to the survey (median age at diagnosis 56
years). Respondents were 71% female (n=52/73), 79% never smokers (49/62).
OA16.06 WILLINGNESS FOR MULTIPLE BIOPSIES TO IMPROVE 71% respondents were otherwise healthy before diagnosis (n=46/65). The
QUALITY OF LUNG CANCER CARE: UNDERSTANDING THE PATIENT majority of respondents were diagnosed with lung cancer (n=68/72); and one
PERSPECTIVE each with gastric, ovarian, cervical and liver cancer. 76% reported metastatic
Upal Basu Roy 1, Susan Mantel2, Margery Jacobson1, Andrea Ferris2 disease (n=52/68) at diagnosis with the most common site of metastases
1 as contralateral lung (65%) and bone (46%). 52% patients reported their
Research and Policy, Lungevity Foundation, Bethesda/MD/United States of
America, 2Lungevity Foundation, Bethesda/MD/United States of America ROS1 cancers were not detected at diagnosis (n=35/67); 80% didnot know
their specific translocation (51/64). 71% patients received molecular
Background: In this era of precision medicine, biomarker testing of cancer testing on physicians’ orders (n=45/63), with 21% self-initiating molecular
tissue is sometimes necessary to match the right patient to the right testing. Despite the availability of targeted treatments and clinical trials,
treatment. A patient might need multiple biopsies if there is recurrence of lung most patients were prescribed chemotherapy in their first (62%), second
cancer, or to determine eligibility for a new drug or participation in a clinical (49%), third (60%) and further lines of therapy. 76% patients reported that
trial. Anecdotal evidence suggests that physicians are unwilling to recommend crizotinib was the therapy that worked best, with 96% reporting significant
additional biopsies because they assume that the patients are likely to refuse. improvement in symptoms and QoL. We found no significant correlations
Methods: To understand this patient-physician communications gap, we asked between oral contraceptive/hormone/anabolic steroid use, occupational
340 lung cancer survivors through an online survey about their willingness to exposure, geographic area of employment/residence, family history of cancer,
undergo additional biopsies. The survey was fielded through various social and incidence of ROS1+ cancer. Conclusion: This is a unique patient and non-
media platforms as well as through an independent research panel. Results: profit advocacy group-driven investigation that seeks to understand factors
Three-quarters of the survivors surveyed indicated their willingness to that may influence development and treatment of ROS1 cancers. The results
have an additional biopsy, regardless of whether they reported any pain or highlight patient-centricity, the importance of upfront molecular testing
complications from their initial biopsy. Specifically, among the survivors who and targeted therapies. We report patient-reported experiences with ROS1
were willing to undergo an additional biopsy: testing and durable responses to targeted treatments e.g. crizotinib. As the
study is ongoing, we will update results in December 2016.
Almost all of the survivors (82%) would do so if it would help their health care
team better match treatment to their specific cancer and personalize their Keywords: molecular testing, patient-driven research, epidemiological study,
care, versus just being told the test was to look for mutations. In other words, ROS1+ cancer
understanding the end benefit of having the test is an important piece of
communication.
Although almost 50% reported pain or complications from their initial biopsy,
this group indicated equal willingness to have another biopsy as those without
any issues. SESSION OA17: ASPECTS OF HEALTH POLICIES
AND PUBLIC HEALTH
If the doctor were to recommend an additional biopsy or a biopsy after the
start of treatment, nearly half would definitely undergo one. About two-thirds
of the survivors felt that their doctor explained the reason for getting their
initial biopsy really well.
OA17.01 ESTIMATE OF ECONOMIC IMPACT OF IMMUNE
Conclusion: The study reinforces the importance of a patient-centric model in CHECKPOINT INHIBITORS FOR NSCLC RELATIVE TO PD-L1
medicine–in which meaningful and timely information is provided to patients EXPRESSION IN THE US
to enable them to be partners in their own care. The study has the following
Pedro Aguiar Jr 1, Ramon De Mello2, Hakaru Tadokoro1, Hani Babiker3, Barbara
implications for different stakeholders:
Gutierres4, Gilberto Lopes5
1
Patients: To ask their doctor about new treatments and discuss the need for Universidade Federal de SÃo Paulo, SÃo Paulo/Brazil, 2Universidade Do
additional biopsies if necessary. Understanding the end benefit of having the Algarve, Faro/Portugal, 3Honor Health, Scottsdale/AZ/United States of America,
4
test is an important piece of communication. Universidade Paulista, SÃo Paulo/Brazil, 5Centro Paulista de Oncologia and
Oncoclinicas Group, SÃo Paulo/Brazil
Patient Advocacy Organizations: To educate patients and physicians about
Background: Delivering high-quality cancer care at an affordable cost
having an open dialogue to help patients become equal partners in their
is the main challenge for health care professionals and policy makers.
treatment decision-making.
Immunotherapy achieved encouraging results in NSCLC. PD-L1 expression
Physicians: To discuss the benefits and the risks of an additional biopsy with is being studied as a predictive biomarker. The objective of our study is to
their patients and how it may help decide course of treatment. assess the economical impact of NIVO and PEMBRO with and without the

use of PD-L1 as a biomarker in the US. Methods: We developed a decision- 40-74 yr-olds having 20 and 30 pk-yr histories result in $92,147 and 74,978/
analytic model to determine the cost-effectiveness of PD-L1 assessment QALY respectively. In all cases of OPP compared to ORG with cessation there
and second-line treatment with NIVO or PEMBRO versus docetaxel. The are net losses of QALY. Notably, ORG with smoking cessation compared to
model used outcomes data from RCTs and costs from the US. We included ORG without yields an ICER of $2800/QALY. Conclusion: OPP screening results
the costs of adverse events and post-progression therapies. Thereafter, we in more incident cases and fewer deaths but more cost from over-diagnosis
used American epidemiology data to estimate the impact of the treatment. and false positives. In Canada, an annual screening program with strict
Results: We included three RCTs (two with NIVO and one with PEMBRO). The adherence to NLST entry criteria could be highly cost-effective. Jurisdictions
estimated number of cases eligible was 37,638. Treating all patients with will have to weigh the benefits and risks of LDCT scanning beyond the
NIVOLUMAB would cost 1.6 billion dollars each year, increasing total oncology currently available evidence.
drug expenditure in the US by 4%. Treating only patients with PD-L1 > 1% with
NIVOLUMAB would cost US$ 850 million each year and would increase total Keywords: screening, organized, opportunistic, cost
oncology drug expenditure by 2%. However, with such patient selection up to
46% of cases would not be treated and 2,509 fewer life-years would be saved.
The cost of each year-of-life saved was improved by PD-L1 selection (from US$
223,000 to US$ 186,000 thousand). Table 1 summarizes our findings. Results OA17: ASPECTS OF HEALTH POLICIES AND PUBLIC HEALTH
were similar with NIVOLUMAB and PEMBROLIZUMAB.
Impact OA17.03 INSURANCE TYPE INFLUENCES STAGE, TREATMENT, AND

Years on Total SURVIVAL IN ASIAN AMERICAN LUNG CANCER PATIENTS
Life- Total
QALY ICER of life Not Cancer Cost/LYS
Scenario Years % Cost Apichat Tantraworasin1, Emanuela Taioli2, Bian Liu2, Andrew Kaufman1, Raja
gain U$ not Treated Drug U$
Saved U$ Flores1
saved Expendi-
ture 1
Thoracic Surgery, ICAHN Medical School at Mount Sinai, New York/NY/United
37,638 100 States of America, 2Population Health Science and Policy, ICAHN School of
Medicine at Mount Sinai, New York/United States of America
NIVO ALL
0.148 124K 7,043 0 0 0 1.6 bi 4% 223K
COMERS Background: Effect of insurance type on lung cancer diagnosis, treatment and
NIVO PD- 850 survival is still under debate in Asian patients living in United States.
0.201 91K 4,534 2,509 17,389 46 2% 186K
L1 > 1% mi Methods: A total of 447,167 patients (18 to 113 years), diagnosed with lung
PEMBRO cancer between 2004 and 2013 in the Surveillance, Epidemiology, and End
971
PD-L1 > 0.138 116K 5,302 NA 12,685 34 2% 183K Results database were analyzed. Patient demographics and clinical
mi
1% characteristics were compared between Asian and Non-Asian patients. In
NIVO ALL Asian patients, patient demographics and characteristics were compared
SQ/>1% 0.216 93K 5,868 1,175 13,303 35 1 bi 3% 178K among insurance types. Multivariable logistic regression analysis was
NSQ performed to identify the effect of insurance types on stage at diagnosis and
PEMBRO treatment modalities. Multivariable cox’s regression analysis was performed
420
PD-L1 > 0.164 97K 2,270 NA 26,912 72 1% 184K to identify the effect of insurance type on cancer-specific death. Results:
mi
50% Asian were significantly more frequently males (56.7% vs. 53.1%), married
Conclusion: The use of PD-L1 expression as a biomarker for treatment with (62.2% vs. 50.2%), with Medicaid (17.4% vs. 8.7%), living in rural area (93.6%
immunotherapy decreases the overall economic impact and the cost per life- vs. 86.9%), in a low income county (26.3% vs. 13.4%), and stage 4 at time of
year saved. Nevertheless, the number of life-years saved with this strategy diagnosis (51.1% vs. 48.0%) than non-Asian patients (all p-value < 0.001).
would be significantly smaller than if we choose to treat all patients. Further Among 26,884 Asian lung cancer patients, uninsured were significant younger
study and societal discussion is warranted in order to find the optimal (61.1±10.8 years) than non-Medicaid (69.1±11.9 years) and Medicaid (70.7±11.7
strategy for patient selection. years), p <0.001, more likely single (18.9 % vs. 8.8% vs. 13.0%); living in a high
income county (41.8% vs. 30.5% vs. 38.6%); more likely to be stage IV (63.7%
Keywords: biomarker, Immunotherapy, Cost of Care, Access vs. 50.0% vs. 51.2%); and not undergo surgery (86.2% vs. 75.4% vs. 82.6%), [all
p-value < 0.001). Localized disease was more frequent in non-Medicaid (21.2%)
and Medicaid (17.3%) compared to uninsured (9.0), (p < 0.001).At multivariable
analyses, insurance type was not associated with cancer-directed surgery and
OA17: ASPECTS OF HEALTH POLICIES AND PUBLIC HEALTH radiotherapy. Insurance was significantly associated with cancer-specific
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 death (uninsured HR 1.37 95%CI 1.07-1.75; non-Medicaid HR 1.17 95% CI
1.07-1.28 vs Medicaid).
OA17.02 POTENTIAL HEALTH AND ECONOMIC CONSEQUENCES OF
ORGANIZED VS OPPORTUNISTIC LUNG CANCER SCREENING IN
CANADA
William Evans 1, Cindy Gauvreau2, Saima Memon2, John Goffin3, Jason
Lacombe2, Michael Wolfson4, Natalie Fitzgerald2, Anthony Miller5
1
Cancer Care Ontario, Toronto/ON/Canada, 2Canadian Partnership Against Cancer,
Toronto/ON/Canada, 3Oncology, Juravinski Cancer Centre, Hamilton/ON/Canada,
4
Populemics, University of Ottawa, Ottawa/ON/Canada, 5Public Health, University
of Toronto, Toronto/ON/Canada
Background: Annual LDCT screening for individuals 55-74 yrs with >30 pack-
year smoking history is supported by evidence from the NLST but has led
to questions of implementation. Compared to organized screening (ORG),
opportunistic screening (OPP) may utilize broader entry criteria and not
include smoking cessation. Methods: Health and economic impacts of ORG
using NLST entry criteria were modelled using population microsimulation
(OncSim – formerly Canadian Risk Management Model v 2.3) and compared to
OPP scenarios. We modeled ORG at a participation rate of 30 and 60%, with
and without smoking cessation, compared to various plausible OPP scenarios:
younger individuals (40-74 yrs); lesser smoking histories (10 or 20 pack-yrs).
Outcomes projected to 20 years included incidence, mortality, number of
Conclusion: Insurance type affects stage at diagnosis and cancer-specific
scans, invasive diagnostics for false positives, and screening and treatment
death but not surgical treatment and radiotherapy in Asian lung cancer
costs. A lifetime horizon and 3% discounting were used to estimate the
patients.
incremental cost-effectiveness ratio (ICER) from a health system perspective.
All costs are in 2016 CAD. Results: A large number of outputs can be presented. Keywords: Disparities, race, cancer-specific death, insurance
At a participation rate of 30%, average annual incremental incident cases of
lung cancer with OPP for 40-74 yr-olds with 10 pack-yr histories are higher by
254 over ORG without cessation, and there would be an average 135 fewer
deaths annually. However, the annual number of CT scans would increase OA17: ASPECTS OF HEALTH POLICIES AND PUBLIC HEALTH
by 433,000 on average and diagnostic tests for false positive results would TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
increase by 1540. Average annual costs would increase by $141 M compared
with ORG without cessation, resulting in an ICER of $133,000/QALY. OPP with OA17.05 SURVIVAL IN A COHORT OF PATIENTS WITH LUNG CANCER:
THE ROLE OF AGE AND GENDER ON PROGNOSIS Administration I n 1976 followed by the comprehensive interventions including
Juliana Franceschini, Sérgio Jamnik, Ilka Santoro smoke-free areas by the royal Thai government in 1991. As a result, the smoking
prevalence went down to 32 percent in Thailand but this still demonstrated
Universidade Federal de SÃo Paulo, SÃo Paulo/Brazil
that one in three adults in 1991. It was found that the role of government and
Background: Lung cancer has a high incidence in Brazil; approximately different civil society organizations in implementing smoke free policies was
thirty-four thousand new cases are diagnosed each year. In Brazil, as in other significant in both countries in this review paper. Although both countries
countries, the majority of patients diagnosed with lung cancer are elderly. issued smoke free policies, there are still challenges on implementation. Iceland
There are few studies that evaluate demographic and clinical characteristics, try to overcome the challenges by developing comprehensive system including
disease staging, treatment modalities and survival in young patients, mostly investigation after complaint and allocating budget for enforcement. Thailand
carried out in developed countries. This study aimed to describe these aspects also implemented 100% Smoke-Free Hospitals with the compliance rate of
in patients with non-small cell lung cancer (NSCLC) according to age. Methods: 86.4 percent according to a research in 2010. Thailand established the Thai
Retrospective cohort consisted of patients diagnosed with NSCLC followed Health Promotion Foundation (ThaiHealth) in 2001 which allowed Thailand
in a referral hospital in SÃo Paulo. During the monitoring the survival time to implement comprehensive tobacco control measures in a sustainable way.
was evaluated. Survival functions were calculated using the method of ThaiHealth used knowledge generation, social mobilization and policy advocacy
Kaplan-Meier. The survival stratified by age was also obtained, according to called tri-power strategy in achieving the success. Conclusion: This paper
distribution of percentages (less than 55; between 55 and 72 years; older than concluded that civil society initiative and continuing efforts on tobacco control
72 years). Differences between survival curves were determined using the log- which leads to adoption of comprehensive tobacco control law is the heart of
rank test. Results: From January 2000 to July 2015 790 patients were followed, the success of tobacco control in both countries.
165 aged less than 55 years, 423 between 55 and 72 years and 202 older than
Keywords: smoke free, policy advocacy, role of government in civil society,
72 years. Higher incidence of adenocarcinoma was seen at the groups up
comprehensive tobacco control law
to 72 years. 575 (73%) patients with advanced disease (IIIB-IV stages) were
observed. The median five-year survival was 12 months [46-4]. The survival of
patients in different age groups was not different.
OA17: ASPECTS OF HEALTH POLICIES AND PUBLIC HEALTH
<55 165 >55<72 423 >72 202 p TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
Male n(%) 87 (53) 279 (66) 127 (63) 0.012*

Smoke n(%) 136 (82) 363 (86) 165 (82) 0.34* OA17.07 TIME FROM THE IDENTIFICATION OF A SUSPICIOUS
Male 78 (90) 263 (94) 121 (95) 0.21* PULMONARY LESION TO THE TREATMENT OF NON-SMALL CELL
Female 58 (74) 100 (69) 44 (59) 0.10*
LUNG CANCER
Claire Hiles 1, Paul Hiles2, Michael Osswald1
Histological type
0.13* 1
Dept Hematology/oncology, San Antonio Military Medical Center, Jbsa Ft Sam
n(%)
Houston/TX/United States of America, 2Dept Pulmonary & Critical Care Services,
Adenocarcinoma 92 (56) 216 (51) 91 (45) San Antonio Military Medical Center, Jbsa Ft Sam Houston/TX/United States of
America
Squamous Cell
52 (32) 170 (40) 91 (45)
Carcinoma Background: Despite guideline recommendations on time intervals in the
Staging n(%) 0.057* care of a lung cancer patient, delays are often experienced. The goal of this
study was to quantify time intervals and identify delays in the workup to
IA/IIIA 34 (21) 127 (30) 52 (26) treatment of non-small cell lung cancer (NSCLC) at our institution. Methods:
IIIB/IV 131 (79) 294 (70) 150 (74) A retrospective review of all NSCLC cases in the Tumor Registry at a tertiary
military medical center diagnosed and treated between July 2011 and July
Deaths n (%) 83 (50) 232 (55) 105 (52) 0.56* 2014 was performed. Dates of radiographic identification of a suspicious
Follow-up (months) 4.4 [1.4- pulmonary lesion, tissue diagnosis, evaluation by the treating specialist,
4.9 [1.3-13.2] 6.5 [2.0-16.3] 0.07†
Median[IIQ] 12.9] and initial treatment (whether surgery, radiation, chemotherapy, or best
supportive care/palliative care) were recorded. Time intervals were calculated
*Chi-square test; † Kruskal-Wallis (Duncan test); ‡oneway ANOVA (Bonferroni from these dates; if any interval was more than 60 days, reasons for delays
test). Conclusion: In the age group of younger patients (<55) women were recorded. Results: The median time from the identification of a
predominated, histological type adenocarcinoma was more frequent, and suspicious pulmonary lesion to the treatment of NSCLC was 74 days (range
there were more patients with advanced stage at the diagnosis and a higher 5-557 days) and the median time from tissue diagnosis to first treatment was
percentage of smokers in both genders. 33 days (range 1-252 days) for the 148 patients included in the analysis. Even
after excluding outliers, the adjusted median time from the identification
Keywords: lung cancer, age, survival
of a suspicious pulmonary lesion to the treatment was 71 days. The most
common reasons for treatment delay were waiting for consultant evaluations,
staging procedures, repeat biopsies, or additional studies (pre-operative risk
stratification, molecular testing). Only 1 patient was upstaged from time of
OA17: ASPECTS OF HEALTH POLICIES AND PUBLIC HEALTH
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 tissue diagnosis to first treatment (from IA to IIB following resection).
Table 1: Critical time intervals

OA17.06 MAKE THE WORLD BEAUTIFUL AND HEALTHY BY MAKING
Time interval Median Range
YOUR COUNTRY SMOKE FREE: CASE STUDY BETWEEN ICELAND
AND THAILAND? Days from suspicious imaging study to first
74 5-557
treatment
May Cho
Days from suspicious imaging study to tissue
Tobacco Control, Southeast Asia Tobacco Control Alliance, Bangkok/Thailand 34 1-556
diagnosis
Background: Globally, 600,000 non-smokers die due to tobacco related diseases Days from suspicious imaging study to evaluation by
50 1-553
and health care cost for tobacco related diseases are soaring especially in treating specialist
developing countries.Cigarette smoke contains 69 known carcinogens out Days from tissue diagnosis to first treatment 33 1-252
of 7000 chemicals causing various health problems in children and infants
Days from tissue diagnosis to evaluation by treating 1-157 10-
including ear infections, bronchitis, pneumonia, frequent and severe asthma 20 21 21
specialist Cardiothoracic surgery Radiation- 56 1-157
attacks, sudden infant death syndrome and cancer. Secondhand smoke can 18 15
oncology Medical-oncology Palliative care 1-64 4-48
cause coronary heart disease, stroke and various kinds of cancer including lung
cancer in adult. 2006 U.S. Surgeon General Report clearly confirmed that there Days from evaluation by treating specialist to first 1-261
16 23 14
is no safe level of exposure to secondhand smoke. Therefore, there is a strong treatment Surgery Radiation Chemotherapy Best 6-261 1-88
16 1
need for comprehensive smoke free law in reducing the burden of tobacco supportive care 1-28 1-28
use in the world. Methods: “Section not applicable” Results: Iceland is a high
Conclusion: Several time intervals identified in the workup to initial
income country with a long history of tobacco control. The comprehensive
treatment of NSCLC patients at our institution exceeded recommendations
tobacco control law was passed in 1984 which included restriction on smoking
from various guidelines. These delays could be addressed with process and
in service areas of public and private buildings, premises of health care
quality improvement projects involving a standardized NSCLC clinical care
facilities, schools, workplaces, and in public transport whereas Thailand is
pathway.
an upper middle income country and once had a very high smoking rate (70
percent for male and around 5 percent for female) in early 1970. Smoking ban Keywords: treatment delay, time interval, non-small cell lung cancer
in movie theaters and buses ordinance was issued by Bangkok Metropolitan

Background: Sunitinib is active in patients with recurrent thymic carcinoma

ORAL ABSTRACT SESSIONS - (TC). We have previously reported an objective response rate of 26%
WEDNESDAY, DECEMBER 7, 2016 and disease control rate (partial response and stable disease) of 91% in
patients with TC when sunitinib is administered at a dose of 50 mg once
daily for 4 weeks followed by 2 weeks off (4/2 dosing schedule). Grade 3 or
SESSIONS OA18: NEW INSIGHTS IN THE TREATMENT OF 4 treatment-related adverse events (TEAEs) occurring in more than 10%
THYMIC MALIGNANCIES of patients included fatigue, oral mucositis and lymphocytopenia (20%
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 each), and hypertension (13%). Grade 3 decrease in left ventricular ejection
fraction (LVEF) was observed in 8% of patients. Alternative dosing schedules
have been evaluated in solid tumors to improve tolerability. As part of an
OA18.01 POSTOPERATIVE RADIOTHERAPY IN THYMIC EPITHELIAL ongoing phase II study (NCT01621568), we evaluated the clinical activity and
TUMORS: INSIGHTS FROM THE RYTHMIC PROSPECTIVE COHORT tolerability of sunitinib in patients with TC using a 2-weeks-on/1-week-off
(2/1) dosing regimen. Methods: Patients with progressive TC after at least
Clémence Basse 1, Sébastien Thureau1, Suzanna Bota2, Eric Dansin3, Pascal
one prior platinum-containing chemotherapy regimen, measurable disease,
Alexandre Thomas4, Eric Pichon5, Hervé Léna6, Carole Massabeau7, Christelle
and adequate end organ function were enrolled and received sunitinib at a
Clément-Duchêne8, Gilbert Massard9, Virginie Westeel10, François Thillays11,
dose of 50 mg orally once daily using a 2/1 schedule until disease progression
Xavier Quantin12, Youssef Oulkhouir 13, Serge Danhier 14, Delphine Lerouge14,
or development of intolerable adverse events. The primary objective was
Luc Thiberville2, Benjamin Besse15, Nicolas Girard16
1
evaluation of response rate. Tumor assessments were performed every 6
Cancer Center, Rouen/France, 2University Hospital, Rouen/France, 3Cancer weeks using RECIST version 1.1 and toxicity was assessed every 3 weeks using
Center, Lille/France, 4University Hospital, Marseille/France, 5University Hospital,
CTCAE version 4.0. Exploratory correlative studies including evaluation
Tours/France, 6University Hospital, Rennes/France, 7University Cancer Center,
Toulouse/France, 8 Cancer Center, Nancy/France, 9University Hospital, Strasbourg/ of immune cell subsets will be reported separately. Results: Between July
France, 10University Hospital, Besançon/France, 11Cancer Center, Nantes/France, 8, 2014 and January 14, 2016, 15 patients were enrolled. Median age was
12
University Hospital, Montpellier/France, 13University Hospital, Caen/France, 62 years (range, 41-76), and 33% were male. A median of 4 (range, 1 – 33+)
14
Cancer Center, Caen/France, 15Department of Cancer Medicine, Gustave Roussy, cycles of sunitinib was administered. Among 13 evaluable patients, there
Villejuif/France, 16Thoracic Oncology, Hospices Civils de Lyon, Lyon/France was 1 (8%) partial response, 11 (85%) stable disease and 1 (8%) progressive
disease. After a median follow-up of 16 months, the median progression-free
Background: Thymic Epithelial Tumors (TET) are rare intrathoracic survival was 5 months and median overall survival was 16 months. Grade 3 or
malignancies, for which surgery represents the mainstay of the treatment 4 TEAEs occurring in more than 10% of patients included lymphocytopenia
strategy. Current practice for postoperative mediastinal radiotherapy is highly (40%), neutropenia and leucopenia (20% each), thrombocytopenia and oral
variable, and there is paucity of prospective, multicentre evidence. RYTHMIC mucositis (13% each). Grade 3 decrease in LVEF was observed in 1 (7%) patient.
is the nationwide network for TET in France, established in 2012. Whether Conclusion: Sunitinib, administered using a 2/1 dosing schedule, has clinical
postoperative radiotherapy (PORT) should be delivered was the most frequent activity in patients with TC, and the frequency of clinically significant TEAEs
question raised at the RYTHMIC multi-disciplinary tumor board (MTB) over the (fatigue, mucositis, hypertension) is acceptable. Studies are ongoing to
past 3 years, accounting for 494 (35%) of a total of 1401 questions. Methods: identify novel immunological biomarkers of activity.
All consecutive patients for whom postoperative adjuvant radiotherapy was
discussed at the RYTHMIC MTB from 2012 to 2015 were identified from the Keywords: Sunitinib, Modified dosing regimen, Clinical activity and
RYTHMIC prospective database. Results: 285 patients were identified, 274 tolerability, Thymic carcinoma
(52% men, 48% women) of whom fulfilled inclusion criteria. Average age at
time of TET diagnostic was 60 years. TET histology was thymoma in 243 (89%)
cases - including type A in 11% of cases, type AB in 28%, type B1 in 17%, type
B2 in 29%, and type B3 in 14% -, and thymic carcinoma in 31 (11%) of cases. OA18: NEW INSIGHTS IN THE TREATMENT OF THYMIC MALIGNANCIES
Complete resection was achieved in 81% of patients. Masaoka-Koga stage WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
was stage I in 29% of cases, IIA in 21%, IIB in 21%, III in 18%, and IVA/B in 11%.
Decision of the MTB was consistent with guidelines in 221 (92%) assessable
OA18.03 SAFETY AND CLINICAL ACTIVITY OF AVELUMAB
cases. Clinical situations for which PORT was indicated in accordance with
(MSB0010718C; ANTI-PD-L1) IN PATIENTS WITH ADVANCED THYMIC
guidelines (84 cases) were thymoma/R1 resection (30 patients), thymoma/R0
resection/stage III (22 patients), thymoma/R0 resection/stage IIB/type B2/ EPITHELIAL TUMORS (TETS)
B3 histology (11 patients), thymic carcinoma/R1 resection (6 patients), thymic Arun Rajan1, Christopher Heery2, Andrew Mammen3, Stefania Pittaluga4,
carcinoma/R0 resection (13 patients), thymoma/R0 resection/stage IIA/type Lauren Lepone2, Renee Donahue2, Italia Grenga2, Jeffrey Schlom2, James
B3 histology (2 patients). Inconsistencies between decision of the MTB and Gulley5, Raffit Hassan1
1
guidelines – 20 (8%) cases - consisted of abstention related to poor general Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, NCI,
condition (10 patients), carcinoid histology (2 patients), and discordance in NIH, Bethesda/MD/United States of America, 2Laboratory of Tumor Immunology
staging (1 patient), and of delivery of radiotherapy related to peroperative and Biology, National Cancer Institute at the National Institutes of Health,
tumor fragmentation (2 patients); for 5 patients who received PORT, a clear Bethesda/MD/United States of America, 3National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda/
explanation for inconsistency with guidelines was not found, but those cases
MD/United States of America, 4Laboratory of Pathology, Center for Cancer
actually corresponded to those in a “grey zone” of guidelines. MTB decision Research, NCI, NIH, Bethesda/MD/United States of America, 5Laboratory of Tumor
for PORT was actually implemented for 99 (85%) of patients; most frequent Immunology and Biology, National Cancer Institute at the National Institutes of
reason for not delivering radiotherapy was prolonged delay since surgery. Health, Bethesda/United States of America
Conclusion: Our data provide with a unique insight into the decision-making
process for PORT in thymic epithelial tumors, highlighting the need for a Background: Avelumab (MSB0010718C) is a fully human, IgG1 anti-PD-L1
systematic discussion at an expert MTB, while stressing the value of current antibody under clinical development. We report safety and clinical activity
available guidelines. in patients with relapsed TETs enrolled in a phase I trial (NCT01772004).
Methods: Patients previously treated with one or more standard therapies,
Keywords: Radiotherapy, Adjuvant treatment, Thymoma, Thymic carcinoma no prior immune checkpoint inhibitors, and with no history of autoimmune
disease were eligible. Treatment consisted of avelumab at doses of 10-20 mg/
kg iv q2 weeks until disease progression or toxicity. Responses were assessed
q6 weeks by RECIST 1.1. Correlative studies included evaluation of tumor cell
OA18: NEW INSIGHTS IN THE TREATMENT OF THYMIC MALIGNANCIES PD-L1 expression and peripheral blood immune subset analysis. Results:
7 patients with thymoma and 1 with thymic carcinoma (TC) were treated
with avelumab; 3 patients with thymoma (2 B3, 1 B2/B3) received avelumab
OA18.02 EVALUATION OF A MODIFIED DOSING REGIMEN (2-WEEKS 20 mg/kg; 4 patients with thymoma (1 B1, 3 B2) and 1 TC received 10 mg/kg.
ON/1-WEEK OFF) OF SUNITINIB AS PART OF A PHASE II TRIAL IN Two (29%) patients with thymoma had a confirmed partial response (PR;1 at
20 mg/kg, and 1 at 10 mg/kg), 2 (29%) had unconfirmed PRs, 2 (29%) stable
THYMIC CARCINOMA
disease (SD) and 1 (14%) progressive disease; the TC patient had SD. Most
Arun Rajan1, Chul Kim1, Udayan Guha1, Eva Szabo1, Arlene Berman1, Linda adverse events (AEs) were mild (grade 1 or 2). Grade 3 and 4 AEs were observed
Sciuto1, A. John Spittler2, Jane Trepel3, Seth Steinberg4, Pamela Harris5, Raffit in 3 (38%) patients each, and included potential immune-related AEs (irAEs)
Hassan1, Patrick Loehrer, Sr.2 in 5 cases. irAEs resolved completely with oral steroids in 3 patients, and
1
Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, NCI, incompletely in 1 patient. One patient required cyclosporine A for treatment
NIH, Bethesda/MD/United States of America, 2Division of Hematology/oncology, of irAEs. All 4 responders experienced irAEs (myositis in 3 patients, all after 1
Indiana University Medical Center, Indianapolis/IN/United States of America,
3 dose of avelumab, and enteritis in 1 patient). Pre- and post-treatment tumor
Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH,
Bethesda/MD/United States of America, 4Biostatistics and Data Management biopsies were available for analysis of PD-L1 expression and intratumoral
Section, Center for Cancer Research, NCI, NIH, Bethesda/MD/United States of immune infiltrates from three patients treated at 20 mg/kg. In one case
America, 5Cancer Therapy Evaluation Program, NCI, NIH, Rockville/MD/United the post-treatment biopsy showed necrotic tissue with no viable tumor. In
States of America the other two cases diffuse, membranous PD-L1 staining of epithelial cells
was seen in both pre- and post-treatment biopsies. The immune infiltrate Cancer Centre, London/United Kingdom
consisted of immature T cells in pre-treatment tumor samples in both cases.
The post-treatment biopsy showed continued presence of immature T cells Background: The treatment of patients with recurrent thymic tumors remains
in one case and a mature CD8+ T cell phenotype in the other case. Decreased uncertain due to limited data because of the rare nature of this disease. This
CTLA4+ regulatory T cells and decreased ratio of granulocytic vs. monocytic retrospective analysis was conducted to investigate clinical characteristics,
myeloid-derived suppressor cells was seen post-treatment at the 20mg/kg outcomes and possible prognostic factors of patients presenting with a first
dose. Conclusion: Avelumab is active in patients with recurrent thymoma. recurrence of thymic tumors. Methods: 107 patients with thymic neoplasms
Strategies need to be developed to reduce the risk of development of irAEs in registered as C37 by ICD10 coding at Guy’s Hospital during the 2007-2016
response to immune checkpoint inhibitor therapy in patients with thymoma. period with first recurrence following primary treatment were selected and
retrospectively reviewed via descriptive analysis. Differences in survival were
Keywords: immune checkpoint inhibitor, Thymoma, avelumab assessed using Kaplan-Meier analysis and uni & multivariate Cox proportional
hazards regression analyses. Results: 25 patients (14 male & 11 female) with
a median age of 51 years (range 36-80 years) experienced a first recurrence of
thymoma (20 patients – 80%) or thymic carcinoma (5 patients – 20%) with a
OA18: NEW INSIGHTS IN THE TREATMENT OF THYMIC MALIGNANCIES median time from diagnosis of 36 months (range, 7-270). At diagnosis, modified
Masaoka disease stage was IIA/IIB/IIIA/IIIB/IVA/IVB in 4/0/8/2/6/5 patients; 18
patients’ (72%) primary resection was R0/R1/R2 in 11/3/4 patients; 9 patients
OA18.05 FDG-PET IN THYMIC EPITHELIAL TUMORS: AN (36%) received radiotherapy; 19 received chemotherapy (76%); CAP (n=10)
EVALUATION OF ONLY RESECTED TUMORS and platinum-etoposide (n=6) regimens. At first relapse, 19 patients (76%)
had thoracic recurrence and 6 patients (24%) extrathoracic recurrence. Nine
Kazuo Nakagawa1, Shoji Takahashi2, Yasuhisa Ohde2, Hiroaki Kurihara3,
patients (26%) underwent redo surgery, 3 of which recieved chemotherapy
Takashi Terauchi4
prior to resection. Overall resection status was 2/5/1 (1 patient’s data is not
1
Thoracic Surgery, National Cancer Center Hospital, Tokyo/Japan, 2Thoracic Surgery, yet assessable) R0/R1/R2. Chemotherapy was administered in 17 patients
Shizuoka Cancer Center, Shizuoka/Japan, 3Diagnostic Radiology, National Cancer
(68%) with a median cycle of 4 (range, 1-6): 16 patients received combination
Center Hospital, Tokyo/Japan, 4Nuclear Medicine, Cancer Institute Hospital of
Japanese Foundation for Cancer Research, Tokyo/Japan
chemotherapy consisting of platinum etoposide (n=10) or cisplatin-
anthracycline based (CAP/CAV/AC n=5). Dose reduction and withdrawal
Background: 18F-Fluorodeoxy glucose positron emission tomography (FDG- were reported in 3 (18%) and 7 (41%) patients, respectively. In 4 out of these
PET) is thought to be useful for predicting the histologic grade in thymic 7 patients withdrawal was due to PD; disease control rate (=CR+PR+SD)
epithelial tumors (TETs). Although there have been many reports on the was 67% (in 10 out of 15 assessable patients). Three patients (12%) received
use of FDG-PET for evaluating TETs, no previous studies have included only radiotherapy of which one was treated exclusively with radiotherapy. Time
resected cases. Therefore, we investigated the relationship between the to progression since the first recurrence was 12 months (range 2-52 months);
degree of FDG-uptake in the tumor and either the WHO histologic subtype or in 16 patients extrathoracic recurrence was seen in 4 patients (25%) and
the tumor stage in patients with resected TETs. Methods: We retrospectively thoracic in 12 patients (75%). Eight recurring patients (50%) received further
reviewed FDG-PET findings in 112 patients with TETs (92 with thymomas chemotherapy. With a median follow-up of 32.5 months, 19 patients (75%) are
and 20 with thymic carcinomas) resected at 2 institutes in Japan. The alive and 2 (8%) disease-free; median OS has not been reached, median PFS was
Spearman rank correlation coefficient was used to assess the association 29.5 months (range, 26.3-33.2). Analysis of possible prognostic factors will be
between the maximum standardized uptake value (SUV max) in the tumor presented. Conclusion: Patients with first recurrence of thymic tumors may
and both the histologic subtype and tumor stage. The cut-off value of SUV benefit from combination chemotherapy and surgery when feasible.
max for differentiating thymoma from thymic carcinoma was calculated
using a receiver operating characteristic (ROC) curve analysis. Results: The Keywords: relapse, treatment, Thymoma, Thymic carcinoma
Table shows the relationship between SUV max in the tumor and the WHO
histologic subtype. SUV max according to each tumor stage was 3.9 ± 1.7
(mean ± SD) in stage I (n = 89), 4.7 ± 1.7 in stage II (n = 3), 7.4 ± 5.3 in stage III
OA18: NEW INSIGHTS IN THE TREATMENT OF THYMIC MALIGNANCIES
(n =11), and 7.6 ± 3.9 in stage IV (n = 9). SUV max was strongly related to both WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
the WHO histologic subtype and tumor stage (Spearman rank correlation
coefficient = 0.485 and 0.432; p = 0.000 and 0.000, respectively). The optimal
cut-off value of SUV max for differentiating thymoma from thymic carcinoma OA18.07 QUALITY OF RESECTION AND OUTCOME IN STAGE III TETS:
was 4.6, with a sensitivity of 80% and a specificity of 70%. THE FRENCH RYTHMIC NETWORK EXPERIENCE
Maria Bluthgen1, Eric Dansin2, Dan Ou3, Hervé Léna4, Julien Mazieres5, Eric
SUV max Pichon6, François Thillays7, Gilbert Massard8, Xavier Quantin9, Youssef
Oulkhouir 10, Thierry Nguyen11, Luc Thiberville12, Christelle Clément-Duchêne13,
Histologic subtype No. of patients Mean ± SD Range
Colin Lindsay1, Pascale Missy14, Thierry Molina15, Nicolas Girard16, Benjamin
A 12 3.5 ± 1.3 1.3 – 6.3 Besse17, Pascal Alexandre Thomas18
1
AB 45 3.5 ± 1.3 1.2 – 6.9 Cancer Medicine, Gustave Roussy, Villejiuf/France, 2Département de Cancérologie
Générale, Centre Oscar Lambret, Lille/France, 3Department of Radiation Oncology,
B1 19 4.1 ± 0.9 2.5 – 6.5 Gustave Roussy, Villejiuf/France, 4 CHU Rennes - Hôpital Pontchaillou, Rennes/
France, 5Hôpital Rangueil, Toulouse/France, 6CHU Tours-Bretonneau, Tours/France,
B2 10 4.2 ± 1.0 2.7 – 5.9 7
Institut de Cancérologie de L’Ouest, St. Herblain/France, 8University Hospital,
Strasbourg/France, 9University Hospital, Montpellier/France, 10University Hospital,
B3 6 4.8 ± 2.6 2.4 – 8.6
Caen/France, 11Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz,
Thymic carcinoma 20 8.0 ± 4.7 3.0 – 21.8 Besançon/France, 12Centre Hospitalier Universitaire, Rouen/France, 13Cancer
Center, Nancy/France, 14French Cooperative Thoracic Intergroup (IFCT), Paris/
Total 112 4.5 ± 2.8 1.2 – 21.8 France, 15University Hospital Necker, Paris/France, 16Thoracic Oncology, Hospices
Civils de Lyon, Lyon/France, 17Department of Cancer Medicine, Gustave Roussy,
Conclusion: Our results suggest that FDG-PET is useful for differentiating Villejiuf/France, 18University Hospital, Marseille/France
thymoma from thymic carcinoma. Further studies will be needed to assess
other potential clinical applications of FDG-PET for the evaluation of TETs. Background: Stage III TET represents a heterogeneous population and
their optimal approach remains unclear; most of the available literature is
Keywords: FDG-PET, Thymic epithelial tumors, WHO histologic subtype composed of small series spanned over extended periods of time. RYTHMIC
(Réseau tumeurs THYMiques et Cancer) is a French nationwide network for
TET with the objective of territorial coverage by regional expert centers and
systematic discussion of patients management at national tumor board.
OA18: NEW INSIGHTS IN THE TREATMENT OF THYMIC MALIGNANCIES We reviewed our experience in stage III thymic tumors in order to evaluate
the value of tumor board recommendations and multidisciplinary approach.
Methods: We conducted a retrospective analysis of patients (pts) with stage
OA18.06 TREATMENT, OUTCOME AND PROGNOSTIC FACTORS III TET discussed at the RYTHMIC tumor board from January 2012 to December
OF PATIENTS WITH THYMIC EPITHELIAL TUMORS AT FIRST 2015. Clinical, pathologic and surgical data were prospectively collected in
RECURRENCE a central database. Survival rates were based on Kaplan-Meier estimation.
Cox proportional hazard models were used to evaluate prognostic factors
Giuseppe Banna1, Ankur Sheel2, Varun Sheel3, Andrea Bille4, Tom Routledge4,
for disease free survival (DFS) and overall survival (OS). Results: 150 pts
Shalini Fernando4, Arjun Nair4, Rohit Lal4
were included in the analysis. Median age was 64 years [18 – 91], 56% males,
1
Division of Medical Oncology, Cannizzaro Hospital, Catania/Italy, 2Department of thymoma A-B2/ B3-thymic carcinoma in 52% and 47% respectively; 12%
Medicine, University of Massachusetts School of Medicine, Worcester/MA/United
presented with autoimmune disorder (76% myasthenia). Local treatment
States of America, 3Department of Biology, University of Massachusetts Amherst,
was surgery in 134 pts (90%) followed by radiotherapy (RT) in 90 pts; 26 pts
Amherst/MA/United States of America, 4 Medical Oncology Department, Guy’s
received preoperative chemotherapy (CT). Complete resection rate (R0) was

53%. Among 38 pts considered non-surgical candidates at diagnosis, 26 pts

became resectable after induction CT with a R0 rate of 58%; 12 pts received
CT-RT and/or CT as primary treatment. Recurrence rate was 38% (n=57), first
sites were pleural (n=32) and lung (n=12). The 5-year OS and DFS were 88%
and 32% respectively. Gender (HR: 0.2 [95%CI 0.04 - 0.97] p=0.04), histology
(HR: 0.19 [95%CI 0.05 - 0.70] p=0.02) and surgery (HR: 0.4 [95%CI 0.01 - 0.20]
p<0.001) as primary treatment modality were significant prognostic factors
for OS in multivariate analysis. Histology (HR: 0.5 [95%CI 0.30 - 0.90] p=0.02)
and adjuvant RT (HR: 0.4 [95%CI 0.20 – 1.00] p=0.05) were significantly
associated with DFS. Completeness of resection was not associated with
survival in our cohort. Conclusion: Surgery followed by radiotherapy improves
outcome irrespectively of R0. Stage III TET not candidate to surgery should be
reassessed for resection after induction chemotherapy.
Keywords: TETs, stage III, outcome
Background: High-throughput gene expression profiling led to proposal of

SESSION OA19: TRANSLATIONAL RESEARCH IN EARLY multiple expression-based prognostic signatures for squamous cell lung
carcinoma (SCC), but none has been validated. A multi-institutional squamous
STAGE NSCLC lung cancer consortium of investigators is developing prognostic signatures
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 through the US NCI Lung SPECS (Strategic Partnership for Evaluation of
Cancer Signatures) program. Six institutions contributed tumor specimens
and published/unpublished expression-based prognostic signatures for
OA19.01 A STANDARDIZED AND VALIDATION OF PROGNOSTIC validation using standardized sample cohorts (a primary validation cohort
GENE EXPRESSION SIGNATURES FOR SQUAMOUS CELL LUNG comprising institutional cases, and additional validation cohorts from two
CARCINOMA BY THE SPECS LUNG CONSORTIUM prospective cooperative group studies) and quality controlled assessment in
independent laboratory and statistical cores. Here, we report the results of
William Richards1, Raphael Bueno2, David Beer3, Karla Ballman4, Ramaswamy
the primary validation. Methods: Cases of primary SCC (by central pathology
Govindan5, Ming Tsao6, Mark Watson7, Daniel Merrick8, Adriaan Van
review) meeting clinical (Stage I-II; surgical treatment only; 3-year followup)
Bokhoven9, Frances Shepard6, David R. Gandara10, Wilbur Franklin8, David
and specimen quality criteria (Tumor cellularity >= 50%; necrosis <= 20%) were
Harpole11, Guoan Chen3, Zhengming Chen4, Lucian Chirieac1, Herman Chui6,
submitted. Clinical, pathological and outcome data were uploaded to a central
Carlo Genova12, Mary-Beth Joshi11, Ashley Kowalewski9, Mark Onaitis11,
database. Frozen tumor samples underwent centralized mRNA extraction
Christopher Rivard9, Thomas Sporn11, Fred R. Hirsch9
1 (Qiagen Symphony), quality control (RIN >= 6.0) and microarray profiling
Surgery, Brigham and Women Hospital, Boston/MA/United States of America,
2 (Affymetrix U133) in core labs. An independent statistical core assessed
Division of Thoracic Surgery, Brigham and Women’s Hospital/ Harvard Medical
School, Boston/MA/United States of America, 3 6304 Cancer Center, U. of Michigan, validation of 7 pre-existing mRNA signatures and generated new models using
University of Michigan, Ann Arbor/MI/United States of America, 4Biostatistics MCP clustering. Results: Among 250 cases meeting entry criteria, median age
and Epidemiology, Weill Cornell University, New York/United States of America, was 70 (43-92), 161 (65%) were male, and most were former (70%) or current
5
Medical Oncology, Washington University School of Medicine, St. Louis/MO/ (28%) smokers. Surgery was pneumonectomy: 5%; bilobectomy: 2%;
United States of America, 6Princess Margaret Hospital, Toronto/ON/Canada, lobectomy: 74%; sublobar: 18%. Pathologic staging was T1: 49%; T2: 50%; T3:
7
Washington University School of Medicine, St. Louis/MO/United States of 1%; N0: 88%; N1: 12%, and grade was G1: 4%; G2: 50%; G3: 44%. At followup,
America, 8Pathology, University of Colorado Anschutz Medical Campus, Aurora/ 148 (59%) were deceased. Three mRNA signatures demonstrated significant
CO/United States of America, 9Division of Medical Oncology, University of Colorado
univariable association with OS and added independent prognostic value (see
Anschutz Medical Campus, Aurora/CO/United States of America, 10 Division of Hem-
Oncology, UC Davis Comprehensive Cancer Center, Sacramento/CA/United States Figure) to a multivariable model accounting for age, sex and stage (c-index =
of America, 11Department of Surgery, Duke University Medical Center, Durham/NC/ 0.641). Conclusion: The validated signatures, along with two novel signatures
United States of America, 12U.O.S. Tumori Polmonari, IRCCS San Martino-Ist Istituto generated from the current dataset, are currently undergoing further
Nazionale Per La Ricerca Sul Cancro, Genova/Italy validation studies using two prospective co-operative group cohorts.
Keywords: Squamous cell lung cancer, gene expression signature
OA19: TRANSLATIONAL RESEARCH IN EARLY STAGE NSCLC

OA19.02 SEX DIFFERENCES ARE DETECTED IN THE PROFILE OF

TUMOR ASSOCIATED INFLAMMATORY CELLS (TAICS) ARE LUNG
ADENOCARCINOMA
Carmen Behrens 1, Edwin Parra2, Jaime Rodriguez-Canales2, Pamela
Villalobos2, Boris Sepesi3, Annikka Weissferdt4, Neda Kalhor4, John Heymach1,
Cesar Moran4, Don Gibbons1, Ignacio Wistuba5
1
Thoracic/head and Neck Medical Oncology, Houston/TX/United States of America,
2
Translational Molecular Pathology, Houston/TX/United States of America,
3
Thoracic and Cardiovascular Surgery, Houston/TX/United States of America,
4
Pathology, Houston/TX/United States of America, 5Translational Molecular
Pathology, Thoracic and Cardiovascular Surgery, Houston/TX/United States of
America
Background: A number of studies have characterized TAICs in lung cancer

and associated their levels of infiltration with patients’ outcome. There is
limited information about the correlation of TAICs infiltration with clinical
and pathological features of lung cancer. We investigated the association
between patterns of tumor infiltrating lymphocytes and macrophages
with detailed clinical and pathological features in lung adenocarcinoma.
Methods: We studied archival tumor tissue from 93 surgically resected
lung adenocarcinomas, stages I to III. Density of TAICs expressing CD3,
CD4, CD8, and CD68 was evaluated using immunohistochemistry (IHC)
and image analysis. TAICs density was correlated with tumor’s histological
characteristics and patients’ characteristics. Results: We found significant
differences in the TAICs infiltrate density of lung adenocarcinomas based
on patients’ characteristics. Overall: a) females showed higher levels of
CD8+ (P=0.01) and CD3+ (P=0.03) cell density than males; b) smaller tumors
(<3cms) showed more CD4+ (P=0.01) and CD3+ (P=0.03) cells than larger
tumors; and, c) tumors with solid histology pattern showed higher levels of Goodyear/AZ/United States of America
CD8+ (P=0.03) cells than non-solid pattern. No overall significant differences
on TAICs infiltrates were detected by age, tobacco exposure by pack-years Background: Most human cancers express proteoglycans modified with
and TTF-1 IHC expression score. However when TAICs density of tumors was distinct oncofetal chondroitin sulfate (CS) chains that are normally restricted
examined by sex we found the following: a) in larger tumor (>3cms), females to placental tissue. Oncofetal CS chains can be conveniently detected and
demonstrated higher levels of CD8+ cells (P=0.0007) than males; b) tumors targeted by recombinant VAR2CSA (rVAR2) proteins derived from the malaria
from females older than the median age (63 years) showed more CD4+ parasite Plasmodium falciparum. In the present study, we have analyzed
(P=0.04), CD8+ (P=0.009) and CD3+ (P=0.042) cells than males; c) tumors from the expression landscape of oncofetal CS modifications in early-stage
females with <40 pack-years of tobacco history showed significantly higher non-small cell lung cancer (NSCLC). Methods: Tissue microarrays from four
levels of CD3+ (P=0.004) and CD68+ (P=0.004) cells than males; d) tumors from separate patient cohorts representing a total of 493 clinically annotated
females with high levels of TTF1 expression (score >150) showed higher levels stage I-II NSCLC cases were stained for oncofetal CS using rVAR2. Data were
of CD8+ cells(P=0.03) than males; e) females with tumors having non-solid analyzed for correlation between low and high oncofetal CS presentation by
histology pattern showed higher CD8+ (P=0.02) and CD3+ (P=0.02) cells than immunohistochemical (IHC) staining of tumor and stroma compartments
males. Finally, tumors expressing low levels of TTF-1 and lower CD4+ cells in respect to EGFR and KRAS mutations, as well as to clinical characteristics
correlated significantly with worse overall recurrence free survival and overall including relapse-free survival (RFS) and overall survival (OS). Results: There
survival in both males (P<0.0001) and females (P=0.0072). Conclusion: In lung were 351 patients with low (IHC score 0-1) and 142 with high (IHC score 2-3)
adenocarcinoma, TAICs infiltration correlates with clinical characteristics of expressing tumors. We identified 331 adenocarcinomas, 145 squamous cell
patients and pathological features of tumors, particularly, sex, age, size and carcinomas, and 12 cases with other NSCLC subtypes. There were 314 stage I
TTF-1 expression. Compared with men, lung adenocarcinomas from females and 179 stage II cases by AJCC 7th edition. High oncofetal CS expression was
showed higher levels of TAICs, particularly at older age, larger tumor size, less significantly associated with shorter RFS (vs. high expressiors; 58 vs. 39
exposure to tobacco, and more differentiated histological patterns. (UT Lung months, respectively, p=0.034) and OS (vs. high expressors; 69 vs. 51 months,
SPORE and MD Anderson Moon Shot Program). respectively, p=0.044). High oncofetal CS expression was significantly
associated with shorter RFS vs. low expression in men (p=0.024), smokers
Keywords: Lung adenocarcinoma, tumor associated inflammatory cells, sex (p=0.011), and in patients with squamous cell tumors (p=0.012). High oncofetal
differences CS was also significantly associated with shorter OS in men (p=0.005)
and smokers (p=0.028). There were no significant RFS or OS differences in
oncofetal CS expressions when stratifying the patients according to their
EGFR or KRAS statuses. In multivariate survival analyses, histology, stage,
OA19: TRANSLATIONAL RESEARCH IN EARLY STAGE NSCLC and high oncofetal CS expression was significantly associated with shorter
RFS vs. high expression (HR, 1.8; 95% CI, 1.32–2.48; p < 0.001). Conclusion: This
is the first study showing that high oncofetal CS expression is an independent
OA19.03 IDENTIFY LUNG ADENOCARCINOMA IN SITU AMONG prognostic factor of poor RFS in NSCLC and validates high oncofetal CS
PULMONARY MICRO-NODULES THROUGH BLOOD GENE expression as a prognostic factor of poor OS. In contrast to non-smoker
females, oncofetal CS appears to be a prognostic for OS in males and smokers.
EXPRESSION PROFILES
Our work promotes oncofetal CS as a candidate target for rVAR2-based
Baohui Han1, Huiming Wang1, Changming Cheng2, Xueyan Zhang1, Wenjia therapeutic intervention in NSCLC patients with poor RFS/OS.
Yang1, Fangfei Qian1, Xue Dong1
1
Shanghai Chest Hospital, Shanghai/China, 2National Engineering Center for Keywords: prognostic factor, oncofetal chondroitin sulfate expression, Early-
Biochip at Shanghai, Shanghai/China stage NSCLC
Background: The national lung cancer screening test (NLST) confirmed: low
dose CT screening could reduce lung cancer mortality. However, the high
false-positive rates of LDCT screening, especially the difficulty of diagnosis of OA19: TRANSLATIONAL RESEARCH IN EARLY STAGE NSCLC
micro-nodules with size less than 10 mm highlight the need of complementary WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
biomarkers to discriminate micro-nodular lung cancer from benign pulmonary
diseases. Methods: The blood gene expression profiles of 46 lung cancer
patients, 38 pulmonary lesions and 51 healthy were investigated to identify
OA19.06 ADJUVANT CHEMOTHERAPY DECISIONS BASED ON
the lung cancer-specific genetic signatures. The lung cancer patients MOLECULAR RISK STATUS IMPROVES OUTCOMES IN EARLY STAGE,
containing micro-nodules less than 10 mm were surgically and pathologically NON-SMALL CELL LUNG CANCER
diagnosed as lung adenocarcinoma in situ Results: A self-training logistic Gavitt Woodard1, Jane Crockard1, Clara Zoon-Besselink1, Johannes Kratz1,
regression method was used to identify the lung cancer-specific gene Matthew Gubens2, Thierry Jahan2, Collin Blakely2, Kirk Jones3, Michael Mann1,
signatures as we previously reported. Six genes, including DDX51, PSME2, David Jablons1
ACTL6A, GMEB1, FAM200B, GEMIN6, were identified for discriminating lung 1
Surgery, University of California, San Francisco, San Francisco/CA/United States of
adenocarcinoma in situ from health and benign pulmonary diseases. The America, 2Hematology and Oncology, University of California, San Francisco, San
performance of the six-gene panel for diagnosis of lung adenocarcinoma in Francisco/CA/United States of America, 3Pathology, University of California, San
situ identified was exhibited in Table 1. Through self-training SVM classifier, Francisco, San Francisco/CA/United States of America
the logarithmic odds of each sample was calculated and exhibited, in which
Background: A clinically certified, 14-gene quantitative PCR expression
the cutoff value was set as zero in logarithmic odds for differentiating lung
assay has been found to assess mortality risk more accurately than
cancer from benign and control group. The predictive model based on 6-gene
clinicopathologic criteria in early-stage, non-squamous, non-small cell lung
panel correctly classified 43 of 46 lung cancer, 39 of 42 benign pulmonary
cancer (NSCLC). Clinically validated molecular stratification may provide
diseases with 93% accuracy, 94% sensitivity, and 93% specificity and 0.97 of
a more informative approach to identify early stage NSCLC patients who
ROC AUC. Conclusion: The predictive model based on 6-gene panel (DDX51,
are most likely to benefit from chemotherapy than current National
PSME2, ACTL6A, GMEB1, FAM200B, GEMIN6) can be used for discriminating
Comprehensive Cancer Network (NCCN) high-risk clinicopathologic
between the malignant or benign nodules with size less than 10 mm
features. Methods: Prospective molecular risk-stratification by the 14-gene
Keywords: gene expression profile, lung adenocarcinoma in situ, micro- quantitative PCR expression assay was performed on 91 consecutive patients
nodules with stage I-IIA non-squamous NSCLC after complete surgical resection
at a single institution. Information from molecular risk profiling was used
in conjunction with pathologic stage and NCCN criteria to make adjuvant
chemotherapy recommendations. Fisher’s exact test was used to compare
OA19: TRANSLATIONAL RESEARCH IN EARLY STAGE NSCLC recurrence rates, and Kaplan-Meier analysis and log-rank tests were used
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 to evaluate differences in disease free survival. Results: Median age was 69
years, 57% were female and median follow up was 23±2 months. Among all
patients, 33 (36%) met NCCN high-risk criteria for adjuvant chemotherapy
OA19.05 HIGH ONCOFETAL CHONDROITIN SULFATE EXPRESSION
and 27 (30%) were molecular high risk. Recommendations for adjuvant
IS AN INDEPENDENT PROGNOSTIC FACTOR OF POOR SURVIVAL IN chemotherapy were discordant in 18 (55%) of NCCN high-risk patients and in
EARLY-STAGE NSCLC 12 (44%) who were molecular high-risk. Twelve (44%) of molecular high-risk
Zoltan Lohinai1, Htoo Oo2, Gunjan Kumar3, Jeffrey Allen4, Nhan Tran5, Balazs patients agreed to receive adjuvant chemotherapy. Whereas recurrence was
Dome6, Judit Moldvay1, Glen Weiss7, Mads Daugaard3 observed in 33% of molecular high-risk patients who did not receive adjuvant
1
Tumor Biology, National Koranyi Institute of Pulmonology, Budapest/Hungary, chemotherapy, none of the molecular high-risk patients who underwent
2
Vancouver Prostate Centre, Vancouver/BC/Canada, 3Department of Urologic chemotherapy recurred (log-rank p=0.001). Conclusion: This prospective
Sciences, University of British Columbia, Vancouver/Canada, 4Kootenai Health, single-institution study demonstrates the clinical utility of molecular testing
Post Falls/ID/United States of America, 5Translational Genomics Research Institute, of early-stage NSCLC to supplement pathologic stage and NCCN guidelines
Phoenix/AZ/United States of America, 6Division of Thoracic Surgery, Medical
in making adjuvant chemotherapy recommendations. Molecular risk scores
University Vienna, Vienna/Austria, 7Western Regional Medical Center, Ctca,
better differentiated prospective recurrence rates than did NCCN risk criteria.

This study provides preliminary evidence that molecular testing followed trial comparing atezolizumab vs docetaxel; BIRCH/FIR: single-arm, 1L/2L+
by adjuvant chemotherapy in molecularly high-risk patients may prevent a PD-L1-selected trials) were available for targeted genetic sequencing using
significant number of recurrences and improve outcomes. the F1 panel of 315 cancer-related genes. TMB was quantified using an
updated TMB algorithm and efficacy was assessed in groups defined by
Keywords: NCCN guidelines, molecular risk, adjuvant chemotherapy, the 75th (high) and 50th (median) percentile of each study-specific TMB.
prognostic assay Atezolizumab efficacy was examined at Dec 1, 2015 (POPLAR and BIRCH);
and Jan 7, 2015 (FIR) data cutoffs. Results: Across samples, median TMB was
similar in 1L and 2L+ patients (9/MB and 9.9/MB, respectively). In 1L and 2L+
PD-L1–selected patients, atezolizumab benefit was increased in those with
OA19: TRANSLATIONAL RESEARCH IN EARLY STAGE NSCLC ≥ TMB cut-offs (Table). In unselected 2L+ patients from POPLAR, the OS,
PFS, and ORR benefits of atezolizumab vs docetaxel were also enhanced in
patients with increased TMB. TMB and PD-L1 expression were independently
OA19.07 DIFFERENCE OF POSTOPERATIVE SURVIVAL DUE TO THE associated with improved atezolizumab efficacy. TMB associations with PD-L1
TYPE OF EGFR GENE MUTATION IN SURGICALLY RESECTED LUNG expression, tumor-infiltrating lymphocyte infiltration and T-effector cell gene
ADENOCARCINOMAS expression will be presented. Conclusion: For the first time, we demonstrate
that TMB assessed with F1 targeted sequencing is associated with improved
Kazuki Hayasaka1, Satoshi Shiono1, Yuki Matsumura2, Naoki Yanagawa3,
atezolizumab outcomes in 1L and 2L+ NSCLC. Moreover, this is the first
Hiroyuki Suzuki2, Jiro Abe4, Motoyasu Sagawa5, Akira Sakurada6, Masato
study demonstrating the association of TMB with improved anti-PD-L1/PD-1
Katahira1, Yuichiro Machida7, Satomi Takahash4, Yoshinori Okada6
1
efficacy in a randomized trial. Importantly, the association between TMB
Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, and atezolizumab efficacy occurred in both unselected and PD-L1-selected
Yamagata/Japan, 2Department of Regenerative Surgery, Fukushima Medical
patients. Therefore, in addition to PD-L1, TMB may be an independent
University, Fukushima/Japan, 3Pathology, Yamagata Prefectural Central Hospital,
Yamagata/Japan, 4Department of Thoracic Surgery, Miyagi Cancer Center, Natori/ predictor of improved responsiveness to atezolizumab in advanced NSCLC.
Japan, 5Tohoku Medical and Pharmaceutical University, Sendai/Japan, 6Tohoku
University Hospital, Miyagi/Japan, 7Thoracic Surgery, Kanazawa Medical University, Atezolizumab efficacy by TMB subgroups
Uchinada/Japan
PD-L1-selected
Background: Epidermal growth factor receptor (EGFR) gene mutation is a
robust prognostic factor in patients with advanced lung adenocarcinomas. 1L 2L+
Recently, on the other hand, there are some reports proposing the difference
of survival due to the type of EGFR mutation. In this study, we analyzed the BIRCH+FIR n=102 n=371
difference of postoperative survivals between two most common mutations, Median High Median High
that is, exon 19 deletions (DEL) and exon21 L858R (PM), using multi- (≥9/MB) (≥13.5/MB) (≥9.9/MB) (≥17.1/MB)
institutional data of patients with surgically resected lung adenocarcinomas.
Methods: We retrospectively collected 1,063 consecutive patients who OS,HRa 0.79 0.45 0.87 0.7
underwent surgical resections for lung adenocarcinoma between 2005 and
(95% CI) (0.39-1.58) (0.17-1.16) (0.65-1.16) (0.49-1.00)
2012 in five institutions, and who were examined their EGFR mutation status.
The patients with minor EGFR mutations were excluded. We compared their PFS,HR a 0.58 0.54 0.64 0.5
clinicopathological characteristics among DEL, PM, and wild type (WT) group.
We also analyzed postoperative recurrence-free survival (RFS) and overall (95% CI) (0.36-0.94) (0.3-0.97) (0.5-0.8) (0.38-0.67)
survival (OS) according to the type of EGFR mutation. Results: The number ORR,above/
of patients with DEL, PM, and WT was 218 (20.5%), 301 (28.3%), and 544 28%/13% 25%/20% 25%/14% 29%/16%
below cutoff
(51.2%) respectively, and their median follow-up period was 47.6 months.
The patients of PM were older and earlier pathological staged than those
with DEL, whereas no significant difference was observed among other
2L+ unselected n=92
clinicopathological factors. Five-year RFS and OS of DEL, PM, and WT were
67.3/85.9%, 76.4/88.6%, 59.2/71.5%, respectively, and both survivals of each Biomarker-
POPLAR Median High
mutant were significantly better than those of WT. Regarding the difference
between DEL and PM, RFS curve of DEL was significantly worse than that of evaluable
(≥9.9/MB) (≥15.8/MB)
PM (p = 0.027), but OS curves of both mutant weren’t significantly different. population
(p = 0.16). In multivariate analysis, the type of EGFR mutation (DEL vs PM) was 0.65 0.48 0.5
OS,HRb
not an independent factor both in RFS and OS. Conclusion: Exon 21 L858R
might be a more favorable recurrence-risk factor than exon 19 deletions in (95% CI) (0.38-1.12) (0.23-1.04) (0.15-1.67)
patients with surgically resected lung adenocarcinomas.
PFS,HRb 0.98 0.49 0.49
Keywords: lung adenocarcinoma, postoperative survival, Exon 19 deletions,
exon21 L858R (95% CI) (0.63-1.53) (0.25-0.93) (0.19-1.3)
ORR,
atezolizumab/ 13%/15% 20%/4% 20%/8%
docetaxel
SESSION OA20: IMMUNOTHERAPY AND MARKERS a

HR:efficacy-evaluable patients, atezolizumab at/above cutoff vs below.
b
HR:efficacy-evaluable patients, atezolizumab vs docetaxel at/above
cutoff.
OA20.01 TUMOR MUTATION BURDEN (TMB) IS ASSOCIATED WITH
IMPROVED EFFICACY OF ATEZOLIZUMAB IN 1L AND 2L+ NSCLC Keywords: Immunotherapy, mutational load, NSCLC, Biomarkers
PATIENTS
Marcin Kowanetz 1, Wei Zou1, David Shames1, Craig Cummings1, Naiyer
Rizvi2, Alexander Spira3, Garrett Frampton4, Vincent Leveque1, Susan Flynn1,
OA20: IMMUNOTHERAPY AND MARKERS
Simonetta Mocci1, Geetha Shankar 1, Roel Funke1, Marcus Ballinger 1, Daniel WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
Waterkamp1, Daniel Chen1, Alan Sandler 1, Garret Hampton1, Lukas Amler 1,
Priti Hegde1, Matthew Hellmann5
1
Genentech, Inc, South San Francisco/CA/United States of America, 2Columbia OA20.02 NEOANTIGEN TARGETING IN NSCLC PATIENTS WITH
University, New York/NY/United States of America, 3Us Oncology Research, the COMPLETE RESPONSE TO ANTI-PD-1 IMMUNOTHERAPY
Woodlands, Tx; Virginia Cancer Specialists Research Institute, Fairfax/VA/United Kellie Smith1, Valsamo Anagnostou1, Patrick Forde1, Julie Brahmer2, Victor
States of America, 4Foundation Medicine, Cambridge/MA/United States of America,
5 Velculescu1, Drew Pardoll1
Memorial Sloan Kettering Cancer Center, New York/NY/United States of America 1
Oncology, Johns Hopkins University School of Medicine, Baltimore/MD/United
Background: In NSCLC, atezolizumab (anti-PDL1) efficacy correlates with States of America, 2Oncology, Johns Hopkins Kimmel Cancer Center, Baltimore/MD/
PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC). United States of America
Here we examined the association between atezolizumab efficacy and TMB
Background: Anti-PD-1 immunotherapy has resulted in durable clinical
assessed by FoundationOne (F1) sequencing panel. Methods: Pretreatment
responses in heavily pretreated patients with non-small cell lung cancer
tumor specimens from 102 1L and 465 2L+ NSCLC patients enrolled on
(NSCLC). While NSCLC is typically seen as non-immunogenic, there is a 15-20%
three Ph 2 atezolizumab monotherapy trials (POPLAR: randomized 2/3L
objective response rate and a median duration of response of 17 months in

patients treated with the PD-1 inhibitor, nivolumab. This duration of response
has not been reported with other systemic therapies in advanced NSCLC.
While tumor PD-L1 expression may be a biomarker of sensitivity to anti-
PD-1 therapy, and the number of somatic mutations may play a role in PD-1
upregulation on T cells, the mechanisms underlying response vs. progressive
disease have yet to be fully elucidated. Methods: Whole exome sequencing
and mutation-associated neoantigen (MANA) prediction was performed on
tumor sections from two advanced NSCLC patients with complete response
to nivolumab. Peptides representing MANAs were synthesized and tested
against PBMC in a 10-day cultured IFNg ELISpot assay. Reactive MANAs were
assessed in binding and stability assays. TCR sequencing was performed on
reactive cell cultures and on DNA obtained from tumor resections to match
MANA-reactive TCR clones with clones that were infiltrating the tumor.
Results: The mean mutational burden in NSCLC as reported previously is 360
sequence alterations. In our study, patient 1 had 30 sequence alterations and
patient 2 had 314. Despite the difference in mutational load, MANA reactivity
was detected in peripheral blood of both patients >1 year after being declared Keywords: lung cancer, Tumor infiltlating lymphocytes, Target therapy,
cancer-free. TCR clones of MANA-reactive peripheral T cells were detected microenvironment
in tumor resections and were expanded in MANA-stimulated T cell cultures.
Binding and stability assays confirmed that these MANAs bind to their
cognate HLA with high affinity and stability. Conclusion: These findings show
that NSCLC tumors with differential mutational burden can show regression OA20: IMMUNOTHERAPY AND MARKERS
following checkpoint blockade and suggest that the quality of mutations may
be more influential in immunogenicity than the overall quantity of mutations.
Our data also show that MANA reactivity may be the underlying mechanism OA20.05 THE INFLUENCE OF NEOADJUVANT CHEMOTHERAPY,
by which T cells eliminate tumor following anti-PD-1 immunotherapy. ON IMMUNE RESPONSE PROFILE IN NON-SMALL CELL LUNG
Additional studies should evaluate mechanisms of enhancing MANA reactivity
CARCINOMAS
in patients who do not respond to checkpoint blockade and should further
validate the link between MANA reactivity and clinical response to anti-PD-1. Edwin Parra1, Jaime Rodriguez-Canales2, Carmen Behrens3, Mei Jiang2,
Apar Pataer4, Arelene Correa5, Stephen Swisher5, Boris Sepesi6, Annikka
Keywords: Immunotherapy, Neoantigens, T cells, Anti-PD-1 Weissferdt7, Neda Kalhor8, William William Jr9, Jack Lee10, John Heymach11,
Cesar Moran7, Jianjun Zhang11, Don Lynn Gibbons12, Ignacio Wistuba2
1
U.T.-M.D. Anderson Cancer Center, Transelational Molecular Pathology, Houston/
TX/United States of America, 2U.T.-M.D. Anderson Cancer Center, Translational
OA20: IMMUNOTHERAPY AND MARKERS Molecular Pathology, Houston/TX/United States of America, 3U.T.-M.D. Anderson
WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 Cancer Center, Thoracic Head and Neck Medical Oncology, Houston/TX/United
States of America, 4U.T.-M.D. Anderson Cancer Center, Department of Thoracic and
Cardiovascular Surgery, Houston/TX/United States of America, 5U.T.-M.D. Anderson
OA20.03 TUMORAL IL-7 RECEPTOR IS A POTENTIAL TARGET FOR Cancer Center, Thoracic and Cardiovascular Surgery, Houston/TX/United States of
LUNG ADENOCARCINOMA IMMUNOTHERAPY America, 6U.T.-M.D. Anderson Cancer Center, Thoracic and Cardiovascular Surgery,
Houstn/AL/United States of America, 7U.T.-M.D. Anderson Cancer Center, Surgery
Ming-Ching Lee1, Takashi Eguchi1, Zachary Tano 1, Kyuichi Kadota2, David
Pathology, Houston/TX/United States of America, 8U.T.-M.D. Anderson Cancer
Jones1, Prasad Adusumilli1 Center, Surgical Pathology, Houston/AL/United States of America, 9U.T.-M.D.
1
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, Anderson Cancer Center, Thoracic Surgery, Houston/TX/United States of America,
New York/NY/United States of America, 2Department of Diagnostic Pathology, 10
U.T.-M.D. Anderson Cancer Center, Biostatistics, Houston/TX/United States of
Kagawa University, Kagawa/Japan America, 11U.T.-M.D. Anderson Cancer Center, Thoracic/head and Neck Medical
Oncology, Houston/TX/United States of America, 12U.T.-M.D. Anderson Cancer
Background: IL-7/IL-7 receptor (IL-7R) interactions have been shown to Center, Thoracic/Head & Neck Medical Oncology, Houston/TX/United States of
prevent apoptosis in lung cancer cells and promote stromal pro-tumor America
immune cell homing and differentiation. The aim of this study is to
investigate the correlation between tumoral IL-7R expression and stromal Background: The clinical efficacy observed with PD-1/PD-L1 inhibitors in
pro-tumor immune cells (FoxP3+ Tregs and CD163+ M2 macrophages) and to non-small cell lung carcinoma (NSCLC) has prompted to characterize the
determine prognostic impact of the combination of these markers in lung immune response in lung tumors treated with chemotherapy. Our goal was
adenocarcinomas. Methods: In resected stage I lung adenocarcinoma (n=913; to determine the characteristics of immune microenvironment of localized,
1995-2009), antigen expression of IL-7R, FoxP3 and CD163 was evaluated by surgically resected, NSCLCs from patients who received and did not receive
immunohistochemistry (IHC) using tissue microarrays and mRNA expression neo-adjuvant chemotherapy. Using multiplex immunofluorescence (mIF) and
was quantified by RT-PCR. Prognosis was analyzed by both recurrence free image analysis, we investigated PD-1/PD-L1 expression, and quantified tumor
probability (RFP) and lung cancer-specific survival (LCSS). Results: In IHC infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs).
analysis, high tumoral IL-7R, stromal FoxP3, and stromal CD163 expression Methods: We studied formalin-fixed and paraffin embedded (FFPE) tumor
were individually associated with lymphatic/vascular invasion, and increasing tissues from 111 stage II and III resected NSCLC, including 61 chemonaïve
percentage of solid histological patten. A correlation was seen between IL-7R, (adenocarcinoma, ADC=33; squamous cell carcinoma, SCC=28) and 50
FoxP3 and CD163 expression by mRNA and IHC analyses (Figure1). The co- chemotherapy-treated (ADC=30; SCC=20) tumors. mIF was performed using
existence of high expression of these 3 markers was found in 16% of patients the Opal 7-color fIHC Kit™ and analyzed using the Vectra™ multispectral
and was associated with worse outcomes (Figure2). In multivariable analysis, microscope and inForm™ Cell Analysis software (Perkin Elmer, Waltham, MA).
triple marker co-existence was an independent risk factor for RFP (p=0.004) The markers studied were grouped in two 6-antibody panels: Panel 1, AE1/AE3
and LCSS (p=0.008). Conclusion: Tumoral IL-7 receptor is a potential target for pancytokeratins, PD-L1 (clone E1L3N), CD3, CD4, CD8 and CD68; and Panel 2,
lung adenocarcinoma immunotherapy. AE1/AE3, PD1, Granzyme B, FOXP3, CD45RO and CD57. Results: Positive PD-L1
expression (>5%) in malignant cells (MCs) was detected in 48% (n=53/111) of
NSCLCs. Overall, chemotherapy-treated tumors showed significantly higher
percentages of MCs expressing PD-L1 (median, 18.2%) than chemo-naïve cases
(median, 1.8%; P=0.033). Higher densities of inflammatory cells expressing
granzyme B (P=0.036), CD57 (P=0.001) and PD-1 (P=0.016) were detected
in chemotherapy-treated NSCLCs compared with chemo-naïve tumors. In
contrast, lower densities of FOXP3-positive regulatory T cells were detected
in chemotherapy-treated tumors when compared with chemo-naïve cases
(P=0.032). Following chemotherapy ADCs exhibited significantly higher
levels of CD57-positive cells (P<0.0001) and lower density of FOXP3-positive
cells (P=0.002) than chemo-naïve tumors. Chemotherapy-treated SCCs
demonstrated higher density of PD-1-positive cells than chemo-naïve tumors
(P=0.004). In chemotherapy-treated cancers, lower levels of CD4 helper T
positive cells and tumor associated macrophages (TAMs) CD68-positive
cells were associated with worse overall survival (OS; P=0.04 and P=0.005,
respectively) in univariate analysis. In chemotherapy-treated ADC patients,
lower levels of CD68-positive (P=0.010) and higher levels of FOXP3-positive
cells correlated with worse OS (P=0.044). Conclusion: We developed a robust

mIF panel of 10 markers to study inflammatory cells infiltrates in FFPE NSCLC Haiying Cheng 1, Murali Janakiram1, Alain Borczuk2, Juan Lin1, Wanglong Qiu1,
tumor tissues. Chemotherapy-treated NSCLCs exhibited higher levels of PD-L1 Huijie Liu1, Jordan Chinai1, Balazs Halmos1, Roman Perez-Soler 1, Xingxing Zang1
expression and T cell subsets compared to chemo-naïve tumors, suggesting 1
Albert Einstein College of Medicine/montefiore Medical Center, Bronx/United
that chemotherapy activates specific immune response mechanisms in States of America, 2Weill Cornell Medicine, New York/NY/United States of America
lung cancer. (Supported by CPRIT MIRA and UT Lung SPORE grants, and MD
Anderson Moon Shot Program). Background: Immunotherapy with antibodies against B7/CD28 family
members, including PD-1, PD-L1, and CTLA-4 has shifted the treatment
Keywords: Multiplex Immunofluorescence, neoadjuvant chemotherapy, Non- paradigm for non-small-cell lung carcinoma (NSCLC) with improved clinical
small cell lung carcinoma, Immune Response Profile outcome. HHLA2 is a newly discovered member of the family. By regulating
T-cell function, HHLA2 could contribute to tumor immune suppression and
thus be a novel target for cancer immunotherapy. There is limited information
and critical need to characterize its expression profile and clinical significance
OA20: IMMUNOTHERAPY AND MARKERS in NSCLC. Methods: We performed immunohistochemistry with an HHLA2-
specific antibody (clone 566.1) using tissue microarrays constructed from
679 NSCLC tumor tissues, including 392 cases in the discovery set and
OA20.06 PROSPECTIVE IMMUNOGENOMIC PROFILING OF NON- 287 cases in the validation cohort. We also studied clinico-pathological
SMALL CELL LUNG CANCER - THE ICON PROJECT characteristics of these patients. Results: Overall, HHLA2 was not detected
in most of normal lung tissue but expressed in 66% of NSCLC across different
Boris Sepesi1, Icon Team2, John Heymach3, Padmanee Sharma4, James Allison5,
subtypes. In particular, EGFR–mutated NSCLC was significantly associated
Bingliang Fang1, Jianjun Zhang6, Heidi Wagner4, Elena Bogatenkova5, Ignacio
with higher tumor HHLA2 expression in both discovery (EGFR vs. WT: 76% vs.
Wistuba7, Stephen Swisher8, Chantale Bernatchez5, Don Lynn Gibbons9
53%, P=0.01) and validation cohorts (89% vs. 69%, P=0.01). In one of the two
1
Thoracic and Cardiovascular Surgery, UT MD Anderson Cancer Center, Houston/ cohorts, HHLA2 expression was higher in lung adenocarcinoma as compared
TX/United States of America, 2The University of Texas MD Anderson Cancer Center,
to squamous and large cell histology, non-Hispanic White vs. Hispanics,
Houston/United States of America, 3Thoracic, Head & Neck Medical Oncology, The
University of Texas M. D. Anderson Cancer Center, Houston/TX/United States of
and tumors with high tumor infiltrating lymphocyte (TIL) density. In the
America, 4The University of Texas M.D. Anderson Cancer Center, Houston/TX/United multivariate analysis, EGFR mutation status and high TIL intensity were
States of America, 5The University of Texas M.D. Anderson Cancer Center, Houston/ independently associated with HHLA2 expression in lung adenocarcinoma.
United States of America, 6Department of Thoracic/head and Neck Medical Conclusion: HHLA2 is widely expressed in NSCLC and is associated with EGFR
Oncology, The University of Texas MD Anderson Cancer Center, Houston, Hx/TX/ mutation and high TILs in lung adenocarcinoma. It is potentially a novel target
United States of America, 7Translational Molecular Pathology, The University for lung cancer immunotherapy.
of Texas M.D. Anderson Cancer Center, Houston/TX/United States of America,
8
Thoracic and Cardiovascular Surgery, UT MD Anderson Cancer Center, Houston/ Keywords: immune checkpoint, lung cancer, HHLA2, mutation
United States of America, 9Thoracic/Head & Neck Medical Oncology, University of
Texas MD Anderson Cancer Center, Houston/TX/United States of America
Background: Previous attempts to define tumor and stromal immunologic

environment in non-small cell lung cancer (NSCLC) utilized archival tissue.
We established prospective comprehensive immonogenomic profiling
SESSION OA21: PALLIATIVE AND SUPPORTIVE CARE
protocol in NSCLC (ICON Project). The goal is to integrate immunomic, FOR LUNG CANCER PATIENTS
genomic, transcriptomic, proteomic, demographic, clinical, pathologic, and WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
outcome data from 100 surgically resected early stage NSCLC. Methods:
Tumor and normal lung tissue are collected at the time of surgery, blood
samples before and after surgery. Tumor samples are processed for tumor OA21.01 POOLED ANALYSIS OF THE INCIDENCE AND RISK OF
infiltrating lymphocyte (TILs) isolation and expansion; development of TREATMENT-RELATED PNEUMONITIS WITH ANTI-PD-1/PD-L1
patient derived xenografts (PDX), immunohistochemical immune markers,
THERAPIES IN CANCER PATIENTS
and immunopeptidome profiling. Blood samples are analyzed with flow
cytometry. Results: 57 patients with median age of 65 years (27 males) have Shaodong Hong, Wenfeng Fang, Yan Huang, Li Zhang
been enrolled within 5 months, of which 33 (66%) contributed samples to Sun Yat-Sen University Cancer Center, Guangzhou/China
the study. Four were never smokers, with others being former or current
Background: Blockade of programmed death 1 (PD-1), or its ligand, PD-L1,
smokers. Majority (N=27) had adenocarcinoma, 4 squamous cell carcinoma,
could restore T-cell immunity. Anti-PD-1/ or anti-PD-L1 antibodies have
and 2 pleomorphic carcinoma. 15 patients had stage I, 11 stage II, and 7 stage
demonstrated promising efficacy in the treatment of cancer patients. The
III disease; 5 patients received induction chemotherapy. Median tumor size
toxicity spectrum of PD-1/PD-L1 blockers is distinct from chemotherapy or
was 3.5 cm and 29 underwent R0 and 4 R1 resection. Pre-REP TIL expansion
other target agents. Pneumonitis is one of the major side effects of these
was successful in the majority of samples (68.2%, n=22). Twelve PDX models
drugs, and reported incidences vary substantially between clinical trials.
with a take rate of 40% have been generated. Interim analysis of tumor
We tried to investigate the overall incidence and risk of treatment-related
samples by IHC demonstrated higher median distribution of all cell types:
pneumonitis with anti-PD-1/PD-L1 therapies in cancer patients. Methods: A
CD3+ T cells, cytotoxic T cells CD8+, PD1+ cells, tumor associated macrophages
systematic search of literature up to January 2016 was performed in EDLINE,
(TAM) CD68+, TAM CD68+PD-L1+, CD20+B cells, memory T cells CD45R0,
EMBASE, and Cochrane databases to identify relevant clinical trials. Paired
natural killer cells CD57+, regulatory FOXP3+ T cells, and cytotoxic granzyme
reviewers independently selected articles for inclusion and extracted data.
B cells (cells/mm2) in the stroma as compared to the tumor compartment.
Incidence and relative risk (RR) of hypertension were calculated using a
Intra-tumoral regulatory FOXP3+T cells were more abundant in squamous
random-effects or fixed effects model, depending on the heterogeneity of
cell carcinomas compared to adenocarcinomas (median 312 vs 51 cells/mm2, p
the included studies. Results: A total of 23 clinical trials with 5333 patients
= 0.05). Higher concentration of intra-tumoral CD68+PD-L1+ expressing cells
were included. The overall incidence of all- and high-grade pneumonitis
was observed following neoadjuvant chemotherapy (median 97 vs 60 cells/
in cancer patients receiving anti-PD-1/PD-L1 therapies were 3.5% (95% CI,
mm2 no chemo; p= 0.077), as was the concentration of memory T cells CD45R0
2.9% to 4.3%) and 1.3% (95% CI, 1.1% to 1.9%), respectively. Anti-PD-1/PD-L1
(median 129 vs 30 cells/mm2, no chemo; p = 0.077). Mass spectrometry-
antibodies were associated with a significantly increased risk of all-grade
based immunopeptidome analysis identified several thousand peptides,
pneumonitis in patients with cancer with an RR of 5.47 (95% CI, 2.17 to 13.81;
of which 4 promising antigens have been chosen for further development
p<0.001) compared with controls. The risk of high-grade pneumonitis was also
as immunotherapeutic T-cell targets. Conclusion: The ICON is an ongoing,
increased with the use of anti-PD-1/PD-L1 antibodies, though not statistically
ambitious prospective project that aims to define the baseline immunologic
significant (RR 3.86; 95% CI 0.98 to 15.22; p=0.054). Conclusion: Patients
characteristics of surgically resectable NSCLC. The rapid enrollment
with cancer receiving anti-PD-1/PD-L1 therapies have a significant risk of
illustrates the enthusiasm for tumor immunoprofiling amongst patients
developing pneumonitis. Early and appropriate management is strongly
and physicians alike. Data from this patient cohort will serve as a baseline
recommended to avoid unnecessary dose reductions and transitory or
comparison for upcoming neoadjuvant immunotherapy trials.
definitive treatment discontinuations due to pneumonitis.
Keywords: NSCLC, immunomic, genomic, TILs
Keywords: pneumonitis, PD-1, PD-L1, Cancer
OA20: IMMUNOTHERAPY AND MARKERS

WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30 OA21: PALLIATIVE AND SUPPORTIVE CARE FOR LUNG CANCER PATIENTS
OA20.07 HHLA2, A NEW IMMUNE CHECKPOINT MEMBER OF THE

OA21.02 ALK-REARRANGED NON-SMALL CELL LUNG CANCER IS
B7 FAMILY, IS WIDELY EXPRESSED IN HUMAN LUNG CANCER AND
ASSOCIATED WITH A HIGH RATE OF VENOUS THROMBOEMBOLISM
ASSOCIATED WITH MUTATIONAL STATUS
Alona Zer 1, Mor Moskovitz2, David Hwang 3, Anat Hershko-Klement4, Ludmila they or their loved one experienced during and after treatment, as well as 5+
Fridel1, Grzegorz Korpanty3, Elizabeth Dudnik1, Nir Peled1, Tzippy Shochat1, years after diagnosis. They also indicated which of these side-effects were
Natasha Leighl5, Geoffrey Liu6, Ronald Feld6, Ronald Burkes4, Mira Wollner2, most problematic during those time periods. Respondents were also for
Ming Tsao7, Frances Shepherd8 demographic information and for open-ended responses about their unmet
1
Rabin Medical Center, Petach Tikva/Israel, 2Rambam Medical Center, Haifa/Israel, needs during care and follow-up. Results: Respondents indicated a high
3
Princess Margaret Cancer Centre, University Health Network (UHN), Toronto/ON/ rate of side effects, with over 95% reporting at least one. Importantly, both
Canada, 4 Mount Sinai Hospital, Toronto/ON/Canada, 5Medical Oncology, Princess patients and caregivers reported that physical side effects were significantly
Margaret Cancer Centre, Toronto/Canada, 6Princess Margaret Cancer Centre, more problematic during treatment but that emotional side effects were
Toronto/Canada, 7Departments of Pathology, Princess Margaret Cancer Centre and more problematic after treatment and in the long-term. Patients rated
University of Toronto, Toronto/Canada, 8Princess Margaret Cancer Centre, Toronto/ anxiety, fatigue, and shortness of breath as the most problematic short and
ON/Canada
long-term post-treatment side effects, with 18-29% of patients indicating
Background: Patients with lung cancer are at increased risk for venous these items at a particular time period. During treatment, gastrointestinal
thromboembolism (VTE), particularly those receiving chemotherapy. It is issues including constipation (18%), diarrhea (17%), and nausea (14%) were
estimated that 8-15% of patients with advanced non-small cell lung cancer also identified as highly problematic side effects by the patients. Caregivers
(NSCLC) experience a VTE in the course of their disease. The incidence in reported similar effects but also rated pain as problematic across all time
patients with specific molecular subtypes of NSCLC is unknown. We periods (15-24%) and identified loss of appetite (28%) and weight loss (25%)
undertook this review to determine the incidence of VTE in patients with during treatment. When questioned about unmet needs during treatment
ALK-rearranged NSCLC. Methods: We identified all patients with ALK- and survivorship, respondents frequently commented that their treatment
rearranged NSCLC, diagnosed and/or treated at the Princess Margaret Cancer team focused on treatment and survival and not on managing side effects.
Centre (PM CC) in Canada between July 2012 and January 2015. Retrospective Conclusion: Side effect management is a clear unmet need for lung cancer
data were extracted from electronic medical records. We then included a patients and to help support their caregivers. Our data show high levels of
validation cohort comprising all consecutive patients with ALK-rearranged emotional and physical side effects and a perceived lack of support for proper
NSCLC treated in two tertiary centers in Israel. Results: Within the PM CC management. Notably, emotional side effects are prevalent after treatment
cohort, of 55 patients with ALK-rearranged NSCLC, at a median follow-up of for lung cancer into long-term survivorship and are frequently cited as the
22 months, 23 (42%) experienced VTE. Patients with VTE were more likely to most problematic issue for those no longer in active treatment.
be Caucasian (p=0.006). The occurrence of VTE was associated with a trend
Keywords: supportive care, side effects, survivorship, lung cancer
towards worse prognosis (overall survival HR=2.88, p=0.059). Within the
validation cohort (N=43), VTE rate was 28% at a median follow-up of 13
months. Combining the cohorts (N=98) the VTE rate was 36%. Patients with
VTE were younger (age 52 vs 58, p=0.04) and had a worse ECOG performance
OA21: PALLIATIVE AND SUPPORTIVE CARE FOR LUNG CANCER PATIENTS
status (p=0.04). VTE was associated with shorter OS (HR=5.71, p=0.01). WEDNESDAY, DECEMBER 7, 2016 - 11:00-12:30
OA21.05 WET M1A NON-SMALL CELL LUNG CANCER: IS IT POSSIBLE

TO PREDICT RECURRENCE OF PLEURAL EFFUSION?
Fernando Abrao1, Igor Abreu1, Mariana Oliveira2, Geisa Viana2, Riad Younes 1
1
Oncology Center Hospital AlemÃo Oswaldo Cruz, SÃo Paulo/Brazil, 2 Santa
Marcelina Medical School, SÃo Paulo/Brazil
Background: Pleural and oncological treatment options for malignant

pleural effusion (MPE) are increasing and hence, more accurate prognosis
at presentation may help to identify patients with the higher risk of pleural
recurrence, in order to individualize more intensive treatment strategies.
The aim of this study was to identify predictors of malignant pleural effusion
recurrence in patients with M1a non-small cell lung cancer (NSCLC) Methods:
All patients with NSCLC and MPE submitted to pleural palliative procedures
including simple pleural drainage, videothoracoscopic pleural drainage,
pleurodesis and indwelling pleural catheter were enrolled in a prospective
study between 2014 and 2015, and divided into two groups. Group I included
patients who had pleural recurrence, and Group II with no pleural recurrence
after the palliative procedures. Prognostic factors for pleural recurrence were
identified by univariate analysis, using Fisher’s exact test for the analysis
of categorical variables and Student’s t test for quantitative variables.
Conclusion: We found the rate of VTE in our ALK-rearranged cohort is 3-5-fold Subsequently the significant variables were entered into a multivariate
higher than previously reported for the general NSCLC population. This logistic regression analysis (with p< 0.05 considered significant). The cutoff
warrants confirmation in larger cohorts. points for any significant continuous variables were determined by receiver
operating characteristics (ROC) analysis. Results: A total of 82 patients
Keywords: ALK, VTE, Thrombosis, NSCLC were included in the analysis. Median follow-up time for surviving patients
was 81 days (range 1 to 1070 days). There were 15 patients (18.3%) in Group I
and 67 patients (81.7%) in Group II. Univariate analysis of factors affecting
postoperative recurrence were: adenosine deaminase concentration in
OA21: PALLIATIVE AND SUPPORTIVE CARE FOR LUNG CANCER PATIENTS pleural fluid < 16 mg/dl (p=0.04), albumin concentration in pleural fluid < 2.4
mg/dl (p= 0.03), administration of second-line palliative chemotherapy (p=
0.018) and type of procedure (simple pleural drainage vs. videothoracoscopic
OA21.03 UNMET NEEDS IN PHYSICAL AND EMOTIONAL SIDE pleural drainage, pleurodesis and indwelling pleural catheter) (p= 0.023).
EFFECTS DURING LUNG CANCER TREATMENT AND SURVIVORSHIP At the multivariate analysis, only the type of procedure (simple pleural
drainage)( p= 0.031) was identified as independent predictor of recurrence.
Jennifer King 1, Jamal Bankhead2, Maureen Rigney3
1 Conclusion: In our cohort of NSCLC patients with MPE submitted to pleural
Science & Research, Lung Cancer Alliance, Washington/DC/United States of
palliative procedures, simple pleural drainage was the only significantly factor
America, 2Medical Outreach, Lung Cancer Alliance, Washington/DC/United States
of America, 3Support Services, Lung Cancer Alliance, Washington/DC/United States associated with recurrence of MPE. The identification of this factor may assist
of America the choice of the optimal palliative technique, at the first episode of MPE in
NSCLC patients. Definitive procedure as pleurodesis is recommended, the
Background: Previous research has shown that supportive care needs in lung indwelling pleural catheter or videothoracoscopic drainage are options for
cancer patients are high and that this population may have significantly patients whom lung are trapped.
more unmet care needs than other cancer patients. Our goals for this study
were to determine the most prevalent and problematic side-effects of lung Keywords: Carcinoma, Non-Small-Cell Lung, palliative care, recurrence
cancer and lung cancer treatment in our community and to understand
where both patients and caregivers felt there were unmet needs. Methods:
A Community Needs Assessment survey was distributed to lung cancer
patients and caregivers electronically between 11/9/2015 and 2/8/2016. 820 OA21: PALLIATIVE AND SUPPORTIVE CARE FOR LUNG CANCER PATIENTS
people responded, including 471 patients/survivors and 349 caregivers, 181
of whom identified as the primary caregiver. The overall completion rate
was 72.6%, similar for both groups. Respondents identified all side effects OA21.06 TURNING BEST SUPPORTIVE CARE INTO ACTIVE CARE. A

SERVICE DEVELOPMENT FOR PATIENTS WITH ADVANCED LUNG that historical control has an exponential survival distribution and a median
CANCER IN NHS FIFE, SCOTLAND survival of 12.1 Months (Vogelzang et al.). The sample size provides 80%
power with a two sided alpha of 0.05 to detect a Hazard Ratio of 0.67 for
Joanna Bowden, Catriona Macpherson, Steinunn Boyce, Morag Lyell, Stephen
OS, compared to the historical data. Results: To date, 42 patients have been
Fenning, Sheena Scragg
enrolled in the trial with an average follow up time of 11.5 months. Median
Palliative Care, NHS Fife, Su/United Kingdom
age is 67±9 (range 43-78), 79% are male and 48% smokers. 14% (6 patients)
Background: In South East Scotland, 40% of patients with newly-diagnosed have metastatic disease and 33% (14 patients) have an ECOG score of 1.
lung cancer are unfit for anti-cancer treatment and are for ‘best supportive Median survival has not been reached at this time. The 12-month survival
care’ (BSC). Many more become for BSC following palliative anti-cancer rate is 79.7% (95% CI 57.2-91.2) and median PFS is 7.3 months (95% CI 5.6-NA).
treatment or disease relapse. But there is no consensus about what No device-related serious adverse events (AEs) have been reported to date.
constitutes BSC and who should deliver it. Patients and families are left Expected TTFields-related dermatitis was reported in 55% (23 patients).
unclear about realistic goals of care, and about what support and follow-up Only 2 patients had grade 3 dermatitis. The following severe (grade 3-4)
they can expect. Given the typically short prognosis (2012 data from NHS systemic AEs were reported: hematological (26%), hepatobiliary (2%),
Fife reveals a median survival of 73 days), rapidly changing needs and high respiratory (2%). Conclusion: These interim results of the ongoing STELLAR
risk of hospital admission, the lack of consistency in BSC can be a serious study demonstrated no safety concerns for the combination of TTFields to
barrier to high quality end of life care. Therefore, Fife Specialist Palliative the thorax together with standard chemotherapy for previously untreated
Care have developed and piloted a model of ‘proactive best supportive care’ mesothelioma patients. The 12-month survival rate was significantly higher,
for patients with incurable lung cancer and those close to them. Methods: and PFS longer, than that of historical controls reported by Vogelzang et al.
The new model of best supportive care was based around the following Final analysis of the study will be performed after enrollment and follow up of
framework: *Robust identification of all patients for BSC *Comprehensive all 80 patients in the study are completed.
palliative care assessment and care planning *Care coordination and follow-
Keywords: TTFields, Tumor Treating Fields, mesothelioma, STELLAR
up Every assessment began with sensitive discussion about the lung cancer
diagnosis and BSC. Detailed assessments of physical, psychological, practical
and spiritual needs followed and immediate care plans were agreed. Where
appropriate, anticipatory care planning was started. Structured letters were
OA22: NOVEL TRIALS AND BIOMARKERS IN MPM
available online to all health professionals within two days. Patients were WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
followed-up and supported for as long as they lived. Results: 246 patients
were supported by the new model of care during its first 15 months. Patients
were assessed wherever they were. Most were assessed and followed-up at OA22.02 NINTEDANIB PLUS PEMETREXED/CISPLATIN IN PATIENTS
home or in the acute hospital, with a minority fit to attend clinic. Unnecessary WITH MPM: PHASE II FINDINGS FROM THE PLACEBO-CONTROLLED
outpatient appointments were cancelled. Patients and families appreciated LUME-MESO TRIAL
the potential to maintain independence afforded by knowing where to access Federica Grosso 1, Nicola Steele2, Silvia Novello3, Anna Nowak4, Sanjay Popat5,
support when needed. The process of care coordination was not directly Laurent Greillier6, Thomas John7, Natasha Leighl8, Martin Reck9, Paul Taylor 10,
visible to them, but the quality of care it provided was deeply appreciated. Nick Pavlakis11, Jens Benn Sørensen12, David Planchard13, Giovanni Ceresoli14,
Under the new model of care, patients spent significantly less time in the Brett Hughes15, Julien Mazieres16, Mark Socinski17, Martha Mueller 18, Ute Von
acute hospital before they died, with both length of stay and total bed Wangenheim18, Arsene Bienvenu Loembe19, Nassim Morsli20, Jose Barrueco21,
days reduced by almost a third (comparisons with local data from 2012). Giorgio Scagliotti3
Conclusion: A new model of proactive BSC in lung cancer has been successfully 1
Department of Oncology, Ss Antonio E Biagio Hospital, Alessandria/Italy, 2The
developed and piloted in NHS Fife. Patients and those close to them are Beatson West of Scotland Cancer Centre, Glasgow/United Kingdom, 3Department
now consistently supported from the point of diagnosis, with the impact of of Oncology, University of Turin, Turin/Italy, 4School of Medicine and Pharmacology
improved quality of care and more appropriate use of healthcare resources. Qeii, Medical Centre Unit, University of Western Australia, Crawley/WA/Australia,
5
Royal Marsden NHS Foundation Trust, London/United Kingdom, 6 Assistance
Keywords: proactive best supportive care, care coordination, appropriate use Publique - Hôpitaux de Marseille, Aix Marseille University, Marseille/France, 7Olivia
of healthcare resources, quality of care and experience Newton-John Cancer Centre, Austin Health, Melbourne/VIC/Australia, 8Princess
Margaret Cancer Centre, Toronto/ON/Canada, 9Department of Thoracic Oncology,
Lung Clinic Grosshansdorf, Member of the German Center for Lung Research (Dzl),
Grosshansdorf/Germany, 10University Hospitals of South Manchester NHS Trust,
Manchester/United Kingdom, 11Northern Cancer Institute, Sydney/NSW/Australia,
12
Rigshospitalet Blegdamsvej, København Ø/Denmark, 13Department of Medical
SESSION OA22: NOVEL TRIALS AND BIOMARKERS IN MPM Oncology, Gustave Roussy, Villejuif/France, 14Department of Oncology, Cliniche
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 Humanitas Gavazzeni, Bergamo/Italy, 15The Prince Charles Hospital, Chermside/
QLD/Australia, 16Onco, Hop Larrey, Toulouse/France, 17University of Pittsburgh,
Pittsburgh/PA/United States of America, 18Boehringer Ingelheim Pharma Gmbh
& Co. Kg, Biberach/Germany, 19Boehringer Ingelheim B.V., Alkmaar/Netherlands,
OA22.01 STELLAR - INTERIM RESULTS OF A PHASE 2 TRIAL OF 20
Boehringer Ingelheim France S.A.S., Paris/France, 21Boehringer Ingelheim
TTFIELDS WITH CHEMOTHERAPY FOR FIRST LINE TREATMENT OF Pharmaceuticals Inc., Ridgefield/CT/United States of America
MALIGNANT MESOTHELIOMA
Background: Standard first-line treatment for patients with unresectable
Federica Grosso1, Jarek Mądrzak2, Rodryg Ramlau3, Susana Cedres Perez4,
malignant pleural mesothelioma (MPM) is pemetrexed/cisplatin, yielding a
Lucio Crinò5, Antonio Chella6, Manlio Mencoboni7, Birgitta Hiddinga8,
median overall survival (OS) of only ~1 year, thus new approaches are required.
Giovanni Ceresoli9
1
As demonstrated by the bevacizumab MAPS study, inhibition of the VEGF
Department of Oncology, Ss Antonio E Biagio Hospital, Alessandria/Italy, pathway is of interest as a treatment approach for MPM. Nintedanib is an
2
University Hospital Gdansk, Gdansk/Poland, 3Department of Oncology, Poznan
oral, triple angiokinase inhibitor of VEGFR, PDGFR and FGFR. This study will
University of Medical Sciences, Poznan/Poland, 4 Medical Oncology, Vall D´hebron
Institute of Oncology/vall D´hebron University Hospital, Barcelona/Spain, 5Perugia evaluate the efficacy and safety of nintedanib plus pemetrexed/cisplatin in
Hospital, Perugia/Italy, 6 A.O. Universitaria Pisana – Ospedale Cisanello, Pisa/Italy, patients with advanced MPM. Methods: Patients with unresectable MPM
7
Villa Scassi, Genova/Italy, 8Department of Radiology, Antwerp University Hospital (chemo-naïve, ECOG PS 0–1) were stratified by histology (epithelioid/biphasic)
and University of Antwerp, Edegem/Belgium, 9 Cliniche Humanitas Gavazzeni, and randomised (1:1) to receive up to 6 cycles of pemetrexed (500 mg/m2)/
Bergamo/Italy cisplatin (75 mg/m2) on Day 1 plus nintedanib (200 mg bid)/placebo on Days
2–21. Patients without disease progression received maintenance treatment
Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional with nintedanib/placebo. The primary endpoint was progression-free survival
treatment modality, based on low intensity alternating electric fields (PFS). Results: 87 patients were randomised to receive pemetrexed/cisplatin,
delivered non-invasively using a portable, home use, medical device. In-vitro, plus nintedanib/placebo. Patient characteristics were comparable between
human mesothelioma cells were found to be highly susceptible to TTFields. the groups. PFS was longer in the nintedanib vs the placebo arm, in both the
TTFields have been shown to extend survival of patients with glioblastoma overall study population and in epithelioid patients (Table 1). Preliminary OS
when added to standard of care chemotherapy. Methods: The trial will accrue data also favour nintedanib. All patients experienced at least one adverse
a total of 80 patients with unresectable, previously untreated mesothelioma. event (AE, any grade), with 7% of patients in the nintedanib arm discontinuing
Patients are treated with TTFields in combination with pemetrexed and due to AEs, vs 15% with placebo. Serious AEs occurred in 36% vs 42% of
cisplatin or carboplatin. Continuous TTFields at 150 kHz for a minimum of patients in the nintedanib and placebo arms, respectively. The most common
18 hours/day are applied to the thorax together with standard dosing of ≥grade 3 AEs occurring in nintedanib vs placebo patients were neutropenia
chemotherapy. Inclusion criteria include ECOG 0-1, pathological evidence (34% vs 10%), ALT increase (14% vs 2%) and gamma glutamyltransferase
mesothelioma and at least one measurable lesion according to modified increase (14% vs 0%). Conclusion: Nintedanib plus pemetrexed/cisplatin
RECIST criteria. Patients are followed q3 weeks (CT scan q6 weeks) until demonstrated clinical efficacy with improved PFS and a tolerable safety
disease progression. The primary endpoint is overall survival (OS) and profile in patients with unresectable MPM. Based on these promising
secondary endpoints are response rate, progression free survival (PFS) and findings, this Phase II study was extended to a confirmatory Phase III trial,
treatment-emergent toxicity. This prospective, single arm study assumes which is currently enrolling patients. Clinical trial identifier: NCT01907100.
Keywords: malignant pleural mesothelioma, phase II, angiogenesis, asymptomatic asbestos-exposed individuals, 16 individuals with benign
antiangiogenesis asbestos-related diseases and fourteen healthy non-exposed persons were
included. After 2 hours of fasting, participants breathed tidally for 5 minutes
through a mouthpiece connected to a VOC filter. Subsequently, a full vital
capacity was captured in a Tedlar bag of which 500 ml was immediately
OA22: NOVEL TRIALS AND BIOMARKERS IN MPM transferred on a TenaxGR -column. Samples were thermally desorbed followed
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 by GC-MS analysis (Agilent 6890A–Thermo Focus DSQII). VOCs were manually
selected in the chromatogram and standardised to an internal standard
OA22.03 HMGB1, A TARGET FOR MESOTHELIOMA THERAPY AND A (toluene-d8). Only VOCs with a S/N-ratio>10 were used. Using SPSSv23,
significant differences were searched and ROC-curves for discriminating MPM
BIOMARKER TO DETECT ASBESTOS EXPOSURE AND TO IDENTIFY
from all control groups were constructed. VOCs which had an AUCROC>0.80 are
MESOTHELIOMA PATIENTS
reported. Results: 114 VOCs were selected of which 17 were significantly
Haining Yang 1, Harvey Pass2, Michele Carbone1 different between MPM patients and controls. Of these, 7 had AUCROC>0.80
1
University of Hawaii Cancer Center, Honolulu/HI/United States of America, and are possible markers for MPM diagnosis.
2
Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York/
NY/United States of America
Background: Millions of people have been potentially exposed to asbestos,

the primary cause of malignant mesothelioma (MM). Presently, no reliable
biomarkers are available to identify among potentially exposed people,
those individuals who have actually been exposed and who are at high risk
of MM. High Mobility Group Box Protein-1 (HMGB1) is a key mediator of
asbestos-induced inflammation and MM pathogenesis. Recently, HMGB1
hyper-acetylation has been functionally associated to its active release by
inflammatory cells. Here, we compared the serum levels of total and hyper-
acetylated HMGB1 in individuals professionally exposed to asbestos, MM
patients and healthy unexposed controls. Methods: We compared the serum
levels of total and hyper-acetylated HMGB1 in individuals professionally
exposed to asbestos, MM patients and healthy unexposed controls. Conclusion: The large discriminative power and good sensitivity and
Previously proposed MM biomarkers fibulin-3, osteopontin, and mesothelin specificity imply the possibility to use breath analysis for MPM screening.
were also blindly measured in blood collected from participants to the Therefore, persons exposed to asbestos with a positive test should be
study. Results: HMGB1 serum levels reliably distinguished asbestos-exposed considered for follow-up in a cost-effective way, decreasing the need for
individuals and MM patients from unexposed controls. Moreover, the levels of CT-scans and radiation exposure in low-risk persons. Further work includes
total and hyper-acetylated HMGB1 were significantly higher in MM patients combining models for discrimination and validating these findings.
compared to asbestos-exposed individuals, and did not vary with tumor
stage, suggesting that early lesions are also associated to increased HMGB1 Keywords: Mesothelioma, biomarker, breath analysis, volatile organic
levels. At a cutoff value of 2.00 ng/mL, the sensitivity and specificity of hyper- compounds
acetylated serum HMGB1 in differentiating MM patients from asbestos-
exposed individuals was 100%, outperforming, in parallel experiments, other
previously proposed biomarkers: osteopontin, fibulin-3, and mesothelin.
When comparing MM patients to patients with other non-MM cytologically OA22: NOVEL TRIALS AND BIOMARKERS IN MPM
benign or malignant pleural effusion, the combination of two biomarkers, WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
HMGB1 and fibulin-3, provided the highest sensitivity and specificity in
differentiating these two groups. Moreover, we found that HMGB1 drives OA22.06 REFINEMENT OF THE PROGNOSTIC MIR-SCORE FOR USE
MM development and sustains MM progression, and we demonstrated that
IN DIAGNOSTIC SPECIMENS FROM CHEMO-NAÏVE MALIGNANT
targeting HMGB1 inhibits MM cell growth and motility in vitro, reduced tumor
growth in vivo and prolonged survival. Conclusion: Despite the relatively
PLEURAL MESOTHELIOMA PATIENTS
small size of our cohorts, our results are of exceptional significance and Michaela Kirschner 1, Bart Vrugt2, Martina Friess1, Mayura Meerang1, Peter
clinical relevance as they provide the first biomarker of asbestos exposure Wild2, Nico Van Zandwijk 3, Glen Reid3, Walter Weder 1, Isabelle Opitz1
1
and indicate that hyper-acetylated HMGB1 is a very sensitive and specific University Hospital Zurich, Division of Thoracic Surgery, Zurich/Switzerland,
2
biomarker to differentiate MM patients from individuals occupationally University Hospital Zurich, Institute of Surgical Pathology, Zurich/Switzerland,
3
exposed to asbestos and unexposed controls. Moreover, our results on Asbestos Diseases Research Institute, Concord/NSW/Australia
HMGB1 inhibitors indicate that HMGB1 targeting hampers the malignant
Background: A 6-microRNA signature (miR-Score, Kirschner et al 2015) was
phenotype of MM, offering a novel potential therapeutic approach to
previously demonstrated to show high prognostic accuracy in a series of
patients afflicted with this dismal disease.
surgical specimens (with and without induction chemotherapy). In the
Keywords: biomarker, HMGB1, Mesothelioma, asbestos present study we investigated these microRNAs in an independent cohort
of MPM patients all treated with induction chemotherapy followed by
extrapleural pneumonectomy (EPP). The main focus of the study was to
evaluate the possible effects of induction chemotherapy on microRNA
OA22: NOVEL TRIALS AND BIOMARKERS IN MPM expression and to refine and validate the miR-Score for use in chemo-naïve
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 diagnostic specimens. Methods: We identified a cohort of 120 MPM patients
who received chemotherapy followed by EPP between 1999 and 2014 at
University Hospital Zurich. At present microRNA analysis (RT-qPCR) has
OA22.05 BREATH ANALYSIS BY GAS CHROMATOGRAPHY-MASS been carried out in 34 pairs of chemo-naïve (diagnostic biopsy) and chemo-
SPECTROMETRY CAN BE USED TO SCREEN FOR PLEURAL treated (EPP) specimens. Paired-samples t-test was employed to determine
MESOTHELIOMA differences in microRNA expression pre- and post-chemotherapy. Accuracy
Kevin Lamote 1, Lore Vandermeersch2, Herman Van Langenhove2, Joris Van of the miR-Score in predicting a good prognosis (>20 months survival post-
Cleemput3, Kristiaan Nackaerts4, Jan Van Meerbeeck5 surgery) was evaluated by ROC curve analysis. In addition, binary logistic
1
Internal Medicine, Ghent University, Gent/Belgium, 2Environmental Organic regression modelling was used to build a refined miR-Score. Results: Applying
Chemistry and Technology (Envoc), Ghent University, Ghent/Belgium, the miR-Score to chemo-naïve diagnostic specimens revealed an area under
3
Occupational Health Service, Eternit Nv, Kapelle-Op-Den-Bos/Belgium, 4University the ROC curve (AUC) of 0.65 (95% CI: 0.46-0.84), and the same analysis on
Hospitals KU Leuven, Leuven/Belgium, 5Thoracic Oncology, Antwerp University the EPP specimens gave an AUC of 0.57 (95% CI: 0.37-0.77). Therefore, the
Hospital, Edegem/Belgium accuracy of the miR-Score was lower than observed in the previous study.
However, pairwise comparison of microRNA expression before and after
Background: Malignant pleural mesothelioma (MPM) is an asbestos-related
chemotherapy showed that although not reaching statistical significance, the
tumour with poor prognosis. Since MPM is diagnosed at advanced stage due
levels of several microRNAs were lower following induction chemotherapy.
to non-specific symptoms and investigations, it is thought that only an early
We next employed binary logistic regression modelling on microRNA levels in
diagnosis will improve patient’s outcome. Breathomics allows to detect
chemo-naïve tissue to determine whether a refined microRNA signature less
volatile organic compounds (VOCs) in breath which can be used as non-
susceptible to chemotherapy-induced changes could be created. A refined
invasive biomarkers. Although we were able to discriminate MPM patients
miR-Score consisting of miR-221 and miR-30e, the two microRNAs least
from controls using ion mobility spectrometry breathomics, we were not able
affected by chemotherapy, achieved AUCs of 0.77 (95% CI: 0.61-0.94) and
to identify specific VOCs. Therefore, we aimed to identify VOCs in the breath
0.80 (95% CI: 0.64-0.96) in diagnostic and EPP specimens, respectively. When
of MPM persons and persons at risk with gas chromatography-mass
applied to samples from the previous study, the refined score resulted in an
spectrometry (GC-MS). Methods: Fourteen MPM patients, eighteen
AUC of 0.72 (95% CI: 0.54-0.90). Conclusion: This validation and refinement

study has shown that the expression of several miR-Score microRNAs appears
to be affected by standard chemotherapy. A refined miR-Score was generated OA23.01 ANTI-EGFR MONOCLONAL ANTIBODIES PLUS
which is less susceptible to the effect of chemotherapy and may have CHEMOTHERAPY IN THE FIRST-LINE TREATMENT OF ADVANCED
prognostic value when applied to diagnostic specimens. Further validation NSCLC: A META-ANALYSIS
in additional paired samples and investigation of the effect of cisplatin,
Gustavo Stock1, Pedro Aguiar Jr 1, Ilka Santoro1, Hakaru Tadokoro1, Ramon De
pemetrexed and gemcitabine on microRNA expression are ongoing.
Mello2, Gilberto Lopes 3
1
Keywords: malignant mesothelioma, microRNA, Prognosis Universidade Federal de SÃo Paulo, SÃo Paulo/Brazil, 2Universidade Do Algarve,
Faro/Portugal, 3HCOR Cancer Center, SÃo Paulo/Brazil
Background: Monoclonal Antibodies (mAbs) against the Epidermal Growth

Factor Receptor (EGFR) in association with platinum-based doublet
OA22: NOVEL TRIALS AND BIOMARKERS IN MPM
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 chemotherapy have emerged as a potential first-line treatment option for
advanced non-small cell lung cancer (NSCLC). This study was conducted
to systematically review available data and evaluate the efficacy and
OA22.07 CORRELATION OF CT SCAN BASED TUMOR VOLUME toxicity of anti-EGFR mAbs plus chemotherapy vs chemotherapy alone for
MEASUREMENT TO ACTUAL RESECTED TUMOR VOLUME - A NEW advanced NSCLC. Methods: We carried out a search on network databases
T-FACTOR? and oncology conference abstracts for studies between 1990 and January
Olivia Lauk1, Martina Friess1, Thi Dan Linh Nguyen-Kim2, Thomas 2016. Only prospective randomized clinical trials were included. Primary
Frauenfelder2, Sven Hillinger 1, Burkhardt Seifert3, Ilhan Inci1, Walter Weder 1, endpoints were overall survival (OS) and toxicity frequency. Secondary
Isabelle Opitz 1 endpoints were progression-free survival (PFS) and overall response rate
1 (ORR). Subgroup analysis was performed assessing histological subtypes,
University Hospital Zurich, Division of Thoracic Surgery, Zurich/Switzerland,
2
University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, EGFR protein expression by immunohistochemistry (IHC), EGFR gene copy
Zurich/Switzerland, 3Eth Zurich, Zurich/Switzerland number by fluorescence in-situ hybridization (FISH), EGFR mutation status,
and smoking status. Results: Seven studies (2 with necitumumab and 5 with
Background: Tumor volume has been reported to be a valuable prognosticator cetuximab) were included with 5,057 patients. Compared to chemotherapy
for malignant pleural mesothelioma (MPM) survival. We wanted to assess alone, significant benefits were demonstrated by the addition of anti-EGFR
the precision of CT scan based preoperatively measured tumor volume mAb to chemotherapy in OS (HR 0.90; 95%CI 0.84-0.95), PFS (HR 0.93;
when correlated to the actual resected tumor weight and tumor volume 95%CI 0.87-0.98), and ORR (OR 1.27; 95%CI 1.06-1.51). In subgroup analyses,
after pleurectomy/decortication. Methods: From 10/2012 – 06/2016 the the association of anti-EGFR mAb was associated with improved OS among
tumor weight of surgery specimens was measured in 32 patients undergoing patients with squamous histology (HR 0.84; 95%CI 0.76-0.92), tumours with
macroscopic complete resection by (extended) pleurectomy/decortication ((e) high EGFR expression by IHC (HR 0.83; 95%CI 0.70-0.98), and smokers (HR
P/D). The median tumor weight of all patients was (n=32) 443g (95-783g). In 0.87; 95%CI 0.79-0.96). Patients with squamous histology and high EGFR
all patients tumor volume was measured in the CT or PET-CT scans performed expression by IHC achieved the highest benefit with the association (HR 0.71;
before surgery as described previously (Frauenfelder 2011). Tumor volume of 95%CI 0.59-0.86). The OS with the association also seemed to be higher in
the resected specimen was additionally measured in 21 patients. Relations EGFR FISH negative and in EGFR wild-type tumours, but without statistical
between tumor weight, tumor volume at surgery, CT-volume, cT stage and pT significance. Chemotherapy plus anti-EGFR mAb caused more grade 3 or
stage were analyzed using Spearman rank correlation. Results: Median time worse adverse events (OR 1.73; 95%CI 1.50-2.00), remarkedly these known to
between CT scan and surgery was 18 days (range 1-48). The analysis revealed be associated with anti-EGFR therapy, such as acne-like rash (OR 34.13; 95%CI
a moderate correlation between CT tumor volume and weight (p=0.001, 16.40-71.00) and hypomagnesemia (OR 6.23; 95%CI 3.04-12.77). Conclusion:
correlation coefficient 0.58, CT volume and tumor volume at surgery showed Anti-EGFR therapy plus platinum-based doublet chemotherapy as first-line
strong correlation (p=0.001, correlation coefficient 0.65). No significant treatment demonstrated significant efficacy benefits with acceptable
correlation was observed between cT stage and tumor weight (p=0.1, toxicity for advanced NSCLC. This benefit is more expressive among squamous
correlation coefficient 0.31), but a moderate correlation between cT stage and histology with high EGFR expression. EGFR protein expression by IHC seems
CT volume (p=0.001, correlation coefficient 0.58) as well as specimen volume to be a predictive marker for survival in the association group. Further
(p=0.008, correlation coefficient 0.58). There was a moderate correlation research is needed to corroborate these findings.
of tumor weight with pT stage (p=0.02, correlation coefficient 0.42), but
no correlation of CT volume (p=0.1, correlation coefficient 0.31) as well as Keywords: anti-EGFR, biomarker, Targeted therapy, Individual Medicine
specimen volume with the pT stage (p=0.2, correlation coefficient 0.32).
OA23: EGFR TARGETED THERAPIES IN ADVANCED NSCLC

OA23.02 EFFICACY AND SAFETY OF NECITUMUMAB CONTINUATION

MONOTHERAPY IN PATIENTS WITH EGFR-EXPRESSING TUMORS IN
SQUIRE, A PHASE 3 STUDY
Tudor Ciuleanu1, Mark Socinski2, Coleman Obasaju3, Alexander Luft4,
Aleksandra Szczęsna5, Rodryg Ramlau6, Beatrix Bálint7, Olivier Molinier8,
Henrik Depenbrock9, Shivani Nanda10, Luis Paz-Ares11, Nick Thatcher 12
1
Institute of Oncology Ion Chiricuta and Umf Iuliu Hatieganu, Cluj Napoca/Romania,
2
Florida Hospital Cancer Institute, Orlando/FL/United States of America, 3Eli Lilly
and Company, Indianapolis/IN/United States of America, 4Leningrad Regional
Clinical Hospital, St. Petersburg/Russian Federation, 5Regional Lung Disease
Hospital, Otwock/Poland, 6Department of Oncology, Poznan University of Medical
Sciences, Poznań/Poland, 7Csongrád County Hospital of Chest Diseases, Deszk/
Hungary, 8Hospital Center, Le Mans/France, 9Medical Oncology, Lilly Deutschland
Gmbh, Bad Homburg/Germany, 10Statistics-Oncology, Eli and Company,
Bridgewater/NJ/United States of America, 11University Hospital Virgen Del Rocio,
Seville/Spain, 12The Christie Hospital, Manchester/United Kingdom
Background: SQUIRE (NCT00981058) demonstrated adding necitumumab (N)

to gemcitabine/cisplatin (GC) improved survival in patients with Stage IV
Conclusion: The correlation between preoperatively assessed CT tumor squamous NSCLC (SQ-NSCLC). Retrospective analysis revealed consistent
volume and volume of the resected specimen showed a strong correlation. treatment effect in favor of patients receiving N monotherapy as
To assess the prognostic role of CT measured tumor volume a correlation to continuation after chemotherapy (CT) (GC+N continuation patients) versus
prognosis has to be performed before implementation as a new T-factor. continuation therapy-eligible GC arm patients (GC non-progressors). In the
EU, N is approved for patients with EGFR-expressing tumors. We repeated the
Keywords: Tumor weight, Tumor volume, Mesothelioma, TNM staging analysis in this patient population. Methods: Patients with Stage IV
SQ-NSCLC were randomized 1:1 for ≤6 cycles of G (1250 mg/m2 iv, Days [d] 1,8)
and C (75 mg/m2 iv, d1) either with or without N (800 mg iv, d1,8). Patients in
SESSION OA23: EGFR TARGETED THERAPIES IN GC+N without progression continued N until progressive disease (PD). SQUIRE
ADVANCED NSCLC included mandatory tissue collection. EGFR protein expression was assessed
by IHC in a central lab (Dako EGFR PharmDx kit). Analyses were done in
EGFR-expressing patients (EGFR >0). Patients who received ≥4 cycles of CT
without PD were included. Overall survival (OS) and progression-free survival Hypothesis-generating analysis of archived tumor samples and blood serum
(PFS) were calculated by Kaplan-Meier method. 95% CIs and hazard ratios was undertaken to identify possible molecular/clinical biomarkers. Methods:
estimated using stratified Cox proportional hazards model. Results: Of 1093 Tumor samples were retrospectively analyzed using FoundationOneTM
patients (ITT population), 982 patients (89.8%) had evaluable IHC assay next-generation sequencing (NGS); EGFR expression was determined by
results; 935/982 (95.2%) had EGFR>0. GC+N arm continuation therapy immunohistochemistry. Pre-treatment serum samples were analyzed with
patients included 228 patients with EGFR>0 and 194 patients (EGFR>0) were VeriStrat®, a MALDI-TOF mass spectrometry test, and classified as VeriStrat-
GC arm non-progressors. Baseline characteristics were similar except gender Good or VeriStrat-Poor-risk. Results: 15/398 patients treated with afatinib
(Males: 81% in GC+N vs 91% in GC arm). CT exposure was balanced. Median OS were long-term responders. Median duration of treatment was 16.6 months
from randomization in GC+N vs GC was 16.1 vs 14.9 months; HR 0.76 (95% CI, (range: 12.3-25.8). Patient characteristics were similar to the overall dataset
0.61, 0.95). Median PFS in GC+N vs GC was 7.4 vs 6.9 months; HR 0.81 (95% CI, (median age: 65 years [range: 54-81]; male: 80.0%; Asian: 13.3%; ECOG 0/1:
0.66, 1.00). 40.0%/60.0%; best response to chemotherapy CR or PR/SD: 53.3%/46.7%;
current and ex-smokers: 80.0%). Median PFS was 16.2 months (range:
2.8-24.0); median OS was 23.1 months (range: 12.9-31.5). The most common
treatment-related AEs (all grade/grade 3) were: diarrhea (73.3%/6.7%); rash/
acne (66.7%/6.7%); stomatitis (13%/7%). AEs generally occurred soon after
treatment onset (median onset, days [range]: diarrhea 11 [5-48]; rash/acne
17 [9-107]; stomatitis 15 [11-19]). Four patients required a dose reduction to
30mg/day due to treatment-related AEs (diarrhea, rash, stomatitis, diarrhea/
rash). NGS was undertaken in 9 patients and details will be presented at the
meeting. Genomic aberrations in the ErbB/FGF gene families were identified
in 44.4%/55.6% of long-term responders (overall dataset: 29.4%/58.0%). Of 14
patients assessed by VeriStrat, 85.7% were VeriStrat-Good (overall dataset:
61.6%). Immunohistochemistry data was available for two patients; one
overexpressed EGFR (≥10% positive cells; H-score ≥200) Conclusion: Baseline
characteristics of long-term responders to afatinib were similar to the overall
dataset. In this sub-group, afatinib conferred a survival benefit of nearly 2
years. Afatinib was well tolerated with predictable and transient AEs that
occurred soon after treatment onset. The dataset was too small to identify
any clear NGS/VeriStrat predictive signals. Further studies are required to
predict long-term response to afatinib.
Conclusion: In patients with EGFR-expressing tumors, a consistent treatment Keywords: afatinib, Squamous cell carcinoma of the lung, NSCLC
effect in favor of GC+N continuation maintenance compared to GC non-
progressors was observed, similar to ITT population with no unexpected
increases in AEs.
Keywords: NSCLC, EGFR, squamous, Necitumumab WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
OA23.05 FIRST-LINE AFATINIB VERSUS GEFITINIB IN EGFRM+

ADVANCED NSCLC: UPDATED OVERALL SURVIVAL ANALYSIS OF
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 LUX-LUNG 7
Keunchil Park 1, Eng Huat Tan2, Li Zhang 3, Vera Hirsh4, Ken O’Byrne5, Michael
Boyer6, James Chih-Hsin Yang7, Tony Mok8, Ki Hyeong Lee9, Shun Lu10, Yuankai
OA23.03 SECOND-LINE AFATINIB FOR ADVANCED SQUAMOUS CELL
Shi11, Sang-We Kim12, Janessa Laskin13, Dong-Wan Kim14, Scott Laurie15, Karl
CARCINOMA OF THE LUNG: ANALYSIS OF AFATINIB LONG-TERM
Kölbeck16, Jean Fan17, Nigel Dodd18, Angela Märten19, Luis Paz-Ares20
RESPONDERS IN THE PHASE III LUX-LUNG 8 TRIAL 1
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/
Glenwood Goss 1, Manuel Cobo2, Shun Lu3, Kostas Syrigos4, Alessandro Korea, Republic of, 2Medical Oncology, National Cancer Centre, Singapore,
Morabito5, Istvan Albert6, Gabriella Herodek7, Samuel Chan8, Gyula Ostoros9, Singapore/Singapore, 3State Key Laboratory of Oncology in South China,
Veronika Sarosi10, Zsolt Kiraly11, Deric Savior 12, Rachael Barton13, Francisco Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University,
Medina14, Sundaram Subramanian15, Andrea Ardizzoni16, Enriqueta Felip17, Guangzhou/China, 4 McGill University, Montreal/QC/Canada, 5Princess Alexandra
Shirish Gadgeel18, Vassilis Georgoulias19, James Love20, Claudia Bühnemann21, Hospital and Queensland University of Technology, Brisbane/QLD/Australia, 6Chris
O’Brien Lifehouse, Camperdown/NSW/Australia, 7National Taiwan University
Neil Gibson22, Eva Ehrnrooth23, Jean-Charles Soria24, Nicholas Dupuis25
Hospital and National Taiwan University Cancer Center, Taipei/Taiwan, 8Key
1
Division of Medical Oncology, University of Ottawa, Ottawa/ON/Canada, Laboratory of South China, the Chinese University of Hong Kong, Hong Kong/
2
Department of Medical Oncology, Hospital Carlos Haya, Malaga/Spain, 3Shanghai China, 9 Chungbuk National University Hospital, Cheongju, Chungbuk/Korea,
Chest Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Republic of, 10Shanghai Chest Hospital, Shanghai/China, 11National Cancer Center,
Shanghai/China, 4 Athens School of Medicine, Athens/Greece, 5Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical
Unit, Thoracic Department, Istituto Nazionale Tumori “Fondazione G.Pascale”- College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted
IRCCS, Naples/Italy, 6Mátrai Gyógyintézet, Mátraháza/Hungary, 7Aladar Petz Drugs, Beijing/China, 12 Asan Medical Center, Seoul/Korea, Republic of, 13BC Cancer
County Teaching Hospital, Györ/Hungary, 8Harrogate and District NHS Foundation Agency, Vancouver/BC/Canada, 14Seoul National University Hospital, Seoul/Korea,
Trust, Harrogate/United Kingdom, 9Department of Pulmonology, Semmelweis Republic of, 15The Ottawa Hospital Cancer Centre, Ottawa/ON/Canada, 16Karolinska
University, Budapest/Hungary, 10 Department of Respiratory Medicine, Medical University Hospital, Solna, Stockholm/Sweden, 17Boehringer Ingelheim
University, Pécs/Hungary, 11Veszprem County Lung Hospital, Farkasgyepü/ Pharmaceuticals, Inc., Ridgefield/CT/United States of America, 18Boehringer
Hungary, 12Temple University Cancer Center, Philadelphia/PA/United States of Ingelheim Ltd Uk, Bracknell/United Kingdom, 19Boehringer Ingelheim Pharma
America, 13Scarborough District General Hospital, Scarborough/United Kingdom, Gmbh & Co. Kg, Ingelheim Am Rhein/Germany, 20 Hospital Universitario Doce de
14
Oca Hospital, Monterrey International Research Center, Monterrey/Mexico, Octubre and Cnio, Madrid/Spain
15
V.S. Hospitals, Chennai/India, 16University Hospital, Bologna/Italy, 17Vall D’
Hebron University Hospital, Barcelona/Spain, 18Karmanos Cancer Institute/wayne Background: The irreversible ErbB family blocker afatinib and the reversible
State University, Detroit/MI/United States of America, 19University Hospital of EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+
Heraklion, Heraklion/Greece, 20 Boehringer Ingelheim Corporation, Ridgefield/CO/
NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib
United States of America, 21Boehringer Ingelheim Pharma Gmbh & Co., Kg Biberach/
Germany, 22Boehringer Ingelheim Pharma Gmbh & Co., Biberach/Germany,
in this setting. Methods: LUX-Lung 7 assessed afatinib (40 mg/day) versus
23
Boehringer Ingelheim, Danmark A/s, Copenhagen/Denmark, 24Department of gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC
Medicine, Gustave Roussy Cancer Campus and University Paris-Sud, Paris/France, harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints
25
Biodesix Inc., Boulder/CO/United States of America were PFS (independent review), time to treatment failure (TTF) and OS. Other
endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-
Background: Squamous cell carcinoma (SCC) of the lung is a genetically related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum).
complex and difficult-to-treat cancer. In LUX-Lung 8, afatinib (40mg/day) The primary analysis of PFS/TTF was undertaken after ~250 PFS events.
significantly improved OS (median 7.9 vs 6.8 months, HR=0.81 [95% CI, 0.69- The primary OS analysis was planned after ~213 OS events and a follow-up
0.95], p=0.008), PFS (2.6 vs 1.9 months, HR=0.81 [0.69-0.96], p=0.010) and DCR period of ≥32 months. Results: 319 patients were randomised (afatinib: 160;
versus erlotinib (150mg/day) in patients with relapsed/refractory SCC of the gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57-
lung (n=795). Notably, 12-month (36 vs 28%; p=0.016) and 18-month survival 0.95], p=0.017), TTF (0.73 [0.58-0.92], p=0.007) and ORR (70 vs 56%, p=0.008)
(22 vs 14%; p=0.016) was significantly higher with afatinib than erlotinib, were significantly improved with afatinib versus gefitinib. The most common
indicating that some patients derive prolonged benefit from afatinib. grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and
Here, we present post-hoc analysis of baseline characteristics and efficacy/ elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib
safety of afatinib in long-term responders (treatment for ≥12 months). had ≥1 dose reduction due to AEs; dose reductions were more common in

females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose 6
Astrazeneca, Lp, Wilmington/DE/United States of America, 7United Biosource
reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR Corporation, Chevy Chase/MD/United States of America, 8United Biosource
[95% CI]: 1.34 [0.90-2.00]) but reduced incidence and severity of drug-related Corporation, Munich/Germany, 9 Astrazeneca Lp, Gaithersburg/MD/United States
grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the of America
same in each arm (6%). The data cut-off for primary OS analysis occurred on 8
Background: In 2011, following gefitinib (IRESSA®) NDA voluntary withdrawal,
April 2016. At this time, median treatment duration (range) was 13.7 (0-46.4)
US patients benefiting from gefitinib were eligible to continue gefitinib
versus 11.5 (0.5-48.7) months with afatinib and gefitinib. 25% (afatinib) and
through the IRESSA Clinical Access Program (ICAP), an IRB-approved
13% (gefitinib) of patients received treatment for >24 months. 73% and 77%
protocol. A subset of ICAP investigators subsequently collected additional
of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic
retrospective data on their ICAP patients through another IRB-approved
anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI
project (“chart-review subset”). Methods: For all enrolled ICAP patients,
including osimertinib (14%)/olmutinib (14%). OS data, including subgroup
demographic and serious adverse event (SAE) reports were reviewed. All
analysis with respect to subsequent therapy will be presented at the meeting.
ICAP investigators were invited to participate in chart review; 47 accepted
Conclusion: Afatinib significantly improved PFS, TTF and ORR versus gefitinib
and collected data on patient/tumor characteristics and safety/tolerability
in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-
of prolonged gefitinib therapy among their 79 ICAP patients. Results:
related discontinuations. Dose adjustment of afatinib reduced drug-related
Across 137 US sites, 191 patients enrolled in ICAP. As of September 2016, 75
AEs without compromising efficacy. Primary OS analysis will be reported.
(39%) remain on gefitinib; discontinuations were due to progression (36%),
Keywords: afatinib, gefitinib, NSCLC, EGFR death (34%), AEs (13%), or other (17%). Sixty-four (34%) patients reported
162 SAEs; 5 (2.6%) patients had 12 SAEs considered to be gefitinib-related
by investigators. The chart-review subset included 79 (41%) patients with
median age of 69 years at ICAP enrollment, who were predominantly female
OA23: EGFR TARGETED THERAPIES IN ADVANCED NSCLC (70%) and white (84%); 95% had a confirmed NSCLC diagnosis. Due to
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 the evolving understanding of genetic mutations in NSCLC at the time of
gefitinib initiation, the majority of patients (79%) never had EGFR sequencing
performed. Although tissue is not available for EGFR status confirmation, we
OA23.06 OVERALL SURVIVAL (OS) OF EGFR MUTATION POSITIVE assume these patients are nearly exclusively EGFR mutation-positive. Median
NON-SMALL CELL LUNG CANCER PATIENTS: REAL-WORLD total length of gefitinib was 11.1 years (6.5-15.1; Table). Long-term gefitinib
TREATMENT PATTERNS OF 1,660 JAPANESE PATIENTS was well-tolerated; 5% discontinued due to a gefitinib-related AE. Ten-year
Kazushi Yoshida1, Yuichiro Ohe1, Akira Inoue2, Toru Kumagai3, Masayuki survival rate from first-ever initiation of gefitinib was 86% and 15-year was
Takeda4, Nobuyuki Yamamoto5, Takashi Seto6, Isamu Okamoto7, Naoki 59%. Table. Gefitinib treatment patterns and tolerability among ICAP chart-
Tashiro8, Satoshi Morita9, Masahiro Fukuoka10 review patients.
1
Thoracic Oncology, National Cancer Center Hospital, Tokyo/Japan, 2Tohoku
University, Sendai/Japan, 3Osaka Medical Center for Cancer and Cardiovascular Parameter n, % Observed Population (N=79)
Diseases, Osaka/Japan, 4 Medical Oncology, Kinki University Faculty of Medicine,
Total time on gefitinib, prior to and during ICAP
Osaka-Sayama/Japan, 5Internal Medicine, Wakayama Medical University,
Wakayama/Japan, 6Department of Thoracic Oncology, National Kyusyu Cancer Median duration, y, range 11.1 (6.5-15.1)
Center, Fukuoka/Japan, 7Research Institute for Diseases of the Chest, Graduate Prior to ICAP
School of Medical Sciences, Kyushu University, Fukuoka/Japan, 8 Astrazeneca Kk,
Osaka/Japan, 9Kyoto University, Kyoto/Japan, 10 Izumi Municipal Hospital, Osaka/ Median duration, y, range 7.8 (5.4-10.9)
Japan Starting dose 250 mg/day 67 (84.8)
No dose changes due to AEs 75 (94.9)
Background: Since the epidermal growth factor receptor-tyrosine kinase
inhibitor (EGFR-TKI) was launched in Japan, the survival periods of advanced/ During ICAP
recurrent EGFR mutation positive (EGFR m+) non-small cell lung cancer
Median duration, y, range 3.5 (0.04-4.7)
(NSCLC) patients have been getting longer. However, clinical factors which
contributed to the extension of survival periods of these patients remain Dose: 250 mg/day 76 (96.2)
unclear. We investigated overall survival, prognostic factors and treatments Treatment-related AEs Grade 1-2 Grade ≥3
13 (16.5) 1 (1.3) 2 (2.5)
patterns of EGFR m+ NSCLC patients in real-world clinical practice. Methods: Grade unknown
This is a multi-center, observational, retrospective study. Histologically or Dose reductions due to treatment-related
cytologically diagnosed EGFR m+ NSCLC patients who were started first-line 1 (1.3)
AEs
treatment from 1/1/2008 to 31/12/2012 were enrolled. The primary objective
Discontinuations due to treatment-related
was the estimated OS. The secondary objectives were to determine prognostic 4 (5.1)
AEs
factors, real-world treatment patterns. Results: 1,660 EGFR m+ NSCLC
patients were enrolled from 17 hospitals in Japan (median age 67.0 years, Discontinuations due to progressive
11 (28.9)
female 64.8%, 38.9% had smoking history, ECOG-performance status 0, 1, 2, disease
3, 4 were 39.5%, 41.1%, 7.1%, 4.9%, 0.7%, respectively, adenocarcinoma 95.2%, Conclusion: The majority of this subset of patients who participated in ICAP
50.1% exon 19 deletion, 66.7% at stage IV). Median estimated OS was 29.7 based on long-term clinical benefit from gefitinib continue to do well with
months. Cox regression analysis revealed age, smoking history, performance gefitinib, demonstrating good tolerance of therapy and survival for a median
status, histological diagnosis, EGFR mutation type and clinical stage were duration of more than 10 years.
independently associated with OS. Five year survival rate of stage IV patients
was 13.8%. The median number of treatment regimens was two. EGFR-TKI Keywords: gefitinib, NSCLC, EGFR-TKI, Long-term
and platinum-doublet chemotherapy were most frequently used as first-
and second-line treatments. Conclusion: Real world treatment of the large
data-set of 1,660 EGFR m+ NSCLC patients was retrospectively investigated.
Median OS was 29.7 months and EGFR-TKIs are major components of the
treatment regimens for these patients in Japan. (NCT0247520) SESSION OA24: RADIOTHERAPY OF LUNG CANCER:
Keywords: NSCLC, Real world, overall survival, EGFR
RECENT DEVELOPMENTS
OA23: EGFR TARGETED THERAPIES IN ADVANCED NSCLC OA24.01 RADIOTHERAPY QUALITY ASSURANCE OF CONCURRENT
CHEMORADIOTHERAPY IN PROCLAIM PHASE III TRIAL
Anthony Brade 1, Frederik Wenz2, Friederike Koppe3, Yolande Lievens4, Belen
OA23.07 ANALYSIS OF OUTCOMES IN US IRESSA CLINICAL ACCESS San Antonio5, Neill Iscoe6, Anwar Hossain7, Nadia Chouaki8, Suresh Senan9
PROGRAM (ICAP) PATIENTS ON GEFITINIB FOR MORE THAN 10 1
Trillium Health Partners, Mississauga/ON/Canada, 2University Hospital Mannheim,
YEARS Mannheim/Germany, 3Institute Verbeeten, Tilburg/Netherlands, 4Radiation
Oncology Department, Ghent University Hospital, Ghent/Belgium, 5Lilly EspaÑa,
Fred R. Hirsch1, Lecia Sequist2, Ira Gore3, Meghan Campo2, George Simon4, Madrid/Spain, 6Eli Lilly Canada Inc., Toronto/ON/Canada, 7Oncology, Eli Lilly
Elisabeth Croft5, Diana Devincenzo6, Jiefen Munley6, Dara Stein7, Klaus and Company, Indianapolis/IN/United States of America, 8 Oncology, Eli Lilly and
Freivogel8, Frangiscos Sifakis9, Paul Bunn, Jr.1 Company, Neuilly-Sur-Seine/France, 9VU University Medical Center, Amsterdam/
1
University of Colorado Cancer Center, Aurora/CO/United States of America, Netherlands
2
Cancer Center, Massachusetts General Hospital, Boston/MA/United States of
America, 3 Alabama Oncology- St. Vincent’S Birmingham, Birmingham/AL/United Background: Trials of chemoradiotherapy for different tumors, including lung
States of America, 4Thoracic Medical Oncology, MD Anderson Cancer Center, cancer, have shown a correlation between protocol deviations and adverse
Houston/TX/United States of America, 5 Astrazeneca, Cambridge/United Kingdom, outcomes. Radiation quality assurance (RTQA) was mandated for all patients
treated in the PROCLAIM (NCT00686959) trial evaluating two different and the documented low rate of marginal failures makes the adaptive
chemoradiotherapy regimens. Methods: The study was open to accrual approach a modern option for future randomized studies. The best scenario to
between 2008-2012. Planned chemoradiotherapy dose was 60-66 Gy in daily confirm tumor activity is its application in neoadjuvant chemoradiation trials.
2 Gy fractions. Quality was assessed through review of radiation treatment
plans and monitoring of protocol violations. Review of the radiation plan was Keywords: Locally advanced NSCLC, chemoradiation, adaptive radiotherapy
mandated for all patients; prior to radiation start for the first enrolled patient
at each site. Real-time review was performed randomly in 20% of additional
patients with nonreal-time review performed for the remainder. Parameters
assessed for major violations per protocol included: <95% of planned total OA24: RADIOTHERAPY OF LUNG CANCER: RECENT DEVELOPMENTS
volume (PTV) received by 93% of prescribed dose; >1 cm3 contiguous volume
within or outside the PTV received >115% of prescribed dose; V20 (volume of
lung receiving ≥20 Gy) >38%; and maximum point dose to spinal cord of >48 OA24.03 CARDIAC TOXICITY AFTER RADIATION FOR STAGE
Gy. Overall survival (OS) and progression-free survival (PFS) were analyzed III NSCLC: POOLED ANALYSIS OF DOSE-ESCALATION TRIALS
using Kapan-Meier methodology and groups were compared by log-rank test DELIVERING 70-90 GY
and Cox proportional hazard modeling. Results: Of 598 patients randomized
Kyle Wang 1, Michael Eblan1, Matthew Lipner 1, Allison Deal2, Timothy Zagar 1,
in 126 investigational sites, 554 received study assigned chemoradiotherapy.
Carrie Lee3, Brian Jensen1, Panayiotis Mavroidis1, Julian Rosenman1, Thomas
The median dose delivered was 66 Gy, with 92.6% of patients receiving
Stinchcombe3, Lawrence Marks1
planned chemoradiotherapy dose (60-66 Gy). A total of 40 patients, enrolled 1
at twenty-eight sites had major RTQA violations. Seven sites enrolled ≥2 Radiation Oncology, University of North Carolina Hospitals, Chapel Hill/NC/United
States of America, 2Biostatistics, University of North Carolina Hospitals, Chapel
patients with major violations. Patients with major violations has a higher
Hill/NC/United States of America, 3Medical Oncology, University of North Carolina
incidence of Stage IIIB disease (70.0% vs. 50.6%) and larger tumors (median Hospitals, Chapel Hill/NC/United States of America
planned PTV=653 vs. 523cc) than patients with no violations. Patients
treated at sites with ≥2 patients with violations (n=86), had a lower median Background: Radiation (RT) associated cardiac injury in patients with lung
OS (median 21.1 vs. 29.8 months; HR 1.442) and median PFS (median 7.3 vs. cancer is of unclear significance. RTOG 0617 demonstrated reduced overall
11.3 months; HR 1.345) than patients at sites where none had violations. survival (OS) with dose-escalated RT for Stage III NSCLC, with higher heart
Conclusion: Major chemoradiotherapy protocol violations were uncommon doses predicting for worse OS. We assessed the impact of heart doses on
in the PROCLAIM study, which may be a reflection of the mandatory RTQA. toxicity and survival for patients enrolled on several prospective RT dose-
Protocol violations were more frequent in patients with Stage IIIB and larger escalation trials. Methods: From 1996-2009, 133 patients with Stage III
tumors, which generally require more complex chemoradiotherapy plans. NSCLC (ECOG PS 0-1) were treated on six prospective trials using induction/
The observation of discrepant outcomes at centres with multiple major RTQA concurrent chemotherapy and dose-escalated conformal RT to 70-90 Gy.
violations is hypothesis-generating but should be interpreted with caution Broad clinical outcomes (e.g. OS) were prospectively assessed. RT plans
due to the small number of patients. were reviewed, cardiac structures were defined, and dose/volume metrics
were computed. Patient records were retrospectively reviewed for post-
Keywords: pemetrexed, Radiotherapy, quality assurance RT symptomatic cardiac events (symptomatic pericardial effusion, acute
coronary syndrome, and pericarditis). Baseline cardiac risk was calculated
using the World Health Organization / International Society of Hypertension
(WHO/ISH) score. A competing risks model accounting for the risk of death
OA24: RADIOTHERAPY OF LUNG CANCER: RECENT DEVELOPMENTS
was used for statistical analysis. Results: 112 patients were included in the
final analysis. Median f/u was 19 mo. (75 mo. for the 39 patients without
documented progression). Median OS and PFS were 22 and 12 mo. Median
OA24.02 LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER: prescribed RT dose was 74 Gy. 15 patients (13%) had symptomatic cardiac
RADIOTHERAPY WITH ADAPTIVE STRATEGY (LARTIA TRIAL) events (6 pericardial effusion, 5 myocardial infarction, 2 unstable angina, 2
Sara Ramella1, Michele Fiore2, Sonia Silipigni2, Massimo Jaus3, Maria Cristina pericarditis) at median 26 mo. post-RT (range, 7-68). On univariate analysis,
Zappa3, Antonio Alberti3, Paolo Matteucci2, Elisabetta Molfese2, Patrizia Heart mean dose (p=0.001), Heart V5Gy (p<0.001), and Heart V30Gy (p=0.002)
Cornacchione2, Lucio Trodella2, Edy Ippolito2, Rolando D’Angelillo2 were associated with symptomatic cardiac events, whereas baseline WHO/ISH
1 score (p=0.204) and coronary artery disease (p=0.109) were not. Heart doses
Radiation Oncology, Campus Bio-Medico University, Rome/Italy, 2Campus Bio-
Medico University, Rome/Italy, 3Sandro Pertini Hospital, Rome/Italy
were higher in patients with vs without events (mean 22Gy vs 11Gy, V5Gy
60% vs 35%, V30Gy 35% vs 14%). On multivariate pair analysis accounting for
Background: Anatomical change of tumor contour during radiotherapy baseline risk, heart doses remained significant predictors of cardiac events
contributes to target missing. Adaptation of tumor volume could however (e.g. Heart mean dose, p=0.001, HR 1.05 / 1Gy). 2-year competing risk-adjusted
result in an increased incidence of recurrences in the area of target reduction. rate of symptomatic cardiac events was 11.1% vs 1.5% for Heart mean dose
This study aims to investigate the incidence of failure of adaptive approach ≥15Gy vs <15Gy (p=0.003, HR 6.7). 34 patients (30%) had asymptomatic
in evaluating the risk of local recurrence in the area excluded during pericardial effusions. There was no association between heart doses and
replanning. Methods: In this prospective study, LA-NSCLC patients treated OS. Conclusion: Clinically significant symptomatic cardiac events following
with concomitant chemoradiation underwent weekly chest-CT simulation high-dose thoracic RT for Stage III NSCLC occurred in 13% of patients at a
during therapy. In case of tumor shrinkage, a new tumor volume (TV) was median 2 years post-RT, with the rate appearing to be heart dose dependent.
delineated and a new treatment plan outlined (replanning). Patterns of RT-associated cardiac toxicity in the definitive treatment of Stage III NSCLC
failure were classified as: in field (persistence or recurrence in TV post- may occur earlier than historically understood, and heart doses should be
replanning), marginal (recurrence in the area of initial TV excluded from the minimized. Supported in part by NIH grant CA69579.
post-replanning TV) and out of field (recurrence outside of initial TV). Toxicity,
OS, and PFS were reported. Results: A total of 217 NSCLC patients were Keywords: radiation heart toxicity, Stage III NSCLC, cardiac, dose escalation
treated in our centre from 2012 to 2014. In 50 cases a target volume reduction
was recorded and replanning outlined. A mean initial and replanning CTV
of 154.9cc and 90.7cc were reported with an average CTV shrinkage of 42%
between simulation CT and replanning CT. With a median follow-up of 20.5 WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
months, 30% of patients experienced local failure which was in field, marginal
and out of filed in 20%, 6% and 4% of cases respectively. Acute G3 pulmonary
and esophageal toxicity was reported in 2% and 4% of patients respectively. OA24.05 THE NORDIC HILUS-TRIAL - FIRST REPORT OF A PHASE II
TRIAL OF SBRT OF CENTRALLY LOCATED LUNG TUMORS
Karin Lindberg 1, Per Bergström2, Odd Terje Brustugun3, Silke Engelholm4,
Vitali Grozman5, Morten Hoyer6, Kristin Karlsson5, Azza Khalil6, Charlotte
Kristiansen7, Ingmar Lax5, Britta Löden8, Jan Nyman9, Gitte Persson10, Lotte
Rogg11, Peter Wersäll5, Rolf Lewensohn1
1
Oncology and Pathology, Karolinska Institutet, Stockholm/Sweden,
2
Norrlands University Hospital, UmeÅ/Sweden, 3Department of Oncology,
Ouh-Radiumhospitalet, Oslo/Norway, 4SkÅnes University Hospital, Lund/
Sweden, 5Karolinska University Hospital, Stockholm/Sweden, 6Oncology, Aarhus
University Hospital, Aarhus C/Denmark, 7Department of Clinical Oncology, Odense
University Hospital, Odense C/Denmark, 8 Centralsjukhuset, Karlstad/Sweden,
9
Sahlgrenska University Hospital, Gothenburg/Sweden, 10 Department of Oncology,
Rigshospitalet, Copenhagen University Hospital, Copenhagen/Denmark, 11Oslo
University Hospital UllevÅl, Oslo/Norway
Figure 1: (A) Tumor volume delineation at first CT simulation; (B) the reduced
target volume at replanning CT Conclusion: The possibility to reduce toxicity Background: Early attempts of stereotactic body radiation therapy (SBRT)

of centrally located lung tumors resulted in high toxicity, questioning the Keywords: early stage NSCLC, Patterns of failure, SBRT, Adenocarcinoma
utility of the method in this situation. Since then, different risk adapted
fractionation schedules with acceptable toxic effects have been reported
from various institutions. However, consensus on the tolerability of
centrally located structures to high-fraction doses is still lacking and the OA24: RADIOTHERAPY OF LUNG CANCER: RECENT DEVELOPMENTS
clinical toxic effects in relation to dose to organs at risk (OAR) need to be WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
evaluated. Methods: We here report a first toxicity analysis of the HILUS-
trial – a prospective Nordic multicenter non-randomized phase II trial of SBRT OA24.07 THE IMPACT OF POPULATION HETEROGENEITY ON THE
to centrally located lung tumors. Patients with a centrally located tumor
EFFICACY OF SBRT TO THE LUNG
(defined as ≤1cm from the proximal bronchial tree) from either a primary non-
small cell lung cancer (NSCLC) or a progressive metastasis from another solid Neil Woody1, Chandana Reddy1, Mohamed Abazeed2
1
tumor were eligible for the trial. Maximum tumor diameter was 5 cm. Patients Radiation Oncology, Cleveland Clinic, Cleveland/OH/United States of America,
2
receiving concomitant systemic anticancer therapy or with tumors reaching Translational Hematology Oncology Research, Cleveland Clinic, Cleveland/OH/
through the wall of a main bronchus were not eligible. All the patients were
treated with 7Gyx8 and stratified to either arm A (=tumors close to a main Background: Stereotactic Body Radiation Therapy (SBRT) is the standard of
bronchus) or arm B (=tumors close to a lobar bronchus). The aim was to include care for medically inoperable patients with early-stage non-small cell lung
30 patients in each arm. Follow-up was conducted every 3rd month during cancer (NSCLC). However, NSCLC is comprised of several histological subtypes
the first 2 years and thereafter every 6th month. The trial was approved by and the impact of this heterogeneity on SBRT treatments has yet to be
ethical committees in each country. Results: Seventy-four patients (42 in arm established. Methods: We analyzed 740 early-stage NSCLC patients treated
A and 31 in arm B) were included between 2011 and 2016. Sixty-five patients definitively with SBRT from 2003 through 2015. We calculated cumulative
experienced side effects from the study treatment; the most common being incidence curves using the competing risk method and identified predictors of
grade 1-2 dyspnea, grade 1-2 cough and grade 1-2 fatigue. Twenty-one patients local failure using Fine and Gray regression. Results: Overall, 72 patients had a
(28%) experienced grade 3-5 side effects (atrioventricular block, bleeding, local failure with a cumulative incidence of local failure at three years of 11.8%.
dyspnea, empyema, fatigue, fever, fistula, lung infection, pain, pneumonitis, On univariate analysis, squamous histology, younger age, fewer medical
pneumothorax and ventricular arrhythmia). Seven patients (6 in group A and comorbidities, higher BMI, higher PET SUV, central tumors and lower radiation
1 in group B) may have suffered grade 5 side effects; six patients experienced dose were associated with an increased risk of local failure. On multivariable
lethal hemoptysis after a median of 15.5 months (2.5-21months) and one analysis, squamous histology (HR 2.4 p = 0.008) was the strongest predictor
patient suffered from a lethal pneumonitis 5 months post study treatment. of local failure. Patients with squamous cancers fail SBRT at a significantly
Grade 4-5 side effects occurred more frequently in group A than in group B higher rate than those with adenocarcinomas or NSCLC-not otherwise
(19% vs 3%). Further analyses of risk factors for serious toxicity in relation specified, with three-year cumulative incidences of local failure of 18.9% (95%
to dose-volume parameters and patient- and tumor characteristics will be CI= 12.7-25.1%), 8.7% (95% CI= 4.6-12.8%), 4.1% (95% CI= 0-9.6%), respectively.
presented. Conclusion: SBRT of centrally located tumors may be afflicted with Conclusion: Our results demonstrate an increased rate of local failure after
high risk of serious toxicity and further evaluation of clinical and dose-volume SBRT in patients with squamous cell carcinoma. Standard approaches for
dependent risk factors are highly warranted. radiotherapy that demonstrate efficacy for a population may not achieve
optimal results for individual patients. Establishing the differential dose-
Keywords: side effects, SBRT, stereotactic, central lung tumors
responses of SBRT across histological groups is likely to improve efficacy and
inform ongoing and future studies that aim to expand indications for SBRT.
Keywords: SBRT, Squamous cell carcinoma, precision medicine, local failure

OA24.06 HISTOLOGIC SUBTYPE OF EARLY-STAGE LUNG

ADENOCARCINOMA IS A PREDICTOR OF FAILURE PATTERNS AFTER
STEREOTACTIC BODY RADIATION THERAPY
Jonathan Leeman1, Andreas Rimner2, Joseph Montecalvo2, Meier Hsu2,
Zhigang Zhang2, Donata Von Reibnitz2, Kelly Panchoo2, Ellen Yorke2, Prasad
Adusumilli3, William Travis4, Abraham Wu5
1
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New
York, Ny/United States of America, 2Memorial Sloan Kettering Cancer Center, New
York, NY/NY/United States of America, 3Memorial Sloan Kettering Cancer Center,
New York/United States of America, 4 Memorial Sloan Kettering Cancer Center, New
York, Ny/United States of America, 5Radiation Oncology, Memorial Sloan Kettering
Cancer Center, New York/United States of America
Background: Stereotactic body radiation therapy (SBRT) has emerged as

an effective treatment for early-stage lung cancer. Histologic subtyping
in surgically resected lung adenocarcinomas is recognized as a prognostic
factor, with the presence of solid or micropapillary patterns predicting poor
outcomes. Herein, we describe outcomes following SBRT for early-stage
lung adenocarcinoma by histologic subtype. Methods: We identified 119
consecutive patients (124 lesions) with stage I-IIA lung adenocarcinoma who
were treated with definitive SBRT at our institution between August 2008
and August 2015 and had undergone core biopsy. Histologic subtyping was
performed according to the 2015 WHO Classification. Thirty-seven tumors
(30%) were of high risk subtype, defined as containing a component of
solid and/or micropapillary pattern. Cumulative incidences of local, nodal,
regional and distant failure were compared between high risk vs. non-high
risk adenocarcinoma subtypes with Gray’s test, and multivariable-adjusted
hazard ratios were estimated from propensity score-weighted Cox regression
models. Results: Median follow-up for the entire cohort was 17 months and 21
months for surviving patients. The 1-year cumulative incidence of local, nodal,
regional and distant failure, respectively, in high risk and non-high risk lesions
were 7.3%, 14.8%, 4.0%, 22.7% and 2.7%, 2.6%, 1.2%, 3.6%. Hazard ratios for
local, nodal, regional and distant failure, respectively, of high risk lesions
compared to non-high risk were 16.8 (95% CI 3.5-81.4), 3.8 (95% CI 0.95-15.0),
20.9 (95% CI 2.3-192.3), 6.9 (95% CI 2.2-21.1). No significant difference was
seen with regard to overall survival. Conclusion: Outcomes following SBRT for
early-stage adenocarcinoma of the lung are highly correlated with histologic
subtype, with micropapillary and solid tumors portending significantly higher
rates of locoregional and metastatic progression. In this context, histologic
subtype based on core biopsies is a novel prognostic factor and may have
important implications for patient selection, adjuvant treatment, biopsy
methods and clinical trial design.
Health Sciences Center, Denver/CO/United States of America, 8Yuma Regional

MINI ORAL ABSTRACT SESSIONS - Cancer Center, Yuma/AZ/United States of America
MONDAY, DECEMBER 5, 2016
Background: The LuCED test for early stage lung cancer detects rare abnormal
cells that are exfoliated from tumors into sputum and promotes cancer case
SESSION MA01: IMPROVEMENT AND IMPLEMENTATION detection with >92% sensitivity and >95% specificity. Additionally, the LuCED
OF LUNG CANCER SCREENING test detects endobronchial lung dysplasia to triage patients with pre-cancer
MONDAY, DECEMBER 5, 2016 - 11:00-12:30 to chemoprevention therapy involving drugs such as Iloprost that show
potential for reversing dysplasia. This test is complementary to lung cancer
screening methods such as LDCT that do not detect dysplasia. We discuss the
performance of the LuCED test for the non-invasive detection of
MA01.01 DETECTION OF LUNG CANCER AND EGFR MUTATIONS BY
endobronchial dysplasia. Methods: We analyzed 23,188 normal, 690 cancer,
ELECTRONIC NOSE SYSTEM and 65 moderate/severe dysplasia cells from patient sputum. Each individual
Dekel Shlomi1, Manal Abud-Hawa2, Ori Liran3, Jair Bar4, Naomi Gai Mor3, Maya cell was imaged in 3D using the Cell-CT. Cells were analyzed to measure 594 3D
Ilouze5, Amir Onn4, Alon Ben-Nun6, Hossam Haick2, Nir Peled5 structural biomarkers. Classifiers were developed with cytopathology as the
1
Clalit Health Services, Petach Tiqwa/Israel, 2Department of Chemical Engineering, gold standard to predict stages of carcinogenesis, from normal to dysplasia
Russell Berrie Nanotechnology Institute, Technion, Haifa/Israel, 3The Thoracic and cancer. The classifier output was binned into two diagnostic indications:
Cancer Research and Detection Center, Sheba Medical Center, Ramat-Gan/Israel, 1) cancer vs. all other cell types; and 2) moderate/severe dysplasia vs. all other
4
Lung Cancer Unit, Sheba Medical Center, Ramat-Gan/Israel, 5Thoracic Cancer Unit,
cell types. Results: Areas under ROC curves for the two diagnostic bins were
Davidoff Cancer Center, Petach Tiqwa/Israel, 6Department of General Thoracic
both = 0.993. Thresholds were chosen to yield case specificity >95%. Using
Surgery, Sheba Medical Center, Ramat-Gan/Israel
these thresholds, cell classification sensitivity of 75% was measured for
Background: Early detection of LC has been well established as a significant cancer and dysplasia detection. Since abnormal sputum typically contains at
key point for patient survival and prognosis. New sensitive nanoarray sensors least three abnormal cells the cancer case detection sensitivity is at least
for exhaled Volatile Organic Compounds (VOCs) were developed and coupled {100% x [1 – (1 - 0.75)3]} = 98%.
with powerful statistical programs; diseases such as LC could be suspected.
Methods: Breath samples were taken from patients who were evaluated for
pulmonary nodules, LC patients before treatment and other control patients.
‘Breath-prints’ were recognized by nanomaterial based sensor array/Artificial
Olfactory System (NaNose®) and Pattern recognition methods were used.
Results: A total of 139 patients participated in this study, 30 patients with
benign nodules, 89 LC patients (16 early and 73 advanced disease) and 20
controls. We revealed significant discrimination between all groups with
accuracy of 75.6% to 90.9%. Discrimination of LC from benign nodules had
79% accuracy, while benign nodules could be discriminated from early LC
lesions with positive and negative predicted values (PPV and NPV) of 87.7
and 87.5% respectively, and accuracy of 87%. Also, we could discriminate
LC patients who harbor EGFR mutations (19) from wild-type (34) with an
accuracy of 83%, a sensitivity of 79% and a specificity of 85%.
Figure 1 shows ROC curves plus examples of cells imaged in 3D by the Cell-CT.
Conclusion: Breath analysis could discriminate LC patients from benign Conclusion: This study demonstrates the feasibility of using the LuCED test
pulmonary nodules and between EGFR positive and negative mutations. to detect endobronchial dysplasia in the lung, achieving an estimated 98%
In future, a portable, non-expensive, simple and user-friendly device may case sensitivity and 95% case specificity. Future efforts will include testing
support evaluation of pulmonary nodules. on independent sets. Importantly, the non-invasive detection of dysplasia by
LuCED testing may enable chemoprevention of lung cancer using drugs such
Keywords: lung cancer, EGFR mutations, breath analysis, pulmonary nodules as Iloprost.
Keywords: Dysplasia, Iloprost, LuCED, Non-Invasise
MA01: IMPROVEMENT AND IMPLEMENTATION OF LUNG CANCER SCREENING

MONDAY, DECEMBER 5, 2016 - 11:00-12:30

MONDAY, DECEMBER 5, 2016 - 11:00-12:30
MA01.02 NON-INVASIVE LUCED® TEST FOR ENDOBRONCHIAL
DYSPLASIA, ENABLING CHEMOPREVENTION THERAPY WITH
DRUGS SUCH AS ILOPROST MA01.03 THE NON-INVASIVE LUCED® TEST FOR DETECTION OF
Michael Meyer 1, Rahul Katdare2, Chris Presley1, David Wilbur3, David EARLY STAGE LUNG CANCER
Steinhauer 1, Jianming Liang4, Javier Zulueta1, Robert Keith5, York Miller6, Michael Meyer 1, Timothy Bell1, Daniel Sussman1, David Wilbur2, Chris Presley1,
Wilbur Franklin7, Grgory Yang8, Jon Hayenga1, Alan Nelson1 Jon Hayenga1, Frances Lakers1, Jonus Reyna1, Michael Davies3, John Field4,
1
Visiongate, Phoenix/AZ/United States of America, 2Visiongate, Phoenix/United Gregory Yang5, Christy Lancaster 1, Javier Zulueta1, Alan Nelson1
States of America, 3Visiongate Consultant, Boston/AL/United States of America, 1
Visiongate, Phoenix/AZ/United States of America, 2Visiongate Consultant, Boston/
4
Arizona State University, Tempe/AZ/United States of America, 5Pulmonary MA/United States of America, 3Molecular and Clinical Care Medicine, University
Medicine, Denver Veteran Affairs Medical Center, Denver/CO/United States of of Liverpool, Liverpool/United Kingdom, 4 Cancer Research Centre, University
America, 6Pulmonary and Critical Care Medicine, University of Colorado Anschutz of Liverpool, Liverpool/United Kingdom, 5Yuma Regional Medical Center, Yuma/
Medical Campus, Aurora/CO/United States of America, 7University of Colorado United States of America

Background: LDCT screening for lung cancer often triggers follow-up scans for the NELSON program for lung cancer screening in different scenarios in
indeterminate nodules. The non-invasive LuCED test for detection of early order to assess the robustness of the chosen approach. We are looking to
stage lung cancer may resolve nodule findings and reduce LDCT false develop a model that allows for testing the imaging protocol performance
positives. In LuCED, patient sputum is analyzed by the Cell-CT® which using various high-risk screening populations. Our Objective is to work out a
computes 3D images of single cells allowing measurement of 3D structural simulator adaptive to multiple screening scenarios. In a first step, we tested
biomarkers to identify potential abnormal cells. Final case disposition is a simulation of the NELSON triage algorithm by using published statistics as
determined through cytology review of these cells. Example images of input data: the distribution of nodule size, the precision of nodule volume
abnormal cells identified by LuCED are shown in the figure. measurements and the distribution of nodules growth. Methods: We modeled
the baseline round of NELSON triage algorithm. We simulated 10,000,000
ground truth (GT) data where the axial diameter of nodules followed a chi2
(df=1) distribution between 3 mm and 20 mm. For each of the GT nodule, we
modeled also a chi2 (df=1) distribution of volume doubling time between 90
and 1000 days. We included into the model a Gaussian distribution of the time
between visits (average: 105 days, standard deviation: 5 days). We modeled
volume measurement of the nodules by adding a Gaussian random error as
documented by the Quantitative Imaging Biomarker Alliance (QIBA) screening
profile. We performed a by-nodule comparison between nodule classification
by the triage algorithm and the corresponding GT in the first round. At each
step of the triage algorithm, we evaluated Sensitivity (Se), Specificity (Sp),
Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Results:
Sensitivity of the triage algorithm for classifying nodules into size categories
was for 96,6% for NODCAT2, 86.9% for NODCAT3 and 90.7% for NODCAT4.
Classification of GROWCAT C yielded Se=66.2% / Sp=21.2%. We found an
overall performance of the NELSON triage algorithm of Se/Sp 94.0%/80.3%.
PPV was 11.3%, and NPV was 99.8% Conclusion: Mathematical modeling
gives valuable insights into the performance of different components of
triage algorithms in lung cancer screening. We found a markedly different
test performance for size versus growth assessment of the NELSON triage
algorithm. Future work will extent the model to non-solid nodules and
multiple rounds of screening. Moreover, it may have the potential to optimize
triage algorithms in the design of screening programs.
Keywords: Lung Screening, Modelling, triage algorithm, volume of nodules

MONDAY, DECEMBER 5, 2016 - 11:00-12:30
MA01.06 LONG-TERM FOLLOW-UP OF SMALL PULMONARY

GROUND-GLASS NODULES STABLE FOR 3 YEARS: PROPER FOLLOW-
UP PERIOD AND RISK FACTORS FOR SUBSEQUENT GROWTH
Methods: Sputum samples from 127 patients were processed by LuCED: 65
patients had biopsy-confirmed lung cancer; and 62 patients were normal Jaeyoung Cho, Eun Sun Kim, Se Joong Kim, Yeon Joo Lee, Jong Sun Park, Young-
controls. Sensitivity was computed as the percentage of cancer cases where Jae Cho, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
abnormal cells were found by LuCED. Generally, abnormal cells found in a case Internal Medicine, Seoul National University Bundang Hospital, Seongnam/Korea,
otherwise understood to be normal could constitute a diagnostic overcall and Republic of
counted as a false positive. However, a finding of abundant (>5) abnormal cells
Background: It is uncertain how long persistent and stable ground-glass
in cases understood to be normal indicates discovery of a possible occult
nodules (GGNs) should be followed although a minimum of 3 years is
cancer or dysplastic lesion. Accordingly, these cases were not included in
suggested. Here, we aimed to evaluate the proportion of GGNs showing
specificity calculations. Results: For cancer cases, the histology included
subsequent growth after initial 3 years among GGNs that had been stable
adenocarcinoma (29 cases), squamous cancer (24), small cell lung cancer (5)
during the initial 3 years, and to determine clinical and radiologic factors
and undifferentiated cancer (7); representing stages 1 (14), 2 (11), 3 (25), 4 (14),
associated with subsequent growth. Methods: We retrospectively analyzed
and unknown (1). Abnormal cells were found in 61 of 65 cancer cases for
patients who underwent further computed tomography after the initial
sensitivity of 93.8%. For stage 1 and 2 cancer, sensitivity was 88%. Ten cells
3-year follow-up period showing a persistent and stable GGN (at least 5-year
exhibiting changes consistent with atypical adenomatous hyperplasia were
follow-up from initial CT). Results: Between May 2003 and June 2015, 453
found in one case. After removal, there remained two false positive cases,
GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218 patients. Of
leading to specificity of 96.7% (N = 61). Conclusion: The LuCED test
the 218 patients, 14 patients had 15 GGNs showing subsequent growth after
demonstrates accurate detection of early stage lung cancer with the potential
the initial 3 years during the median follow-up period of 6.4 years. For the
of detecting pre-cancerous conditions of the lung. Results suggest that
person-based analysis, frequency of subsequent growth of GGNs that had
suspicious nodules may be efficiently reconciled by LuCED when used
been stable during initial 3 years was 6.7% (14/218). For the nodule-based
adjunctively with LDCT.
analysis, the frequency was 3.3% (15/453). In a multivariate analysis, age ≥
Keywords: indeterminate nodules, LuCED, Non-Invasise, LDCT 65 years (odds ratio [OR], 5.51; p = 0.012), history of lung cancer (OR, 6.44; p =
0.006), initial size ≥ 8 mm (OR, 5.74; p = 0.008), presence of a solid component
(OR, 16.58; p = 0.009), and an air bronchogram (OR, 5.83; p = 0.015) were
independent risk factors for subsequent GGN growth.Between May 2003 and
June 2015, 453 GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218
MA01: IMPROVEMENT AND IMPLEMENTATION OF LUNG CANCER SCREENING patients. Of the 218 patients, 14 patients had 15 GGNs showing subsequent
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
growth after the initial 3 years during the median follow-up period of 6.4
years. For the person-based analysis, frequency of subsequent growth of
MA01.05 PREDICTIVE PERFORMANCES OF NELSON SCREENING GGNs that had been stable during initial 3 years was 6.7% (14/218). For the
PROGRAM BASED ON CLINICAL, METROLOGICAL AND nodule-based analysis, the frequency was 3.3% (15/453). In a multivariate
POPULATION STATISTICS analysis, age ≥ 65 years (odds ratio [OR], 5.51; p = 0.012), history of lung cancer
(OR, 6.44; p = 0.006), initial size ≥ 8 mm (OR, 5.74; p = 0.008), presence of a solid
Hubert Beaumont 1, Nathalie Faye2, Antoine Iannessi3, Dag Wormanns4
1
component (OR, 16.58; p = 0.009), and an air bronchogram (OR, 5.83; p = 0.015)
Sciences, Median Technologies, Valbonne/France, 2Medical, Median Technologies, were independent risk factors for subsequent GGN growth. Conclusion: For
Valbonne/France, 3Radiology, Centre Antoine Lacassagne, Nice/France, 4Radiology,
the individuals with GGNs having risk factors described above, the longer
Evangelische Lungenklinik Berlin, Berlin/Germany
follow-up period is required to confirm subsequent GGN growth.
Background: The balance of benefits and harms of screening programs
Keywords: ground glass nodule, follow-up, growth, computed tomograpy
depends on multiple factors such as the scenario of patient selection, the
triage algorithm and the imaging methods. Because of the multifactorial
nature of the outcome of screening programs, it is important to evaluate
the performance of its components. We modeled the triage algorithm of
MA01: IMPROVEMENT AND IMPLEMENTATION OF LUNG CANCER SCREENING All subjects, enrolled from 2004-2009,were followed up for lung cancer
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
incidence and mortality (average: 8.3 and 9.3 years, respectively);
characteristics of enrolled subjects are presented in Table1.
MA01.07 INFLUENCE OF NODULE MORPHOLOGY ON INTER-READER
VARIABILITY OF VOLUME AND DIAMETER MEASUREMENTS IN CT
LUNG CANCER SCREENING
Marjolein Heuvelmans 1, Daiwei Han1, Rozemarijn Vliegenthart1, Gonda De
Jonge2, Joan Walter 1, Peter Van Ooijen2, Harry De Koning 3, Matthijs Oudkerk4
1
Department of Radiology, University Medical Center Groningen, Umcg, Center for
Medical Imaging- North East Netherlands, Groningen/Netherlands, 2Department
of Radiology, University of Groningen, University Medical Center Groningen,
Groningen/Netherlands, 3Public Health, Erasmus MC, Rotterdam/Netherlands,
4
University Medical Center Groningen, Umcg, Center for Medical Imaging- North
East Netherlands, Groningen/Netherlands
Background: The high number of false positive screen results is a major

disadvantage of lung cancer screening by low-dose chest computed
tomography (CT). Measurement strategy influences the false-positive
rate, and nodule morphology may influence measurement of nodule size.
Comparison between inter-reader variation for semi-automatic volume
measurements and manual diameter measurements are scarce. Therefore,
we aimed to evaluate the influence of nodule morphology on inter-
reader variability and assessment of growth for semi-automatic volume
measurements and manual diameter measurements, in intermediate-sized
solid nodules found in CT lung cancer screening. Methods: Twenty-five
nodules of each morphological category: smooth, lobulated, spiculated and
irregular, were randomly selected from 93 participants of the Dutch-Belgian
randomized lung cancer screening trial (NELSON). Semi-automatic volume
measurements were performed using Syngo LungCARE® software. Two
chest radiologists independently measured maximum and mean diameters
manually. The impact of nodule morphology on inter-reader variability was
evaluated based on the systematic error and 95% limits of agreement (LoA).
Inter-reader variability was compared to volume change cutoff at 3-month
follow-up based on NELSON for nodule growth and Lung-RADS diameter
cutoff. Results: For manual diameter measurements, a significant systematic
deviation was found between readers in smooth, lobulated, and spiculated
nodules. The deviation was up to 1.5 mm based on maximum diameter
measurements, and 1.2 mm based on mean diameter measurements. For
semi-automatic volume measurements, no statistically significant systematic
deviation was found. For lobulated, spiculated, and irregular nodules, the
95%-LoA for mean diameter measurements was up to 66% larger than the
1.5 mm cutoff for nodule growth. For volume measurements, the 95%-LoA
exceeded the 25% growth cutoff for spiculated and irregular nodules, but
only by up to 12%. Conclusion: Nodule morphology has a greater effect
on size assessment based on manual diameter measurements than based
on volume measurements. The larger inter-reader variability for manual
diameter measurement may cause misclassification of spiculated nodules
Results: Reductions of 17% (RR=0.83; 95%: 0.67-1.03) for overall and 30%
when assessing growth in 24% of cases. Therefore, semi-automatic volume
(RR=0.70; 95%CI: 0.47-1.03) for LC-specific mortality were estimated. 67 lung
measurement is recommended for nodule size and growth determination in
cancers were diagnosed in the active, compared with 72 in the control group
CT lung cancer screening.
(RR=0.92; 95%CI: 0.66–1.28). A greater proportion of Stage I (36% vs 6%,
Keywords: lung nodule, inter-reader variability, semi-automatic volume (p<0.0001) was observed in the active group. Conclusion: LDCT screening
measurement, manual diameter measurement could reduce LC-specific and overall mortality. The number of Lung cancer
diagnosed in the two groups did not suggest over-diagnosis, after 8.5 years of
follow-up time.
Keywords: efficacy, lung cancer, Screening, Overdiagnosis

MONDAY, DECEMBER 5, 2016 - 11:00-12:30
MA01.09 MORTALITY, SURVIVAL AND INCIDENCE RATES IN THE MA01: IMPROVEMENT AND IMPLEMENTATION OF LUNG CANCER SCREENING
ITALUNG RANDOMISED LUNG CANCER SCREENING TRIAL (ITALY) MONDAY, DECEMBER 5, 2016 - 11:00-12:30
Eugenio Paci1, Donella Puliti2, Andrea Lopes Pegna3, Laura Carrozzi4, Giulia
Picozzi5, Fabio Falaschi6, Francesco Pistelli4, Ferruccio Aquilini4, Marco MA01.10 PERFORMANCE OF ACR LUNG-RADS IN THE 1ST BRAZILIAN
Zappa7, Francesca Carozzi8, Mario Mascalchi9 LUNG CANCER SCREENING TRIAL (BRELT1)
1
Formerly at Clinical Descriptive Epidemiology Unit, Institute for Cancer Prevention
Ricardo Santos 1, Juliana Franceschini1, Mário Ghefter 1, Rodrigo Chate1, André
and Research (Ispo), Florence/Italy, 2Clinical Descriptive Epidemiology Unit,
Luiz Trajano1, Roberto Saad Junior2
Institute for Cancer Prevention and Research (Ispo), Florence/Italy, 3Formerly at
1
Cardio-Thoracic-Vascular Dept., Careggi Hospital, Florence/Italy, 4 Cardio-Thoracic Hospital Israelita Albert Einstein, SÃo Paulo/Brazil, 2Faculdade de Ciências
and Vascular Dept, University Hospital of Pisa, Pisa/Italy, 5Diagnostic Imaging Unit, Médicas Da Santa Casa de SÃo Paulo, SÃo Paulo/Brazil
Institute for Cancer Prevention and Research (Ispo), Florence/Italy, 6Diagnostic
Radiology, University Hospital of Pisa, Pisa/Italy, 7Clinica Descriptive Epidemiology Background: In BRELT1 we found a significant number of low dose CT
Unit, Institute for Cancer Prevention and Research (Ispo), Florence/Italy, (LDCT) considered positive (nodules > 4mm). The aim of this study was to
8
Prevention Laboratory Unit, Institute for Cancer Prevention and Research (Ispo), assess the effect of applying ACR Lung-RADS and Pre-Test Probability of
Florence/Italy, 9“Mario Serio”Department of Experimental and Clinical Biomedical Malignancy (PTPM) in suspicious nodules > 8mm founded in a clinical CT
Sciences, University of Florence, Florence/Italy lung screening program. Methods: Clinical LDCT (baseline and follow up)
containing nodules > 8mm were retroactively reclassified using the new ACR
Background: Low Dose Computed Tomography (LDCT) screening for lung
Lung-RADS™ structured reporting system and PTPM. The model used in this
cancer (LC) is still not recommended in Europe. Methods: 71.232 invitation
study to predict the probability of malignancy was designed by Swensen
letters were sent to subjects registered with local General Practitioners, aged
et al and included patient’s age, current or former smoker, diameter of the
5569 years. (Fig.1) From eligible respondents, we randomised 3206 eligible
nodule, speculation and location. All LDCT had initially been interpreted by
subjects, smokers and ex- smokers (< 10 years), to the active arm receiving 4
radiologists accredited in CT lung screening reporting following the National
annual LDCT (n=1613) and to control arm receiving usual care (n=1593). Each
Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology:
LDCT was read by 2 radiologists and size of Non Calcific Nodules measured
Lung Cancer Screening (version 1.2012), which considered as positive the
manually. Study design and performance data were already published.
same criteria from the National Lung Screening Trial. Results: In BRELT1

were recruited 790 current or former smokers, with a heavy smoking history. these extracellular vesicles have been shown to play a key role in cancer
A total of 552 nodules were found in 312 positive LDCT at baseline (39%). development, growth, progression and angiogenesis. These extracellular
LDCT follow up was performed in 89.1% of this population. From them 74 vesicles are loaded with functional mRNAs, miRNAs and proteins which can
patients presented solid or semi solid nodules > 8mm in the highest diameter. be transferred from one cell to another. Extracellular vesicles have been
According to ACR Lung-RADS™ 39 baseline LDCT were classified as 4A (52.7%), known to enter neighboring cells including the surrounding stroma, and
6 as 4B (8.1%), 17 as 4X (22.9%) and 10 as 2 (13.5%). Follow-up LDCT showed even enter biofluids. Our research shows that miRNAs transferred from
reduction in the category in more than 80% of cases. Using the PTPM, 44 lung adenocarcinoma cells through extracellular vesicles influence gene
cases were considered at moderate risk (between 6 and 60%) and 30 cases expression in endothelial cells and enhance their ability to form new blood
of high risk for malignancy (over 60%). None was considered low risk (5% or vessels. Methods: Using 5 lung adenocarcinoma cell lines (H1395, H1437,
less). Among 26 patients who underwent biopsy in BRELT1, we found 12 cases H2073, H2228 and H2347) we isolated extracellular vesicles using differential
of lung cancer, of which 90% were stage IA or IB. Conclusion: The application ultracentrifugation. RNA was extracted from the extracellular vesicles as well
of ACR Lung-RADS and PTPM associated with careful multidisciplinary as the cells from which they were derived and profiled for 742 miRNAs using
assessment can help in the decision process. The follow-up of patients with the miRCURY LNATM Universal RT miRNA PCR system (Exiqon) to identify
positive nodules requires careful analysis of the main factors related to miRNAs that were enriched by at least 4-fold in the extracellular vesicles. Tube
malignancy. formation assays were conducted on a commonly used endothelial cell line
HMEC-1. Results: We found an enrichment of a select set of miRNAs within
Keywords: Screening, lung cancer, nodules lung adenocarcinoma extracellular vesicles. These miRNAs have previously
been identified as tumor suppressors: miR-142-3p, miR-143-3p, miR-144-3p,
miR-145-5p, miR-150-5p, miR-223-3p, miR-451a, miR-486-5p, miR-605-5p in
various cancer types. When extracellular vesicles are isolated from miR-143
MA01: IMPROVEMENT AND IMPLEMENTATION OF LUNG CANCER SCREENING and miR-145 over expressing adenocarcinoma lines they contain an increase
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
in their over expressed miRNAs. When these miRNA enriched exosomes
were incubated with HMEC-1 cells, we observed an increase in their ability to
MA01.11 IMPLEMENTATION OF LDCT LUNG CANCER SCREENING form new blood vessels and a decrease in the expression of CAMK1D in the
INTO PRACTICE. RESULTS OF REGIONAL EARLY DETECTION endothelial cells. miR-143-3p and miR-145-5p were also found to be enriched in
PROGRAM serum samples draining directly from lung adenocarcinoma tumors compared
to arterial serum. Conclusion: Extracellular vesicles originating from lung
Maciej Bryl1, Beata Nikisch2, Wojciech Dyszkiewicz3, Cezary Piwkowski3,
adenocarcinoma cells can enter into endothelial cells and increase their ability
Mariusz Kasprzyk 3, Wojciech Kasprzak4, Aleksander Barinow-Wojewodzki5
1
to form new blood vessels through extracellular vesicle transfer of miR-145/
Oddzial Onkologii, Wielkopolskie Centrum Pulmonologii I Torakochirurgii, Poznan/ miR-143 suggesting that this form of communication increases angiogenesis
Poland, 2 Zaklad Radiologii, Wielkopolskie Centrum Pulmonologii I Torakochirurgii,
within lung adenocarcinoma tumors.
Poznan/Poland, 3Oddzial Torakochirurgii, Wielkopolskie Centrum Pulmonologii
I Torakochirurgii, Poznan/Poland, 4 Oddzial Pulmonologiczno-Internistyczny,
Keywords: Extracellular Vesicle, Endothelial, microRNA, lung adenocarcinoma
Wielkopolskie Centrum Pulmonologii I Torakochirurgii, Poznan/Poland, 5Oddzial
Pulmonologiczno-Rehabilitacyjny, Wielkopolskie Centrum Pulmonologii I
Torakochirurgii, Poznan/Poland
Background: Lung cancer is the leading cause of cancer deaths both in men MA02: RNA IN LUNG CANCER
and women in either Wielkopolska and the whole Poland. Wielkopolska MONDAY, DECEMBER 5, 2016 - 14:15-15:45
is one of Polish regions (voivodships) with about 3,4 mln inhabitants and
incidence of lung cancer aprox. 1900 new cases every year. Screening by MA02.02 A NOVEL 5-MIR SIGNATURE SHOWS PROMISE AS A
low dose computer tomography (LDCT) showed reduction of lung cancer
DIAGNOSTIC TOOL AND AS A PREDICTOR OF CISPLATIN RESPONSE
mortality in NLST trial. Regional authorities covered this program from local
budget beside Polish health system. Methods: Since october 2009 program
IN NSCLC
of early detection of lung cancer started in 5 centers of Wielkopolska region. Lauren Mac Donagh1, Steven Gray1, Sinead Cuffe2, Stephen Finn3, Niamh
Till the end of 2015 N=17222 subjects were screened. The entry criteria were: Fitzgerald2, Vincent Young4, Ronan Ryan4, Siobhan Nicholson5, Niamh
age between 55 and 70 years and smoking ≥ 20 packyears. Every person has Leonard6, Kenneth O’Byrne7, Martin Barr 8
1
the LDCT performed. Results were first clasified as normal or abnormal. Thoracic Oncology Research Group, Trinity College Dublin/st. James’ Hospital,
Abnormalities were divided into 6 categories: <5mm single, <5 mm multiple, Dublin/Ireland, 2Oncology, Hope Directorate, Dublin/Ireland, 3Dept. of
5-15 mm single, 5-15 mm multiple, >15 mm single, >15 mm multiple. Patient Histopathology and Morbid Anatomy, Trinity College Dublin, Dublin/Ireland,
4
Cardio-Thoracic Surgery, Sacc Directorate, Dublin/Ireland, 5Histopathology, St.
received also recomendation for further actions. Results presented are based
James’ Hospital, Dublin/Ireland, 6Histopathology, Labmed Directorate, Dublin/
on annual reports for regional authorities. Results: More than 85% of the Ireland, 7Institute of Health and Biomedical Innovation, Queensland University
images were clasified as abnormal. Nodes of any kind were found in about of Technology, Brisbane/Australia, 8Thoracic Oncology Research Group, St. James’
47% of entire population. More than 3000 patient received recomendation Hospital & Trinity College Dublin, Dublin/Ireland
for further diagnostic evaluation. Finally 108 patients underwent surgery (37
lobectomies, 41 wedge resections, 30 thoracotomies/thoracoscopies). There Background: MicroRNAs are a class of small non-coding RNAs that range in
were 92 cases of lung cancer confirmed (11 SCLC, 78 NSCLC, 3 carcinoids) and 1 size from 19-25 nucleotides. They have been shown to regulate a number
case of mesothelioma. Conclusion: Lung cancer screening program identifies of processes within tumour biology, including metastasis, invasion and
magnitude of lung changes. Many patients requires further diagnostic angiogenesis. More recently, miRNAs have been linked to chemoresistance
procedures. Most of them are fibrotic, post inflammatory changes. It is in solid tumours, including lung cancer. Methods: MicroRNA expression
possible to diagnose lung cancer in early presymptomatic stage but numbers within an isogenic panel of age-matched parent (PT) and cisplatin resistant
are low and risk models or biomarkers should be implemented to better define (CisR) NSCLC cell lines was profiled using the 7th generation miRCURY LNA
patients / nodules at risk. arrays (Exiqon). Significantly altered miRNAs within the CisR sublines were
manipulated using antagomirs (Exiqon) and Pre-miRs (Ambion) and functional
Keywords: Screening, LDCT studies were carried out in the presence and absence of cisplatin. To examine
the translational relevance of these miRNAs, their expression was examined
in a cohort of chemo-naïve patient-matched normal and lung tumour tissue
and serum from NSCLC patients of different histologies. To create a xenograft
model of cisplatin resistance 1x103 cells H460 PT or CisR cells were injected
SESSION MA02: RNA IN LUNG CANCER into 5-7week old NOD/SCID mice. Tumour volume was measured over time and
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 harvested once the tumour mass measured 500mm3 and formalin-fixed and
paraffin embedded (FFPE). Expression of the 5-miR signature was analysed
within FFPE murine tumours and cisplatin resistance was investigated
MA02.01 EXTRACELLULAR VESCICLE MIRNAS REGULATE GENE relative to cisplatin sensitive controls. Results: Profiling and subsequent
EXPRESSION IN LOCAL LUNG ADENOCARCINOMA ENDOTHELIAL validation revealed a 5-miR signature associated with our model of cisplatin
resistance (miR-30a-3p, miR-30b-5p, miR-30c-5p, miR-34a-5p, miR-4286).
CELLS
Inhibition of the miR-30 family and miR-34a-5p reduced clonogenic survival
James Lawson1, Christopher Dickman1, Rebecca Towle1, James Jabalee1, of CisR cells when treated cisplatin. Expression of the miRNA signature
Stephen Lam2, Cathie Garnis3 was significantly altered in both adenocarcinoma (AD) and squamous cell
1
Integrative Oncology, BC Cancer Research Center, Vancouver/BC/Canada, carcinoma (SCC) relative to matched normal lung tissue and between SCC
2
Integrative Oncology, BC Cancer Agency, Vancouver/Canada, 3Department of and AD tissue. miR-4286 was significantly up-regulated in SCC sera compared
Surgery, University of British Columbia, Vancouver/Canada to normal control and AD sera. Similarly to the cell line expression of the
Background: Extracellular vesicles are small vesicles released from all cell miRNAs, the miR-30 family members and miR-34a-5p were up-regulated in
types which can be used as a form of cell to cell communication. Recently the CisR xenograft FFPE tissue relative to PT. Conclusion: A novel miRNA
signature associated with cisplatin resistance was identified in vitro, genetic
manipulation of which altered clonogenic response to cisplatin. The 5-miR type with a heterogeneous pattern of growth classified as lepidic, acinar,
signature shows both diagnostic and prognostic biomarker potential across a papillary, solid, and micropapillary. For ADC there are restricted available
number of diagnostically relevant biological mediums. therapeutic options except for patients that could benefit from target
therapy. A valuable therapeutic strategy is represented by angiogenesis
Keywords: MicroRNAs, Cisplatin resistance, Biomarkers inhibitors such as bevacizumab that has been approved for the treatment
of NSCLC patients. However, there are concerns about its treatment-related
toxicity and the identification of new reliable biomarkers to stratify patients
who can really benefit from antiangiogenic drugs is urgently needed. Using
MA02: RNA IN LUNG CANCER miRNA target prediction tools, we selected and investigated the expression
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
level of a panel of miRNAs togheter with their mRNA target involved in the
angiogenesis pathway. Methods: We designed a custom codeset including
MA02.03 EXPRESSION OF ONCOFETAL MIRNAS INACTIVATES NFIB, probes for six genes (VEGF-A, FLT1, KDR, FLT4, PDGFRa and PDGFRb) and
A DEVELOPMENTAL TRANSCRIPTION FACTOR LINKED TO TUMOUR sixteen miRNAs. The expression analysis was performed by the nCounter
AGGRESSIVENESS IN LUNG ADENOCARCINOMA System® (NanoString Technologies) directly on RNA, enriched of small RNA,
purified from the formalin-fixed and paraffin-embedded tumor tissues
Daiana Becker-Santos 1, Brenda Minatel2, Kim Lonergan2, Kelsie Thu2, John
of 80 ADC patients. Of these 25 were predominatly lepidic (31.25%), 24
English3, Victor Martinez2, Calum Macaulay2, William Lockwood2, Wendy
were predominatly solid (30%), 20 were predominatly acinar (16%), 11
Robinson4, Igor Jurisica5, Stephen Lam2, Wan Lam2
1
were predominatly papillary (13.75%). Results: Comparing the expression
Department of Integrative Oncology, British Columbia Cancer Research Centre, levels of mRNAs with the different histological ADC subtypes we found a
Vancouver/BC/Canada, 2Integrative Oncology, British Columbia Cancer Research
significant higher expression of VEGF-A in papillary than in other subtypes
Centre, Vancouver/BC/Canada, 3Department of Pathology, Vancouver General
Hospital, Vancouver/BC/Canada, 4 Medical Genetics, University of British Columbia, (p=0.02). In contrast PDGFRa and PDGFRb were upregulated in lepidic and
Vancouver/BC/Canada, 5University Health Network, Princess Margaret Cancer downregulated in papillary subtypes (both p=0.03). Among 16 miRNAs that
Centre, Toronto/Canada target the angiogenic mRNA, 6 were significantly downregulated in papillary
compared to other groups. Conclusion: Our data suggest a distinct angiogenic
Background: Fetal and tumour development share striking similarities, such miRNA-mRNA expression profile among the subtypes of ADC. The higher
as intense cell proliferation, angiogenesis, increased cell motility, and immune level of VEGF-A in papillary than in lepidic subtypes could represent a useful
evasion. Molecular regulators, including microRNAs (miRNAs), play important biomarker to stratify patients who can effectively treated with bevacizumab,
roles in both fetal lung development and in the malignant transformation of which is directed against VEGF. Moreover, the regulation of angiogenic mRNA
adult lung cells. Consequently, investigation of lung tumour biology in the factors by miRNAs could provide a novel therapeutic approach based on their
context of lung development may reveal key regulatory mechanisms that expression pattern specific for distinct ADC subtypes. Further studies are
tumours hijack from normal development, which potentially play critical nedeed in a larger cohort of patients to confirm our results and to investigate
roles in the pathology of lung cancer. Methods: 131 pairs of non-small cell lung whether different rates of response to treatment are observed among
cancer (NSCLC) tumour and non-malignant lung tissues and 15 human fetal patients stratified according to the proposed biomarkers.
lung tissue samples were profiled by miRNA-sequencing. Genes controlled
by the oncofetal miRNAs identified were first investigated by miRNA-Data- Keywords: lung adenocarcinoma subtypes, angiogenesis, VEGF-A, MicroRNAs
Integration-Portal (mirDIP) prediction, followed by luciferase-reporter
assays. Associations between patient survival and mRNA expression of
oncofetal miRNA-gene targets were evaluated in independent samples
(>1,400 cases) across multiple NSCLC cohorts. Immunohistochemical analysis MA02: RNA IN LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
of oncofetal miRNA targets was performed on 96 lung adenocarcinoma
(LUAD) specimens. Results: We describe for the first time a comprehensive
characterization of miRNA expression in human fetal lung tissue, and MA02.07 EVALUATION OF EXOSOMAL MIRNAS FROM PLASMA AS
identified numerous miRNAs that recapitulate their fetal expression patterns POTENTIAL BIOMARKER FOR NSCLC
in NSCLC. Nuclear Factor I/B (NFIB), a transcription factor essential for lung
Xiance Jin1, Congying Xie2
development, was identified as being frequently targeted by these oncofetal
1
miRNAs. Overexpression of the oncofetal miRNA miR-92b-3p, significantly Radiotherapy and Chemotherapy, The 1St Affiliated Hospital of Wenzhou Medical
University, Wenzhou/China, 2Radiation Oncology, The 1St Affiliated Hospital of
reduced NFIB levels in vitro. Concordantly, analysis of NFIB expression in
Wenzhou Medical University, Wenzhou/China
multiple NSCLC cohorts revealed its frequent underexpression in tumours
(~40-70%). This is in contrast with its recurrent oncogenic overexpression Background: Non-small-cell lung cancer (NSCLC) is one of the most common
recently reported in SCLC. Low expression of NFIB was significantly and high mortality rate carcinoma in China which biomarkers for diagnosis are
associated with poorer survival in LUAD patients but not in squamous cell limited. Therefore, novel biomarkers and methods with increased specificity
carcinoma patients, consistent with the functional role of NFIB in distal lung for diagnosis are explored and required. For now, liquid biopsy for lung
cell differentiation (i.e., precursor cells of LUAD). Furthermore, an NFIB- cancer oncogenes and next generation sequencing technique are extensive
related gene signature was identified in LUAD tumours, comprising several employed in NSCLC. However, increasing evidence illustrates that exosomal
well-known lung differentiation markers (e.g., TTF-1, SFTPB, ABCA3). The microRNAs in circulating fluids provide a promising way as biomarkers for
underexpression of NFIB protein was ultimately validated in LUAD specimens, noninvasive cancer diagnosis. Exosomes are 30–150 nm particles which are
which also revealed that tumours presenting lower levels of this transcription released from cells into the extracellular environment and stable miRNAs
factor are associated with higher grade, biologically more aggressive LUAD have been identified in plasma exosomes, which play important role in cell
(invasive mucinous, micropapillary and solid subtypes). Conclusion: This communication. Furthermore, exosomal miRNAs present different profiles
work has revealed a prominent mechanism for the downregulation of NFIB, between patients with cancer and healthy individuals. Whether exosomal
a transcription factor essential for lung differentiation, which we found to miRNAs could benefit NSCLC patient diagnosis remains to be explored.
be associated with aggressive phenotypes of LUAD and consequently, poor Methods: Blood samples were collected from 40 NSCLC patients and 24
patient survival. Restoration of NFIB expression, specifically in LUAD, has healthy volunteers matched with age, gender and blood collection time.
the potential to induce lung cell differentiation and thereby reduce tumour Plasma exosomes were accessed by 110,000×g ultracentrifugation and
aggressiveness. visualized by NS300 equipment. The raw data of exosomal miRNA profiles of
NSCLC patients and healthy individuals were generated by NGS around 400×
Keywords: lung adenocarcinoma, lineage transcription factors, lung
read depth and its expression were measured by Taqman probe quantitive
developmental pathways, miRNA
PCR Results: In the present study, we revealed that nearly half of exosome
RNA was miRNA and NSCLS patients expressed a set of exosomal miRNAs
with specificity compared with healthy volunteers. We demonstrated
that miR-126-5p and miR-21-3p were down-regulated in NSCLC patients. In
MA02: RNA IN LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 addition, we showed that the expression level of miR-124-3p and miR-99a-3p
in NSCLC patients was higher than that of healthy individuals. Furthermore,
we found miR-99a-3p was clinical stages related in NSCLC patient plasma
MA02.05 DISTINCT ANGIOGENIC MICRORNA-MRNA EXPRESSION and miR-375-3p was a potential biomarker for diagnosis and prognosis in
PROFILES AMONG SUBTYPES OF LUNG ADENOCARCINOMA NSCLC. Conclusion: Exosomal miRNAs in plasma could indicate the progress
Mirella Giordano 1, Laura Boldrini1, Adele Servadio1, Marco Lucchi1, Franca of NSCLC and a combination of the explored miRNA could serve as a promising
Melfi2, Alfredo Mussi1, Gabriella Fontanini1 biomarker for NSCLS diagnosis and prognosis.
1
Department of Surgical, Medical, Molecular Pathology and Critical Area, University
Keywords: NSCLC diagnosis, Exosomal miRNA
of Pisa, Pisa/Italy, 2Unit of Thoracic Surgery, University Hospital of Pisa, Pisa/Italy
Background: Non-small cell lung cancer (NSCLC) accounts for 80% of all lung
cancers and adenocarcinoma (ADC) represents the most common histological

MA02: RNA IN LUNG CANCER gene expression. Significantly differentially expressed lncRNAs located
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
within pseudogene loci were identified by sign-rank test (p<0.001). Mann
Whitney U-tests were used to identify lncRNA-parent gene pairs which
MA02.08 DEREGULATION OF CIS-ACTING LONG NON-CODING RNAS significantly correlated expression, and survival analysis was performed
IN NON-SMALL CELL LUNG CANCER using a Cox proportional hazard model. Results: Our analysis has identified
172 lncRNAs expressed from pseudogene loci that were significantly
Adam Sage 1, Greg Stewart1, David Rowbotham2, Katey Enfield2, Victor
deregulated in LUAD. Remarkably, many of these lncRNAs were expressed
Martinez1, Stephen Lam1, Wan Lam1
from the loci of pseudogenes related to known cancer genes. One of these
1
Integrative Oncology, BC Cancer Research Centre, Vancouver/BC/Canada, lncRNAs, CTD-2583A14.8, was expressed from a pseudogene to ubiquitin-
2
Integrative Oncology, BC Cancer Research Centre, Vancouver/Canada
conjugating enzyme E2C (UBE2C), which regulates tumor growth, apoptosis,
Background: Lung cancer remains the cause of the most cancer-related deaths and angiogenesis through phospho-ERK1/2. We find CTD-2583A14.8 as well
each year, with a 5 year survival rate of less than 17%. Targeted therapeutics as the UBE2C parent gene to be significantly upregulated in LUAD tumours
have been developed against drivers of the lung adenocarcinoma (AC) compared to matched normal tissue. Furthermore, tumours with higher levels
subtype, but are relevant only to the proportion of patients harbouring of CTD-2583A14.8 have significantly higher levels of UBE2C expression than
these genetic aberrations, emphasizing the need to explore alternative tumours with low levels of CTD-2583A14.8, indicating that CTD-2583A14.8
mechanisms of AC development. Natural antisense transcripts (NATs) are long may positively regulate UBE2C in trans. Conclusion: Here we show expression
non-coding RNA (lncRNA) products expressed from the opposite strand of of lncRNAs within pseudogene loci is deregulated in LUAD, and can correlate
coding mRNAs. NATs can function in cis or trans to regulate the transcriptional with the expression of their protein-coding counterparts. Many of these
activity of their cognate gene partner in either a positive or negative fashion. genes associated with this putative lncRNA-pseudogene-protein-coding
Here we take a novel approach to identify cis- NATs deregulated in lung AC, axis have previously been implicated in cancer. Therefore, this represents an
and explore the function of these genes with regards to their protein coding alternative mechanism of cancer gene deregulation, and may represent novel
partner genes. Methods: We performed RNA-sequencing on a set of 36 therapeutic intervention points for the treatment of LUAD.
lung AC and matched non-malignant lung tissues. A sign-rank test was used Keywords: non-coding RNA, pseudogenes, long non-coding RNAs
to identify NATs and partner genes with significantly altered expression
between tumor and matched normal tissues. These findings were validated
in an external dataset of 50 lung AC tumors with matched non-malignant
tissue obtained from The Cancer Genome Atlas (TCGA). Survival analysis was
performed using a Cox Proportional hazard model, as well as the log-rank SESSION MA03: EPIDEMIOLOGY, RISK FACTORS
method. Results: Analysis of Illumina Hi-seq data from TCGA revealed the
majority (79%) of deregulated sense-antisense partnerships observed in AC
AND SCREENING
displayed concordant regulation. However, several discordant cis-NAT pairs MONDAY, DECEMBER 5, 2016 - 14:15-15:45
were identified including an antisense to OPA INTERACTING PROTEIN 5 (OIP5),
a gene required for chromatin segregation, as well as an antisense to HIGH
MOBILITY GROUP A1 (HMGA1) a gene involved in the metastatic progression MA03.01 GENDER DISPARITIES IN NON-SMALL CELL LUNG CANCER:
of many cancer types. Both the antisense to OIP5 (OIP5-AS1) as well as A SYSTEMATIC REVIEW
the antisense to HMGA1, (HMGA1-AS1) were significantly underexpressed Noor Alsaadoun1, Karen Kopciuk2, Dr. Desiree Hao2, Karl Riabowol1, Morley
in AC, while we find the overlapping protein coding partner genes to be Hollenberg Hollenbrg 3, Gwyn Bebb2
significantly overexpressed, suggesting that these genes may negatively 1
Cumming School of Medicine, University of Calgary, Calgary/AB/Canada,
regulate their sense counterparts. In addition both OIP5 and HMGA1 are 2
Alberta Health Services, Calgary/AB/Canada, 3Department of Physiology and
significantly associated with 5-year survival. Patients with higher expression Pharmacology, University of Calgary, Calgary/AB/Canada
levels of either of these genes had a significantly shorter overall survival
time than patients with low expression levels, highlighting the potential Background: Although lung cancer is the second most-often diagnosed
clinical importance of these genes. Conclusion: This study characterizes the malignancy in both men and women, and the biggest cancer killer of both
landscape of antisense expression in AC and highlights novel mechanisms of genders, evidence suggests that the lung cancer experience differs in women
oncogene regulation through natural antisense transcripts. Characterizing compared to men. Lung cancer incidence in men has steadily decreased since
these oncogene regulatory mechanisms could uncover therapeutic the mid-1980s, while in women it has increased. Partly, these patterns reflect
intervention points and further our understanding of AC biology. sex differences in smoking behavior over the previous two decades. Additional
epidemiological evidence suggests that gender impacts most facets of the
Keywords: lung adenocarcinoma, long non-coding RNAs, gene regulation lung cancer experience, including the incidence, susceptibility, severity, and
molecular basis of the disease. However, there is a lack of consensus on both
the magnitude and etiology of these gender-based differences. The aim of
this currently ongoing systematic literature review is to more precisely define
MA02: RNA IN LUNG CANCER this gender disparity among non-small cell lung cancer (NSCLC) patients
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
worldwide and summarize current opinions about the molecular basis for
these observations. Methods: A preliminary rapid review was launched to
MA02.09 LONG NON-CODING RNA EXPRESSION FROM outline gender disparity among NSCLC patients in North America, Europe
PSEUDOGENE LOCI AS A NOVEL MECHANISM OF CANCER GENE and South Asia. Independent studies were utilized from Medline; Embase;
REGULATION Cochrane Central Register of Controlled Trials, and Cochrane Database of
Systematic Reviews for the period between 1996 and 2016. Based on these
Greg Stewart 1, Katey Enfield2, Victor Martinez2, Erin Marshall3, Stephen
results, a systematic literature review was carried out for the period between
Lam4, Wan Lam5
1
1996 and 2016 using Medline and Embase databases worldwide. The main
Integrative Oncology, BC Cancer Research Centre, Vancouver/BC/Canada,
2 outcome measures are incidence and factors influencing NSCLC between
Integrative Oncology, BC Cancer Research Centre, Vancouver/Canada, 3BC Cancer
the genders. A validated scoring system was used to appraise eligible studies
Research Centre, BC Cancer Research Centre, Vancouver/BC/Canada, 4Integrative
Oncology, BC Cancer Agency, Vancouver/Canada, 5Department of Integrative for methodological quality and level of evidence. Results: The preliminary
Oncology, British Columbia Cancer Research Center, Vancouver/BC/Canada rapid search identified 17 eligible articles for review. Analysis suggests that
females are more susceptible to tobacco related carcinogens, have a younger
Background: The advent of next generation sequencing has lead to the age at diagnosis and higher survival rates. We also observed an increase
discovery of the functional importance of non-coding RNAs (ncRNAs) in a wide in the inclusion of female patients in the clinical studies over this period.
variety of cellular processes, and these genes can be exploited by tumours Based on pre-specified selection criteria, the systematic review generated
to drive the hallmarks of cancer. Pseudogenes are DNA sequences that are a total of 367 studies which have been retrieved and considered for further
defunct relatives of their functional parent genes but retain high sequence analysis. We will determine gender differences in NSCLC incidence and its
homology. Long non-coding RNAs (lncRNAs) have been shown to regulate molecular aberration utilizing data from independent studies based on
protein-coding genes; however, complex folding patterns make lncRNA rapid analysis of observational studies published globally. Conclusion: Our
function difficult to predict. Several lncRNAs expressed from pseudogene systematic literature review will help validate our preliminary findings that
loci have been shown to regulate the protein-coding parent genes of these gender disparities in lung cancer do exist. Our findings will provide a platform
pseudogenes in trans due to sequence complementarity. The biological for policy makers, researchers and clinicians to design clinical trials and
impact of this mechanism has not been investigated in lung adenocarcinoma interventions that account for these disparities.
(LUAD). We hypothesize that expression changes in lncRNAs expressed
from pseudogene loci can affect the expression of corresponding protein- Keywords: Gender disparities, Incidence, Molecular aberration, NSCLC
coding parent genes in trans, and that these events provide an alternative
mechanism of cancer gene deregulation in LUAD tumourigenesis. Methods:
We analysed RNA-seq data from 50 LUAD with matched non-malignant
tissue obtained from the TCGA for both protein-coding and non-coding
MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING ratio for second primary lung cancer was 16.08 in the patients whose primary
MONDAY, DECEMBER 5, 2016 - 14:15-15:45
breast cancer was diagnosed at age younger than 50 years and 1.43 for those
diagnosed at age older than 50 years. These results supported the national
MA03.02 LUNG CANCER IN WOMEN 1929 TO 2016: COLD-BLOODED cohort study findings that early-onset female breast cancer patients bear
ORIGINS OF AN EPIDEMIC a relative high risk for second primary lung cancer. Conclusion: Our findings
suggest a relative high risk for second primary lung cancer among patients
Fred Grannis
whose primary female breast cancer is diagnosed at age less than 50 years.
Surgery, City of Hope National Medical Center, Duarte/United States of America
Keywords: Breast cancer, Early onset, Double primary, lung cancer
Background: The epidemiologic profile of lung cancer mortality in the U.S.
is highly unusual. Mortality in males began to rise rapidly early in the 1920s
and continued to increase through the 1990s before leveling off. Mortality
in women did not begin to rise until decades later and did not approximate MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING
mortality in men until the early years of the twenty first century. This unusual MONDAY, DECEMBER 5, 2016 - 14:15-15:45
pattern of disease can be explained by review of tobacco industry documents
and court records. Methods: A search was conducted in the Legacy Tobacco
Documents library at the University of California, San Francisco, as well as
MA03.05 COST EFFECTIVENESS ANALYSIS OF CT VS CHEST X-RAY
review of testimony and legal reports from state and federal court decisions. (CXR) VS NO SCREENING FOR LUNG CANCER (LC) IN THE PLCO AND
Results: The beginning of the epidemic of lung cancer in women in the U.S. can NLST RANDOMIZED POPULATION TRIALS (RPTS)
be reliably traced back to Easter Sunday in 1929. On that date, a publicity stunt John Paul Flores 1, Alejandro Moreno-Koehler2, Matthew Finkelman3, Jaime
crafted by Edward Bernays was reported in the New York Times as the “parade Caro4, Gary Strauss5
of torches” supposedly representing an expression of freedom by American 1
Hematology/Oncology, Tufts Medical Center, Boston/United States of America,
women who would henceforward not be constrained from smoking in public. 2
Biostatistics, Tufts Medical Center, Boston/MA/United States of America,
3
The public relations effort was supplemented by an advertising campaign Biostatistics, Tufts School of Dental Medicine, Boston/MA/United States of
orchestrated by Chicago marketing expert Albert Lasker. Female smoking rates America, 4Evidera, Waltham/MA/United States of America, 5Hematology/Oncology,
began to rise after this date, culminating over the succeeding decades in a Tufts Medical Center, Boston/MA/United States of America
sharp increase in lung cancer cases and deaths among women. A second phase
Background: NLST was the first RPT to demonstrate a significant LC mortality
of marketing of cigarettes to women and girls in the U.S. began in the 1970s
reduction, when comparing CT to CXR-screening. Consequently, CT-screening
as Philip Morris executive Joseph Cullman collaborated with tennis star Billie
is now being incorporated into clinical practice. Nonetheless, questions
Jean King to market a new “slim” cigarette to young women via the Virginia
about the value of CT-screening remain given costs of CT and workup of
Slims tennis tournament under the slogan “You’ve come a long way baby.” A
false-positives. A prior cost-effectiveness analysis of CT-screening using NLST
further contribution to the lung cancer mortality arose out of the efforts of
data concluded that CT was generally cost-effective (NEJM:371,1793,2014).
the Council for Tobacco Research (CTR) and the Council for Indoor Air Research
That analysis was performed under the assumption that CXR-screening only
(CIAR) to manufacture controversy regarding the danger of smoking as well
added costs without benefit. In an independent analysis of PLCO comparing
as involuntary second hand smoking to provide cover for legislators voting
CXR to no screening, we found that CXR-screening is associated with a highly
against tobacco control legislation. As a direct result, many thousands of non-
significant LC survival advantage. This benefit was unrelated to conventional
smoking women have had major involuntary exposure to tobacco carcinogens
screening biases, including overdiagnosis. As CXR is less expensive than CT
in the workplace causing lung cancer. Conclusion: Lung cancer cases presenting
with a lower false-positive rate, its cost-effectiveness relative to CT should be
today originated in deliberate campaigns by tobacco executives, marketers
assessed. Data from PLCO and NLST allows comparison of no screening, CXR,
and public relations experts to convince women and girls to smoke, despite
and CT. Methods: Costs of screening, diagnostic studies, and LC treatment
their clear understanding that the products they were aggressively marketing
were calculated based on original PLCO and NLST trial data obtained from
would inevitably result in hundreds of thousands of deaths.
NCI. These were estimated in 2015 US dollars from the Medicare perspective.
Keywords: cigarettes, second hand smoke, tobacco marketing, lung cancer Outpatient costs were calculated using the Medicare-2015B fee schedule.
Inpatient costs were calculated using a national payment average by assigning
a DRG based on procedures performed. Survival data was generated using the
Kaplan-Meier method for each study and mean survival was calculated using
MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING available data. These estimates were used to calculate incremental cost per
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 life-year gained The NLST-eligible subset of PLCO was also used to facilitate
comparison of no screening, CXR, and CT. Results: Analysis of PLCO data
demonstrate that CXR compared to no screening was associated with a gain
MA03.03 HIGH RISK FOR SECOND PRIMARY LUNG CANCER IN of 0.0152 life-years per person at an additional cost of $244 per-person for a
TAIWANESE EARLY-ONSET FEMALE BREAST CANCER PATIENTS cost per-life-year gained of $19,175. In the NLST-eligible subset of PLCO, CXR
Pei-Ying Lin1, Ching-Yao Yang1, Ching-Heng Lin2, Tzu-Pin Lu3, James Chih-Hsin cost an additional $350 with a gain of 0.0262 life-years per-person for a cost-
Yang1, Chong-Jen Yu1, Kinwei Chan3, Pan-Chyr Yang1 per-life-year gained of $13,377. In NLST, CT compared to CXR cost an additional
1
National Taiwan University Hospital, Taipei/Taiwan, 2Taichung Veterans General $1,181 per-person and with a gain of 0.0157 life-years per-person, or $75,180
Hospital, Taichung/Taiwan, 3National Taiwan University, Taipei/Taiwan per-life-year gained. Using the NLST-eligible subset of PLCO for comparison,
the ratio for CT compared to no screening was $36,552. Conclusion: CT-
Background: Female lung and breast cancers are two distinct disease screening is both effective and cost-effective and represents the optimal
entities in East Asia. Although studies on second primary cancers following method of screening for LC. However, the survival advantage associated with
the first breast cancer event have been carried out, no in-depth survey on CXR-screening in comparison to no screening and relatively low cost make CXR
double primary breast and lung cancers has been done. This study analyzed a reasonable alternative to CT-screening, particularly in regions of the world
the association between these two distinct cancer types. Methods: In the where cost and availability limit access to CT-screening.
exploratory cohort study, the data were obtained from the Taiwan National
Health Insurance Research Database, which contained information on Keywords: CT, Screening, Cost-effectiveness, chest X-ray
approximately 24.7 million insured individuals. The Taiwan Population Census
and National Cancer Registry Databases were used to identify patients with
breast and lung cancers. The cohort included individuals with newly diagnosed
primary breast cancer between 2000 and 2011. An age- and sex-matched MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING
systematic random-sampling method was used for subject selection in the MONDAY, DECEMBER 5, 2016 - 14:15-15:45
reference non-breast cancer cohort. Multivariate Cox proportional hazard
regression analysis was used to determine the effects of breast cancer on the MA03.06 COST EFFECTIVENESS OF CHEST SCAN SCREEING FOR
risk of lung cancer, as shown by hazard ratios (HRs) with 95% CIs. Detailed
LUNG CANCER IN ABESTOS OCCUPATIONAL EXPOSURE SUBJECTS:
medical record and pathological reviews were done on the National Taiwan
University Hospital (NTUH) patient cohort to validate the national cohort
A MODEL BASED STUDY
study results. The national lung cancer incidence rate was used as reference Juliette Vella-Boucaud1, Jean Claude Pairon2, Anne Duburcq3, Patrick
incidence rate in the validation cohort. Results: A total of 88,439 patients Brochard4, Soizic Chamming’S2, Amandine Luc5, Bruno Detournay3,
were diagnosed with female breast cancer between 2000-2011 in the national Christophe Paris5, Pascal Andujar2, Christos Chouaid1
1
cohort. The HR for subsequent lung cancer was 1.27 (95% CI, 1.09-1.48). When Chest Departement, Grc Oncoest Creteil, Creteil/France, 2Inserm U955, Ist, Creteil/
stratified by age, the HR was 5.29 (95% CI, 2.26-12.4) in the patients aged less France, 3Cemka, Bourg La Reine/France, 4Inserm 1045, Bordeaux/France, 5Inserm
than 40 years, 1.67 (95% CI, 1.18-2.30) in the group aged 40-49, 1.27 (95% CI, U754, Nancy/France
0.97-1.67) in the group aged 50-59, 1.09 (95% CI, 0.81-1.49) in the group aged
Background: The National Lung Screening trial (NLST) showed that screening
60-69, and 0.70 (95% CI, 0.48-1.02) in the group older than 70 years. A total
with low-dose computed tomography (CT) compared with chest radiography
of 13,517 primary female breast cancer patients were identified in the NTUH
reduced lung-cancer mortality. There is very few data’s on subjects with
electronic medical record system between 2006-2015. The incidence rate

occupational abestos exposure. We examined the cost-effectiveness of CANCER SCREENING PROGRAM

CT lung cancer screening in a french cohort of abestos post professional Andrea Borondy Kitts 1, Shawn Regis2, Andrea Mckee3, Jacob Sands4, Brady
exposure subjets (APEXS cohort). Methods: We estimated mean lif-years, Mckee5
costs and incremental cost-effectiveness ration (ICER) for screening with 1
Rescue Lung Rescue Life, Lahey Hospital & Medical Center, Burlington/MA/United
low-dose CT compare to no screening in this population of abestose exposed States of America, 2Radiology, Lahey Hospital & Medical Center, Burlington/MA/
subjects. Estimations of life-years gained were based on the efficacy of NLST United States of America, 3Radiation Oncology, Lahey Hospital and Medical Center,
trial aplpied to APEXS cohort, adjusted to sex and age. Costs were limited Burlington/MA/United States of America, 4 Oncology, Lahey Hospital & Medical
to directs costs, from the payer perspective. We also performed sensitiviy Center, Burlington/MA/United States of America, 5Thoracic Imaging, Lahey Hospital
analysis based on several assumptions of screening program efficacy. Results: & Medical Center, Burlington/MA/United States of America
Compared with no screening, screening with low-dose CT, over a period of 2
years, will cost, for 1000 subjects of APEXS cohort 312 645 €, will provide 9.4 Background: United States Preventive Services Task Force (USPSTF) and
additional life-years. The corresponding ICER was 33 102 € per life-gained. Centers for Medicare & Medicaid Services (CMS) recommendations for annual
Sensitiviyt analysis showed that this result is sensitive to screening program screening for lung cancer with low dose CT (LDCT) scans rely on age and
efficacy (number, stage, and survival diagnosed by the program). Conclusion: smoking history to identify those at high risk for lung cancer. The Tammemagi
ICER of low-dose CT lung cancer program in a cohort of abestos post et al. six year lung cancer risk prediction model, PLCOm2012, developed
occupational exposure population appears as acceptable from the French and validated in large lung cancer screening clinical trials, demonstrated
health system. good predictive performance in study participants. A 1.51% PLCOm2012 risk
threshold has been reported to outperform CMS/USPSTF entry criteria. This is
Keywords: lung cancer, Screening, cost effectiveness, abestos the first time the model predictive performance has been evaluated in clinical
practice. Methods: Predictive performance of a reparameterized (no education
predictor variable) six year lung cancer risk prediction model, PLCOm2012noEd,
was retrospectively assessed in 2297 consecutive individuals that underwent
MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING clinical CT lung screening between January 1, 2012 and November 30, 2015.
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 All patients met the National Comprehensive Cancer Network (NCCN) Lung
Cancer Screening Guidelines Group 1 or Group 2 high-risk criteria. Results: 79
cancers were detected in the 2297 screened individuals with a mean follow-up
MA03.08 QUANTIFYING SURVIVAL IN EARLY-STAGE NSCLC:
of 2.12 years (75.9% (60/79) – NCCN Group 1). The model six year mean risk for
IMPLICATIONS OF RELATIVE SURVIVAL VS CAUSE-SPECIFIC
lung cancer was higher for participants with lung cancer, 4.71%, as compared
SURVIVAL to those without lung cancer, 3.54% (p=0.008). Area under the curve (AUC) of
Kay See Tan1, Takashi Eguchi2, Prasad Adusumilli2 the receiver operator characteristics (ROC) was 0.635 (95% CI 0.577 – 0.693). At
1
Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New the 1.51% predicted risk recommended screening threshold overall sensitivity
York/NY/United States of America, 2Thoracic Service, Department of Surgery, = 86.1%, specificity = 29.8%, and PPV = 4.2%. For NCCN Group 1 (similar to
Memorial Sloan Kettering Cancer Center, New York/NY/United States of America CMS/USPSTF entry criteria), sensitivity = 91.7%, specificity = 20.7% and PPV
= 4.04%. For NCCN Group 2 (younger, lighter smoking history, no limit on time
Background: Cancer-related mortality can be measured by two disparate
quit with one additional risk factor) mean predicted risk for participants with
methods: relative survival (RSR, observed survival of cancer patients versus
lung cancer was 2.35% as compared to 1.83% for those without lung cancer but
expected survival of a matched population), and cause-specific survival (CSS,
the difference was not statistically significant; p=0.2374. As the incidence of
based on lung-cancer-specific mortality among cancer patients). Both are
lung cancer was the same in NCCN Group 2 and NCCN Group 1 (3.24% vs 3.51%;
vulnerable to biases: RSR depends on a comparable reference population,
p=0.8566) the sensitivity of the model for NCCN Group 2 at the recommended
while CSS relies on accurate cause-of-death coding. Regardless, RSR is more
1.51% screening threshold was reduced to 68.4% with a specificity of 56.3%.
common in population-based studies as the cause of death is uninvolved. We
Conclusion: Lung cancer risk prediction model, PLCOm2012noEd demonstrated
apply both methods to the same dataset to assess their implications among
reduced sensitivity in individuals meeting NCCN Group 2 high-risk criteria
early-stage NSCLC. Methods: Outcomes of patients diagnosed with stage I/II
undergoing clinical CT lung screening and may not be appropriate to
NSCLC (2000-2013) were obtained from the SEER registry. Five-year
adequately assess risk of lung cancer in this population.
cumulative incidence of death (CID) is estimated by competing risk approach.
Population-level mortality was extracted from the National Center for Health Keywords: lung cancer screening, risk prediction, model predictive
Statistics. The actuarial survival were summarized as RSR (Ederer II) and CSS, performance, NCCN Group 2
stratified by age at diagnosis and stage. In addition, the sensitivity of the
methods is assessed by including patients with unknown cause of death in
CSS (CSS-2). Results: Analyses included 15792 age <60 and 70789 age 60+
patients, with stage I (81%) or II NSCLC. Death with unknown cause was 5% of MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING
all deaths; 5-year CID for lung-cancer, other-known and other-unknown deaths MONDAY, DECEMBER 5, 2016 - 14:15-15:45
were 43%, 14% and 2%. Lung-cancer 5-year CID increased with age, from 22%
(age <44) to 47% (age 75+) among stage I, and 44% to 68% among stage II. CSS
MA03.10 EDUCATIONAL LEVEL AND THE MANAGEMENT AND
were greater than RSR in all cases. Although the bias was negligible for 1-year
OUTCOME IN NON-SMALL CELL LUNG CANCER: A NATIONWIDE
follow-up, the deviation increases with increasing age and years of follow-up.
The estimated CSS-2s were always between RSR and CSS, suggesting that RSR STUDY (SWEDEN)
underestimates the true lung-cancer-survival. Conclusion: In practice, RSR is Mats Lambe1, Anders Berglund2, Stefan Bergström3, Anna Öjdahl Boden 4,
appropriate for short follow-up and aggregate summaries, while caution is Gunnar Wagenius5
1
advised when reporting RSR by age groups for longer follow-up. Accurate Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm/
assessment of the causes of death may alleviate such biases. Sweden, 2Epistat, Uppsala/Sweden, 3Department of Oncology, Gävle Hospital,
Gävle/Sweden, 4Respiratory Medicine and Allergy, Karolinska University Hospital
Huddinge, Huddinge/Sweden, 5Department of Oncology, Karolinska Hospital,
Stockholm/Sweden
Background: Evidence from a variety of settings indicates the presence of

socioeconomic differences not only in the risk of developing cancer, but also
in management and outcomes. We examined the influence of educational
level on stage at presentation, management and mortality in patients with
non-small cell lung cancer (NSCLC) in Sweden, a country with a National
Health System aiming to provide medical care on equal terms to all residents.
Methods: We identified 24,385 patients with a NSCLC diagnosis 2002-2011
in Lung Cancer Data Base Sweden, a research database generated by record
linkage between the Swedish National Lung Cancer Register and several other
population-based registers. In analyses adjusted for comorbidity and other
Keywords: Cause-specific survival, Early-stage NSCLC, epidemiology, Relative
prognostic factors, ORs and HRs were estimated to examine associations
survival
between patients´ educational level and aspects of management and
mortality. Results: Diagnostic intensity CT Thorax, CT upper abdomen and
transthoracal biopsy were more commonly performed in patients with high
education. In multivariable analysis, the likelihood to undergo PET scan and
MA03: EPIDEMIOLOGY, RISK FACTORS AND SCREENING
MONDAY, DECEMBER 5, 2016 - 14:15-15:45 EGFR testing was significantly higher in patients with high compared to low
education OR 1.39 (95% CI 1.23-1.57) and 1.28 (95% CI 1.05-1.55), respectively.
No social gradients in EGFR testing was observed in an analysis restricted to
MA03.09 RETROSPECTIVE PREDICTIVE PERFORMANCE OF A LUNG non-smoking patients with adenocarcinoma. Stage and histopathology Stage
CANCER SCREENING RISK PREDICTION MODEL IN A CLINICAL LUNG at diagnosis did not differ between educational groups. Adenocarcinomas
were proportionally more common in patients with high compared to low CANCERS: AN INTERNATIONAL, RANDOMIZED PHASE II STUDY
education, both in all patients (61.9% vs 53.9%) and among non-smokers Leena Gandhi1, Benjamin Besse2, Julien Mazieres3, Saiama Waqar4, Alexis
(50.7% vs 46.7%). Waiting times There were no differences in waiting times Cortot5, Fabrice Barlesi6, Elisabeth Quoix7, Gregory Otterson8, David
between dates of referral and diagnosis, or between dates of diagnosis and Ettinger9, Leora Horn10, Denis Moro-Sibilot11, Mark Socinski12, Kathryn Gold13,
start of treatment. Multidisciplinary conference and treatment intensity The Jhanelle Gray14, Ana Oton15, Rebecca Suk Heist16, Daniel Costa17, Leanne
odds for treatment decisions being made in a multidisciplinary setting was Mcculloch18, Judith Bebchuk18, Richard Bryce18, Mark Kris19
higher for patients with high compared to low education (OR 1.26; 95% CI 1
Dana Farber Cancer Institute, Boston/MA/United States of America, 2Department
1.04-1.51). In stage IA-IIB disease, the likelihood to undergo surgery was non- of Cancer Medicine, Gustave Roussy, Villejuif/France, 3CHU de Toulouse Hôpital
significantly elevated in patients with high education (OR 1.26; 95% CI 0.98- Larrey, Toulouse/France, 4Washington University School of Medicine, St. Louis/MO/
1.63). Mortality In early stage disease, high education was associated with United States of America, 5CHU de Lille – University Lille, Hôpital Calmette, Lille/
lower all-cause (HR 0.79; 95% CI 0.70-0.89) and cause-specific mortality (HR France, 6 Aix Marseille Université, Aphm, Marseille/France, 7Hôpitaux Universitaires
0.76; 95% CI 0.66-0.88) after adjustment for treatment, sex, age, region, year, de Strasbourg, Strasbourg/France, 8 Ohio State University, Columbus/OH/
comorbidity, smoking, stage, histology and performance status. Conclusion: United States of America, 9The Sidney Kimmel Comprehensive Cancer Center at
We found evidence of social gradients in diagnostic and treatment intensity Johns Hopkins, Baltimore/MD/United States of America, 10Vanderbilt University,
Nashville/TN/United States of America, 11CHU de Grenoble Hôpital Albert
in patients with NSCLC. While there were no difference in stage at diagnosis
Michallon, Grenoble/France, 12Florida Hospital Cancer Institute, Orlando/FL/
between educational groups, a lower mortality in early stage NSCLC was United States of America, 13MD Anderson Cancer Center, Houston/TX/United
observed in patients with high education. States of America, 14 Moffitt Cancer Center, Tampa/FL/United States of America,
15
University of Colorado, Aurora/CO/United States of America, 16Massachusetts
Keywords: non-small cell lung cancer, register, Sweden, socioeconomy General Hospital, Boston/MA/United States of America, 17Beth Israel Deaconess
Medical Center, Boston/MA/United States of America, 18Puma Biotechnology Inc.,
Los Angeles/CA/United States of America, 19Memorial Sloan Kettering Cancer
Center, New York/NY/United States of America
SESSION MA04: HER2, P53, KRAS AND OTHER TARGETS Background: Combined inhibition of HER2 and mTOR is synergistic in models
of HER2 (or ERBB2)-mutant lung cancers. PUMA-NER-4201 is an adaptive,
IN ADVANCED NSCLC multinational, randomized phase II study comparing the pan-HER inhibitor
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 neratinib (Puma Biotechnology) ± the mTOR inhibitor temsirolimus in patients
with advanced HER2-mutant lung cancers. In stage 1 of the study, neratinib +
temsirolimus met predefined criteria for expansion into stage 2 [Besse et al.
MA04.01 NON-AMPLIFICATION MUTATION OF ERBB2 IN EGFR- ESMO 2014]. Methods: Patients with stage IIIB/IV locally determined
MUTATED LUNG CANCER HER2-mutant cancers were randomized to receive oral neratinib 240 mg once
Kyle Gowen1, Balazs Halmos2, Robert Hoyer3, Woondong Jeong4, James Suh1, daily ± intravenous temsirolimus 8 mg once weekly (escalated to 15 mg/week
Julia Elvin1, Jo-Anne Vergilio1, Shakti Ramkissoon5, Siraj Ali1, Alexa Schrock5, after a 3-week cycle if tolerated) with loperamide prophylaxis. Primary
James Sun1, Vincent Miller 1, Philip Stephens1, Jeffrey Ross 6, Laurie Gay1 endpoint: overall response rate (RECIST v1.1). Secondary endpoints: duration
1 of response, progressionfree survival, overall survival, toxicity assessments
Foundation Medicine, Cambridge/MA/United States of America, 2Department
of Hematology/Oncology, Albert Einstein/montefiore Cancer Center, Bronx/NY/ (NCI-CTCAE, v4.0). ClinicalTrials.gov: NCT01827267. Results: Of 62 randomized
United States of America, 3University of Colorado Health, Colorado Springs/CO/ patients, 60 received ≥1 dose of neratinib: neratinib alone (n=17); neratinib +
United States of America, 4University of Texas Health Science Center San Antonio, temsirolimus (n=43). Baseline characteristics: male/female 32%/68%; median
San Antonio/United States of America, 5Foundation Medicine, Cambridge/United age 66 years; never smokers 60%; adenocarcinoma 98%. HER2 (or ERBB2)
States of America, 6 Albany Medical College, Albany/NY/United States of America mutation type: exon 20 insertions 93.5%; missense substitutions 3.2%;
unspecified 3.2%. The most common HER2 allelic variant was A775_
Background: Amplification of ERBB2 in EGFR-mutant lung cancers is a G776insYVMA. Exploratory biomarker analysis from available tumor and
reported mechanism of acquired resistance to tyrosine kinase inhibitor (TKI) plasma samples will be presented at the meeting. Efficacy and safety results
therapy. Comprehensive genomic profiling (CGP) of NSCLC tumors shows are shown in the table. With loperamide prophylaxis, the incidence of grade 3
mutation of ERBB2, most often affecting the encoded HER2 receptor at diarrhea was 12% with neratinib and 14% with neratinib + temsirolimus, which
residue S310, is also prevalent, particularly in the context of EGFR L858R. lasted for a median duration of 1.5 (interquartile range, 1.0-2.0) days and 4.0
Methods: CGP was performed on hybridization-captured, adaptor ligation- (interquartile range, 2.0-16.0) days, respectively.
based libraries for up to 315 cancer-related genes plus select introns from 28
genes frequently rearranged in cancer on 14,887 consecutive cases of lung
cancer. All classes of genomic alterations (GA) were assessed simultaneously,
including base substitutions, indels, rearrangements/fusions, and copy
number changes. Short variants (SV) include base substitutions or indels.
Results: A total of 2,516 (16.9%) samples featured EGFR alterations, including
amplification (amp) and SV. Of these, 2.9% (73/2,516) harbored alterations in
ERBB2 (amp and/or SV). 18 samples (0.7%) harbored SV alterations in ERBB2,
14 of which were mutations at S310. ERBB2 S310 mutations were most often
found with EGFR L858R. The ratio of observed to expected mutation at HER2
S310 in EGFR-mutated lung cancers was 2.12, and the ratio for HER2 S310 in
combination with EGFR L858R was 5.03. The co-occurrence of HER2 S310 and
EGFR L858R was highly significant (p<0.00005). The combination of EGFR
and ERBB2 alterations was more common in women. The ratio of male:female
patients with any lung cancer in this dataset was 1:1.1, whereas the ratio of
male:female with any EGFR alteration was 1:1.7 and for both EGFR and ERBB2
alterations (amp or SV) was 1:3.4. Patients with a combination of EGFR and
ERBB2 alterations have been shown to respond to treatment with the pan-
ERBB inhibitor afatinib, or combinations of afatinib with the HER2-targeted
therapy trastuzumab. Conclusion: Short variant alterations in ERBB2 may be
an additional mechanism for tumors to acquire resistance to treatment with
EGFR-targeted TKIs. Mutations at residue S310, in the extracellular domain
of HER2, are the most common ERBB2 SV observed in EGFR-mutant lung
cancer, and are significantly associated with EGFR L858R. The co-occurence Conclusion: Neratinib (240 mg/day) + temsirolimus (8 or 15 mg/week)
of alterations in ERBB2 and EGFR is far more common in women than in men. produced responses lasting 2 to 18+ months in 19% of patients with
Treatment with the pan-ERBB inhibitor afatinib, alone or in combination with HER2mutant lung cancers. Correlative data will be presented at the meeting.
agents targeting HER2, has been shown to benefit patients with lung cancer Diarrhea was manageable with loperamide prophylaxis.
harboring mutations in both EGFR and ERBB2. Keywords: NSCLC, Neratinib, Temsirolimus, lung cancer
Keywords: EGFR, comprehensive genomic profiling, NSCLC, ERBB2
MA04: HER2, P53, KRAS AND OTHER TARGETS IN ADVANCED NSCLC

MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MA04.03 PRELIMINARY RESULTS OF A PHASE II STUDY ABOUT THE
MA04.02 NERATINIB ± TEMSIROLIMUS IN HER2-MUTANT LUNG EFFICACY AND SAFETY OF PYROTINIB IN PATIENTS WITH HER2

MUTANT ADVANCED NSCLC PFS and OS in EGFR M+ patients were observed depending on p53 M+ status.
Shengxiang Ren1, Caicun Zhou2, Guanghui Gao1, Chunxia Su3, Xiaoxia Chen2, P53 mutational status is predictive when disruptive and non-disruptive p53
Feng Ying Wu4, Xuefei Li5, Chao Zhao2, Weijing Cai5 M+ are differentiated. A p53 WT constellation has a positive effect on OS and
1 PFS. P53 should be tested prospectively in EGFR M+ patients as management
Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine,
Tongji University Cancer Institute, Shanghai/China, 2Department of Medical of patients on 1st line TKI may be different.
Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine,
Shanghai/China, 3Shanghai Pulmonary Hospital, Shanghai/China, 4 Medical
Keywords: NSCLC, molecular diagnostic, p53 mutation
Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai/China,
5
Medical Oncology, Shanghai Pulmonary Hospital, Shanghai/China
Background: There is still an unmet need for targeted drugs in non small MA04: HER2, P53, KRAS AND OTHER TARGETS IN ADVANCED NSCLC
cell lung cancer (NSCLC) patients with HER2 mutation. Pyrotinib is an oral MONDAY, DECEMBER 5, 2016 - 16:00-17:30
tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This phase
II trial is designed to evaluate the safety and efficacy of pyrotinib in patients
MA04.06 SIGNALING NETWORKS IN KRAS-MUTANT ADVANCED
with HER2 mutant advanced NSCLC. Methods: A single arm prospective
NSCLC: A COMPLEX LANDSCAPE INVOLVING IMMUNORESPONSE,
phase II trial was undergone to evaluate the efficacy and safety of Pyrotinib
in patients with HER2 mutant advanced NSCLC in a single center of Shanghai INFLAMMATION AND DNA REPAIR
Pulmonary Hospital, Tongji University(NCT 02535507). Pyrotinib was Sara Baglivo 1, Elisa Baldelli2, Lucio Crinò1, Vienna Ludovini1, Rita Chiari1,
administrated 320mg or 400mg orally once a day. Next generation sequencing Giulio Metro1, Chiara Bennati1, Alex Hodge2, Annamaria Siggillino1, Francesca
or ARMS was used to identify the patients with HER2 mutation. The primary Romana Tofanetti1, Ting Dong2, Lorenza Pistola1, Fortunato Bianconi3, Angelo
endpoint was objective response rate and the secondary endpoints were side Sidoni4, Vincenzo Minotti1, Emanuel Petricoin2, Mariaelena Pierobon2
1
effect, progression free survival and overall survival. Results: From Jul 15 2015 Medical Oncology, Santa Maria Della Misericordia Hospital, Perugia/Italy, 2Center
to Jul 21, 2016, 11 patients with her2 mutated advanced NSCLC were enrolled for Applied Proteomics and Molecular Medicine, George Mason University,
into this study. Among them, the median age was 58 years old, 6 were male, 4 Manassas/United States of America, 3Department of Experimental Medicine,
were smoker, ECOG PS 0/1/2 were 5/6 and all of them were adenocarcinoma. University of Perugia, Perugia/Italy, 4Department of Experimental Medicine,
Pathological Anatomy and Histology Unit, University of Perugia, Perugia/Italy
None of them received pyrotinib as the first line therapy and the median
previous anti-cancer regimen was 2. 9 patients had the details variants of Background: KRAS is the most frequently mutated oncogene in Non-Small
HER2 mutation including 7 with exon 20 776YVMA, 1 with exon 20 770AYVM Cell Lung Cancer (NSCLC) and its role as prognostic and predictive biomarker
and 1 with 2326G>ATTT. All of them evaluated the response, including 54.5% remains widely debated. Unfortunately, KRAS direct targeting strategies have
with partial response(6/11), 27.3% with stable disease(3/11) and 18.2% with been unsuccessful and no approved target therapy exists for KRAS-mutant-
progressive disease(2/11). 1 patient got response to pyrotinib after progressed NSCLC. This pilot study evaluated the activated signaling architecture of
from afatinib. 5 patients were still on the study and the median PFS was 6.2 advanced NSCLC harbouring a KRAS mutation to better characterize the
months. Side effects were mild including 4 with grade I/II diarrhea, 2 with signaling network driving this subgroup of pulmonary malignancies. Methods:
grade II fatigue, 2 with grade I rash and 1 with dispnea. Conclusion: Pyrotinib Twenty Stage IV Formalin-fixed, paraffin-embedded (FFPE) NSCLCs were
showed promising results about the ORR and PFS together with mild toxicity collected from chemo-naïve patients at S. Maria della Misericordia Hospital
in patients with HER2 mutant advanced NSCLC, further multicenter large (Perugia, Italy). Ten tumors were KRAS-wild-type (KRAS-WT) and ten were
scale phase II study is initiated to validate the results in this study. KRAS-Mutant (KRAS-MUT). Whole-tissue lysates were obtained for all
samples. Signaling network analysis was performed using the Reverse Phase
Keywords: non small cell lung cancer, HER2 mutation, clinical trial, Targeted
Protein Array (RPPA) platform to quantitatively evaluate the expression/
therapy
activation of 148 key proteins and phosphoproteins involved in cellular
growth, survival, proliferation, apoptosis, autophagy, inflammation, invasion
MA04: HER2, P53, KRAS AND OTHER TARGETS IN ADVANCED NSCLC and cell motility. Wilcoxon Rank-Sum Test was used to compare the signaling
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 architecture of KRAS-MUT and KRAS-WT tumours. All p-values <0.05 were
considered significant. Non-parametric correlation analysis was performed
MA04.05 P53 NON-DISRUPTIVE MUTATION IS A NEGATIVE to explore the signaling interconnection within each group of patients.
Only correlations with p<0.0001 were considered significant. Results: This
PREDICTIVE FACTOR FOR OS AND PFS IN EGFR M+ NSCLC TREATED
preliminary analysis revealed a statistically significant different activation
WITH TKI level of 20 proteins between the KRAS-MUT and KRAS-WT samples. Five of
Julia Roeper 1, Maria Netchaeva1, Anne Lueers1, Prenzel Regina1, Douglas the proteins that were statistically different in the KRAS-MUT group are
Sriba1, Kay Willborn1, Ursula Stropiep1, Cora Hallas2, Markus Tiemann2, Nicole involved in the inflammatory immunoresponse (ASK1 S83 p<0.01, Axl Y702
Neemann1, Lukas Heukamp3, Frank Griesinger 1, Markus Falk2 p=0.01, Stat2 Y690 p<0.01, Tyk2 Y1054/Y1055 p=0.01 and Twist p<0.01) and six
1
Pius Hospital Oldenburg, Oldenburg/Germany, 2Institut Für Hämatopathologie, in cell cycle control and DNA repair (ATM S1981 p=0.01; Bcl-xL p=0.03; Cleaved
Hamburg/Germany, 3Neo New Oncology, Cologne/Germany Caspase 3 D175 p=0.02; Histone H3 S10 p<0.01; p53 S15 p<0.01; p27 T187
p=0.04). The analytes that were statistically significant were all lower in the
Background: P53 mutations are common in lung cancer, and have also been
KRAS-MUT group compared to the WT (except for p27 T187 which decreased
described in EGFR mutated patients The impact of p53 mutations in EGFR
in the KRAS-MUT group compared to KRAS-WT). Pair-wise correlation analysis
M+ patients is controversial, especially if classified as “disruptive” and “non-
of the signaling proteins showed an overall more complex protein-protein
disruptive” according to their functional effect on the p53 protein as proposed
interaction network and pathway activation (included AKT/mTOR signaling
by Poeta and colleagues. The aim of the study was therefore to systematically
pathway) in the KRAS-MUT population with high number of statistically
analyze EGFR and p53 mutations within a cohort of patients with lung cancer
significant correlations compared to the KRAS-WT group. Conclusion: This
stage IV (UICC 7), to correlate alterations with clinical characteristics and
pilot study indicated that the effect of KRAS mutation status on protein
to investigate a potential impact of p53 mutations on treatment outcome.
signaling in NSCLC was an alteration of the immunoresponse axis and DNA
Methods: 484 patients diagnosed with lung cancer stage IV were studied for
repair network. If validated in a larger cohort of patients, these results could
the presence of EGFR as well as inactivating p53 mutations. Methods for the
have important clinical implications for stratification KRAS-MUT advanced
detection of EGFR mutations included Sanger Sequencing and hybridization
NSCLC patients towards more efficacious targeted treatment and to identify
based COBAS testing, hybrid cage next generation sequencing. P53 mutations
new therapeutic targets based on multi-targets/multi-pathways KRAS
were detected by Sanger Sequencing and either Miseq or hybrid cage NGS.
inhibitory approach. (AIRC-supported study).
Clinical characteristics including smoking status were available for more
than 97%. Results: 484 consecutive patients were studied. The overall EGFR Keywords: RPPA, KRAS, signaling networks, advanced NSCLC
M+ rate was 17.8% (86/484) in all patients, 84.9% (73/86) showing common
mutations of exon 19 or 21. In 21/86 (24.4%) patients’ p53 analysis was not
successful. P53 disruptive mutations were demonstrated in 24.6% (16/65)
of successfully tested patients, and p53 non-disruptive mutation occurred MA04: HER2, P53, KRAS AND OTHER TARGETS IN ADVANCED NSCLC
in 27.7% (18/65) whereas p53 WT configuration was found in 47.7% (31/65). MONDAY, DECEMBER 5, 2016 - 16:00-17:30
Median OS was 28 months in p53 disruptive mutation and 44 month in p53
WT compared to 23 months in p53 non-disruptive mutation (p<0.023). PFS
MA04.07 IMPACT OF MAJOR CO-MUTATIONS ON THE IMMUNE
on 1st line TKI therapy was 14 months in p53 disruptive mutation, 27 months
in p53 WT and 10 months in p53 non-disruptive mutation (p<0.040). Similar
CONTEXTURE AND RESPONSE OF KRAS-MUTANT LUNG
results were shown in the EGFR common mutation subgroup. 11/16 (68.8%) ADENOCARCINOMA TO IMMUNOTHERAPY
patients with a disruptive p53 M+ and 25/29 (86.2%) patients with a p53 Ferdinandos Skoulidis 1, Yasir Elamin1, Vassiliki Papadimitrakopoulou1, Pan
WT constellation achieved an objective response on the 1st line TKI therapy Tong2, Jing Wang2, Jeff Lewis3, Waree Rinsurongkawong 3, Caleb Chu1, Emily
compared to 7/13 (53.8%) patients with a non-disruptive p53 status. The Roarty1, Jianjun Zhang1, Hai Tran1, Jaime Rodriguez-Canales4, Edwin Parra4,
patients with an unknown p53 status achieved an objective response on the Carmen Behrens4, Humam Kadara4, Ignacio Wistuba4, John Heymach1
1st line TKI therapy of 82.4.8% (14/17). Conclusion: Significant differences in 1
Thoracic, Head & Neck Medical Oncology, The University of Texas M. D. Anderson
Cancer Center, Houston/TX/United States of America, 2Bionformatics and NCCN guidelines. KRAS GA were identified in 19.6% of RICTOR amp tumors,
Computational Biology, The University of Texas MD Anderson Cancer Center, compared with 29.8% of all NSCLC, but this difference was not statistically
Houston/TX/United States of America, 3The University of Texas MD Anderson significant. Mean TMB in RICTOR amp tumors was intermediate (14.9 mut/
Cancer Center, Houston/United States of America, 4Translational Molecular
Mb), and is higher than the overall average for NSCLC (9.2 mut/Mb). The
Pathology, M.D. Anderson Cancer Center, Houston/TX/United States of America
number of RICTOR-amplified tumors with high TMB (>20 mut/Mb) was
Background: Activating mutations in the KRAS proto-oncogene define 23%, higher than the rate for non-RICTOR amp NSCLC (12.9%). Examples of
a prevalent and clinically heterogeneous molecular subset of lung patients with RICTOR amplification within late stage NSCLC responding to
adenocarcinoma (LUAC). We previously identified three major subgroups of MTOR inhibitors will be presented. Conclusion: RICTOR amplification, when
KRAS-mutant LUAC on the basis of co-occurring genetic events in TP53 (KP), compared to other non-EGFR known drivers of NSCLC, is a relatively frequent
STK11/LKB1 (KL) and CDKN2A/B (KC) and reported that LKB1-deficient tumors clinically relevant GA that has been shown to respond to MTOR inhibitors. The
exhibit a “cold” tumor immune microenvironment, with reduced expression co-occurrence of RICTOR amplification with mutation of known oncogenic
of several immune checkpoint effector/mediator molecules, including PD-L1 drivers suggests a possible mechanism of acquired resistance to therapy that
(CD274). Here, we extend these findings and examine the clinical outcome of should be explored further. Tumors with RICTOR amp more often have higher
co-mutation defined KRAS subgroups to therapy with immune checkpoint levels of TMB than other NSCLC. Further study of RICTOR amp as a therapy
inhibitors. Methods: We conducted a single-institution analysis of clinical target NSCLC in a clinical trial setting appears warranted.
and molecular data (PCR-based next generation sequencing of panels of 50,
Keywords: NSCLC, Rictor, comprehensive genomic profiling, tumor
134 or 409 genes) prospectively collected from patients enrolled into the MD
mutational burden
Anderson Lung Cancer Moon Shot GEMINI database. KRAS-mutant LUAC were
separated into KP, KL and K (wild-type for TP53 and STK11) groups. The log-
rank test and Fisher’s exact test were used for comparison of progression-free
survival (PFS) and objective response rate (ORR) respectively between the
groups. In addition, automated IF-based enumeration of lymphocyte subsets MONDAY, DECEMBER 5, 2016 - 16:00-17:30
was performed in 40 surgically resected LUAC (PROSPECT cohort) with
available whole exome sequencing data. Results: Among 229 patients with
KRAS-mutant LUAC who consented to the protocol we identified 35 patients MA04.10 LUNG CANCER GROWTH IS SUPPRESSED BY CD26/
with metastatic disease (17 KP, 6 KL, 12 K) that received immunotherapy DPP4-INHIBITION VIA ENHANCED NK CELL AND MACROPHAGE
with nivolumab (N=29), pembrolizumab (N=3), nivolumab/urelumab (N=1) RECRUITMENT
and durvalumab/tremelimumab (N=2) and had robust clinical outcome Jae-Hwi Jang, Florian Janker, Stephan Arni, Yoshito Yamada, Walter Weder,
data. There was no impact of different KRAS alleles (G12C/G12V/G12D) Wolfgang Jungraithmayr
on PFS (P=0.6149, log-rank test) or ORR to immune checkpoint inhibitors
Thoracic Surgery, University Hospital Zürich, Zürich/Switzerland
(P=0.88, Fisher’s exact test, 2x3 contingency table). In contrast, co-mutation
defined KRAS subgroups exhibited significantly different median PFS to Background: Lung cancer is the leading cause of death among cancers.
immunotherapy (KP: 18 weeks, KL: 6 weeks, K: 16 weeks, P=0.0014, log-rank There is broad evidence that immune cells are involved in the growth and
test). Objective responses were observed in 9/17 (52.9%) KP and 3/12 (25%) development of these malignancies. CD26/DPP4 (dipeptidyl peptidase
K tumors compared to 0/6 (0%) KL tumors (P=0.049, Fisher’s exact test, 2x3 4) is a transmembrane glycoprotein, that is constitutively expressed on
contingency table). In the PROSPECT cohort of surgically resected LUACs hematopoetic cells, but also found on lung epithelial and endothelial cells.
with available whole exome sequencing data, somatic mutation in STK11 was We found previously that the activity of CD26/DPP4 of lung cancer patients
associated with reduced intra-tumoral densities of CD3+ (P=0.0016), CD8+ at early stages is four times higher than in normal tissue. Here, we tested
(P=0.0125) and CD4+ (P=0.0036) lymphocytes. Conclusion: Mutations in if CD26/DPP4-inhibition is able to modulate lung cancer growth in mice.
STK11/LKB1 are associated with an inert tumor immune microenvironment Methods: An orthotopic lung tumor model was employed by sc. injections
and poor clinical response of KRAS-mutant LUAC to immune checkpoint of the mouse lung cancer (Lewis Lung Carcinoma (LLC)) and a human lung
blockade. The mechanism that underlies this phenotype and strategies to adenocarcinoma cell line (H460). These were developed in mice C57BL6
overcome it are under investigation. The impact of additional co-mutations on (n=18) and CD1-nude mice (n=20) respectively. The CD26/DPP4-inhibitor
the immune profile and response of KRAS-mutant LUAC to immunotherapy is Vildagliptin was given in drinking water of 50mg/kg daily dose. Tumor
also being explored. growth was evaluated by wet weight of tumor mass at 2 weeks. Histological
assessments included TUNEL, immunohistochemistry (IHC) of CD3, B220,
Keywords: KRAS, Immunotherapy, STK11, Co-Mutations
F4/80 and NKp46. IL-10, Arginase, IL-12, NKp46, NK1.1, IFN-g, Granzyme, and
Perforin 1 were analyzed by RT-PCR. In vitro analysis of surfactant protein
(SP) expression in LLC and H460 were performed by western blotting. For
a proof of concept, macrophage ablation was performed by clodronate-
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 liposome during Vildagliptin treatment. Results: Vildagliptin treatment
significantly reduced the tumor growth of both, LLC and H460 in mice. IHC
showed macrophages (F4/80+) and NK cells (NKp46+) to be significantly
MA04.09 RICTOR AMPLIFICATION IN NON-SMALL CELL LUNG increased by Vildagliptin within tumors, while TUNEL stain and IHC of T-
CANCER: AN EMERGING THERAPY TARGET and B cell infiltration did not show any difference. Gene expression levels
Jeffrey Ross 1, Haiying Cheng2, Roman Perez-Soler3, James Suh1, Dean Pavlick1, of anti-inflammatory markers (IL-10, and Arginase) were unchanged, while
Siraj Ali1, Alexa Schrock1, Julia Elvin1, Jo-Anne Vergilio1, Shakti Ramkissoon1, the pro-inflammatory cytokine IL-12 was significantly elevated. The NK cell
David Fabrizio1, Vincent Miller 1, Philip Stephens1, Laurie Gay1 markers NKp46, NK1.1, IFN-g, Granzyme and Perforin 1 were significantly
1 upregulated within the tumor by Vildagliptin, indicating that inhibition of
Foundation Medicine, Cambridge/MA/United States of America, 2Montefiore
Medical Center, Bronx/NY/United States of America, 3Oncology, Montefiore CD26/DPP4 recruits NK cells into the tumor. Furthermore, we found enhanced
Medical Center, Bronx/NY/United States of America SP expressions in lung cancer cell lines by Vildagliptin treatment in vitro.
Macrophage ablation with clodronate-liposome in Vildagliptin treated
Background: Comprehensive genomic profiling (CGP) can discover novel mice reversed the tumor size significantly. Conclusion: The Inhibition of
therapy targets in NSCLC. Amplification of RICTOR, encoding a component of CD26/DPP4 decreased lung cancer growth in primary models of mouse and
the MTORC2 complex, has recently been identified as a targetable alteration human lung cancer and increased inflammatory macrophages and NK cell
leading to clinical benefit. Methods: CGP was performed on hybridization- cytotoxicity within those tumors. Furthermore, an increased expression of
captured, adaptor ligation-based libraries for up to 315 cancer-related genes SP by Vildagliptin treatment in lung cancer cell lines suggests that surfactant
plus select introns from 28 genes frequently rearranged in cancer on 14,698 production in lung cancer activates macrophages to fight against lung cancer
consecutive cases of NSCLC, comprising lung adenocarcinoma, squamous cell via the recruitment of macrophages and NK cells.
carcinoma (SCC) or NSCLC not otherwise specified (NOS). Tumor mutational
burden (TMB) was determined on 1.1 Mb of sequenced DNA. All classes of Keywords: Lung; Cancer; CD26/DPP4; Immunity
genomic alterations (GA) were assessed simultaneously, including base
substitutions, indels, rearrangements/fusions, and copy number changes.
Results: 747 (5.0%) NSCLC featured RICTOR amplification (amp). There were
380 (51%) male and 367 (49%) female patients with a mean age of 64.1 years MA04: HER2, P53, KRAS AND OTHER TARGETS IN ADVANCED NSCLC
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
(range 18-88 years). The primary tumor was analyzed in 333 (45%) cases and a
metastasis biopsy in 414 (55%) cases. Genes most frequently co-altered with
RICTOR amp included TP53 (79.5%) and FGF10 (64.6%), which is located close MA04.11 MECHANISTIC INSIGHTS INTO CAR T-CELL EFFICACY IN
to RICTOR on chromosome 5 and is frequently co-amplified. Several known THE TREATMENT OF HETEROGENOUS ANTIGEN EXPRESSING LUNG
oncogenes in NSCLC were mutated at significantly higher rates in tumors ADENOCARCINOMA
with RICTOR amp, including EGFR (22%), MET (8.4%), ERBB2 (7%), as well as
FGFR1 (5%), FGFR3 (1.4%), and FGFR4 (1.6%). 42.2% of tumors with RICTOR Aurore Morello1, Masha Zeltsman2, Adam Bograd2, David Jones2, Prasad
amp did not harbor additional alterations in KRAS or genes indicated in the Adusumilli1

1
Thoracic Service and Center for Cell Engineering, Memorial Sloan Kettering Cancer Fluoroscopy was used in all. Sampling included bronchial washing and
Center, New York/NY/United States of America, 2Thoracic Service, Department of brushing (if no direct vision) or biopsy (if lesion directly visualized). Statistical
Surgery, Memorial Sloan Kettering Cancer Center, New York/NY/United States of analyses R-3.2.3. Results: Total of 63 patients (VBN and non-VBN, 21:42).
America Clinical characteristics in table 1. Diagnostic yield was 75% vs 43.9% (p=0.029).
Factors associated to positive diagnosis in table 2. Further diagnostic
Background: Our laboratory has translated (NCT02414269, NCT02792114)
techniques were needed in 14% vs 52% (p=0.001). No differences seen in
mesothelin (MSLN), a cancer-antigen, targeted chimeric antigen receptor
procedure duration or complications.
(CAR) T-cell therapy to solid tumors including for lung adenocarcinoma (ADC)
patients. The goal of this study is to investigate the anti-tumor efficacy of
MSLN CAR T cells against lung ADC with heterogenous MSLN expression, and
further develop mechanistic insights to potentiate the therapy. Methods:
Human CAR T cells transduced with M28z, MSLN CAR with CD28
costimulation, were tested in vitro (cytotoxicity by 51Cr release assay,
proliferation, cytokine secretion, LFA-1/ICAM-1 [lymphocyte function
associated antigen-1/intercellular adhesion molecule 1] adhesion assay, and
flow cytometry) and in vivo (tumor and T-cell bioluminescence imaging [BLI],
survival) against low-, high- or a mixture (50:50 or 70:30) of MSLN-expressing
A549 human lung ADC. Results: MSLN CAR T cells demonstrate antigen-
intensity dependant cytotoxicity against both low- and high- MSLN-
expressing A549 cells with additive bystander cytotoxicity against 51Cr-
labelled low-MSLN A549 cells in the mixture both in vitro (Figure Panel A) and
in vivo (22 days delay in tumor progression by low-MSLN A549 cells). Flow
cytometry demonstrated ICAM-1 overexpression on low-MSLN A549 cells
when treated with effector cytokine-rich supernatant collected by exposure
of CAR T cells to high-MSLN A549 cells (Panel B), LFA-1 expression by
MSLN-activated CAR T cells (Panel B). Activated CAR T cells adherence to
ICAM-Fc coated plates compared to controls (Panel C). LFA-1/ICAM-1
expression promoted adherence of antigen-activated CAR T cells to low
antigen-expressing tumor cells (Panel D), which is inhibited in the presence of
LFA-1 blocking antibody (Panel E).
Conclusion: We provide a mechanistic reason for the antigen-specific,

bystander efficacy of CAR T cells against low-antigen expressing lung cancer
cells. Strategies to augment LFA-ICAM interactions between CAR T cells and
cancer cells can effectively translate mesothelin-targeted CAR T-cell therapy Conclusion: VBN significantly improves the diagnostic yield of ultrathin
against heterogenous antigen-expressing solid tumor, lung cancer. bronchoscopy for diagnosing peripheral pulmonary lesions, especially those
located in the utmost periphery and fluoroscopically not visible. Therefore,
Keywords: lung cancer, mesothelin, Immunotherapy, CAR T-cell use of VBN reduces the need for further diagnostic procedures. Funded by La
MaratóTV3-20133510, FIS-ETES PI09/90917, FUCAP and SEPAR.
Keywords: Peripheral Pulmonary Nodule, bronchoscopy
SESSION MA05: INNOVATIVE TECHNIQUES IN PULMONO-

LOGY AND THE IMPACT ON LUNG CANCER MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MA05.02 ELECTROMAGNETIC NAVIGATION BRONCHOSCOPY:

MA05.01 VIRTUAL BRONCHOSCOPIC NAVIGATION-GUIDED A PROSPECTIVE, GLOBAL, MULTICENTER ANALYSIS OF 1000
ULTRATHIN BRONCHOSCOPY FOR DIAGNOSING PERIPHERAL SUBJECTS WITH LUNG LESIONS
PULMONARY LESIONS Erik Folch1, Javier Flandes2, Sandeep Khandhar 3
Marta Diez-Ferrer, Arturo Morales, Noelia Cubero, Rosa Lopez-Lisbona, Nikos 1
Massachusetts General Hospital, Boston/MA/United States of America,
2
Koufos, Jordi Dorca, Antoni Rosell Pulmonary Department, Iis-Fundacion Jimenez Diaz University Hospital, Ciberes,
Respiratory Medicine, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat/ Madrid/Spain, 3CVTSA/Inova Cancer Center, Fairfax Hospital, Falls Church/VA/
Spain United States of America
Background: Diagnosis of peripheral pulmonary lesions with ultrathin Background: Electromagnetic navigation bronchoscopy (ENB) may aid
bronchoscopy (UTH) has fewer complications than transthoracic needle in accessing smaller, more peripheral lesions and hence facilitate earlier
aspiration (TTNA). However, diagnostic yield with UTH is lower. Virtual diagnosis. ENB may also provide a safer alternative to transthoracic biopsy,
bronchoscopic navigation (VBN) might increase diagnostic performance of and allow adequate tissue capture for molecular testing, diagnosis, staging,
UTH. The main objective was to compare diagnostic yield of UTH with and and localization for surgery in a single anesthetic event. However, usage
without VBN. Methods: Prospective case-control study paired 1:2 for lesion patterns, safety, and performance remain largely unexplored in a prospective,
size and localization, bronchus sign, sex and final diagnosis. LungPoint multicenter study. Methods: NAVIGATE is a global, prospective, multicenter
(Broncus, USA) was used to plan and navigate based upon online image study of ENB using the superDimension™ navigation system (Medtronic,
analysis, putting endoscopic and virtual images in correspondence. Minneapolis). A pre-specified 1-month interim analysis was conducted on the
first 1,000 primary cohort subjects enrolled at 29 centers in the United States Conclusion: A single EBUS-TBNA yields DNA of quantity and quality sufficient
and Europe. Enrollment and 2-year follow-up are ongoing. Results: One-month for molecular analysis, and is expected to be adequate for lung cancer
follow-up was completed in 933/1,000 subjects. Of 1,000 procedures, ENB genotyping.
was intended for lung biopsy in 96.4%, to place fiducial markers in 21.0%, and
for dye marking in 1.7% (multiple indications in 34.9%). Lymph node biopsies Keywords: EBUS-TBNA, lung cancer, Molecular
were attempted in 33.4% of procedures (322/334 using linear endobronchial
ultrasound [EBUS]). General anesthesia was used in 79.7% and radial EBUS
in 54.3%. Among 1,129 lung lesions, fluoroscopy was used in 90.1% and rapid
on-site pathology evaluation in 683/1035 (66.0%). Median lesion size was 20.0 MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
mm (interquartile range 16.0 mm). Most lesions were in the peripheral (62.6%)
or middle (30.1%) lung thirds. A bronchus sign was present in 48.4% and 6.3%
were ground glass. Navigation was subjectively considered successful in 1,036 MA05.05 GENOMIC PROFILES OF LUNG CANCER ASSOCIATED WITH
lesions (91.8%). Site-reported pathology results were read as malignant in IDIOPATHIC PULMONARY FIBROSIS
452 lesions (43.6%), including 38.1% with primary lung cancer. Of 247 lesions
Ji An Hwang, Deokhoon Kim, Soo Hyun Bae, Sung-Min Chun, Joon Seon Song,
with adenocarcinoma or unspecified non-small-cell lung cancer, 70 (28.3%)
Mi Young Kim, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Sojung Park,
were sent for molecular testing with adequate tissue in 56/70 (80.0%).
Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang
Primary lung cancer clinical stage was 52.9% I; 10.7% II, 18.9% III, and 17.3% IV.
Asan Medical Center, Seoul/Korea, Republic of
Preliminary non-malignant results were obtained in 444 lesions (42.9%). An
additional 140 lesions (13.5%) were read as inconclusive. Longer follow-up is Background: Idiopathic pulmonary fibrosis (IPF) is associated with an
required to calculate the true negative rate and diagnostic yield. ENB-related increased risk of lung cancer (LC) independent of the effect of cigarette
pneumothorax was 4.9% (49/1,000) overall and 3.2% Grade ≥2 based on the smoking. The prognosis of IPF-associated LC (IPF-LC) is known to be worse
Common Terminology Criteria for Adverse Events scale. The ENB-related than the lone IPF or LC mainly due to the complications accompanying LC
Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failures treatment with no established or standardized consensus. However, despite
rates were 1.0% and 0.6%. Conclusion: Interim 1-month results suggest a recent progress in the understanding of pathogenesis and the treatment
low adverse event rate in the largest prospective, multicenter ENB study of LC in general population based on the advances in molecular genomics,
conducted to date. Continued enrollment and 2-year follow-up will elucidate the pathogenesis or molecular profiles of IPF-LC has been largely unknown
the real-world utilization patterns, diagnostic yield, factors contributing to to date. Methods: We assessed genomic profiles of IPF-LC using targeted
successful diagnosis, and the impact of ENB on lung cancer management. exome-sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs
surgically resected between 2004 and 2014. Germline and somatic variant
Keywords: prospective clinical study, Electromagnetic Navigation
calling were performed using GATK HaplotypeCaller and MuTect with GATK
Bronchoscopy, Image-Guided Biopsy, lung cancer diagnosis
SomaticIndelocator, respectively. Copy number analysis was conducted using
CNVkit with focal events determined by GISTIC 2.0, and pathway analysis
(KEGG) using DAVID. Results: Germline mutations in TERT (rs2736100,n=33)
and CDKN1A (rs2395655,n=27) linked with IPF risk were detected in most
MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 samples. A total of 410 somatic mutations were identified with an average
of 11.7 per tumor including 69 synonymous, 177 missense, 17 nonsense, 1
nonstop, 11 splice-site mutations, and 135 small coding indels. Spectra of the
MA05.03 A SINGLE EBUS-TBNA PASS YIELDS SUFFICIENT DNA FOR somatic mutations revealed predominant C→T transitions despite extensive
TARGETED MOLECULAR TESTING IN LUNG CANCER smoking histories across most study subjects, suggesting more associations
Tracy Leong 1, Marie-Liesse Asselin-Labat1, Michael Christie2, Gary with APOBEC3B-related mutagenesis in the process of IPF-LC development,
Hammerschlag 3, Louis Irving 3, Daniel Steinfort3 rather than smoking. TP53 (22/35,62.9%) and BRAF (6/35,17.1%) genes were
1
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical found significantly mutated in IPF-LC. Recurrent focal amplifications in 3
Research, Parkville/VIC/Australia, 2The University of Melbourne, Parkville/VIC/ chromosomal loci (3q26.33, 7q31.2, and 12q14.3), and 9p21.3 deletion were
Australia, 3Respiratory Medicine, Royal Melbourne Hospital, Melbourne/Australia identified, and genes associated with JAK-STAT signaling pathway were
significantly amplified in IPF-LC (P=0.012). Conclusion: IPF-LC is genetically
Background: Development of drugs that target molecular pathways in lung characterized by the presence of somatic mutations reflecting viral and
cancer has made it increasingly important for diagnostic sampling to yield immune-related mutagenic processes in the background of specific germline
sufficient material for genotyping. At the same time, minimally invasive mutations, and is associated with potentially targetable alterations such as
sampling techniques such as endobronchial ultrasound-guided transbronchial BRAF mutations.
needle aspiration (EBUS-TBNA) result in smaller volume cytological
specimens. It has been shown that at least 3 EBUS-TBNA passes per lesion are Keywords: idiopathic pulmonary fibrosis, genomic profile, lung cancer
sufficient for cytological subtyping. However, the number of passes needed
for mutational subtyping is unclear. We sought to determine the adequacy
of a single EBUS-TBNA for genotyping clinically actionable mutations.
Methods: Patients undergoing EBUS-TBNA for diagnosis of lung cancer MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER
were prospectively recruited. Paired samples from the same target lesion MONDAY, DECEMBER 5, 2016 - 16:00-17:30
were obtained. The “reference” sample was the routine diagnostic specimen
consisting of ≥3 passes, whereas the “study” sample comprised a single MA05.06 DIAGNOSIS OF CHRONIC OBSTRUCTIVE PULMONARY
pass. DNA was extracted from both samples and subjected to quantitative
DISEASE IN LUNG CANCER - A POPULATION BASED STUDY
and qualitative assessment. Sequencing for EGFR, KRAS, BRAF mutations
was performed in adenocarcinoma/non-small cell lung cancer not otherwise John Goffin1, Grace Tang2, Gregory Pond2, Sophie Corriveau3
1
specified (NSCLC-NOS) cases. Results: Samples were obtain in 41 patients. Oncology, Juravinski Cancer Centre, Hamilton/ON/Canada, 2Oncology, Ontario
Cytological diagnosis was adenocarcinoma/NSCLC-NOS in 25 (61.0%), Clinical Oncology Group, McMaster University, Hamilton/ON/Canada, 3Medicine,
St. Joseph’s Hospital, Hamilton/ON/Canada
squamous cell carcinoma in 10 (24.4%), small cell lung cancer in 5 (12.2%),
and carcinoid in 1 (2.4%) case. DNA extraction yielded a mean of 4.03μg, well Background: Chronic obstructive pulmonary disease (COPD) and lung
above the minimum required quantity for targeted sequencing of 10ng (Table cancer are associated through tobacco. COPD is underdiagnosed in the
1). DNA quality measured by DNA Integrity Number could be calculated in 35 general population. Patients with lung cancer suffer from dyspnea and
(85%) cases with a mean of 8.9, where >7 is acceptable for sequencing (Table hospitalization for respiratory complications, and underdiagnosis of COPD
1). Sequencing results of adenocarcinoma/NSCLC-NOS cases show mutations could confer worse symptoms and morbidity. Using Institute for Clinical
in EGFR in 6, KRAS in 8, BRAF in 1 case. Wild type was demonstrated in 6 cases. Evaluative Sciences (ICES) data, we assessed the diagnosis of COPD in the
Molecular analysis of the corresponding study samples is proceeding. lung cancer population in Ontario, Canada. Methods: Cancer registry, hospital
ICD-10 codes, physician billing data, and vital statistics were abstracted in
Table 1. DNA quantity and quality an anonymized manner from ICES. COPD was defined using the validated
Mean DNA ICES-derived COPD cohort and spirometry use was assessed through billing
Mean DNA
Cases, n Integrity codes. Cancer stage was available from cancer registry data. Analysis was
Histological subtype quantity
(%) Number conducted using ICES’s confidential, analytic virtual environment using SAS
(μg)
(DIN) v9.3 in the population age >39 years. The local ethics board approved the
Adenocarcinoma/NSCLC-NOS 25 (61.0) 3.83 8.8 study. Results: From 2004-2014, 90,783 individuals were diagnosed with
Squamous cell carcinoma 10 (24.4) 2.65 9.0 lung cancer and 608,347 individuals diagnosed with COPD. Of individuals
with lung cancer, 52.7% were male, median age at diagnosis was 65-69 years,
Small cell lung carcinoma 5 (12.2) 5.28 9.0
and 82.8% have died. Of individuals with COPD, 51% were male, median age
Carcinoid 1 (2.4) 16.24 9.1 at diagnosis was 60-64 years, and 24.7% have died. The diagnosis of COPD
Overall 41 4.03 8.9 was made at a rate of 8.7 persons per 1000 person-years. Among individuals

having COPD, 48.4% underwent spirometry. 30.2% of individuals with lung esophageal cancer, who received the thoracic radiotherapy, were enrolled
cancer were also diagnosed with COPD and 60.8% underwent spirometry in the present study. Each patients underwent the exhaled nitric oxide
at any time. Among those with a diagnosis of both lung cancer and COPD, measurement before the radiotherapy and at the end of radiotherapy.
73.6% underwent spirometry. For individuals with registry recorded stage Pneumonitis toxicity was scored using the Common Terminology Criter
data, 12,110 persons had stage I-II lung cancer, of whom 90.7% had spirometry Results: Of the 68 patients, 65 were evaluable. The pneumonitis toxicity grade
and 55.9% had a diagnosis of COPD. Conversely, among 31,392 persons with were grade 3 for 6, grade 2 for 11 and grade0-1 for48. The exhaled NO measured
stage III-IV lung cancer, 54.6% had spirometry and 46% were diagnosed with before radiotherapy and at the end of radiotherapy were 23.05±9.59 (range
COPD (p<0.001 vs early stage for both). Conclusion: The diagnosis of COPD is 10-53) and 22.89±8.60 (range 11-60) ppbs.For the exhaled NO ratio, the AUC
not based on spirometry in half of cases. More patients with early stage lung is 0.879 (95%CI0.774-0.984). The accuracy of predicting the symptomatic
cancer underwent spirometry and a higher rate of spirometry was associated patients was identified “good” according to the predictive ability criteria
with more diagnosis of COPD. Increased use of spirometry may improve the and the optimal cutoff value was tested as 1.305. For the exhaled at the end
accuracy of a COPD diagnosis and may increase the diagnosis of COPD in of RT, the AUC is 0.774 (95%CI 0.656-0.892). The accuracy of predictive the
advanced stage lung cancer, allowing improved dyspnea management in this symptomatic patients was evaluated “fair” ,The optimal cutoff value was
population. identified 19.5 ppbs. Conclusion: The exhaled nitric oxide ratio>1.305 or the
exhaled nitric oxide at the end of radiotherapy>19.5ppbs was found to have a
Keywords: dyspnea, lung cancer, emphysema, spirometry closely relation with radiation pneumonitis.
Keywords: Radiation pneumonitis, radiation oncoloty, exhaled Nitric Oxide

MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MA05.07 IDENTIFYING COMORBID DISEASE ON CHEST CT SCANS
IN A LUNG CANCER SCREENING-ELIGIBLE COHORT
Elizabeth Regan1, Barry Make1, Gregory Kinney2, Matthew Budoff3, MA05.10 CELL-FREE DNA TESTING FOR EGFR MUTATIONS IN
Debra Dyer 1, Jeffrey Curtis4, Russell Bowler 1, Meilan Han4, Terri Beaty5, CLINICAL PRACTICE - FACTS AND FIGURES FROM AN AUSTRIAN
John Hokanson6, Elizabeth Kern1, David Lynch1, Edwin Van Beek7, Edwin LUNG CANCER CENTER
Silverman8, James Crapo1, James Finigan9 David Lang 1, Elmar Brehm1, Thomas Gitter2, Christian Paar3, Jörg Berg 3, Bernd
1
Medicine, National Jewish Health, Denver/United States of America, 2University Lamprecht1
of Colorado Denver, Aurora/CO/United States of America, 3Los Angeles Biomedical 1
Department of Pulmonology, Kepler University Hospital, Linz/Austria, 2Central
Research Institute, Torrance/CA/United States of America, 4University of Michigan Radiology Institute, Kepler University Hospital, Linz/Austria, 3Institute of Medical
Health System, Ann Arbor/United States of America, 5Johns Hopkins Bloomberg and Chemical Laboratory Diagnostics, Kepler University Hospital, Linz/Austria
School of Public Health, Baltimore/MD/United States of America, 6Epidemiology,
Colorado School of Public Health, Aurora/CO/United States of America, 7Clinical Background: Detection of EGFR mutations using cell-free DNA in plasma
Radiology, Queen’s Medical Research Institute - University of Edinburgh, has recently emerged as a novel diagnostic approach to lung carcinoma. This
Edinburgh/United Kingdom, 8Brigham and Women’s Hospital, Boston/MA/United
“liquid biopsy” (LB) may also be useful for monitoring disease activity in
States of America, 9Medicine, National Jewish Health, Denver/CO/United States of
America
EGFR-mutated tumors as well as in the management of EGFR-tyrosine kinase
inhibitor (TKI) therapy. We present data collected in one year of use and
Background: Lung cancer screening (LCS) with chest CT scans in high-risk report on applicability and diagnostic value in daily clinical practice. Methods:
smokers has been demonstrated to save lives. Medicare and private insurers EGFR Mutations were analyzed using the semi-quantitative Roche cobas®
now cover these scans for beneficiaries under specific criteria. However, EGFR Mutation Test v2, comprising 42 mutations. Cell free DNA was extracted
most smokers will die of comorbid smoking-related diseases rather than lung from EDTA-Blood with the Qiagen QIAsymphony circulating DNA Kit. LB was
cancer itself. Important information about comorbid conditions is available initially used for follow-up of known EGFR-mutated tumors and/or in patients
on screening chest CT scans, but the prevalence of these comorbidities under TKI-therapy. Subsequently, we introduced routine LB testing in the
has not been comprehensively assessed. Methods: COPDGene subjects primary diagnostic workup of lung cancer patients. Results: From July 2015 to
from the Phase 1 visit who met USPSTF criteria for LCS (age > 55, >30 pack June 2016 we performed a total of 92 liquid biopsies in 77 patients (60% male,
years smoking, current or former smokers within 15 years of smoking mean age 65y) in whom EGFR mutations could be detected in 10 cases (13%).
cessation or current smokers) were assessed for coronary calcification, EGFR status from histological samples was available in 40 patients, in 14 (18%)
emphysema, gas trapping, airway wall thickening and vertebral bone density of them mutations were reported. Compared to histological EGFR status, LB
on standard dose CT scans. A new diagnosis of emphysema, osteoporosis, reached a sensitivity and specificity of 0.57 and 0.96, respectively. A total of 9
or cardiovascular disease was assumed when there was no self-report of patients had multiple LB testing during follow-up. Three of them initially had
diagnosis or medication use. Results: In 76% of CT scans from LCS-eligible detectable mutations by LB, which turned undetectable upon tumor-specific
COPDGene subjects, we found abnormal emphysema (>5% low attenuation treatment. Two patients remained EGFR-positive during follow-up despite
area @-950 Hounsfield units), airway wall thickening or gas trapping (>20% of therapy, whereas four patients remained negative throughout follow-up
low attenuation area @-856 Hounsfield units). Osteoporosis was identified and therapy. Resistance mutations under TKI-therapy were not observed.
in 54% of all CT scans, and abnormal coronary artery calcium was present in Primary LB (before initiation of any tumor-specific therapy) was obtained
51%. In non-COPD smokers a new diagnosis of emphysema, osteoporosis or from 47 patients (72% male, mean age 66y). EGFR mutations by LB were
coronary calcification was found in 741 (48%) subjects. Overall, 75% of LCS detected in 2 patients (4%; 1 Ins. Exon-20, 1 L858R), while histology revealed
eligible CT scans showed one or more non-cancer diagnoses. Conclusion: EGFR mutations in 2 out of 22 patients (9%; both L858R). Comparison yielded
Enhanced readings of the lung cancer screening scans could identify a sensitivity of 0.5 and a specificity of 0.95 for LB. Conclusion: Testing for
individuals with previously undiagnosed osteoporosis, atherosclerotic heart EGFR mutations using cell-free DNA has been established as a new powerful
disease, emphysema and COPD. Identification and treatment for these tool in the field of pulmonary oncology. Apart from sole detection of EGFR
conditions may reduce morbidity and mortality, improve quality of life and mutations, especially the application of LB in following patients over time will
enhance smoking cessation. provide valuable new opportunities in clinical routine and decision making
Keywords: Screening, emphysema, coronary artery disease, osteoporosis Keywords: liquid biopsy, EGFR mutation, follow-up, TKI
MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MA05.09 THERE IS A CLOSELY RELATION BETWEEN EXHALED MA05.11 PHOTODYNAMIC THERAPY FOR PERIPHERAL LUNG
NITRIC OXIDE AND RADIATION PNEUMONITIS CANCER USING COMPOSITE-TYPE OPTICAL FIBERSCOPE OF 1.0 MM
Jiancheng Li1, Xiaobin Fu2 IN DIAMETER
1
Department of Radiation Oncology, Fujian Cancer Hospital, Fuzhou,fujian/China, Jitsuo Usuda, Tatsuya Inoue, Takayuki Ibi, Kenta Hasumi
2
Fujian Medical University, Fuzhou/China Division of Thoracic Surgery, Nippon Medical School, Tokyo/Japan
Background: Radiation pneumonitis is a major toxicity after the thoracic Background: Photodynanic therapy (PDT), is a treatment modality for many
radiotherapy, with no method available to accurately predict the individual cancers, and uses a tumor-specific photosensitizer and laser irradiation. PDT
risk. This was a prospective study to evaluate the exhaled nitric oxide as a is recommended as a treatment option for centrally located early lung cancer.
predictive biomarker for radiation pneumonitis in the patients received the The detection of peripheral lung cancers is increasing, and stereotactic body
thoracic radiotherapy Methods: A total of 68 patients with lung cancer or radiotherapy (SBRT) and percutaneous thermal ablation are emerging as
alternatives to surgical resection, but PDT has not been a modality. Recently, MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND
TREATMENT CHOICES
we have developed a new minimally invasive laser device using a 1.0 mm in MONDAY, DECEMBER 5, 2016 - 16:00-17:30
diameter composite-type optical fiberscope (COF), which could transmit
laser energy and images for observation in parallel. In this study, we aimed to
develop a new endobronchial treatment for peripheral cancer using PDT and a MA06.02 DOES PATHOLOGICAL STAGING FOLLOWING
1.0 mm in diameter composite-type optical fiberscope (COF), and we evaluated NEOADJUVANT THERAPY (YPTNM) REFLECT THE REALITY?
the feasibility of PDT using COF for peripheral lung cancer. Methods: This Huseyin Melek 1, Hasan Kara2, Adalet Demir3, Mehmet Erol1, Ahmet Sami
phase I study enrolled patients with peripheral lung cancers (primary tumor< Bayram1, Akif Turna2, Alper Toker3, Cengiz Gebitekin4
20 mm, stage IA), which were definitively diagnosed by bronchoscopic 1
Thoracic Surgery, Uludag University, Bursa/Turkey, 2Department of Thoracic
modalities using radial-probe endobronchial ultrasound (EBUS) and guide Surgery, Istanbul University Cerrahpasa Medical School, Istanbul/Turkey, 3Thoracic
sheaths. We conducted irradiation using a diode laser (664 nm) and optical Surgery, Istanbul University, Istanbul/Turkey, 4Thoracic Surgery, Uludag University,
fiberscope (COF), four hours after the administration of NPe6 40 mg/m2. Faculty of Medicine, Bursa/Turkey
Before performing PDT, we evaluated the tumor lesions using EBUS through
the guide sheaths for peripheral small lesions. Then, we introduced the COF Background: Complete histopathological response or downstaging has been
into the peripheral lung cancer, observed the lesions and irradiated of red reported as a good prognostic factor for locally advanced non-small cell lung
light 664 nm (120 mW, 50 J/cm2). Results: Three patients met our criteria, cancer (NSCLC) patients who received neoadjuvant therapy and underwent
and 2cases were adenocarcinoma and 1 case squamous cell carcinoma. We surgical resection. However, it is yet to be known if the prognosis of pStage
were able to observe the cancer lesions at the peripheral lung by the COF, I patients is similar to that of ypStage I cases. In this study we aimed to
and feasibly irradiated. Two weeks and 3 months after NPe6-PDT, there was compare the long-term survival following surgical excision between locally
no morbidity including pneumothorax, pneumonia, skin photosensitivity. advanced NSCLC that have been downstaged to stage I after neoadjuvant
Conclusion: The 1.0 mm COF was a very useful device of NPe6-PDT for therapy versus stage I NSCLC treated by direct surgery. Methods: In this
peripheral lung cancers, and PDT using the COF was a feasible and non- is multi-centered study we retrospectively analyzed the medical data of
invasive treatment. Now, we have started phase II study of PDT using the COF NSCLC patients undergoing surgery (segmentectomy or more) between
for peripheral lung cancers. In the future, for non-invasive adenocarcinoma January 1998 and December 2014. According to the histopathological results
such as AIS, NPe6-PDT using COF will play an important role. patients with Stage 1 (T1-2aN0) disease (n=427) were included into the study.
Patients were divided into two groups Group 1: patients who underwent
direct surgical resection without any preoperative therapy (n=291), Group
2: Patients who had locally advanced disease (T3-4N0-1 or T1-3N2) and
received neoadjuvant treatment (chemotherapy or chemoradiation) for
SESSION MA06: LOCALLY ADVANCED NSCLC: RISK locally advanced NSCLC (n=136). The survival rates and effecting factors
GROUPS, BIOLOGICAL FACTORS AND TREATMENT CHOICES were analyzed. Results: All but 64 patients were male with a mean age of
60y (20-87y). According to tumor type; 192(45%) patients had squamous
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 cell carcinoma, 158(37%) adenocarcinoma and 77 (18%) patients NSCLC.
Neoadjuvant treatment consisted of chemotherapy in 89 (65,4%) and
chemoradiation in 47(34,5%) patients. Histopathological investigation of the
MA06.01 OVERALL SURVIVAL CHARACTERIZATION OF INCIDENTAL resected specimen revealed stage Ib (T2aN0) in 205 patients (group 1; n=140,
N2 NON-SMALL CELL LUNG CANCER OVER 14 YEARS AT A SINGLE group 2;n= 65, p=0,95). Overall morbidity rate for all patients was 30,9%
CANADIAN INSTITUTION (132/427) with 1.8% mortality. Five year survival rate in all patiens was 71%
Cara Van Der Merwe 1, Adrijana D’Silva1, Shannon Otsuka2, Gary Gelfand3, (77% in group I and 57% in group 2). The difference was statistically different
Andrew Graham3, Sean Grondin3, Sean Mcfadden3, Gwyn Bebb2 between the groups, p<0,001. Conclusion: This study showed that survival
1
University of Calgary, Calgary/AB/Canada, 2Medicine, University of Calgary and
of patients after surgical excision was different in ypStage 1 compared to
Alberta Health Services, Calgary/Canada, 3 Alberta Health Services, Calgary/AB/ pStage 1. Histopathological staging does not reflect to the survival figures.
Canada Our impression is that IASLC recommendations for staging of NSCLC should
be subdivided or revised according to ypTNM staging following neoadjuvant
Background: Incidental stage IIIA non-small cell lung cancer (NSCLC) cases treatment.
have positive N2 mediastinal lymph node involvement discovered at the time
of surgery, resulting in stage reclassification. These patients represent a small Keywords: neoadjuvant therapy,restaging, survival, pathological stage
group within the stage III patient spectrum with limited data regarding their
outcome. This study’s aim is to characterize the survival of incidental stage
IIIA disease and compare these outcomes to patients diagnosed with stage
II and IIIA disease. Methods: Using the Glans-Look Lung Cancer database MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND
TREATMENT CHOICES
and electronic patient charts, a retrospective review identified patients MONDAY, DECEMBER 5, 2016 - 16:00-17:30
consulted at the Tom Baker Cancer Center from 1999 to 2012 who were defined
as incidental stage III NSCLC. Their outcome was compared with stage II
patients who underwent resection and stage IIIA patients treated with MA06.03 RECURRENCE DYNAMICS AFTER TRIMODALITY THERAPY
concurrent chemotherapy and radiation (CCR). These groups were selected for (NEOADJUVANT CHEMORADIOTHERAPY AND SURGERY) IN STAGE
comparison because they represent patients who received the recommended IIIA(N2) LUNG CANCER
standard of care for their respective diagnosis. A Kaplan-Meier analysis Jung Hee Lee 1, Hong Kwan Kim1, Byung Jo Park1, Yong Soo Choi2, Jong Ho Cho1,
was conducted to compare overall survival (OS) among the groups. Results: Jae Ill Zo1, Young Mog Shim1, Sumin Shin1, Hong Ryull Pyo3, Yong Chan Ahn3, Jin
Fifty-eight incidental stage III NSCLC patients were identified: median age Seok Ahn4, Myung-Ju Ahn4, Keunchil Park5, Jhingook Kim1
was 63 years (SE ±10.3), 46.6% male, and 63.8% received adjuvant therapy. 1
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center,
There were 225 individuals treated with CCR; median age 64 years (SE ±9.0), Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of,
56.0% male. The stage II group contained 248 individuals, the median age was 2
Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan
64 years (SE ±10.2), 53.6% were males, and 30.6% received adjuvant therapy. University School of Medicine, Seoul/Korea, Republic of, 3Radiation Oncology,
The OS of the incidental group was 47.4 months (95% CI 20.0-74.7). The OS for Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/
patients treated with CCR only was 24.0 months (95% CI 20.8-27.2) and 55.3 Korea, Republic of, 4Division of Hematology-Oncology, Department of Medicine,
months (95% CI 43.7-66.9) for stage II resected cases. There was a significant Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/
difference in OS between CCR-treated stage IIIA and incidental cases (p = .001) Korea, Republic of, 5Division of Hematology/Oncology, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of
but not between stage II and incidental (p = .264). The five-year survival rates
were 44.6% (SE ±6.5) for incidental IIIA, 21.0% (SE ±2.7) for CCR-treated IIIA, Background: In IIIa(N2) Non-small cell lung cancer (NSCLC), various strategies
and 46.9% (SE ±3.2) for resected stage II. Conclusion: This study demonstrates to cure have been tried but the major cause of mortality is still the recurrence.
that incidental stage IIIA-N2 patients are a distinct group whose median Therefore, understanding of the dynamics of recurrence is important to
OS closely resembled stage II patients. The benefit of resection for stage improve the treatment outcome. We investigated the timing and patterns
IIIA patients suggests that the traditional influence of stage in dictating of recurrence after treatment of IIIA(N2) NSCLC with trimodality treatment
treatment is changing. Further investigation is needed to identify which stage (neoadjuvant chemoradiotherapy and surgery). Methods: An institutional
IIIA patients benefit the most. Ongoing analysis will include a comparison of database of consecutive patients between 1997 and 2013 (N = 574) was
progression-free survival between the three groups, impact assessment of reviewed retrospectively. Eligible patients had pathologically proven N2
post-operative treatment on OS, and a description of the diagnostic process disease of NSCLC and completion of a planned trimodality treatment. First
evolution over time leading to an incidental N2 diagnosis. events involving the development of loco-regional recurrence, distant
metastases or both were considered. The hazard rate function was used to
Keywords: Incidental, outcomes, locally advanced disease
evaluate the dynamics of recurrence. Results: The 5-year overall survival
rate was 47% and the 5-year recurrence free survival rate was 29%. Among
the 299 patients (52.1% of total) who experienced recurrence, 26 (8.7%) had

loco-regional recurrences, 248 (82.9%) had distant metastases, and 25 (8.4%) CANCER
had both. The most frequent sites of distant metastases were lung (n=102, Qin Zhang, Xiaolong Fu, Xuwei Cai, Wen Feng
41%), brain (n=63, 25%), and bone (n=63, 25%). The hazard rate function
Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University,
for the overall recurrence revealed the peak at approximately 8 months Shanghai/China
after surgery then the down-slope pattern before 38 months. A similar risk
pattern was found in distant metastasis but low and steady risk pattern was Background: Tumor-infiltrating lymphocytes (TILs) and tumor budding were
detected in loco-regional recurrence. In distant metastases, similar patterns all the markers of tumor microenvironment. This study aimed to explore the
were found in individual organs, however, earlier peak at approximately 5 potential association of tumor microenvironment with brain metastases (BM)
months presented in brain metastasis. A comparison of histology showed in patients with completely resected stage IIIA(N2) NSCLC. Methods: 301
that adenocarcinoma exhibited higher recurrence hazard rate of distant consecutive patients with pathological stage IIIA(N2) NSCLC who underwent
metastasis than squamous cell carcinoma with similar pattern of recurrence complete surgery were reviewed between January 2005 and July 2012.
(p=0.03). The status of nodal clearance after induction therapy exhibited Full-face hematoxylin and eosin-stained sections from surgical specimens for
that ypN2 patients (n= 229, 39.9%) had highest hazard rate (p=0.03). The each case were evaluated for the density of TILs. Patients were stratified into
recurrence hazard rate of ypN0 was the least, but the extent was not smaller, TIL- and TIL+ groups based on pathologic evaluation. Tumor budding was
they showed approximately one of third of ypN2 at peak. Conclusion: The defined as single cancer cells and clusters composed of up to four cancer cells.
hazard rate of loco-regional failure after trimodality therapy was low. But the According to the number of tumor budding per field, the cases were classified
hazard rate of distant metastasis was considerably high yet and shifted to left into two groups: grade 1, up to five budding foci; and grade 2, six or more
with the peak within 12 moths after surgery. This study guides the intensive budding foci. The relationship between tumor microenvironment and BM at
surveillance immediate after completion of trimodality therapy to identify the initial presentation was analyzed. Results: Brain was the most common
risk groups of early recurrence and to develop therapeutic strategy. site of distant failure, and 92.5% BM developed in 3 years after the complete
resection. 53 (17.6%) patients had BM as the first failure. Although, univariate
Keywords: N2, NSCLC, recurrence dynamics, pattern of recurrence analysis showed that TIL was not significantly associated with an increased
risk of developing BM as the first site of failure in 3 years (P=0.196), a higher
density of TILs was associated with improved postoperative survival time
(P=0.058). Patients with the tumor budding >5 experienced increased BM in 3
MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND
TREATMENT CHOICES
years versus patients with the tumor budding ≤5 (P=0.068). Multivariate
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 analysis showed that adenocarcinomas and multiple N2 stations were
significantly associated with the high risk of BM as the initial site of failure in
3 years.
MA06.05 SCREENING FOR BRAIN METASTASES IN PATIENTS WITH
STAGE III NSCLC, MRI OR CT? A PROSPECTIVE STUDY
Janna Schoenmaekers 1, Lizza Hendriks2, Paul Hofman2, Gerben Bootsma3,
Marcel Westenend4, Machiel De Booij3, Wendy Schreurs3, Ruud Houben5, Dirk
De Ruysscher6, Anne-Marie Dingemans2
1
Pulmonary Medicine, Mumc, Maastricht/Netherlands, 2Pulmonology, Mumc,
Maastricht/Netherlands, 3Pulmonary Medicine, Zuyderland Ziekenhuis, Heerlen/
Netherlands, 4Pulmonary Medicine, Viecuri Ziekenhuis Venlo, Venlo/Netherlands,
5
Radiation Oncology, Maastro Clinic, Maastricht/Netherlands, 6Radiation Oncology
(Maastro Clinic), Maastricht University Medical Center, Maastricht/Netherlands
Background: In all current non-small cell lung cancer (NSCLC) guidelines it

is advised to screen all stage III patients for brain metastases, preferably
by magnetic resonance imaging (MRI), or otherwise a contrast-enhanced
computed tomography (CE-CT). Access to MRI can be problematic and a
dedicated brain CE-CT can be incorporated in the staging 18Fluodeoxoglucose-
positron-emission-tomography (18FDG-PET)-CT scan. The additive value of
a brain MRI after a dedicated brain CE-CT scan is unknown. Methods: In this
observational prospective multicentre study all consecutive stage III NSCLC
patients scheduled for treatment with curative intent from three Dutch
hospitals who underwent a dedicated brain CE-CT incorporated in the staging
18
FDG-PET and an additional brain MRI were included. Patients with another
Conclusion: In patients with completely resected stage IIIA(N2) NSCLC, tumor
primary tumour within 2 years of NSCLC diagnosis were excluded. Data
budding >5 had a tendency to experience more BM. TIL seems to be a potential
regarding patient characteristics and imaging results were collected. Primary
role in predicting survival of patients in completely resected stage IIIA(N2)
endpoint was the percentage of patients diagnosed with brain metastases
NSCLC.
on MRI without suspect lesions on CE-CT. 118 patients were needed to show a
clinically relevant considered difference of 2%. Results: Between December Keywords: Tumor Budding, brain metastases, stage IIIA(N2) NSCLC, tumor-
14th 2012 and July 15th 2016, 264 consecutive patients had an extracranial infiltrating lymphocytes
stage III NSCLC based on 18FDG-PET. 111 out of these 264 patients (42.0%) were
excluded because of no dedicated brain CE-CT 57 (51.4%) had only a low dose
CT for attenuation correction, 54 (48.6%) had a CE-CT but without dedicated
brain imaging protocol). Fourty (26.1%) of the remaining 153 patients were MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND
excluded because of asymptomatic brain metastases on dedicated CE-CT TREATMENT CHOICES
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
brain (N=8), second primary (N=6) or no brain MRI (N=26). 113 stage III patients
were included (updated results of 118 patients will be presented). 57.5% of the
included patients were male; mean age was 67.0 years, 84.1% had WHO PS 0-1, MA06.07 IMPACT OF TYPE 2 DIABETES MELLITUS AND ITS
60.2% had stage IIIA (before MRI brain) and 42.5% had an adenocarcinoma. METABOLIC CONTROL ON PROGNOSIS OF UNRESECTABLE NON-
Median time (range) between 18FDG-PET-CE-CT and MRI was 2.0 (0.0 -8.1)
SMALL CELL LUNG CANCER PATIENTS
weeks. 5/113 (4.4%) patients had a solitary brain metastasis on MRI despite
no suspect brain lesions on CE-CT. In retrospect, in one of these five patients Milana Bergamino Sirvén1, Aj Rullan1, Maria Saigi1, Inmaculada Peiró2, Eduard
a solitary brain metastasis could be identified on the 18FDG-PET–CE-CT. Montanya3, Ramon Palmero1, Jose Carlos Ruffinelli1, Arturo Navarro-Martin4,
Conclusion: Although asymptomatic brain metastasis were detected in Marta Domenech ViÑolas1, Ana Ortega Franco1, Susana Padrones5, Samantha
staging CE-CT, MRI brain is in daily practice clinically relevant superior to a Aso5, Isabel Brao1, Ernest Nadal1, Felipe Cardenal1
1
CE-CT in screening for brain metastases in stage III NSCLC Medical Oncology, Catalan Institut of Oncology -Ico Hospitalet, Hospitalet Del
Llobregat/Spain, 2Nutritional Unit, Catalan Institut of Oncology -Ico Hospitalet,
Keywords: MRI versus CT, NSCLC, brain metastases, Screening Hospitalet Del Llobregat/Spain, 3Endocrinology Department, Bellvitge Hospital,
Barcelona/Spain, 4Radiation Oncology Department, Catalan Institute of Oncology
-Ico Hospitalet, Barcelona/Spain, 5Respiratory Department, Bellvitge Hospital,
Barcelona/Spain
MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND Background: Type 2 Diabetes Mellitus (T2DM) has been associated with an
TREATMENT CHOICES
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 increased risk of relapse and mortality in several cancer locations, but the
prognostic value of T2DM or its metabolic control (MC) in patients (pts) with
stage III non-small cell lung cancer (NSCLC) have not been studied yet. The
MA06.06 TUMOR MICROENVIRONMENT AND BRAIN METASTASES purpose of this study is to evaluate the influence of T2DM and its MC on the
IN COMPLETELY RESECTED STAGE IIIA(N2) NON-SMALL CELL LUNG prognosis of pts with NSCLC treated with concurrent chemoradiotherapy
(cCT-RT). Methods: 170 pts with NSCLC stage III treated with cCT-RT at the were treated (66 in oV-P and 68 in E-P arms). Results based on this 134 pts are
Catalan Institute of Oncology from 2010-2014 were retrospectively reviewed. presented. Median age 62 years [39-76]; PS 0/1, 45%/55%; current smoker 51%;
The overall survival (OS) and progression free survival (PFS) were calculated squamous cell 51%; stage IIIB 54%. 244 and 131 cy were given in the oV-P and
using Kaplan-Meier method and multivariate Cox model was adjusted E-P arms, respectively. All irradiated pts in oV-P arm received at least 60Gy, 7
by: age, histology, stage, ECOG PS and smoking history. Results: Patient pts in the E-P arm received less than 60Gy (4 due to toxicity). 1 pt (1.5%) in oV-P
characteristics: median age 64y (37-87), male 87%; ECOG≤1 92%; smoking arm and 12 pts (17.6%) in E-P arm presented esophagitis G3/4 (p=0.002). 121
history: current 49%, former 46%, never 5%; histology: adenocarcinoma 34%, confirmed eligibility for efficacy analysis. ORR were 39 (64%) and 40 pts (67%)
squamous 43%, NOS 23%. Platinum doublet CT: Cisplatin 64%, Carboplatin in the oV-P and E-P arms, respectively (p=0.889). After 16 m [1-43] of follow-up,
36%. RT between 60-70 Gys: 94%. At a median follow-up of 38 months (m), 66% pts progressed and 43% pts died. Median PFS is 11.4 m (IC95%; 6-17)
108 patients relapsed (63%), mPFS; 13m (95% CI 10-16) and mOS: 28m (95% CI in oV-P arm and 11.8 m (IC95%; 7-16) in E-P arm (p=0.374). Conclusion: Both
22-34). 54 pts (32%) had been diagnosed with T2DM before NSCLC diagnosis. regimens achieve similar efficacy however oV-P has less toxicity, especially
In the overall population mean baseline glycemia was 6.75 mmol/L (3-17). esophagitis G3/4. Further follow-up is needed for the survival analysis.
OS and PFS were significantly shorter in patients with T2DM (mOS 17m vs
31m, p=0,005; mPFS 10m vs 16m; p =0,003). T2DM pts were classified into 3 Keywords: Locally advanced NSCLC, Oral Vinorelbine, chemotherapy,
groups of MC based on glycated hemoglobin (HbAc1) before treatment: good Radiotherapy
MC (HbAc1 <7%), n=26pts; moderate MC (HbAc1 between 7.1-8.5%), n=18pts
and poor MC (HbAc1 >8.6%), n=10pts. Poor MC was significantly associated
with shorter mOS (11m) as compared with moderate MC (20m) and good
MC (28m; p=0.029). T2DM pts treated with insulin had shorter mOS (8m MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND
TREATMENT CHOICES
vs 20m; p=0.002) and mPFS (7m vs 12m; p=0.002) than non-insulin treated MONDAY, DECEMBER 5, 2016 - 16:00-17:30
pts. However there were no differences based on whether pts were taking
metformin or not. T2DM was not associated with higher risk of treatment
toxicity (pneumonitis or esophagitis). In the multivariate analysis, baseline MA06.10 A POOLED ANALYSIS COMPARING THE OUTCOMES
glycemia and T2DM were both independent prognostic factors for OS (HR OF ELDERLY TO YOUNGER PATIENTS ON NCTN TRIALS OF
1.2; IC95%1.17-1.3 and HR 1.51; IC95% 1.02 -2.27, respectively). Conclusion: Our CONCURRENT CCRT FOR STAGE 3 NSCLC
data suggest that T2DM and poor MC is associated with worse prognosis in Thomas Stinchcombe 1, Ying Zhang2, Everett Vokes3, Joan Schiller4, Jeffrey
pts with stage III NSCLC treated with cCT-RT. Optimal control of T2DM and Bradley5, Karen Kelly6, Walter Curran7, Steven Schild8, Benjamin Movsas9,
prevention of hyperglicaemia might benefit those pts, and further studies are Gerald Clamon10, Ramaswamy Govindan11, George Blumenschein12, Mark
warranted. Socinski13, Neal Ready1, Wallace Akerley14, Harvey Cohen1, Herbert Pang15,
Xiaofei Wang16
Keywords: T2DM, NSCLC, HbAc1, cCT-RT 1
Department of Medicine, Duke University, Durham/NC/United States of America,
2
Department of Public Health Sciences, Pennsylvania State University, Hershey/
AL/United States of America, 3University of Chicago Medicine & Biological Sciences,
Chicago/IL/United States of America, 4Inova Schar Cancer Institute, Falls Church/
MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND VA/United States of America, 5Radiation Oncology, Washington University School
TREATMENT CHOICES
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
of Medicine, Chesterfield/MO/United States of America, 6Hematology Oncology,
UC Davis Comprehensive Cancer Center, Sacramento/CA/United States of America,
7
Radiation Oncology, Emory University Winship Cancer Institute, Atlanta/GA/
MA06.09 EFFICACY RENO STUDY RESULTS OF ORAL VINORELBINE United States of America, 8 Mayo Clinic Arizona, Scottsdale, Az/United States of
America, 9Radiation Oncology, Henry Ford Hospital, Detroit/MI/United States of
OR ETOPOSIDE WITH CISPLATIN & CHEMO-RADIATION IN STAGE III America, 10University of Iowa Hospital and Clinics, Iowa City/AL/United States of
NSCLC. SLCG 10/02 America, 11Medical Oncology, Washington University School of Medicine, St. Louis/
Dolores Isla1, Ramón De Las PeÑas2, Raquel Marsé3, Amelia Insa Molla4, MO/United States of America, 12University of Texas MD Anderson Cancer Center,
Natividad Martínez-Banaclocha5, Teresa Morán6, Pilar Mut7, Maria Ángeles Houston/TX/United States of America, 13Florida Hospital Cancer Institute, Orlando/
FL/United States of America, 14Huntsman Cancer Institute, Salt Lake City/UT/
Sala8, Bartomeu Massuti9, Ana Laura Ortega Granados10, José Miguel Jurado11,
United States of America, 15The University of Hong Kong, Hong Kong/China, 16Duke
Miguel Artal Cortés12, Maria Vázquez13, Vanesa Gutiérrez14, Pilar Diz Taín15, University, Durham/United States of America
José Gómez-Codina16, Inma Maestu Maiques17, Carlos Camps18, Núria ViÑolas
Segarra19, Santiago Ponce Aix 20, Melchor Álvarez De Mon Soto21, Ramón García Background: Concurrent chemoradiotherapy (CCRT) is the standard
Gómez22, Mariano Provencio23 treatment (TRT) for stage 3 NSCLC. Elderly patients (pts) are common, may
1 have increased toxicity,& poorer results from CCRT Methods: Individual
Medical Oncology, University Hospital Clínico Lozano Blesa, Zaragoza/Spain,
2
Medical Oncology, Provincial Hospital de Castellón, Castellón/Spain, 3Medical patient data (IPD) from NCTN phase 2/3 trials of CCRT for stage 3 NSCLC from
Oncology, University Hospital Son Espases, Palma de Mallorca/Spain, 4 Medical 1990-2012 was collected. We compared the overall survival (OS), progression-
Oncology, University Hospital Clínic de Valencia, Valencia/Spain, 5Medical free survival (PFS), & adverse events (AE’s) for pts age ≥70 years (yrs) (elderly)
Oncology, General University Hospital de Elche, Elche/Spain, 6Medical Oncology,
vs. <70 yrs (younger). Unadjusted & adjusted Hazard Ratios (HRs) for survival
Catalan Institute of Oncology-Hospital Germans Trias I Pujol, Badalona/Spain,
7
Medical Oncology, Hospital Son Llàtzer, Palma de Mallorca/Spain, 8 Medical
time & their confidence intervals (CIs) were estimated by single-predictor
Oncology, University Hospital de Basurto, Bilbao/Spain, 9Medical Oncology, & multivariable Cox models. Unadjusted & adjusted Odds Ratio (OR) for
Alicante University Hospital, Alicante/Spain, 10 Medical Oncology, Complejo AE’s & their CIs were obtained from single-predictor & multivariable logistic
Hospitalario de Jaén, Jaen/Spain, 11Medical Oncology, University Hospital San regression models Results: IPD from 16 trials were analyzed; 2,768 pts were
Cecilio, Granada/Spain, 12Medical Oncology, University Hospital Miguel Servet, younger & 832 were elderly. Median OS & PFS for elderly & younger pts are
Zaragoza/Spain, 13Medical Oncology, University Hospitality Complex of Santiago, in the table. In the unadjusted & multivariable models elderly pts had worse
Santiago de Compostela/Spain, 14 Medical Oncology, Regional University Hospital OS (HR=1.23; 95%CI =1.13-1.35, and 1.20; 95%CI=1.10-1.32, respectively). In the
of Málaga, Málaga/Spain, 15Medical Oncology, Assistent Complex of León, Leóin/
unadjusted & multivariable models, elderly & younger pts had a similar PFS
Spain, 16Medical Oncology, University and Polythecnic Hospital La Fe, Valencia/
Spain, 17Medical Oncology, University Hospital Doctor Peset, Valencia/Spain,
(HR=1.02; 95% CI=0.94-1.11 and 1.01, 95% CI=0.92-1.10, respectively). Elderly pts
18
Medical Oncology, Consorcio Hospital General Universitario de Valencia, had a higher rate of grade ≥3 AE’s in the unadjusted & multivariable models
Valencia/Spain, 19Medical Oncology, Univesity Hospital Clínic de Barcelona, (OR=1.25; 95% CI=1.00-1.57 and 1.30; 95%CI=1.03-1.62, respectively). A lower
Barcelona/Spain, 20 Medical Oncology, University Hospital 12 de Octubre, Madrid/ percentage of elderly pts compared to younger completed TRT (47% and 57%,
Spain, 21Medical Oncology, University Hospital Príncipe de Asturias, Alcalá de respectively; P<0.0001) & higher percentage stopped due to AE’s (20% and
Henares/Spain, 22University Hospital Gregorio MaraÑón, Madrid/Spain, 23Medical 13%; P<0.0001). Grade ≥ 3 AE’s (occurring at a rate ≥ 2.5%) with a higher rate in
Oncology, University Hospital Puerta de Hierro, Majadahonda/Spain the elderly: neutropenia, dyspnea, fatigue, anorexia, vomiting, dehydration,
hypoxia, hypotension, & pneumonitis (P<0.05).
Background: This study aims to compare efficacy and safety of two
widely used combinations of cisplatin (P) in this setting: as etoposide (E)
and vinorelbine. This last, in its oral formulation (oV) which has achieved Age ≥ 70yrs Age < 70 yrs P-valuea
comparable results as the IV formulation and patients (pts) prefer it.
Methods: Pts between 18-75years, with histologically proven untreated and Median OS (months) 17.0 20.7 < 0.01
unresectable locally-advanced NSCLC (LA-NSCLC), adequate respiratory Median PFS (months) 8.7 9.1 0.68
function, V20≤35% and ECOG-PS 0-1, were randomized 1:1 to oV-P arm: 2
induction cycles (cy) of oV-P followed by 2 cy more with RT; or to E-P arm: 2 All toxicities grade ≥3 86% 84% 0.04
cy of E-P concomitants to RT. Both arms with a total radiation dose of 66Gy Hematologic AE’s grade ≥3 65% 61% 0.04
administered 2 Gys daily. Primary endpoint was progression free survival
(PFS) by RECIST 1.1. Secondary endpoints: overall response rate (ORR), overall Non-hematologic AE’s ≥3 68% 62% <0.01
survival (OS) and safety. With α-error of 0.05 (one-tailed test) and 0.1 β-error, Grade 5 AE’s 9.0% 4.4% <0.01
median PFS unacceptable for the oV-P arm of 10 months (m) (p0) and a very
acceptable of 15 m (p1), 122 eligible pts were required. Results: 140 pts from TRT related deaths b 3.2% 2.0% 0.12
23 institutions of SLCG were randomized between 08/2011-12/2014. 134 pts

a: Log-rank test for survival times, chi-square test for AE’s, and Fisher’s exact Ji-Youn Han16, Walter Bordogna17, Sophie Golding17, Ali Zeaiter 17, Shirish
test for deaths. The P-values from these tests are unadjusted. Gadgeel18
1
University of California, Irvine School of Medicine, Orange County/CA/United
b: Data available on 2,091 patients Conclusion: Elderly pts in CCRT trials had States of America, 2Dana-Farber Cancer Institute, Boston/MA/United States of
worse OS, similar PFS, & a higher rate of severe AE’s. America, 3Massachusetts General Hospital, Boston/MA/United States of America,
4
Washington University School of Medicine, St. Louis/AL/United States of America,
Keywords: Stage 3 non-small cell lung cancer, Chemoradiotherapy, treatment 5
Florida Hospital Cancer Institute, Orlando/FL/United States of America, 6Medical
outcomes and toxicity, Geriatric Oncology Oncology, University of Colorado, Denver/CO/United States of America, 7Karolinska
University Hospital, Stockholm/Sweden, 8Seoul National University Hospital,
Seoul/Korea, Republic of, 9Moffitt Cancer Center, Tampa/FL/United States of
America, 10Thoracic Oncology Unit, Chest Department, Pôle Thorax Et Vaisseaux,
MA06: LOCALLY ADVANCED NSCLC: RISK GROUPS, BIOLOGICAL FACTORS AND CHU de Grenoble, Grenoble/France, 11Medical Oncology, Perugia University Medical
TREATMENT CHOICES School, Perugia/Italy, 12Istituto Europeo Di Oncologia (Ieo), Milan/Italy, 13Centre
MONDAY, DECEMBER 5, 2016 - 16:00-17:30 Oscar Lambret, Lille/France, 14Evangelische Lungenklinik Berlin, Berlin/Germany,
15
National Taiwan University Hospital, Taipei/Taiwan, 16Center for Lung Cancer,
National Cancer Center, Goyang/Korea, Republic of, 17F. Hoffmann-La Roche, Basel/
MA06.11 PHASE II STUDY OF NIMOTUZUMAB + CONCURRENT Switzerland, 18Karmanos Cancer Institute/wayne State University, Detroit/MI/
CHEMORADIOTHERAPY (CRT) FOR STAGE III NON-SMALL CELL United States of America
LUNG CANCER (NSCLC): 5-YEAR FOLLOW-UP RESULTS
Background: Based on two single-arm, multicentre, phase II studies (NP28673
Kazushige Hayakawa1, Yasumasa Nishimura2, Hideyuki Harada3, Toshinori [NCT01801111] and NP28761 [NCT01871805]), the FDA approved the ALK
Soejima4, Kayoko Tsujino4, Takuyo Kozuka5, Masahiro Tanaka6, Tomonari inhibitor alectinib for use in ALK+ NSCLC patients after prior crizotinib.
Sasaki7, Nobuyuki Yamamoto8, Kazuhiko Nakagawa9 Alectinib was well tolerated in both phase II studies and showed efficacy
1
Radiology and Radiation Oncology, Kitasato University, Sagamihara/Japan, against both systemic and central nervous system (CNS) disease, the
2
Radiation Oncology, Kindai University Faculty of Medicine, Osakasayama/Japan, latter being a common progression site in ALK+ NSCLC. This analysis uses
3
Radiation and Proton Therapy Center, Shizuoka Cancer Center, Suntougunn/Japan,
4 pooled data from the latest cut-offs (22 Jan 2016 for NP28761; 1 Feb 2016
Radiation Oncology, Hyogo Cancer Center, Akashi/Japan, 5Radiation Oncology, The
for NP28673) to examine the long-term CNS efficacy of alectinib. Methods:
Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo/Japan,
6
Osaka City General Hospital, Osaka/Japan, 7Health Sciences, Kyushu University, Both studies enrolled crizotinib-refractory patients ≥18 years with ECOG PS
Fukuoka/Japan, 8 Medical Oncology, Wakayama Medical University Hospital, 0–2 and locally advanced or metastatic ALK+ NSCLC (confirmed by FDA-
Wakayama/Japan, 9Medical Oncology, Kindai University Faculty of Medicine, approved test). CNS metastases were permitted if asymptomatic. Patients
Osaka-Sayama/Japan received 600mg oral alectinib BID. The primary endpoint in both studies was
objective response rate (ORR) by independent review committee; secondary
Background: Nimotuzumab, a humanized IgG1 monoclonal anti-EGFR CNS endpoints included CNS ORR, CNS duration of response (DoR), and CNS
antibody, is approved and widely used in patients (pts) with head and disease control rate (DCR). CNS response and progression were determined by
neck cancer or malignant glioma in combination with radiotherapy (RT) in RECIST v1.1. All patients had baseline imaging to assess CNS metastases, with
several countries. On in-vitro and in-vivo experiments using NSCLC cell lines, further imaging every 6 or 8 weeks for NP28761 and NP28673, respectively.
nimotuzumab showed a radio-sensitizing effect. Methods: This phase II study Results: The overall pooled analysis population comprised 225 patients (n=87
evaluated the tolerability and efficacy of nimotuzumab in combination with from NP28761; n=138 from NP28673); median follow-up for this updated
concurrent CRT in pts with unresectable locally advanced NSCLC. All eligible analysis was 18.8 (0.6–29.7) months (>6 months additional follow-up). At
pts received concurrent thoracic RT (60 Gy, 2 Gy/day, 6 weeks from day 1) and baseline, 50 patients had measurable and 86 had non-measurable CNS
4 cycles of chemotherapy (cisplatin 80 mg/m2 on day 1, vinorelbine 20 mg/ disease; together, these groups comprised 136 patients, 60% of the overall
m2 on days 1 and 8) once every 4 weeks as scheduled. Nimotuzumab (200 mg) pooled population. Seventy percent of patients had prior CNS radiotherapy;
was administrated once a week from cycle 1 to 4. The primary endpoint was 58% of these completed radiotherapy >6 months before study entry. Updated
tolerability in combination with concurrent CRT, which was measured by CNS data are shown in the Table and are consistent with systemic results.
the percentage of pts who completed 60 Gy of RT within 8 weeks, completed
2 cycles of chemotherapy and received more than 75% of nimotuzumab.
Measurable CNS Measurable and
Results: Of 40 pts enrolled between June 2009 and May 2010, 39 eligible pts
disease at baseline non-measurable CNS
received the study treatment. The pts characteristics were as follows: 62 years
(n=50) disease at baseline
(median); male/female, 34/5; stage IIIA/B, 21/18; PS0/1, 25/14. Thirty-four pts
(n=136)
met the criteria for treatment tolerability, and 38 pts completed 60 Gy of
RT within 8 weeks. Infusion reaction, >grade 3 skin rash, >grade 3 radiation CNS ORR, n (%) [95% CI] 32 (64.0) [49.2–77.1] 60* (44.1) [35.6–52.9]
pneumonitis, or >grade 4 nonhematological toxicity were not observed. The Complete response (CR), n (%) 11 (22.0) 39* (28.7)
3-year and 5-year overall survival rates for the 39 pts were 66.4% and 58.4%, 45 (90.0) [78.2–
respectively. The median PFS was 16.9 months, and the 5-year PFS rate for CNS DCR, n (%) [95% CI] 117 (86.0) [79.1–91.4]
96.7]
pts with squamous cell carcinoma (Sq; n = 16) was 50%, while that for pts
Median CNS DoR, months
with non-squamous cell carcinoma (non-Sq; n = 23) was 13.7%. In terms of the 11.1 [7.6–NE] 18 13.8 [11.0–21.5] 32
[95% CI] Patients with event,
first relapse site, in-field relapse rates were low for both Sq (4/16; 25%) and (56.3) (53.3)
n (%)
non-Sq (4/23; 17%). However, the distant relapse rate was significantly higher
for non-Sq (15/23; 65%) than that for Sq (4/16; 25%). Cytologic or histologic * N.B. Non-measurable disease
specimens were examined for the expression of EGFR protein/mutations response can only be classified
using the EGFR IHC/FISH methods in 20 pts. EGFR 2+/3+ expression was as CR, non-CR/non-progressive
shown more frequently in sq (8/10) than non-sq (4/10). EGFR mutation was disease (PD) or PD
observed in only 2 pts with non-sq. Conclusion: Addition of nimotuzumab to Conclusion: This updated pooled analysis with mature data confirms that
the concurrent CRT in this setting was well tolerated with clinical benefit to alectinib can provide long-term control of CNS metastases in ALK+ NSCLC,
the patients. The low in field relapse rates may be attributed to the radio- with a high CR rate.
sensitizing effect of nimotuzumab.
Keywords: Chemoradiotherapy, locally advanced non-small cell lung cancer,

nimotuzumab, molecular targeting drug
MA07: ALK-ROS1 IN ADVANCED NSCLC
MINI ORAL ABSTRACT SESSIONS -

MA07.02 UPDATED EFFICACY AND SAFETY DATA FROM THE PHASE
TUESDAY, DECEMBER 6, 2016
2 NP28761 STUDY OF ALECTINIB IN ALK-POSITIVE NON-SMALL-
CELL LUNG CANCER
SESSION MA07: ALK-ROS1 IN ADVANCED NSCLC D. Ross Camidge1, Shirish Gadgeel2, Sai-Hong Ou3, Leena Gandhi4, Gregory
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 Riely5, Jeremy Cetnar6, Howard West7, Mark Socinski8, Alberto Chiappori9,
Tarek Mekhail10, Bo Chao11, Hossein Borghaei12, Kathryn Gold13, Walter
Bordogna14, Bogdana Balas14, Johannes Noe14, Sophie Golding14, Ali Zeaiter 14,
MA07.01 UPDATED POOLED ANALYSIS OF CNS ENDPOINTS IN TWO Alice Shaw15
1
PHASE II STUDIES OF ALECTINIB IN ALK+ NSCLC University of Colorado, Aurora/CO/United States of America, 2Karmanos Cancer
1 2 3 4
Institute/wayne State University, Detroit/MI/United States of America, 3University
Sai-Hong Ignatius Ou , Leena Gandhi , Alice Shaw , Ramaswamy Govindan , of California Irvine School of Medicine, Orange/CA/United States of America,
Mark Socinski5, D. Ross Camidge6, Luigi De Petris7, Dong-Wan Kim8, Alberto 4
Dana-Farber Cancer Institute, Boston/MA/United States of America, 5Memorial
Chiappori9, Denis Moro-Sibilot10, Michaël Duruisseaux10, Lucio Crinò11, Sloan Kettering Cancer Center, New York/NY/United States of America, 6Oregon
Tommaso De Pas12, Eric Dansin13, Antje Tessmer 14, James Chih-Hsin Yang15, Health and Sciences University, Portland/OR/United States of America, 7Swedish
Cancer Institute, Seattle/WA/United States of America, 8University of Pittsburgh the comparison between 2 ALK inhibitors will be valuable in determining
Medical Center, Pittsburgh/PA/United States of America, 9Moffitt Cancer Center, therapeutic strategy for ALK+ NSCLC patients (pts). We conducted the
Tampa/FL/United States of America, 10 Florida Hospital Cancer Institute, Orlando/ randomized open-label Phase III trial designed to prove the superior PFS of
FL/United States of America, 11Ohio State University, Columbus/OH/United States ALC to CRZ in ALK-inhibitor naïve ALK+ NSCLC. Methods: ALK+ NSCLC pts were
of America, 12Fox Chase Cancer Center, Philadelphia/PA/United States of America, randomized 1:1 either to receive ALC (300 mg b.i.d.) or CRZ (250 mg b.i.d.) and
13
Thoracic Medical Oncology, MD Anderson Cancer Center, Houston/TX/United
stratified by ECOG PS (0/1 vs 2), treatment line (1st vs 2nd), and clinical stage
States of America, 14F. Hoffmann-La Roche, Basel/Switzerland, 15Massachusetts
General Hospital, Boston/MA/United States of America (IIIB/IV vs recurrence). Primary endpoint was PFS according to the blinded
independent review board. Secondary endpoints included overall survival,
Background: Alectinib, a CNS-active and highly selective ALK inhibitor, has objective response rate, and safety. Under an assumption of expected hazard
efficacy in patients with ALK-positive NSCLC with and without previous ratio (HR) of 0.643, 164 events were required to have 80% power with 2-sided
crizotinib treatment. Updated efficacy and safety from the alectinib phase alpha of 0.05. Three interim analyses (IA) for early stopping due to efficacy
2 North American NP28761 study (NCT01871805) of patients with ALK- were planned after 33%, 50%, and 75% of required PFS events occurred.
positive NSCLC previously treated with crizotinib, with 15 months’ additional Results: 207 pts were enrolled at 41 centers in Japan between November 2013
follow-up from the primary analysis and 9 months’ additional follow-up from and August 2015. Independent data monitoring committee recommended the
the previous analysis are presented. Methods: Patients ≥18 years old with release of study data because the superiority in PFS had been demonstrated
ALK-positive NSCLC (FDA-approved FISH test), disease progression following for ALC based on second IA. The PFS HR of ALC arm to CRZ arm was 0.34
crizotinib, and ECOG PS ≤2 were enrolled. Patients received oral alectinib (99.6826% CI: 0.17-0.70, stratified log-rank p<0.0001). Median PFS was not
(600mg) twice daily until progression, death or withdrawal. Primary endpoint: reached (95% CI: 20.3-Not Reached (NR)) in ALC arm while it was 10.2 months
overall response rate (ORR) by independent review committee (IRC; RECIST (95%CI: 8.2-12.0) in CRZ arm. ALC demonstrated favorable result of PFS in
v1.1.) Secondary endpoints: investigator-assessed ORR; progression-free each sub-group for instance, treatment line (1st line: HR = 0.30, ALC: NR vs CRZ:
survival (PFS); overall survival (OS), CNS ORR (CORR); disease control rate 10.2 months, 2nd line: HR = 0.39, ALC: 20.3 months vs CRZ: 8.2 months), brain
(DCR); safety. Results: At the updated cut-off (22 January 2016) an additional metastases at baseline (yes: HR = 0.08, ALC: NR vs CRZ: 10.2 months, no: HR
15 months’ follow-up from the primary analysis, 87 patients were enrolled. = 0.39, ALC: 20.3 moths vs CRZ: 10.0 months) and clinical stage (stage IIIb/IV:
Median follow-up: 17.0 months (range 1.1–28.6). ORR in the response evaluable HR = 0.31 ALC: 20.3 months vs CRZ: 8.3 months, recurrence: HR = 0.49, ALC: NR
population (REP; n=67) by IRC: 52.2% (95% CI 39.7–64.6), median duration of vs CRZ: 11.6 months). Grade 3-4 AEs (ALC: 26% vs CRZ: 52%), discontinuation
response: 14.9 months. Median PFS and OS: 8.0 and 22.7 months, respectively. of study drug due to AEs (ALC: 9% vs CRZ: 20%) and dose interruptions
Table 1 presents other efficacy endpoints. Grade ≥3 AEs were reported in due to AEs (ALC: 29% vs CRZ: 74%) occurred with lower rate in the ALC arm.
41% of the safety population (n=87); most common: elevated levels of blood There were no treatment-related deaths in either arm. Conclusion: ALC
creatine phosphokinase (8%), alanine aminotransferase (6%), aspartate demonstrated prolonged PFS compared with CRZ in all sub-groups with a
aminotransferase (5%). Two patients withdrew due to AEs; 28% had AEs favorable AE profile representing a potential new standard treatment for 1st
leading to dose modification/interruption. Mean dose intensity was 92.0%. line ALK+ NSCLC pts.
Keywords: ALK Inhibitor, ALK+ NSCLC

IRC REP Responders, n CR, n (%) PR, n (%) n=67* 35 0 (0) 35 (52.2) 18
SD, n (%) PD, n (%) Missing/NE, n (%) DCR, (26.9) 11 (16.4) 3 (4.5) 79.1
% (95% CI) (67.4,88.1)
Investigator REP Responders, n ORR, % n=87 46† 52.9 (41.9, 63.7) MA07: ALK-ROS1 IN ADVANCED NSCLC
(95% CI) TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
Measurable baseline CNS lesions (IRC) n=16 12‡ 75.0 (47.6, 92.7) n=52
II Responders, n CORR, % (95% CI) 21§ 40.4 (27.0, 54.9) MA07.05 EUCROSS: A EUROPEAN PHASE II TRIAL OF CRIZOTINIB IN
Measurable/non-measurable baseline CNS
ADVANCED ADENOCARCINOMA OF THE LUNG HARBORING ROS1
lesions (IRC) Responders CORR,II % (95% CI)
REARRANGEMENTS - PRELIMINARY RESULTS
*n=20 did not have measurable disease per IRC and were not included in the IRC Sebastian Michels 1, Masyar Gardizi1, Petra Schmalz2, Meike Thurat1, Eva
REP; †2 CR; ‡ 4 CR; §13 CR; IInon-measurable disease classified as CR, non-CR/non- Pereira3, Martin Sebastian4, Enric Carcereny5, Jesus Corral6, Luis Paz-Ares7,
PD or PD; NE=not evaluable/estimable Conclusion: Alectinib demonstrated Enriqueta Felip8, Christian Grohé9, Delvys Rodriguez Abreu10, Amelia Insa
durable responses, encouraging OS findings, good tolerability and an Molla11, Helge Bischoff 12, Martin Reck13, Niki Karachaliou14, Andreas Scheel15,
acceptable safety profile consistent with previous reports in this update of Vanessa Brandes1, Fischer Rieke1, Lucia Nogova1, Matthias Scheffler 1, Jeremy
the NP28761 study with extended follow-up. Franklin16, Martin Hellmich16, Bartomeu Massuti17, Reinhard Buettner 15,
Rafael Rosell18, Jürgen Wolf 1
Keywords: Alectinib, NSCLC, US, ALK-inhibitor 1
Lung Cancer Group Cologne, University Hospital of Cologne, Cologne/Germany,
2
Clinical Trial Center Cologne, Cologne/Germany, 3Spanish Lung Cancer Group,
Barcelona/Spain, 4Universitätsklinik Frankfurt Am Main, Frankfurt/Germany,
5
Medical Oncology, Catalan Institute of Oncology-Hospital Germans Trias I Pujol,
MA07: ALK-ROS1 IN ADVANCED NSCLC Badalona/Spain, 6Hospital Universitario Virgen Del Rocío, Sevilla/Spain, 7Hospital
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 Universitario Virgen Del Rocio, Sevilla/Spain, 8Vall D’Hebron University Hospital,
Barcelona/Spain, 9Evangelische Lungenklinik, Berlin/Germany, 10University
Hospital Materno-Infantil de Canarias, Las Palmas de Gran Canaria/Spain, 11Medical
MA07.03 ALECTINIB (ALC) VERSUS CRIZOTINIB (CRZ) IN ALK- Oncology, University Hospital Clínic de Valencia, Valencia/Spain, 12Thoraxklinik
POSITIVE NON-SMALL CELL LUNG CANCER (ALK+ NSCLC): PRIMARY Heidelberg, Heidelberg/Germany, 13Lungclinic Grosshansdorf, Grosshansdorf/
RESULTS FROM PHASE III STUDY (J-ALEX) Germany, 14Hospital Sagrat Cor and Germans Trias I Pujol Health Sciences Institute
and Hospital, Barcelona/Spain, 15Institute of Pathology, University Hospital of
Young Kim1, Toyoaki Hida2, Hiroshi Nokihara3, Masashi Kondo4, Koichi Cologne, Cologne/Germany, 16Institute of Medical Statistics, Informatics and
Azuma5, Takashi Seto6, Yuichi Takiguchi7, Makoto Nishio8, Hiroshige Epidemiology, University Hospital of Cologne, Cologne/Germany, 17Medical
Yoshioka9, Fumio Imamura10, Katsuyuki Hotta11, Satoshi Watanabe12, Koichi Oncology, Alicante University Hospital, Alicante/Spain, 18Hospital Germans Trias I
Goto13, Kazuhiko Nakagawa14, Tetsuya Mitsudomi15, Nobuyuki Yamamoto16, Pujol, Catalan Institute of Oncology, Barcelona/Spain
Hiroshi Kuriki17, Ryoichi Asabe17, Tomohiro Tanaka18, Tomohide Tamura19
1
Kyoto University, Kyoto/Japan, 2 Aichi Cancer Center Hospital, Nagoya/Japan, Background: ROS1 rearrangements are present in the tumors of 1-2%
3
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo/ of patients with lung adenocarcinoma (LAD). This patient subgroup is
Japan, 4Respiratory Medicine, Nagoya University, Nagoya/Japan, 5Department characterized by non-smoking history and younger than average age
of Internal Medicine, Division of Respirology, Neurology, and Rheumatology, compared to the overall NSCLC population. In a phase I trial the ALK/ROS1/
Kurume University School of Medicine, Kurume/Japan, 6National Kyushu Cancer MET inhibitor crizotinib has shown to be highly effective in these patients
Center, Fukuoka/Japan, 7Department of Medical Oncology, Graduate School of (NCT00585195). EUCROSS is a prospective phase II trial of the Lung Cancer
Medicine, Chiba University, Chiba/Japan, 8The Cancer Institute Hospital of Japanese Group Cologne in collaboration with the Spanish Lung Cancer Group to
Foundation for Cancer Research, Tokyo/Japan, 9Kurashiki Central Hospital,
evaluate crizotinib in ROS1-positive LAD. Here, we present preliminary data
Kurashiki/Japan, 10 Osaka Medical Center for Cancer and Cardiovascular Disease,
Osaka/Japan, 11Okayama University Hospital, Okayama/Japan, 12Osaka Medical on efficacy and safety. Methods: Patients with advanced LAD harboring
Center for Cancer and Cardiovascular Disease, Niigata/Japan, 13Department of ROS1 rearrangements as confirmed by central FISH were eligible for the
Thoracic Oncology, National Cancer Center Hospital East, Chiba/Japan, 14Kindai trial irrespectively of the number of prior treatment lines. Patients received
University Faculty of Medicine, Osaka-Sayama/Japan, 15Division of Thoracic treatment with crizotinib 250 mg BID - doses were adapted for management
Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka- of AEs. Trial design: Fleming’s single stage phase II design. Primary endpoint:
Sayama/Japan, 16Internal Medicine, Wakayama Medical University, Wakayama/ ORR (95% CI, H0: ORR≤20% vs. H1: ORR>20%). Secondary endpoints: a.o.
Japan, 17Chugai Pharmaceutical Co., Ltd, Tokyo/Japan, 18 Clinical Science & Strategy PFS, OS and safety. All efficacy endpoints were assessed by investigator’s
Dept., Chugai Pharmaceutical Co., Ltd, Tokyo/Japan, 19St Luke’S International
RECIST v1.1 and will be analyzed by IRB at a later stage. Baseline tumor tissue
Hospital, Tokyo/Japan
was analyzed by DNA-sequencing to identify the translocation Partners
Background: ALK inhibitors are the standard treatment for ALK+ NSCLC and of ROS1, to validate FISH results and to identify additional biomarkers
for prediction of response. Data-cut off for this report was March 2016.

Results: In total, 34 patients were enrolled in EUCROSS at the time of data Byoung Chul Cho 1, Sun Min Lim2, Hye Ryun Kim3, Jong-Seok Lee4, Ki-Hyeong
cut-off. Twenty-nine patients were eligible for efficacy assessment. Tumor Lee5, Yun-Gyoo Lee6, Young Joo Min7, Eun Kyung Cho8, Seung-Sook Lee9, Hyo
tissue of 20 of these patients was suitable for further sequencing - 18 were Sup Shim10, Jin-Haeng Chung11, Yoon-La Choi12, Myung-Ju Ahn13
sequenced positive for ROS1 fusion. The fusion partners involved were CD74 1
Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College
(N=9;50%), EZR (N=4;22%), SCL34A2 (N=3;17%), TPM3 and SDC4(N=1;6% of Medicine, Seoul/Korea, Republic of, 2Department of Internal Medicine,
each). The investigator assessed ORR was 69% (95% CI, 49.1-84.3) in the Yonsei Cancer Center, Seoul/Korea, Republic of, 3Yonsei Cancer Center, Seoul/
overall trial population and 83% (95% CI, 67.7-94.2) in the ROS1-positive by Korea, Republic of, 4Seoul National University Bundang Hospital, Seongnam/
sequencing population (N=18;P=0.324 for difference of ORR). Three patients Korea, Republic of, 5Chungbuk National University, Cheongju/Korea, Republic of,
6
(10.3%;95% CI, 3.6-26.4) exhibited primary progression, two of them were Kangbuk Samsung Hospital, Seongnam/Korea, Republic of, 7Ulsan University
Hospital, University of Ulsan College of Medicine, Ulsan/Korea, Republic of,
sequenced ROS1-negative. All patients were included in the safety population 8
Division of Hematology and Oncology, Department of Internal Medicine, Gachon
(N=34). Most common AEs irrespectively of relatedness or grade were visual University Gil Medical Center, Incheon/Korea, Republic of, 9INJE University
disorders (N=16;48%), edema (N=14;41%), diarrhea (N=13;38%) and bradycardia Haeundae Paik Hospital, Busan/Korea, Republic of, 10 Department of Pathology,
(N=11;32%). Conclusion: Crizotinib is a highly effective and safe treatment Severance Hospital, Yonsei University College of Medicine, Seoul/Korea, Republic
in the subset of ROS1 rearranged NSCLC patients as determined by FISH and of, 11Pathology, Seoul National University Bundang Hospital, Seoul/Korea, Republic
DNA-sequencing. Although, the number of patients with tissue available for of, 12Department of Pathology and Translational Genomics, Sungkyunkwan
sequencing was low at the time of data cut-off, sensitivity and specificity University School of Medicine, Seoul/Korea, Republic of, 13Meidicine, Samsung
support sequencing as the potential new gold-standard for the identification Medical Center Sungkyunkwan University School of Medicine, Seoul/Korea,
Republic of
of clinically relevant ROS1 gene-rearrangements.
Background: ROS1 rearrangement is a distinct molecular subset of non-
Keywords: NSCLC, crizotinib, ros1
small-cell lung cancer (NSCLC). We investigated the efficacy and safety of
ceritinib in patients with ROS1-rearranged NSCLC. Methods: We enrolled 32
patients with advanced NSCLC who tested positive for ROS1 rearrangement
by fluorescent in situ hybridization (FISH). ROS1 immunohistochemistry
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 (IHC) and next-generation sequencing (NGS) was performed in available
tumor samples. Ceritinib 750mg was administered once daily and the primary
endpoint was objective response rate (ORR) by central independent radiologic
MA07.06 CRIZOTINIB IN ROS1 REARRANGED OR MET review. The secondary endpoints included disease control rate (DCR), duration
DEREGULATED NON-SMALL-CELL LUNG CANCER (NSCLC): of response, progression-free survival (PFS), overall survival (OS), toxicity and
PRELIMINARY RESULTS OF THE METROS TRIAL concordance between FISH and IHC. ROS1 fusion partners were identified
Lorenza Landi1, Antonio Chella2, Rita Chiari3, Marcello Tiseo4, Roberta Buosi5, with the use of next-generation sequencing (NGS) in available tumor samples.
Claudio Dazzi6, Cesare Gridelli7, Fausto Barbieri8, Angelo Delmonte9, Greta Results: Between June 7, 2013, and February 1, 2016, a total of 404 patients
Alì10, Gabriella Fontanini10, Lucio Crinò3, Frederico Cappuzzo6 underwent ROS1 prescreening, and 32 ROS1+ (by FISH) patients were enrolled.
1
Oncology, Istituto Toscano Tumori, Livorno/Italy, 2Pneumologia Universitaria,
All patients except two (who did not respond to ceritinib) were crizotinib
Dipartimento Cardiotoracico E Vascolare, Ospedale Cisanello, Pisa/Italy, 3Medical naïve. The median age of all patients was 62 years, and there were 24 females
Oncology, Santa Maria Della Misericordia Hospital, Perugia/Italy, 4 Medical (75%). The majority of patients (84%) were never smokers, and all had
Oncology, University Hospital of Parma, Parma/Italy, 5 A.O.U. “maggiore Della adenocarcinoma histology. The median number of previous treatments before
Carità”, Novara/Italy, 6 Ausl Romagna, Ravenna/Italy, 7Azienda Ospedaliera “s.G. study enrollment was 3 (range, 2-7) and 17 (53%) patients had received three
Moscati”, Avellino/Italy, 8University Hospital Policlinico of Modena, Oncology Unit, or more lines of chemotherapy. At the time of the data cut-off (April 18, 2016),
Modena/Italy, 9Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori the median follow-up was 7.5 months, and 15 (47%) patients had discontinued
(IRST) - IRCCS, Meldola/Italy, 10 Dipartimento Di Patologia Molecolare E Di Area
treatment. Of the 32 patients enrolled, 28 patients were evaluable for
Critica/programma Di Patologia Pleuro Polmonare, Università Di Pisa, Pisa/Italy
response by independent radiologic review. ORR was 63% (95% CI, 45.7-79.3),
Background: Crizotinib is an orally active inhibitor of receptor tyrosine with 1 complete response and 19 partial responses. The median duration of
kinases effective in NSCLC with ALK rearrangement. Recent data showed that response was 10.0 months (range, 0.4+-18.4+). Among 11 tumors that were
this agent is dramatically effective in patients with ROS1 rearrangement and tested by NGS, we identified 7 ROS1 fusion partners including ROS1-CD74,
at least in some patients with MET deregulation, particularly individuals with ROS1-SLC34A2, and ROS1-EZR. The median progression-free survival was 19.3
exon 14 skipping mutations or with high levels of MET amplification. Methods: months (95% CI, 7.2-not reached), with 17 (53%) patients still in follow-up for
The METROS trial is a multicenter prospective phase II study designed to progression. The median overall survival was not reached at the time of the
assess the efficacy and safety and tolerability of Crizotinib in pretreated data cut-off. Of 5 patients with retrospectively confirmed brain metastases,
metastatic NSCLC with MET amplification or MET exon 14 mutation or ROS1 intracranial disease control was reported in 4 patients (80%). Gastrointestinal
rearrangement. The co-primary end-point was response rate to crizotinib in adverse events (vomiting, nausea, diarrhea) mostly grade 1-2, were the most
two cohorts of patients: cohort A) ROS1+: patients with ROS1 rearrangement; frequent adverse events (80%); these events were manageable. Conclusion:
B) MET+: patients with MET amplification defined as ratio MET/CEP7 >2.2 Ceritinib demonstrated potent clinical activity in patients with advanced,
on FISH testing or MET exon 14 skipping mutations. Eligible patients were ROS1-rearranged NSCLC, who received at least one prior line of platinum-
treated with with crizotinib at the standard dose of 250 mg BID p.o. Results: based chemotherapy. ROS1 rearrangement defines a second molecular
At the time of the present analysis, preliminary data on the MET cohort are subgroup of NSCLC for which ceritinib is highly active (ClinicalTrials.gov
available. A total of 249 patients were screened and 18 resulted as MET+ number, NCT01964157).
(12 amplified and 6 mutated). Among them, 10 patients (9 amplified and 1
Keywords: Non-small-cell lung cancer, Ceritinib, ros1
mutated) were included onto the study and received at least one dose of
crizotinib, 6 patients were not eligibible beacause of not progressing to front
line therapy, whereas 2 patients did not received crizotinib due to rapidly
progressive disease. Characteristics of enrolled patients were: median age
68 years (range 39-77); male/female 8/2; ECOG PS 0/1/2: 6/3/1. In 8 cases TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
crizotinib was offered as second-line therapy. All but one patients were
current or past smokers. According to RECIST criteria, 2 partial responses
and 4 stable disease were so far documented, with an overall disease control MA07.09 MASS SPECTROMETRY PROFILING AND IMAGING
rate of 60%. Three patients are still on treatment. Therapy was generally PLATFORM FOR NOVEL PRECISION DRUG RESISTANCE
well tolerated, with only 1 patient delaying therapy due to adverse events. BIOMARKERS DISCOVERY IN EML4-ALK LUNG ADENOCARCINOMA
Enrollment is still ongoing. Conclusion: Preliminary analysis of the METROS Patrick Ma1, Pamela Cantrell2, Callee Walsh2, Sijin Wen1, Satoshi Komo1,
trial supports the potential efficacy of crizotinib in patients with MET Xiaoliang Wu1, Haixia Yang1, Erin Seeley2
deregulation, with a favorable toxicity profile. Updated results including 1
West Virginia University, Wvu Cancer Institute, Morgantown/WV/United States of
median progression-free survival and survival were will be presented at the America, 2Protea Biosciences, Inc., Morgantown/WV/United States of America
meeting.
Background: Drug resistance emergence is a daunting obstacle that limits
Keywords: MET, crizotinib, NSCLC, METROS long-term outcome benefits in precision cancer therapy. Mechanism of the
initial emergence of molecular tumor resistance is still not fully understood.
Recently, we identified an early precision drug escape mechanism with
adaptive tumor cellular reprogramming emerging within days after drug
MA07: ALK-ROS1 IN ADVANCED NSCLC initiation. Here we present a mass spectrometry imaging (MSI) approach to
profile the biomolecular changes emerging within residual drug resistant
tumor cells under precision ALK inhibitor (ALK-i) treatment. Methods:
MA07.07 CERITINIB IN ROS1-REARRANGED NON-SMALL-CELL LUNG EML4-ALK fusion (ALK+) H3122 lung adenocarcinoma xenograft as well as
CANCER: AN UPDATE OF KOREAN NATIONWIDE PHASE II STUDY an ALK+ patient biopsy-derived cell line (Ma-ALK001.S) were adopted for
the MSI studies. MSI was carried out on FFPE tissues to compare peptide
profiles between control tumors and 7- and 14-day ALK-i treated tumors using primary and metastasis lesions after crizotinib treatment, indicating that
a histology guided mass spectrometry approach. Additionally, frozen control EMT is associated with crizotinib resistance in clinical therapy. Conclusion:
and ALK-i treated tumors were subjected to full section MSI to determine Our findings suggest that EMT is possibly occurred in acquired resistance to
the ALK-i drug distribution as well as the changing landscape of lipids and crizotinib and intermittent use of HDAC inhibitor could be a novel therapeutic
metabolites. In parallel, Ma-ALK001.S cell line was treated with alectinib strategy for overcoming EMT-associated crizotinib-resistance in EML4-ALK
(ALK-i) in culture with samples collected at 0 hr, 8 hr, 3 days, 7 days, and 14 lung cancer.
days. Cells were subjected to both MALDI-MS profiling analysis and Laser
Ablation Electrospray Ionization (LAESI)-MS analysis. Statistical analyses Keywords: miR-200, EML4-ALK, EMT, HDAC inhibitor
were performed using MarkerLynx and SCiLS. Results: ALK+ H3122 lung
adenocarcinoma murine xenograft model in vivo under treatment with/
without ALK-i TAE684 was used in MSI studies at treatment day 0, day 7 and
day 14, during tumor response. Pairwise and 3-way Wilcoxon rank sum tests MA07: ALK-ROS1 IN ADVANCED NSCLC
were carried out and a Bonferroni correction applied. The greatest number
of significant peaks were observed between day 0 and day 14 (677). Pairwise
linear discriminant analysis classification algorithm models were generated MA07.11 SAFETY AND EFFICACY OF LORLATINIB (PF-06463922)
resulting in over 94% classification accuracy in all comparison. Direct MS/ IN PATIENTS WITH ADVANCED ALK+ OR ROS1+ NON-SMALL-CELL
MS fragmentation revealed that ALK-i was detected within the frozen ALK-i LUNG CANCER (NSCLC)
dosed tumors in early drug-escape. Several lipids were identified to expression
E Felip 1, T Bauer2, Benjamin Solomon3, B Besse4, L James5, J Clancy6, K
landscape changes emerging under ALK-i. Biomolecular (peptides, lipids, and
Klamerus7, J-F Martini7, A Abbattista8, A Shaw9
metabolites) profiling of Ma-ALK001.S cell line using combined MALDI and 1
LAESI MSI analysis was successful, which provided novel insights into the Vall D’Hebron Institute of Oncology, Barcelona/Spain, 2 Arah Cannon Cancer
Research Institute/ Tennessee Oncology, PLCC, Nashville/TN/United States of
early mechanisms of molecular drug resistance emergence. Conclusion: MSI
America, 3Peter MacCallum Cancer Center, Melbourne/VIC/Australia, 4 Gustave
allowed for direct in situ determination of the evolving expression landscape Roussy, Villejuif/France, 5Pfizer Oncology, New York/NY/United States of America,
of biomolecules in ALK+ lung cancer under ALK-i precision therapy. These 6
Inventiv Clinical, Princeton/NJ/United States of America, 7Pfizer Oncology, La
results provide a rationale to advance our MSI profiling studies for biomarkers Jolla/CA/United States of America, 8Pfizer Oncology, Milan/Italy, 9Massachusetts
discovery to gain deeper insights into molecular mechanisms of adaptive General Hospital, Boston/MA/United States of America
precision drug resistance emergence.
Background: Patients with anaplastic lymphoma kinase (ALK) and c-ros
Keywords: drug resistance, mass spectrometry, ALK rearranged lung cancer, oncogene 1 (ROS1) NSCLC often become resistant to tyrosine kinase
Precision therapy inhibitor (TKI) therapy; central nervous system (CNS) relapse is common.
Lorlatinib is a selective brain-penetrant ALK/ROS1 TKI, active against most
known resistance mutations. Methods: In Ph I of the ongoing Ph I/II study
NCT01970865, patients had ALK+ or ROS1+ NSCLC ± brain metastases and
MA07: ALK-ROS1 IN ADVANCED NSCLC were treatment naïve or had disease progression after ≥1 TKIs. Patients
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 received lorlatinib on day –7 and then once or twice daily from day 1. Primary
objective was identification of MTD and recommended Ph II dose (RP2D).
MA07.10 HDAC INHIBITION OVERCOMES CRIZOTINIB-RESISTANCE Other objectives were safety and efficacy by RECIST v1.1 including intracranial
activity. Results: Of 54 patients treated in Ph I (cutoff Jan 15, 2016), 41 were
BY MESENCHYMAL-EPITHELIAL TRANSITION (MET) IN EML4-ALK
ALK+, 12 ROS1+, and 1 had mutation status unconfirmed for ALK+ or ROS1+.
LUNG CANCER CELLS
Patients were heavily pretreated: 27 had received ≥2 prior TKIs and 20 had 1
Koji Fukuda1, Shinji Takeuchi1, Ryohei Katayama2, Shigeki Nanjo1, Tadaaki prior TKI; 39 patients had CNS metastases at baseline. Patients were treated
Yamada1, Takeshi Suzuki3, Kengo Takeuchi4, Makoto Nishio5, Seiji Yano1 across 10 dose levels (total daily dose of 10–200 mg). Response rates were:
1
Cancer Research Institute, Division of Medical Oncology, Kanazawa University,
Kanazawa/Japan, 2Cancer Chemotherapy Center, Japanee Foundation for Cancer
Overall RR
Research, Tokyo/Japan, 3Cancer Research Institute, Division of Functional N CR PR uCR uPR
(CR + PR)
Genomics, Kanazawa University, Kanazawa/Japan, 4Pathology Project for
Molecular Targets, the Cancer Institute, Japanee Foundation for Cancer Research, n (%)
Tokyo/Japan, 5Thoracic Medical Oncology, The Cancer Institute Hospital of Jfcr,
Tokyo/Japan ORR in ALK+ and
53 3(6) 22(42) - 1(2) 25(47)
ROS1+
Background: ALK rearrangement, most commonly EML4-ALK, is detected
in approximately 3–7% of non-small cell lung cancer (NSCLC). Crizotinib, an ORR in ALK+ with 1
14 1(7) 7(50) - - 8(57)
ALK tyrosine kinase inhibitor (TKI), shows dramatic clinical efficacy in ALK- prior TKI
rearranged NSCLC patients. However, almost all patients acquire resistance
ORR in ALK+ with
after only 1 to 2 years. A variety of mechanisms, including ALK-secondary 26 2(8) 9(34) - 1(4) 11(42)
≥2 prior TKI
mutations, ALK amplification, and activation of alternative pathway, have
been reported to mediate acquired resistance to crizotinib. While epithelial– IC ORR (target
mesenchymal transition (EMT) was recently reported to be associated with + non-target
39 10(26) 4(10) 1(3) 2(5) 14(36)
resistance to crizotinib in EML4-ALK lung cancer cells in vitro, the underlying lesions) in ALK+
mechanism has not been defined and no optimal therapy to overcome EMT- and ROS+
associated resistance has been identified. Methods: We continuously gave
IC ORR (target
crizotinib treatment to SCID mice inoculated with EML4-ALK lung cancer cell
lesions) in ALK+ 23 7(30 4(17) - 2(9) 11(47)
line A925L into thoracic cavity and established crizotinib resistant A925LCR
and ROS+
cells. After the limiting dilution of A925LCR cells, we obtained several single
cell clones. The effects of the HDAC inhibitor quisinostat on the EMT state ORR, objective response rate; IC ORR, intracranial objective response
and the growth of the cells were examined in vitro and in vivo. Results: rate; CR, complete response; PR, partial response; RR, response rate; u,
We found that some clones acquired EMT phenotypes, such as spindle unconfirmed
shape morphology, expression of EMT-related proteins, and increased cell
motility. Interestingly, Histone deacetylase (HDAC) inhibitor, quisinostat, Median duration of response was 10.5 months (95% CI 2.9– not reached [NR])
induced mesenchymal-epithelial transition (MET) of A925LCR clones in and 12.4 months (95% CI 6.5–NR) for ALK+ and ALK+/ROS1+ pts, respectively.
vitro. Quisinostat reduced ZEB1 expression, induced MET, and thus restored 26 patients remain on treatment. The most common treatment-related
sensitivity to crizotinib. Knockdown of ZEB1 expression in the A925LCR clones adverse events (TRAEs) were hypercholesterolemia (69%) and peripheral
by si-RNA also induced MET and restored sensitivity to crizotinib, suggesting edema (37%). Hypercholesterolemia was the most common (11%) grade ≥3
that quisinostat-induced MET depends on ZEB-1 suppression. MicroRNA TRAE. No patient discontinued due to a TRAE. Analyses of ALK resistance
profile analysis revealed that the A925LCR clones expressed significantly mutations in archival tumor tissue and plasma circulating free DNA collected
lower levels of miR-200 family including miR-200c which targets ZEB1, before lorlatinib treatment are ongoing. Conclusion: Lorlatinib was well
compared with parental A925L cells. Furthermore, quisinostat recovered miR- tolerated and demonstrated durable responses, including intracranial
200c expression and antago-miR-200c abrogated quisinostat-induced MET responses, in ALK+ and ROS1+ NSCLC, most of whom had CNS metastases and
in the A925LCR clone cells. These results indicate that quisinostat induced ≥1 prior TKIs. The RP2D was identified as 100 mg once daily. Ph II is ongoing.
MET by up-regulating miR-200c expression which target ZEB1 and thereby
Keywords: ALK, ros1, non-small cell lung cancer, lorlatinib
re-sensitizing to crizotinib. In a pleural carcinomatosis model with A925LCR
clone cells, quisinostat induced MET and caused remarkable tumor regression
during the subsequent crizotinib re-challenge. Furthermore, we analyzed
tumor tissue obtained at autopsy from an ALK-rearranged NSCLC patient who
acquired resistance to crizotinib. We found that EMT was induced in both

SESSION MA08: TREATMENT MONITORING IN GERMAN REGISTRY IN STAGE IV NSCLC AIO-TRK-0315

ADVANCED NSCLC Frank Griesinger 1, Wilfried Eberhardt2, Norbert Marschner3, Martina Jänicke4,
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 Annette Hipper5, Aysun Karatas5, Martin Sebastian6, Michael Thomas7, Peter
Schirmacher8
1
Pius Hospital Oldenburg, Oldenburg/Germany, 2Department of Medical Oncology,
University Hospital Essen, West German Cancer Centre, University Duisburg-
MA08.01 A HIGHLY SENSITIVE NEXT-GENERATION SEQUENCING Essen, Essen/Germany, 3Praxis Für Interdisziplinäre Onkologie Und Hämatologie,
PLATFORM FOR DETECTION OF NSCLC EGFR T790M MUTATION IN Freiburg/Germany, 4Iomedico Freiburg, Freiburg/Germany, 5 Aio-Studien-GmbH,
URINE AND PLASMA Berlin/Germany, 6University Hospital Frankfurt, Frankfurt/Germany, 7Department
of Thoracic Oncology, Translational Lung Research Center Heidelberg (TLRC),
Heather Wakelee 1, Vlada Melnikova2, Chris Karlovich3, Shirish Gadgeel4,
Member of the German Center for Lung Research (DZL), Thoraxklinik at Heidelberg
Karen Reckamp5, Jonathan W. Goldman6, D. Ross Camidge7, Maurice Pérol8, University Hospital, Heidelberg/Germany, 8University of Heidelberg, Heidelberg/
Sai-Hong Ou9, Stephen Liu10, Helena Yu11, Mark Socinski12, Tarek Mekhail12, Germany
Benjamin Solomon13, Ronald Natale14, Gregory Otterson15, Vassiliki
Papadimitrakopoulou16, Jean-Charles Soria17, Corey Langer 18, Joel Neal1, Darrin Background: Treatment in non-small cell lung cancer is quickly evolving and
Despain3, Sergey Yurasov3, Jason Litten3, Mitch Raponi3, Mark Erlander 19, new agents make it to the routine practice at a rapid pace. Whether outcome
Lecia Sequist20 and PRO data generated in clinical trials with often narrow inclusion and
1
Thoracic Oncology, Stanford Cancer Institute, Stanford/CA/United States of exclusion criteria will hold up in the routine practice is of high interest,
America, 2Clinical Affairs, Trovagene, San Diego/United States of America, 3Clovis especially due to the increasing costs of new drugs. Therefore registry data
Oncology, Boulder/CO/United States of America, 4Thoracic Oncology, Barbara Ann are of ever increasing importance to patients, physicians and reimbursement
Karmanos Cancer Institute, Detroit/MI/United States of America, 5City of Hope institutions. Methods: Therefore, we have started a prospective, clinical
Comprehensive Cancer Center, Duarte/CA/United States of America, 6Medicine/ registry for patients with metastatic non-small cell lung cancer. The purpose
Hematology-Oncology, UCLA, Santa Monica/CA/United States of America, 7Medical
of CRISP is to set up a national clinical research platform to document
Oncology, Univ Colorado, Aurora/CO/United States of America, 8 Groupe Thoracique
Et Orl, Centre Léon Bérard, Lyon/France, 9University of California at Irvine, Orange/ representative data on molecular testing, sequences of systemic therapies
CA/United States of America, 10 Lombardi Cancer Center, Georgetown University and other treatment modalities, course of disease in patients with advanced
Hospital Cancer Center, Washington/DC/United States of America, 11Department or metastatic NSCLC in Germany not amenable to curative treatment. A
of Medicine, Memorial Sloan Kettering Cancer Center, New York/NY/United States particular focus is on molecular biomarker testing of patients before the start
of America, 12Florida Hospital Cancer Institute, Orlando/FL/United States of of first-line treatment. The data shall be used to assess the current state
America, 13Peter MacCallum Cancer Center, Melbourne/ACT/Australia, 14Samuel of care and to develop recommendations concerning topics that could be
Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles/ improved. PRO assessment will provide large-scale data on quality of life and
CA/United States of America, 15The Ohio State University Wexner Medical Center,
anxiety/depression for real-life patients in routine practice. In addition, two
Columbus/OH/United States of America, 16Thoracic/head and Neck Medical
Oncology, MD Anderson Cancer Center, Houston/TX/United States of America, questionnaires (concerning individual quality of life and patient-caregiver
17
Medical Oncology, Gustav Roussy Cancer Center, Villejuif/France, 18University of communication) will be validated in German patients with metastatic NSCLC.
Pennsylvania Abramson Cancer Center, Philadelphia/PA/United States of America, Furthermore CRISP will set up a decentral tissue annotation for future
19
Research and Development, Trovagene, San Diego/United States of America, collaborative, investigational scientific biomarker testing. Results: This study
20
Massachusetts General Hospital, Boston/MA/United States of America will be carried out in up to 150 representative cancer centers in all therapeutic
sectors in Germany. More than 8000 patients will be recruited and followed
Background: Non-invasive genotyping of NSCLC patients by circulating tumor up to a maximum of 3 years, respectively until death. The first patients have
(ct)DNA is a promising alternative to tissue biopsies. However, ctDNA EGFR been included as of December 2015. As of yet, 82 centers have been initiated,
analysis remains challenging in patients with intrathoracic disease, with a 211 patients have been recruited. Preliminary data will be presented at
reported 26-57% T790M mutation detection rate in plasma (Karlovich et al., the meeting in terms of molecular test rates, demographic data as well as
Clin Cancer Res 2016; Wakelee et al., ASCO 2016). We investigated whether a treatment stratification in the 1st line setting. Conclusion: The registry CRISP
mutation enrichment NGS could improve mutation detection in plasma and will be the first to present representative real life data, covering all treatment
urine from TIGER-X, a phase 1/2 study of rociletinib in patients with EGFR settings of patients with NSCLC in Germany. ClinicalTrials.gov Identifier:
mutation-positive advanced NSCLC. Methods: The therascreen (Qiagen) or NCT02622581 CRISP is supported by Grants from AstraZeneca GmbH,
cobas (Roche) EGFR test was used for EGFR T790M analysis in tumor biopsies. Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH
Urine and plasma were analyzed by trovera mutation enrichment NGS assay & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Novartis Pharma
(Trovagene). Results: Of 174 matched tissue, plasma and urine specimens, 145 GmbH, and Pfizer Pharma GmbH.
(83.3%) were T790M+ by central tissue testing, 142 (81.6%) were T790M+ by
plasma, and 139 (79.9%) were T790M+ by urine. Urine and plasma combined Keywords: NSCLC, molecular testing
identified 165 cases (94.8%) as T790M+. Of 25 cases positive by ctDNA but
negative/inadequate by tissue, 16 were double-positive in plasma and urine,
unlikely to be false positive (Figure 1). T790M detection rate was higher for
extrathoracic (n=119) vs intrathoracic (n=55) disease in plasma (87.4% vs MA08: TREATMENT MONITORING IN ADVANCED NSCLC
69.1%, p=0.006) but not urine (81.5% vs 76.4%, p=0.42). Combination of urine TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
and plasma identified T790M in 92.7% of intrathoracic and 95.8% of
extrathoracic cases (p=0.47). In T790M+ patients, objective response rate was
MA08.03 OSIMERTINIB VS PLATINUM-PEMETREXED FOR T790M-
similar whether T790M mutation was identified by tissue, plasma or urine:
MUTATION POSITIVE ADVANCED NSCLC (AURA3): PLASMA CTDNA
37.4%, 33.1% and 36.6%, respectively. 4 of 9 patients T790M+ by urine but
negative by tissue responded, and 2 of 8 patients T790M+ by plasma but ANALYSIS
negative by tissue responded. Conclusion: Mutation enrichment NGS testing Yi Long Wu1, Suzanne Jenkins2, Suresh Ramalingam3, Ji-Youn Han4, Angelo
by urine and plasma combined identified 94.8% of T790M+ cases. Delmonte5, Te-Chun Hsia6, Janessa Laskin7, Sang-We Kim8, Yong He9, Sabina
Combination of urine and plasma may be considered before tissue testing in Patel10, Rachel Hodge10, Marcelo Marotti10, Vassiliki Papadimitrakopoulou11,
EGFR TKI resistant NSCLC, including patients without extrathoracic Tony Mok12
1
metastases. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong
Academy of Medical Sciences, Guangzhou/China, 2 Astrazeneca, Alderley Park/
United Kingdom, 3Medical Oncology, Emory University, Winship Cancer Institute,
Atlanta/GA/United States of America, 4Lung Cancer Branch, National Cancer
Center, Goyang/Korea, Republic of, 5Medical Oncology2-Unit, Istituto Scientifico
Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) IRCCS, Meldola/Italy,
6
Department of Internal Medicine, China Medical University Hospital, Department
of Respiratory Therapy, China Medical University, Taichung/Taiwan, 7Medical
Oncology, BC Cancer Agency, Vancouver/BC/Canada, 8Department of Oncology,
Asan Medical Center, University of Ulsan College of Medicine, Seoul/Korea,
Republic of, 9Department of Respiratory Disease, Daping Hospital, Third Military
Medical University, Chongqing/China, 10 Astrazeneca, Cambridge/United Kingdom,
11
Keywords: liquid biopsy, NSCLC, EGFR T790M, urine Thoracic/head and Neck Medical Oncology, MD Anderson Cancer Center, Houston/
TX/United States of America, 12Key Laboratory of South China, Department of
Clinical Oncology, the Chinese University of Hong Kong, Sha Tin/Hong Kong Prc
Background: AURA3 (NCT02151981) is a Phase III, open-label, randomised

MA08: TREATMENT MONITORING IN ADVANCED NSCLC
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 study assessing the efficacy and safety of osimertinib, a T790M directed
EGFR-TKI, vs platinum-based doublet chemotherapy in patients with EGFR
T790M-positive advanced NSCLC, whose tumours progressed on previous
MA08.02 CLINICAL RESEARCH PLATFORM INTO MOLECULAR EGFR-TKI therapy. Concordance between plasma and tissue testing, and
TESTING, TREATMENT, OUTCOME (CRISP): A PROSPECTIVE efficacy outcomes by baseline plasma T790M status, were evaluated.
Methods: Eligible patients were randomised 2:1 to osimertinib 80 mg orally group (Fig.1A). High maximal tumor shrinkage also did not significantly affect
once daily or platinum-pemetrexed (pemetrexed 500 mg/m2 + cisplatin 75 mg/ OS (HR 0.86, 95% CI 0.54-1.40, p=0.564) (Fig. 1B). In multivariate analysis, CNS
m2 or carboplatin AUC5) every three weeks for up to six cycles. Patients were as site of progression (HR 2.96, 95% CI 1.39-6.29, p=0.005) and first-line
tumour tissue T790M-positive (by cobas® EGFR Mutation Test v2) from a afatinib (HR 0.51, 95% CI 0.29-0.91, p=0.022) were the only factors that
biopsy after disease progression prior to study entry. Blood samples were significantly influenced OS.
taken at baseline for retrospective analysis of T790M mutation status by
plasma ctDNA using the cobas® EGFR Mutation Test v2. Results: Concordance
data are reported in the table. Within the intent-to-treat (ITT) population
(n=419), patients plasma T790M-positive and randomised to treatment
(n=172) had markedly improved progression-free survival (PFS) by investigator
assessment (IA) with osimertinib vs platinum-pemetrexed: hazard ratio 0.42
(95% CI: 0.29, 0.61); median 8.2 vs 4.2 months. Objective response rate (ORR)
by IA was also distinctly improved with osimertinib vs platinum-pemetrexed:
77% vs 39% (odds ratio 4.96 [95% CI: 2.49, 10.15]; p<0.001). This is consistent
with the ITT population: PFS hazard ratio 0.30 (95% CI: 0.23, 0.41); p<0.001
(median 10.1 vs 4.4 months); ORR 71% vs 31% (odds ratio 5.39 [95% CI: 3.47,
8.48]; p<0.001).
Conclusion: The depth of response to first-line gefitinib and afatinib was not
predictive of OS in patients with EGFR-mutated NSCLC.
Keywords: EGFR TKI, depth of response, EGFR mutation-positive NSCLC

MA08.06 IMPACT OF DEPTH OF RESPONSE (DPR) ON SURVIVAL

IN PATIENTS WITH ADVANCED NSCLC TREATED WITH FIRST-LINE
CHEMOTHERAPY
Daniel Morgensztern1, Mary O’Brien2, Teng Ong 3, Mark Socinski4, Pieter
Postmus5, Amy Ko3
1
Washington University School of Medicine in St. Louis, St. Louis/MO/United
States of America, 2Royal Marsden Hospital, London/United Kingdom, 3Celgene
Corporation, Summit/NJ/United States of America, 4Florida Hospital Cancer
Institute, Orlando/FL/United States of America, 5Clatterbridge Cancer Center,
Liverpool/United Kingdom
Conclusion: In plasma T790M-positive patients the clinical benefit of Background: DpR, defined as maximum tumor shrinkage, has emerged as
osimertinib was superior to platinum-pemetrexed, consistent with the a potential predictor for long-term treatment outcome across multiple
ITT T790M-positive population selected by tumour tissue test. PFS with tumors, including NSCLC treated with immunotherapy or targeted therapy.
osimertinib was similar regardless of selection by tissue or plasma T790M- This exploratory analysis evaluated whether DpR correlated with survival in
positive status. Based on these, and AURA Phase II data, routine biopsy patients with advanced NSCLC treated with platinum-doublet chemotherapy
testing is recommended for patients with a plasma T790M-negative test in a phase III randomized clinical trial. Methods: Patients received first-
where feasible. line nab-paclitaxel 100 mg/m2 weekly or paclitaxel 200 mg/m2 q3w, both +
carboplatin AUC 6 q3w. The current analysis evaluated DpR as best percent
Keywords: plasma testing, osimertinib, EGFRm, T790M change from baseline in total target lesion length during treatment. For
patients with tumor shrinkage, data were grouped into quartiles based on
maximum percent shrinkage from baseline (Q1: > 0%-≤ 25%; Q2: > 25%-≤ 50%;
Q3: > 50%-≤ 75%, Q4: > 75%) and compared with data from patients with no
MA08: TREATMENT MONITORING IN ADVANCED NSCLC change or tumor growth (NC/G). Results: Tumor measurement by independent
review (baseline and postbaseline) was evaluable in 959 patients pooled
across treatments. The median (Figure) and 1-year OS increased with each
MA08.05 DEPTH OF RESPONSE TO FIRST-LINE EGFR TKI DOES NOT quartile vs NC/G (NC/G: 4.8 months and 17%; Q1: 10.4 months and 44%; Q2:
PREDICT SURVIVAL IN EGFR-MUTATED NSCLC PATIENTS 14.5 months and 62%; Q3: 19.3 months and 71%; Q4: 23.5 months and 70%)
Ting-Hui Wu1, Emily Hsiue1, Jih-Hsiang Lee2, James Chih-Hsin Yang 3 with HRs for OS vs NC/G of 0.42 for Q1 (95% CI, 0.33-0.53; P < 0.0001), 0.28
1 for Q2 (0.22-0.36; P < 0.0001), 0.23 for Q3 (0.16-0.31; P < 0.0001), and 0.19 for
Department of Oncology, National Taiwan University Hospital, Taipei/Taiwan,
2
Department of Medical Research, National Taiwan University Hospital, Taipei/
Q4 (0.11-0.33; P < 0.0001), respectively. Similar findings were observed for all
Taiwan, 3Department of Oncology, National Taiwan University Hospital, Graduate quartiles vs NC/G for age (≥ 70 and < 70 years) and histology (squamous and
Institute of Oncology & Cancer Research Center, National Taiwan University, Taipei/ nonsquamous) in subset analyses (P < 0.05 for all comparisons). Conclusion:
Taiwan DpR was associated with increased OS in patients with advanced NSCLC
receiving first-line platinum-based doublet chemotherapy, regardless of age
Background: The association between depth of response to EGFR TKI and or histology. These findings underscore the importance of evaluating quality
prognosis of EGFR-mutated NSCLC remains unclear. We aimed to assess the of treatment response in this patient population.
correlation between maximal tumor shrinkage and survival in patients
treated with gefitinib and afatinib. Methods: Patients with advanced
EGFR-mutated NSCLC enrolled in first-line gefitinib and afatinib clinical trials
between 2005 and 2014 at the National Taiwan University Hospital were
reviewed. Patients who had at least one measurable target lesion that shrank
during treatment were included. Overall survival (OS) was defined as time
from date of enrollment to death or May 30th, 2016. Correlation between
tumor shrinkage and OS was analyzed by Pearson correlation coefficient and
Kaplan-Meier method. The influence of high maximal tumor shrinkage
(defined as ≥50% tumor shrinkage), age, gender, types of EGFR mutation,
central nervous system (CNS) involvement at diagnosis, CNS as site of
progression, first-line EGFR TKI (gefitinib or afatinib), and subsequent
treatments (chemotherapy, third-generation TKI) on OS was evaluated by a
multivariate Cox proportional hazard model. Results: A total of 189 trial
patients were screened and 91 patients were eligible for analysis (gefitinib
n=42, afatinib n=49). The median maximal tumor shrinkage during first-line
EGFR TKI treatment was 53% (interquartile range 30.5%). Maximal tumor
shrinkage did not correlate with OS in all patients (R2=0.0225, p=0.169), and
either the gefitinib (R 2=0.0036, p=0.689) or afatinib (R 2=0.0625, p=0.085)

MA08: TREATMENT MONITORING IN ADVANCED NSCLC semi-quantitative index (SQI). Radiologic progression was determined in
accordance with RECIST1.1 criteria. Results: From May 2014, 23 patients were
treated with EGFR TKIs for advanced EGFRmu NSCLC; 20/23 had detectable
MA08.07 PROSPECTIVE SEQUENTIAL COUNTS OF TOTAL CTC OR activating mutations in plasma before any treatment and were therefore
CKIT+CTC IN ADVANCED NSCLC WITH 1ST LINE CHEMOTHERAPY included in our analysis. Dynamic changes of plasma EGFRmu during 1st line
EGFR TKI treatment are shown in Figure 1. Eight patients (40%) experienced
(POLICE)
RECIST 1.1 progression while on treatment, whereas one patient was
Xu-Chao Zhang1, Zhen Wang2, Yan-Ming Deng 3, Wei-Bang Guo1, Jin -Ji Yang4, inevaluable. In 4/8 patients (50%) LBP appeared at the same time as radiologic
Hong-Hong Yan1, Qing Zhou4, Binchao Wang2, Wei-Neng Feng 3, Huajun Chen4, progression, in 3/8 patients (37%) LBP appeared before radiologic progression
Hai-Yan Tu2, Li Zhang5, Xiaoqing Liu6, Qing-Feng Zou7, Yi Long Wu2 (8w, 14w, 20w before, respectively) and in 1 patient (12%) radiologic
1
Medical Research Center, Guangdong Lung Cancer Institute, Guangdong progression appeared 6w before LBP. Among patients who did not experience
General Hospital & Guangdong Academy of Medical Sciences, Guangzhou/China, radiologic progression yet, some dynamic changes in cfDNA were also
2
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong
observed, but alterations in the SQI values were much smaller.
Academy of Medical Sciences, Guangzhou/China, 3Oncology, Foshan the First
People’S Hospital, Foshan/China, 4Division of Pulmonary Oncology,cancer Center,
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong
Academy of Medical Sciences, Guangzhou/China, 5Department of Medical
Oncology, Sun Yat-Sen University Cancer Center, Guangzhou/China, 6Department
of Pulmonary Oncology, 307 Hospital of the Academy of Military Medical Sciences,
Cancer Center, Beijing/China, 7Cancer Center of Guangzhou Medical University,
Guangzhou/China
Background: Circulating tumor cells (CTCs) have been reported prognostic

and predictive in non-small cell lung cancer (NSCLC) and a few of other
cancer types. In 1st line setting, whether EPCAM+CK+CD45 - CTC and/or stem
cell-like cKIT+EPCAM+ CK+CD45 - CTC enumeration and dynamic changes can
be prognostic and/or predictive to standard chemotherapy need further
investigation in Chinese patients with NSCLC. Methods: A prospective study
on the CTC enumeration in advanced NSCLC with 1st line chemotherapy
(POLICE) was started by China Thoracic Oncology Group (CTONG). Patients
with NSCLC naïve for systemic regimens were enrolled since August 2013.
CTCs were detected by Cell Search Platform and identified as positive for
EPCAM+CK+CD45 - phenotype. CD117 (cKIT) marker was added to test the
frequency of stem cell-like cKIT+EPCAM+CK+CD45 - CTCs. Primary endpoints
were CTC counts and its correlation with first line therapy. Results: Totally
180 patients were enrolled. In 174 case total CTC and cKIT+CTC positive (cutoff
>=1) rates were 38.5% (67/172) vs 14.3% (24/168), 21.8% (31/142) vs 6.3%
(9/142), 13.7% (13/95) vs 6.4% (6/94) and 40.4% (38/94) vs 15.0% (13/93) at
time-points of baseline, after first-cycle-chemo, after four-cycles-chemo and
disease progression. At time immediately after first-cycle-chemo, patients in
CTC=0 group got statistically higher ORR (29.0% VS 7.1%, P=0.017) and DCR
(74.2% VS 42.9%, P=0.002) than in CTC>=1 group. At time after four-cycles-
chemo, patients in CTC=0 group got statistically higher DCR (88.3% VS 58.3%,
P=0.026) than in CTC>=1 group. At time either after first-cycle-chemo or after
four-cycles-chemo, patients in CTC>=1 group got worse PFS (5.7m VS 4.0m,
P=0.025; 6.3m VS 4.0m, P=0.001 ) than in CTC=0 group. At time after first-
cycle-chemo, patients in groups cKIT+CTC>=1 and cKIT- CTC>=1 got worse PFSs
(3.1m vs 4.0m vs 5.7m, P=0.001) and worse DCRs (44.4% vs 42.1% vs 73.9%,
P=0.009) than in CTC=0 group. For 142 patients categorized into three groups
Conclusion: Monitoring EGFR mutations in plasma is a feasible and less
of dynamic CTC decrease (17), CTC unchanged (82), and CTC increase (43),
invasive method in routine clinical practice and could be used as a predictive
there were significant differences in terms of DCR (71.8% vs 71.6% vs 33.3%,
marker of progression on treatment with EGFR TKIs.
P=0.018) and PFS (5.2m vs 5.6m vs 3.1m, P=0.037). Conclusion: In first line
setting of advanced NSCLC, at time-points after first-cycle-chemo other than Keywords: plasma EGFR mutations, NSCLC
baseline, total CTC or cKIT+CTC counts could be predictive for worse DCR or
PFS. CTC increase from baseline to after-first-cycle-chemo might be a strong
signal for the inefficacy of first line chemotherapy in the NSCLC patients.
TREATMENT MONITORING IN ADVANCED NSCLC
Keywords: Circulating tumor cell, non-small cell lung cancer, predictive TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
marker, cKIT
MA08.10 DETECTION OF THE T790M MUTATION OF EGFR IN

PLASMA OF ADVANCED NSCLC PATIENTS WITH ACQUIRED
MA08: TREATMENT MONITORING IN ADVANCED NSCLC RESISTANCE TO EGFR-TKI (WJOG8014LTR)
Koichi Azuma1, Takayuki Takahama2, Kazuko Sakai3, Masayuki Takeda2,
Toyoaki Hida4, Masataka Hirabayashi5, Tetsuya Oguri6, Hiroshi Tanaka7,
MA08.09 MONITORING PLASMA EGFR MUTATIONS DURING FIRST Noriyuki Ebi8, Toshiyuki Sawa9, Akihiro Bessho10, Motoko Tachihara11,
LINE TREATMENT WITH EGFR TKIS IN NSCLC PATIENTS Hiroaki Akamatsu12, Shuji Bandoh13, Daisuke Himeji14, Tatsuo Ohira15,
Katja Mohorcic 1, Izidor Kern2, Urska Janzic1, Nina Turnsek Hitij1, Mitja Rot2, Mototsugu Shimokawa16, Nobuyuki Yamamoto12, Yoichi Nakanishi17, Kazuhiko
Tanja Cufer 1 Nakagawa2, Kazuto Nishio3
1
1
Medical Oncology Unit, University Clinic of Respiratory and Allergic Diseases Division of Respirology, Neurology, and Rheumatology, Department of Internal
Golnik, Golnik/Slovenia, 2Pathology Department, University Clinic of Respiratory Medicine, Kurume University School of Medicine, Kurume/Japan, 2Department of
and Allergic Diseases Golnik, Golnik/Slovenia Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama/Japan,
3
Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-
Background: Genotyping cell free circulating DNA (cfDNA) is a non-invasive Sayama/Japan, 4Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya/Japan,
5
Hyogo Prefectural Amagasaki General Medical Center, Hyogo/Japan, 6Nagoya City
method of detecting EGFR mutations (EGFRmu) in plasma and may provide an
University, Aichi/Japan, 7Department of Internal Medicine, Niigata Cancer Center
option to identify patients who progress while treated with EGFR TKIs. The
Hospital, Niigata/Japan, 8Department of Respiratory Oncology, Iizuka Hospital,
aim of our study was to monitor plasma EGFRmu and identify dynamic case Fukuoka/Japan, 9 Cancer Center, Gifu Municipal Hospital, Gifu/Japan, 10 Respiratory
specific changes in plasma EGFRmu during routine treatment of advanced Medicine, Japanese Red Cross Okayama Hospital, Okayama/Japan, 11Division
EGFRmu NSCLC patients. Methods: Plasma was collected from patients with of Respiratory Medicine, Department of Internal Medicine, Kobe University
advanced EGFRmu NSCLC treated with first- or second-generation EGFR TKIs. Graduate School of Medicine, Kobe/Japan, 12Third Department of Internal Medicine,
Plasma EGFRmu were dynamically monitored consecutively at every Wakayama Medical University, Wakayama/Japan, 13Kagawa University, Kagawa/
scheduled visit. Cobas EGFR Mutation Test v1 and v2 (Roche, USA) was used to Japan, 14Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital,
detect 42 mutations at EGFR gene in exons 18 to 21. Liquid biopsy progression Miyazaki/Japan, 15Thoracic Surgery, Tokyo Medical University Hospital, Tokyo/
Japan, 16Clinical Research Institute, National Kyushu Cancer Center, Fukuoka/Japan,
(LBP) was determined as reappearance of EGFRmu in plasma after 17
Kyushu University, Fukuoka/Japan
negativisation during treatment or increase of EGFRmu levels expressed by
Background: NSCLC patients with activating mutations of the EGFR initially

respond well to TKIs, but about half such patients develop TKI resistance MA09.01 DUAL BLOCKADE OF PD-1 AND C5A/C5AR
through acquisition of a secondary T790M mutation. Whereas next-generation SYNERGISTICALLY PROTECTS AGAINST NON-SMALL CELL LUNG
EGFR-TKIs have been developed to overcome T790M-mediated resistance, CANCER TUMOR GROWTH
performance of a second tumor biopsy to assess T790M mutation status can
Daniel Ajona, Sergio Ortiz, Haritz Moreno, Silvestre Vicent, Luis Montuenga,
be problematic. Methods: We developed and evaluated liquid biopsy assays for
Fernando Lecanda, Ruben Pio
detection of TKI-sensitizing and T790M mutations of EGFR by droplet digital
Program in Solid Tumors and Biomarkers, Cima-University of Navarra, Pamplona/
PCR (ddPCR) in EGFR mutation–positive patients with acquired EGFR-TKI
Spain
resistance. Results: A total of 260 patients was enrolled between November
2014 and March 2015 at 29 centers for this West Japan Oncology Group (WJOG Background: Immunotherapy based on PD-1/PD-L1 immune checkpoint
8014LTR) study. Plasma specimens from all subjects as well as tumor tissue inhibitors has emerged as a powerful tool for the treatment of lung cancer.
or malignant pleural effusion or ascites from 41 patients were collected after To further enhance the antitumor efficacy of individual treatments,
the development of EGFR-TKI resistance. All plasma samples were genotyped numerous ongoing studies are trying to identify synergistic combinations
successfully and the results were reported to physicians within 14 days. TKI- that simultaneously block more than one immunomodulatory pathway.
sensitizing and T790M mutations were detected in plasma of 120 (46.2%) and C5aR1 is a G protein-coupled receptor activated by C5a, an anaphylatoxin
75 (28.8%) patients, respectively. T790M was detected in 56.7% of patients released during the activation of the complement system, a major
with plasma positive for TKI-sensitizing mutations. For the 41 patients component of innate immunity. We have previously shown in a murine
with paired samples obtained after acquisition of EGFR-TKI resistance, the model of lung cancer that pharmacological blockade of C5aR1 reduces cancer
concordance for mutation detection by ddPCR in plasma compared with tumor progression by reversing the immunosuppressive microenvironment. Thus,
tissue or malignant fluid specimens was 78.0% for TKI-sensitizing mutations we hypothesized that a combined inhibition of C5aR1 and PD-1 may have a
and 65.9% for T790M. Conclusion: Noninvasive genotyping by ddPCR with synergistic effect in the treatment of lung cancer. Methods: We characterized
cell-free DNA extracted from plasma is a promising approach to the detection the immunosuppressive activity of C5aR1 and evaluated the therapeutic
of gene mutations during targeted treatment. efficacy of the dual administration of PD-1 and C5a/C5aR1 antagonists in
syngeneic non-small cell lung cancer mouse models. The RMP1-14 monoclonal
Keywords: T790M mutation, Acquired resistance, liquid biopsy, digital PCR
antibody was used to block PD-1, and a PEG-modified L-aptamer, which binds
to complement C5 and C5a, was used to inhibit the C5a/C5aR1 interaction.
Results: KrasG12D/+ mice deficient for C5aR (KrasG12D/+;C5aR1Δ/Δ) had a lower
lung tumor burden and survived longer than KrasG12D/+;C5aR1wt/wt littermates.
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30 Interestingly, KrasG12D/+;C5aR1Δ/Δ mice showed a significant reduction of
myeloid-derived suppressor cells (MDSCs), a subpopulation of immune cells
that profoundly influences the effectiveness of cancer immunotherapies. We
MA08.11 MONITORING THE EMERGENCE OF EGFR T790M CTDNA therefore evaluated whether C5a/C5aR blockade may enhance the efficacy
IN URINE FROM EGFR MUTATED NSCLC PATIENTS TO PREDICT of anti-PD-1 therapy by reversing the immunosuppressive microenvironment.
RESPONSE TO 3RD GENERATION ANTI-EGFR TKIS In the Kras/Tp53 mutant 393P syngeneic lung cancer model, the combination
Brian Woodward1, Parissa Keshavarzian1, Ragi Phillips1, Sandeep Pingle2, of C5a and PD-1 blockade dramatically reduced in vivo tumor growth, as
Vlada Melnikova2, Mark Erlander2, Hatim Husain1 compared to the effect of each treatment alone. Similarly, this combination
1 showed a remarkable synergistic antitumor effect in Lewis lung carcinoma
Ucsd Moores Cancer Center, La Jolla/CA/United States of America, 2Trovagene Inc,
San Diego/CA/United States of America (3LL)-bearing mice. Survival analysis confirmed the benefit of the combined
treatment. Finally, the therapeutic combination significantly diminished the
Background: EGFR T790M mutation occurs in about half of EGFR mutated in vivo metastatic capacity of the highly aggressive Lacun3 lung cancer cell
NSCLC patients with acquired EGFR-TKI resistance. It is currently unknown line in syngeneic BALB/c mice, as compared to the effect of anti-PD-1 or anti-
if switching therapy to a third generation anti-EGFR TKI based on circulating C5a drugs as monotherapy. Conclusion: Our study supports the notion that
tumor DNA at first detection with urine is superior to switching therapy based the efficacy of anti-PD-1 therapy is limited by the immunosuppressive tumor
on radiographic progression. Herein we demonstrate the identification of microenvironment. In this context, C5a/C5aR1 blockade concomitant to
T790M in urine months before radiographic progression, patient responses anti-PD1 therapy obliterates the resistance mechanisms mediated by MDSCs,
when treated with an anti-EGFR third generation TKIs, clinical cutoffs that improving antitumor immune responses. These findings provide a framework
may be predictive of benefit, and a novel clinical trial to consider for treatment for the clinical evaluation of this therapeutic strategy.
selection. Methods: From 2014 to 2016 a total of 42 patients with EGFR
activating mutations were followed at UCSD Moores Cancer Center through Keywords: Myeloid-derived suppressor cell, PD-1, Immunotherapy, C5aR1
multiple lines of therapy. 34 patients had serial urine collection every 4-6wks
from time of first visit. Clinical progression was assessed with CT imaging
performed every two months. Results: Among the 42 patients, 35 patients
had metastatic disease (6 with intrathoracic M1a disease and 29 with distant MA09: IMMUNOTHERAPY COMBINATIONS
metastasis M1b). Urine volume ranged from 30-100ml. Average time from first
line TKI start to urine T790M was 15.7mos (CI 9.6-25.6), time from TKI start
to radiographic progression was 21.9mos (CI 10.7-27.0), and time from urine MA09.02 PEMBROLIZUMAB + CARBOPLATIN AND PEMETREXED
T790M to radiographic progression was 3.6mos (CI 0.9-6.8). All patients with AS 1ST-LINE THERAPY FOR ADVANCED NON–SMALL CELL LUNG
>30 copies/105 genome equivalents (GEq) of urine T790M had response to third CANCER: KEYNOTE-021 COHORT G
generation TKIs. In patients who had urine EGFR T790M from 10-30 copies/105
Corey Langer 1, Shirish Gadgeel2, Hossein Borghaei3, Vassiliki
GEq, three serial measurements in the 10-30 range predicted response. EGFR
Papadimitrakopoulou4, Amita Patnaik5, Steve Powell6, Ryan Gentzler 7,
T790M copies of less than 10 copies/105 GEq did not predict response to third
Renato Martins8, James Stevenson9, Shadia Jalal10, Amit Panwalkar 11, James
generation inhibitors. Conclusion: EGFR T790M can be identified in urine
Chih-Hsin Yang12, Matthew Gubens13, Lecia Sequist14, Joseph Fiore15, Joy Ge15,
before radiographic progression and quantitative cut-offs can be predictive
Harry Raftopoulos15, Leena Gandhi16
of response. We are testing this prospectively in a clinical trial with serial 1
University of Pennsylvania, Philadelphia/PA/United States of America, 2Karmanos
ctDNA analyses obtained for resistance monitoring for up to 24 months on
Cancer Institute/wayne State University, Detroit/MI/United States of America, 3Fox
first line TKI therapy. Patients who have urine detection of T790M (>30 copies Chase Cancer Center, Philadelphia/PA/United States of America, 4The University
or three serial collections with 10-30 copies/105 GEq) at 12 months and before of Texas MD Anderson Cancer Center, Houston/TX/United States of America,
progression are randomized to second line third generation TKI therapy 5
South Texas Accelerated Research Therapeutics, San Antonio/TX/United States
or continuation of the first line therapy until progression. Patients with of America, 6Sanford Cancer Center, University of South Dakota Sanford School of
undetectable urinary T790M or <10 copies/105 GEq will continue on the first Medicine, Sioux Falls/ND/United States of America, 7Emily Couric Clinical Cancer
line therapy past 12 months until progression. Overall survival, progression Center, University of Virginia School of Medicine, Charlottesville/VA/United States
free survival, and time to progression will be compared between cohorts to of America, 8Seattle Cancer Care Alliance, Seattle/WA/United States of America,
9
Cleveland Clinic, Cleveland/United States of America, 10 Indiana University School
validate the early detection of T790M by urine ctDNA and understand the
of Medicine, Indianapolis/IN/United States of America, 11Sanford Roger Maris
impact of an early switch in therapy based on ctDNA analyses. Cancer Center, Fargo/ND/United States of America, 12National Taiwan University
Hospital and National Taiwan University Cancer Center, Taipei/Taiwan, 13University
Keywords: EGFR, resistance, ctDNA, urine
of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San
Francisco/CA/United States of America, 14 Massachusetts General Hospital Cancer
Center and Harvard Medical School, Boston/MA/United States of America, 15Merck
& Co., Inc., Kenilworth/NJ/United States of America, 16Dana-Farber Cancer Institute,
Boston/MA/United States of America
SESSION MA09: IMMUNOTHERAPY COMBINATIONS
Background: Platinum doublet chemotherapy ± bevacizumab is standard
first-line therapy for patients with advanced non–small cell lung cancer
(NSCLC) without genetic aberrations. Single-agent pembrolizumab exhibits

robust antitumor activity in PD-L1–positive advanced NSCLC. Cohort G of patient population, Du 15mg/kg q3w and Tr 1mg/kg (multiple doses q6w) or
the multicenter, open-label, phase 1/2 multicohort KEYNOTE-021 study 3mg/kg (3 doses q6w) can be safely combined with full doses of platinum-
(ClinicalTrials.gov, NCT02039674) evaluated the efficacy and safety of doublet chemotherapy. Additional studies with this combination are being
pembrolizumab + carboplatin and pemetrexed compared with carboplatin planned.
and pemetrexed in patients with treatment-naive advanced nonsquamous
NSCLC with any PD-L1 expression. Methods: Cohort G enrollment criteria Keywords: Immunotherapy, tremelimumab, chemotherapy, durvalumab
included patients with stage IIIB/IV nonsquamous NSCLC, no activating EGFR
mutation or ALK translocation, no prior systemic therapy, measurable disease,
ECOG performance status 0-1, and adequate tumor sample for assessment
of PD-L1 status, regardless of PD-L1 expression. Patients were randomized MA09: IMMUNOTHERAPY COMBINATIONS
1:1 to 4 cycles of pembrolizumab 200 mg Q3W + carboplatin AUC 5 (5 mg/mL/
min) + pemetrexed 500 mg/m2 Q3W or carboplatin AUC 5 (5 mg/mL/min) +
pemetrexed 500 mg/m2 Q3W alone, followed by maintenance pemetrexed MA09.05 NIVOLUMAB ALONE OR WITH IPILIMUMAB IN
± pembrolizumab. Pembrolizumab was given for ≤35 cycles. Randomization RECURRENT SMALL CELL LUNG CANCER (SCLC): 2-YEAR SURVIVAL
was stratified by PD-L1 expression (positive [tumor proportion score, or TPS, AND UPDATED ANALYSES FROM THE CHECKMATE 032 TRIAL
≥1%] vs negative [TPS <1%]). Crossover to pembrolizumab monotherapy was
Matthew Hellmann1, Scott Antonia2, Santiago Ponce3, Patrick Ott4, Emiliano
allowed for eligible patients who experienced disease progression (RECIST
Calvo5, Matthew Taylor6, Neal Ready 7, Christine Hann8, Filippo De Braud9,
v1.1) on chemotherapy. Response was assessed by central imaging vendor
Joseph Paul Eder 10, Dirk Jäger 11, Paolo Ascierto12, Leora Horn13, Asim Amin14,
review every 6 weeks for first 18 weeks, every 9 weeks through year 1, and
Jeffry Evans15, Victor Moreno16, Akin Atmaca17, Rathi Pillai18, Jaishree Bhosle19,
every 12 weeks in year 2. The primary end point was objective response
Petri Bono20, Noemi Reguart21, Jeffrey Schneider22, Peter Brossart23, Jennifer
rate (ORR); secondary end points included progression-free survival (PFS),
Diamond24, Padmanee Sharma25, Ulrik Lassen26, Chen-Sheng Lin27, Marina
duration of response, and overall survival (OS). Comparison between arms
Tschaika27, Giovanni Selvaggi27, David Spigel28
was assessed using the stratified Miettinen and Nurminen method (ORR) and 1
stratified log-rank test (PFS, OS). Results: As of January 2016, 123 patients Memorial Sloan Kettering Cancer Center, New York/NY/United States of America,
2
H. Lee Moffitt Cancer Center & Research Institute, Tampa/FL/United States of
(60 in the pembrolizumab + chemotherapy arm, 63 in the chemotherapy arm)
America, 3Hospital Universitario 12 de Octubre, Madrid/Spain, 4 Medical Oncology,
had been enrolled in cohort G. Data on ORR, duration of response, safety, and Dana-Farber Cancer Institute, Boston/MA/United States of America, 5Start Madrid,
preliminary PFS and OS results will be available by August 2016. Conclusion: Centro Integral Oncológico Clara Campal, Madrid/Spain, 6Oregon Health & Science
The conclusion will be updated at the late-breaking submission stage. University, Portland/OR/United States of America, 7Duke University Medical
Center, Durham/NC/United States of America, 8The Sidney Kimmel Comprehensive
Keywords: pembrolizumab, non-small cell lung cancer, platinum doublet Cancer Center at Johns Hopkins University, Baltimore/MD/United States of
chemotherapy America, 9Fondazione IRCCS Instituto Nazionale Dei Tumori Milano, Milan/Italy,
10
Yale Comprehensive Cancer Center, New Haven/CT/United States of America,
11
Nationales Centrum Für Tumorerkrankungen (Nct), University Medical Center,
Heidelberg/Germany, 12Istituto Nazionale Tumori Fondazione Pascale, Naples/
Italy, 13Vanderbilt-Ingram Cancer Center, Nashville/TN/United States of America,
MA09: IMMUNOTHERAPY COMBINATIONS 14
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 Levine Cancer Institute, Carolinas Medical Center, Charlotte/NC/United States
of America, 15University of Glasgow, Glasgow/United Kingdom, 16Start Madrid-Fjd,
Hospital Fundación Jiménez Díaz, Madrid/Spain, 17Krankenhaus Nordwest GmbH
MA09.03 CISPLATIN/PEMETREXED + DURVALUMAB +/- Institut Für Klinisch-Onkologische Forschung, Frankfurt Am Main/Germany,
18
TREMELIMUMAB IN PTS WITH ADVANCED NON-SQUAMOUS
America, 19Royal Marsden Hospital, Chelsea, London/United Kingdom, 20 Helsinki
NSCLC: A CCTG PHASE IB STUDY - IND.226 University Hospital, Helsinki/Finland, 21Hospital Clinic Barcelona, Barcelona/Spain,
22
Rosalyn Juergens 1, Desiree Hao2, Scott Laurie3, Mihaela Mates4, Mustapha Winthrop Hospital, Mineola/NY/United States of America, 23University Hospital
Tehfe5, Penelope Bradbury6, Christian Kollmannsberger 7, Peter Ellis1, John of Bonn, Bonn/Germany, 24University of Colorado Cancer Center, Aurora/CO/United
Hilton3, Pamela Brown-Walker8, Lesley Seymour8 States of America, 25University of Texas MD Anderson Cancer Center, Houston/
1
TX/United States of America, 26Copenhagen University Hospital, Copenhagen/
Oncology, McMaster University - Juravinski Cancer Centre, Hamilton/ON/ Denmark, 27Bristol-Myers Squibb, Princeton/NJ/United States of America,
Canada, 2Oncology, University of Calgary - Tom Baker Cancer Centre, Calgary/ 28
Thoracic Oncology, Sarah Cannon Research Institute/tennessee Oncology, PLCC,
Canada, 3Medical Oncology, The Ottawa Hospital Cancer Centre, University of Nashville/TN/United States of America
Ottawa, Ottawa/ON/Canada, 4 Oncology, Queens University - Kgh Cancer Centre of
Southeastern Ontario, Kingston/ON/Canada, 5Hematology and Medical Oncology, Background: Patients with SCLC and disease progression during/after
Hôpital Notre Dame - CHUM, Montreal/Canada, 6Dept of Medical Oncology and
first-line platinum-based chemotherapy have poor prognoses and limited
Haematology, Princess Margaret Cancer Centre, Toronto/ON/Canada, 7Oncology,
British Columbia Cancer Agency - Vancouver Cancer Centre, Vancouver/BC/Canada,
treatment options. Nivolumab alone and in combination with ipilimumab has
8
Queen’s University - Canadian Clinical Trials Group, Kingston/ON/Canada shown survival benefit and durable responses in multiple tumor types. Here
we present updated results for the SCLC cohort of the phase 1/2 CheckMate
Background: Immune checkpoint inhibitors are now established therapies 032 trial (NCT01928394), which was designed to evaluate nivolumab or
in many advanced cancers. Preliminary studies suggest combining immune nivolumab/ipilimumab in advanced solid tumors. Methods: Patients with
checkpoint inhibitors with platinum-based chemotherapy may enhance advanced SCLC that progressed following ≥1 platinum-based chemotherapy
anti-tumour activity. The primary objective of this multi-centre study was regimens were assigned to receive nivolumab monotherapy (nivolumab-3
to evaluate the safety and tolerability of durvalumab (Du), a PD-L1 inhibitor, Q2W) or nivolumab/ipilimumab combination therapy (nivolumab-1/
± tremelimumab (Tr), a CTLA-4 inhibitor, in combination with one of four ipilimumab-3 or nivolumab-3/ipilimumab-1 Q3W for 4 cycles, then nivolumab-3
standard platinum-doublet regimens (pemetrexed (pem), gemcitabine, Q2W). Patients were eligible regardless of platinum sensitivity or tumor
etoposide (each with cisplatin) or nab-paclitaxel (with carboplatin)), in order programmed death ligand 1 (PD-L1) expression. The primary endpoint was
to establish a recommended phase II dose (R2PD) for each combination. This ORR. Additional endpoints were duration of response (DOR), OS, PFS, safety,
abstract focuses on the pem / cisplatin cohort in non-squamous non-small and correlation of tumor PD-L1 expression with activity. Results: 214 patients
cell lung cancer (NSCLC). Methods: Patients (pts) with advanced NSCLC have been enrolled to date (nivolumab-3, n=98; nivolumab-1/ipilimumab-3,
(no prior treatment for advanced disease) who were eligible for treatment n=61; nivolumab-3/ipilimumab-1, n=55), including 96 and 118 patients treated
with cisplatin and pemetrexed were enrolled into one of four dose levels, with 1 or ≥2 prior regimens, respectively. Efficacy and safety data are shown
regardless of tumour PD-L1 status. Concurrent with chemotherapy, dose level (table). In the nivolumab-1/ipilimumab-3 cohort, ORR was 23% and 1-year
(DL) 0 added Du 15 mg/kg IV q3wks; DL1 added Du 15mg/kg q3wk + Tr 1mg/ OS was 43%. The proportion of patients with PD-L1–expressing tumors
kg x1 dose; DL2a added Du 15mg/kg q3wk + Tr 1 mg/kg q6wk x multiple doses; was substantially lower in previously treated SCLC in this study than that
DL2b added Du 15mg/kg q3wk + Tr 3 mg/kg q6wk (1 dose with cycle 1 and 2 previously observed with pretreated NSCLC (16% vs 53%–54% with ≥1% PD-L1
doses with maintenance pem). Pemetrexed and Du maintenance continued expression). In SCLC, responses were observed regardless of PD-L1 expression.
after completion of 4-6 cycles of pemetrexed and cisplatin. Results: Twenty- ORR and median OS were similar in patients treated with 1 or ≥2 prior
four pts (median age=61 (range 37-78); 50% female, 95% ECOG PS≤1, were regimens. Rate of discontinuation due to treatment-related AEs ranged from
enrolled (5 pts to each of DL 0 and 1 and 7 pts each to DL2a and 2b). Thus far 121 5% to 11%; there were 3 treatment-related deaths.
cycles have been administered. The majority of drug-related adverse events
(AEs) were ≤ grade 2. Most AEs were related to chemotherapy; other AEs (See Table next page)
were chemotherapy or immune-related (renal, hepatic, skin and pulmonary
toxicity). AEs that were considered related to Du or Tr were mainly ≤ grade
2, the most common of which were fatigue (46%), nausea/vomiting (25%),
anorexia (21%) and diarrhea (13%). Two pts (DL2a) had serious related AEs
(febrile neutropenia related to chemotherapy and lung infection/pneumonitis
related to both chemotherapy and Du + T (considered a DLT)). Seventeen of
the 24 patients are currently evaluable for response. The provisional objective
response rate is 52.9% (95% CI: 28 -77%). Conclusion: In this PD-1 unselected
110 mechanism of action, decreased Myeloid Derived Suppressor Cells (MDSC)

in the blood, and increased markers of activated CD8+ T cell subsets by flow
cytometry (CD8+CTLA-4+, CD8+Tim3+). Although the pathology specimens
were sub-optimal in the two responding patients, the limited tissue available
showed lower baseline TILs in both patients. Conclusion: Allogeneic gp96-
based vaccination may have synergistic activity in combination with immune
checkpoint inhibitors.
Keywords: Immunotherapy, Checkpoint Inhibitor, Nivolumab, Vaccine
MA09: IMMUNOTHERAPY COMBINATIONS

MA09.07 PHASE I TRIAL OF IN SITU VACCINATION WITH CCL21

GENE-MODIFIED DC INDUCES SPECIFIC SYSTEMIC IMMUNE
RESPONSE AND TUMOR INFILTRATING CD8+ T CELLS
Jay Lee1, Mi-Heon Lee1, Edward Garon1, Jonathan W. Goldman1, Felicita
Baratelli1, Dorthe Schaue1, Gerald Wang1, Frances Rosen1, Jane Yanagawa1,
Tonya Walser 1, Ying Lin1, Sharon Adams2, Francesco Marincola2, Paul Tumeh1,
Fereidoun Abtin1, Robert Suh1, Karen Reckamp3, William Wallace1, Gang Zeng1,
David Elashoff 1, Sherven Sharma1, Steven Dubinett 1
1
University of California, Los Angeles, Los Angeles/CA/United States of America,
2
National Institutes of Health, Bethesda/MD/United States of America, 3City of
Hope Comprehensive Cancer Center, Duarte/CA/United States of America
Background: Intratumoral (IT) infiltration by activated immune effector cells

is associated with a significantly better prognosis, however, tumor-associated
immune suppression commonly occurs in non-small cell lung cancer (NSCLC).
CD8+ T cell or dendritic cell (DC) infiltration is an independent favorable
Conclusion: Durable objective responses were observed with nivolumab
prognostic indicator. CCL21 is a lymphoid chemokine that chemoattracts both
and nivolumab/ipilimumab in patients with previously treated SCLC, and
lymphocytes and DC. Our aim was to investigate anti-tumor specific systemic
safety profiles were consistent with other tumor types. Updated efficacy
immune responses and tumor-infiltrating CD8+ T cells (CD8+ TIL) in NSCLC
(including 2-year OS and DOR), safety, and additional subgroup analyses will
patients in response to in situ vaccination via IT administration of autologous
be presented from the August 2016 DBL.
DC transduced with a replication-deficient adenoviral (Ad) vector expressing
Keywords: Nivolumab, Ipilimumab, SCLC, PD-L1 the secondary lymphoid chemokine (SLC/CCL21) gene. Here, we conducted
a phase I trial and evaluated safety and immune responses following in situ
vaccination. Methods: Sixteen stage IIIB/IV NSCLC subjects received two
vaccinations (1 x 106, 5 x 106, 1 x 107, or 3 x 107 dendritic cells/injection) by CT- or
MA09: IMMUNOTHERAPY COMBINATIONS bronchoscopic-guided IT injection (days 0 and 7). Immune responses were
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 assessed by tumor antigen-specific peripheral blood lymphocyte induction
of IFN-γ in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by
immunohistochemistry (IHC). Results: Twenty-five percent (4/16) of patients
MA09.06 VIAGENPUMATUCEL-L BOLSTERS RESPONSE TO had stable disease at day 56 follow-up by RECIST criteria. Median survival
NIVOLUMAB THERAPY IN ADVANCED LUNG ADENOCARCINOMA: was 3.9 months. Four possible vaccine-related grade 1 adverse events (AE)
PRELIMINARY DATA FROM THE DURGA TRIAL occurred in 3 patients with no clear association to dose or schedule; the
Daniel Morgensztern1, Wael Harb2, Kurt Schalper3, Melissa Price4, Brandon AE included flu-like symptoms, blood-tinged sputum after each injection,
Early4, Taylor Schreiber4 nausea, and fatigue. ELISPOT assays revealed 38% (6/16) of patients had
1
Oncology, Washington University School of Medicine in St. Louis, St. Louis/ systemic responses against tumor associated antigens (TAA). Tumor CD8+ T
MO/United States of America, 2Horizon Oncology, Lafayette/IN/United States cell infiltration was induced in 54% of subjects (7/13; 3.4 fold average increase
of America, 3Yale Cancer Center, New Haven/CT/United States of America, 4Heat in the number of CD8+ T cells per mm2). Patients with increased intratumoral
Biologics, Durham/NC/United States of America CD8+ T cells following vaccination showed significantly increased PD-L1 mRNA
expression (p=0.02). Conclusion: Intratumoral vaccination with Ad-CCL21-DC
Background: Viagenpumatucel-L (HS-110) is an allogeneic whole-cell vaccine, was well-tolerated and resulted in 1) induction of systemic tumor antigen-
selected for high expression of adenocarcinoma tumor antigens, transfected specific immune responses and 2) enhanced tumor CD8+ T cell infiltration. DC-
to secrete gp96-Ig. Prior studies with HS-110 (and related gp96-Ig vaccines) CCL21 in situ vaccination may be a promising approach to induce tumor CD8+ T
have shown a correlation between increases in CD8+ tumor infiltrating cell infiltration in combination with checkpoint inhibitor therapy.
lymphocytes (TIL) and tumor response. The DURGA trial was designed
evaluate the combination of HS-110 and nivolumab, in an attempt to Keywords: lung cancer, PD-L1, CCL21, dendritic cells
increase tumor inflammation and improve the response rates observed with
nivolumab alone. Clinical Trial identifier: NCT02439450 Methods: Patients
with advanced lung adenocarcinoma who received at least one prior line
of therapy were assigned to two cohorts based on baseline levels of TIL in MA09: IMMUNOTHERAPY COMBINATIONS
patient biopsies: low TIL (≤10% CD8+ T cells) or high TIL (>10% CD8+ T cells). TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
All patients received standard of care nivolumab 3 mg/kg every 2 weeks
and weekly HS-110 for 18 weeks until intolerable adverse events, disease
MA09.09 FIRST-IN-HUMAN PHASE 1 STUDY OF ABBV-399, AN
progression, or death. Each 9-patient Phase 1b cohort could be expanded to
ANTIBODY-DRUG CONJUGATE (ADC) TARGETING C-MET, IN
30 patients in Phase 2 based on exhibited efficacy. The primary endpoint was
safety and tolerability. Biopsies at baseline and Week 10 were used to track PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC)
changes in TIL and PD-L1 staining. Peripheral blood mononuclear cells (PBMC) Eric Angevin1, John Strickler2, Colin Weekes3, Rebecca Heist4, Daniel
were evaluated by flow cytometry for detection of circulating leukocyte Morgensztern5, Xiaolin Fan6, Ozzie Olyaie6, Monica Motwani7, Daniel Afar6,
subsets. ELISPOT was used to track antigen-specific immune response. Louie Naumovski6, Karen Kelly8
1
Results: HS-110 vaccine and nivolumab combination was well tolerated with Départment Innovations Thérapeutiques Et Essais Précoces (Ditep), Gustave
a safety profile consistent with single-agent nivolumab. Among the 8 initial Roussy, Villejuif Cedex/France, 2Duke University Medical Center, Durham/NC/
patients, only 4 had optimal biopsies which showed 2 patients with high United States of America, 3University of Colorado, Aurora/CO/United States of
and 2 with low TILs. PD-L1 was >1% in 3 patients. IFNγ ELISPOT assay defined America, 4 Massachusetts General Hospital for Children Cancer Center, Boston/MA/
United States of America, 5Washington University School of Medicine, St. Louis/
4 patients as immune responders (doubling of IFNγ-secreting cells after
MO/United States of America, 6 Abbvie Inc., Redwood City/CA/United States of
re-stimulation with total vaccine antigen and individual cancer antigens, IR) America, 7Abbvie Inc., North Chicago/IL/United States of America, 8University of
and 4 patients as non-immune responders (NIR). The overall response rate California Davis Comprehensive Cancer Center, Sacramento/CA/United States of
(ORR) was 50% in the IR patients and 0% in the NIR patients. At the time America
of the data cutoff, 6 patients remain alive, including the 4 IR patients, with
ongoing responses for 150 to 326 days. Patients with objective response also Background: The c-Met receptor is overexpressed in ~50% of patients with
exhibited injection site reactions and maculopapular rash consistent with HS- NSCLC. ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met

antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). as a potentially clinically-relevant dose. Conclusion: These results indicate
Preclinical data support ABBV-399 as a unique strategy to deliver a potent XMT-1536 can achieve durable tumor regressions in murine patient-derived
cytotoxin directly to c-Met+ tumor cells. Methods: In a 3+3 dose-escalation NSCLC adenocarcinoma models at doses associated with good tolerability in
design, ABBV-399 was administered at doses ranging from 0.15 to 3.3 mg/ cynomolgus monkey, and support evaluation of XMT-1536 in patients with
kg once every 21 days to patients with advanced metastatic solid tumors NSCLC.
(NCT02099058). ABBV-399 was then studied in a dose-expansion cohort in 16
patients with advanced c-Met+ (immunohistochemistry [IHC] H-score ≥150) Keywords: Novel Therapies, Antibody-drug conjugate, Adenocarcinoma,
NSCLC that had progressed on ≥2 prior lines of therapy. ABBV-399 was also Targeted chemotherapy
studied in combination with erlotinib in 10 patients with NSCLC, 8 of whom
were c-Met+. Overexpression of c-Met was assessed by an IHC assay utilizing
the SP44 antibody (Ventana; Tucson, AZ, USA). Results: As of June 27, 2016,
48 patients with solid tumors received ≥1 dose of ABBV-399. The dose-limiting MA09: IMMUNOTHERAPY COMBINATIONS
toxicity (DLT) for ABBV-399 was febrile neutropenia, which occurred in 2
patients (1 each at 3 and 3.3 mg/kg). There were no treatment-related deaths.
Monotherapy treatment-related adverse events (AEs) occurring in ≥10% of MA09.11 EFFICACY AND SAFETY OF NECITUMUMAB AND
patients (including all dose levels and all grades) were fatigue (25.0%), nausea PEMBROLIZUMAB COMBINATION THERAPY IN STAGE IV
(22.9%), neuropathy (14.6%), decreased appetite (12.5%), vomiting (12.5%), NONSQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC)
and hypoalbuminemia (10.4%). Based primarily on safety and tolerability,
Benjamin Besse 1, Pilar Garrido2, Javier Puente3, Alexis Cortot4, Maria Eugenia
a 2.7-mg/kg dose was chosen for dose expansion in patients with c-Met+
Olmedo2, Maurice Pérol5, Maciej Gil6, Grace Chao7, Javad Shahidi8, Jaafar
advanced NSCLC. Three of 16 (19%) ABBV-399–treated c-Met+ NSCLC patients
Bennouna9
had a confirmed partial response (PR) with duration of response (DOR) 3+, 1
3, and 4.5 months. At week 12, 6 of 16 patients treated (37.5%) had disease Department of Cancer Medicine, Gustave Roussy, Villejuif/France, 2Medical
Oncology Department, Hospital Universitario Ramón Y Cajal, Madrid/Spain,
control. Ten patients received ABBV-399 in combination with erlotinib. No 3
Medical Oncology Dept, Hospital Clínico San Carlos, Madrid/Spain, 4Thoracic
DLTs were observed and AEs related to ABBV-399 occurring in ≥2 patients Oncology, Lille University Hospital, Lille/France, 5Groupe Thoracique Et Orl, Centre
were acneiform rash (40.0%), fatigue (30.0%), and dry skin (20.0%). Three Léon Bérard, Lyon/France, 6Eli Lilly, Warsaw/Poland, 7Eli Lilly and Company,
of 8 (37.5%) evaluable ABBV-399 + erlotinib-treated c-Met+ patients had Bridgewater/NJ/United States of America, 8Eli Lilly and Company Bridgewater,
a confirmed PR with DOR 2+, 4+, and 5+ months. Two of the 3 patients Bridgewater/NJ/United States of America, 9Institut de Cancérologie de L’Ouest,
with PR had EGFR-mutated tumor, and previous TKI- and platinum-based Nantes/France
chemotherapy had failed. Conclusion: ABBV-399 is well tolerated at a dose of
2.7 mg/kg every 21 days and has demonstrated antitumor activity in patients Background: Trials of anti-EGFR necitumumab and anti-PD1 pembrolizumab
with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. demonstrate the anti-tumor activity of each agent in NSCLC. Methods: Single-
Updated data of antitumor activity and safety of ABBV-399 as monotherapy arm, multicenter Phase 1b study to investigate effectiveness and safety of
and in combination with erlotinib in c-Met+ NSCLC patients will be presented. necitumumab combined with pembrolizumab in patients with Stage IV NSCLC
(NCT02451930). In Part A, escalating doses of necitumumab (600 mg and 800
Keywords: antibody drug conjugate, non-small cell lung cancer (NSCLC), mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination
c-Met, Erlotinib with pembrolizumab (200 mg IV) on Day 1 Q3W. In the absence of dose limiting
toxicity, Part B (expansion cohort) was planned with necitumumab 800 mg in
27 squamous and 27 nonsquamous NSCLC patients. Major eligibility criteria
included: progression after ≥1 platinum-based chemotherapy, and ECOG PS
MA09: IMMUNOTHERAPY COMBINATIONS 0-1. Study objectives were to evaluate tolerability and ORR by RECIST 1.1.
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 PD-L1 status was centrally assessed using PD-L1 IHC 22C3 pharmDx assay
(considered negative, weak positive, strong positive if <1%, 1-49%, ≥50%
of tumor cells were stained, respectively). Results: The interim analysis
MA09.10 A NAPI2B ANTIBODY-DRUG CONJUGATE INDUCES
population includes 34 nonsquamous patients (median age 61 years, 68%
DURABLE COMPLETE TUMOR REGRESSIONS IN PATIENT-DERIVED
men, 21% never smokers, PD-L1 status: negative, 50% [17/34]; positive weak/
XENOGRAFT MODELS OF NSCLC strong, 15% [5/34]/15% [5/34]; unknown 21% [7/34[BJ1] ]). Median follow-up
Donald Bergstrom, Natalya Bodyak, Alex Yurkovetskiy, Laura Poling, Mao was 6.0 months. Ten patients (29.4%) had PR (confirmed and unconfirmed)
Yin, Marina Protopopova, Mike Devit, Liuliang Qin, Dmitry Gumerov, Elena (PRs by PD-L1 status: negative, 18% [3/17]; positive weak/strong, 60%
Ter-Ovanesyan, Rebecca Mosher, Timothy Lowinger [3/5]/40% [2/5]; unknown status, 2 patients). DCR was 67.6%. PFS rate at 6
Mersana Therapeutics, Cambridge/MA/United States of America months was 55.1% (95% CI, 36.2-70.6); median PFS was 6.9 months (95% CI,
2.7-NR). Most common Grade ≥3 AEs were skin rash (9%), hypomagnesemia
Background: The sodium-phosphate transporter NaPi2b is expressed at high (9%), VTE (9%) and increased lipase (9%); 1 patient died due to an AE
levels in a majority of non-squamous non-small cell lung cancers (NSCLC), (respiratory tract infection). Five patients (14.7%) discontinued therapy
suggesting it may be an attractive therapeutic target for antibody-drug because of an AE.
conjugate (ADC) development in this disease. However, NaPi2b is also
expressed at high levels in type II alveolar cells, raising the potential for
normal tissue toxicity with this approach. XMT-1536 is an ADC comprised of a
humanized antibody against NaPi2b and approximately 15 auristatin-derived
payload molecules per antibody conjugated via a multivalent hydrophilic
polymer (Fleximer). The auristatin payload is enzymatically cleaved upon ADC
trafficking to the endosome/lysosome compartment, releasing a cytotoxic
auristatin-derivative that is capable of bystander effect killing. Methods:
The anti-tumor activity of XMT-1536 was evaluated in seven patient-derived
xenograft models of NSCLC adenocarcinoma, chosen for high NaPi2b-
expression and representing a spectrum of oncogenic driver mutations
prevalent in NSCLC adenocarcinoma (including tumors without oncogenic
drivers). The standard dose of XMT-1536 used across models was 3 mg/kg
administered intravenously once weekly for 3 weeks (last dose on Day 14).
Experiments ran until tumor growth past a pre-specified endpoint or Day 60.
XMT-1536 was also evaluated for tolerability in a cynomolgus monkey study.
Results: At the 3 mg/kg dose, XMT-1536 was active in 6/7 models: complete
tumor regression in 3 models, partial tumor regression in 1 model, and
significant tumor growth inhibition in 2 models. In 3 of the 4 models where
XMT-1536 induced tumor regression, regressions were durable, with a majority
of the animals maintaining partial or complete regression at Day 60. The
antibody component of XMT-1536 is cross-reactive with cynomolgus NaPi2b
with similar affinity as human NaPi2b. XMT-1536 was well tolerated up to 5
mg/kg (4294 mg/m2 auristatin payload equivalents), the highest dose tested. Conclusion: Safety profile corresponds to individual profiles for both drugs,
There was no body weight loss, no clinical observations attributable to XMT- with no additive toxicities. These preliminary data suggest activity of this
1536, and no evidence of neutropenia. On pathology, there was minimal mixed combination in a pretreated nonsquamous NSCLC population, irrespective of
inflammatory cell infiltrate in the lung in 1 high dose animal at each necropsy PD-L1 status.
time point, but no evidence of significant lung toxicity. Exposure to XMT-1536
Keywords: non-small cell lung cancer, Necitumumab, pembrolizumab
indicated good conjugate stability, low exposure to free drug payload in
plasma (<1 ng/mL), and supported the 3 mg/kg dose level in mouse studies
SESSION MA10: FACING THE REAL WORLD: NEW STAGING edition TNM lung cancer staging system was associated with a significant
increase in discordance between clinical and pathological staging due to
SYSTEM AND RESPONSE EVALUATION IN IMMUNOTHE-
differences in measurement of tumour size and consequently T-stage
RAPY groupings by different modalities. This has implications for prognostication
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 and clinical trial interpretation especially in patients who do not undergo
surgery for pathological stage confirmation.
MA10.01 VALIDATIONS OF THE 8TH AJCC/UICC LUNG CANCER

STAGING SYSTEM IN A LARGE NORTH AMERICA COHORT
Lin Yang 1, Yunyun Zhou2, Guanghua Xiao2, Adi Gazdar3, Yang Xie2
1
Department of Pathology, Cancer Hospital,chinese Academy of Medical Sciences,
Beijing/China, 2The University of Texas Southwestern Medical Center, Dallas/
TX/United States of America, 3Pathology, The University of Texas Southwestern
Medical Center, Dallas/TX/United States of America
Background: The new 8th AJCC/UICC lung cancer staging system was
developed and validated using the International Association for the Study of
Lung Cancer (IASLC) database, which contains 94,708 lung cancer patients
worldwide, but only 5% of patients in this database came from North America.
The goal of this study is to validate the prognostic performance of this new
staging system, focusing on the upgraded “T” and “M” parameters, in North
American lung cancer patients. Methods: We analyzed 1,163,465 non-small
cell lung cancer (NSCLC) cases collected from 2004 to 2013 in the United
States in the National Cancer Database (NCDB). After excluding patients
with more than one malignant primary tumor or tumor size larger than 10 cm,
545,776 NSCLC patients were included in the final data analysis. We defined
8th T and M parameters according to the primary coding guidelines of the
Collaborative Staging Manual and Coding Instructions for the new 8th AJCC/
UICC lung cancer staging system. Kaplan-Meier survival curves and log-rank
tests were used to compare survival difference among different stage groups,
and Cox regression models were used for multivariate analysis adjusting for
potential confounders. Results: We validated that the new staging system
can provide better survival prognosis for NSCLC patients in the NCDB cohort
than the existing 7th staging system. The median survival time for T1a is
58 months (N=15,860), for T1b is 47 months (N=78,379), and for T1c is 25
months (N=79,828) (p<2e-16). The median survival time for T2a is 19 months
(N=111,925), for T2b is 12 months (N=54,601), for T3 is 10 months (N=105,234),
and for T4 is 7 months (N=99,949) (p<2e-16). And the median survival time
for M0 is 25 months (N=411,048), for M1a is 8 months (N=49,352), for M1b
is 5months (N=42,224), and for M1c is 3 months (N=15,926 cases) (p<2e-16).
Multivariate analysis showed that these staging parameters are significantly
associated with survival when adjusting other factors. Conclusion: Both
upgraded “T” and “M” parameters of the 8th AJCC/UICC lung cancer staging
systems are significantly associated with NSCLC patient survival outcomes
using data from the NCDB, indicating a good validation performance in
patients from North America.
Keywords: AJCC/UICC cancer stage, non small cell lung cancer, national cancer
database, survival analysis
MA10: FACING THE REAL WORLD: NEW STAGING SYSTEM AND RESPONSE EVALUATION IN
IMMUNOTHERAPY
MA10.02 CLINICAL STAGING IN THE 8TH EDITION TNM FOR LUNG

CANCER IS INACCURATE
Aleksander Mani1, Ashok Kar 1, Mariano Dimartino2, Josephine Mayer3, Kelvin
Lau1 Keywords: Staging, 7th Edition, lung cancer, 8th Edition
1
Thoracic Surgery, St Bartholomew’S Hospital, London/United Kingdom, 2 St.
Bartholomew’S Hospital, London/United Kingdom, 3Queen’s Hospital, London/
United Kingdom
Background: The new classification for lung cancer refines the T-descriptor MA10: FACING THE REAL WORLD: NEW STAGING SYSTEM AND RESPONSE EVALUATION IN
IMMUNOTHERAPY
criteria into more categories. We examined whether this affects the accuracy TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
of clinical staging, and how this affects the final stage of patients. Methods:
71 patients underwent resection for primary lung cancer from January 2014 to
December 2014. T-component was measured based on the maximum tumour MA10.03 INVESTIGATING THE POTENTIAL UTILITY OF
size on CT, PET-CT and histology report. The possible effect on staging based THE ALTERNATIVE 9TH EDITION IASLC NODAL STAGING
on T-component was compared between both TNMs. Results: PET-CT more CLASSIFICATION IN NSCLC
accurately estimates the pathological size of the tumor (mean difference from Timothy Edwards, Haval Balata, Charlene Tennyson, Philip Foden, Anshuman
histology: CT 3mm (range -1.6 to 2.6cm) and PET-CT 1.3mm (-2 to 2.5cm). Chaturvedi, Philip Crosbie, Richard Booton, Matthew Evison
Discordance between radiological and pathological T-stage was higher with University Hospitals of South Manchester, Manchester/United Kingdom
the 8th edition (7th edition concordance CT 42(59%) and PET-CT 31(43%), 8th
edition CT 31(44%) and PET-CT 29(41%) (CT p=0.01; PET-CT p=0.7)). The final Background: The IASLC lung cancer staging project recently published
stage groupings was also more discrepant in the 8th edition. Concordance was recommendations for the 8th edition of the TNM classification of lung cancer.
for CT 7th Edition 37(54%) vs 8th Edition 21(31%) (p<0.001), and for PET-CT This recommends the same N descriptors be used, however, further analysis
34(48%) vs 19(28%) (p<0.001). The discrepancy in stage grouping is of an alternative system (proposed 9th Edition) was recommended. The aim
contributed significantly by T-stage discordance. In the 30 patients who were of this retrospective study was to assess the utility of this proposed nodal
not upstaged pathologically by pleural invasion or nodal staging, there is a staging system at a large UK tertiary lung cancer centre. Methods: Patients
over 50% increase in inaccuracy of clinical staging in the 8th edition. The CT who underwent surgical resection for non-small cell lung cancer between
concordance was 7th edition 24(80%), 8th edition 13(43%) (p<0.001); and for 2011-2014 (allowing minimum of 2 years follow-up) were identified from a
PET-CT 23(77%) vs 10(33%) (p<0.001). Conclusion: We showed that the 8th prospective database (n=1308). Stratification of pathological N-stage as per

the IASCLC proposal was performed: N0, single station N1 (N1a), multi-statin
N1 (N1b), single station N2 without N1 involvement – skip metastases - (N2a1),
single station N2 with N1 involvement (N2a2), multi-station N2 (N2b) and
N3. Survival data was obtained from national death registries. Results: IMMUNOTHERAPY
There a significant effect of N-stage on mortality using Cox proportional TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
hazards regression analysis, using pN0 (n=848) as the reference group and
adjusting for sex, age and histology (table 1). There appears to be similar
survival outcomes between multi-station N1 (pN1b) and single station N2 skip MA10.06 CENTRALITY DEFINITION IN NON SMALL CELL LUNG
metastases (pN2a1), and single station N2 with N1 involvement (pN2a2) and CANCER. PREDICTOR FOR OCCULT MEDIASTINAL LYMPH NODE
multi-station N2 (pN2b). INVOLVMENT
David Sanchez-Lorente 1, Lucía Milla2, Angela Guirao1, Rudith Guzman1, Marc
Table 1. Boada1, Josep Maria Gimferrer 1, Guillermina Sanchez3, Laureano Molins1
1
General Thoracic Surgery, Hospital Clinic of Barcelona, Barcelona/Spain, 2Hospital
N-stage Hazard Ratio 95% CI p-value Clinic of Barcelona, Barcelona/Spain, 3Nurse of Thoracic Surgery Department,
pN1a (n=146) 1.68 (1.26, 2.26) 0.001 Hospital Clinic of Barcelona, Barcelona/Spain
pN1b (n=55) 2.25 (1.49, 3.39) <0.001 Background: Central tumour location is considered as an independent risk
factor for occult mediastinal metastases in patients with non-small cell lung
pN2a1 (n=50) 2.24 (1.46, 3.45) <0.001
cancer (NSCLC) after negative computerized tomography (CT) and integrated
pN2a2 (n=81) 2.94 (2.15, 4.03) <0.001 positron emission tomography/CT. However, the distinction between a
central and a peripheral tumour has not been codified, some authors consider
pN2b (n=67) 2.99 (2.09, 4.27) <0.001
any tumour in the innerthird of the hemithorax to be central, and others in the
th
Conclusion: The proposed 9 edition N-staging classifications appear to add inner twothirds. The objective of this study is to identify the best centrality
additional insight into prognosis. However, interpretation is limited by the tumour definition for detecting occult mediastinal metastasis. Methods: We
small numbers of patients within the pN1/pN2 sub-groups. 65% of this large retrospectively reviewed our thoracic surgery database for cases between
cohort were pN0 and acted as the reference group and a further 5% were January 2011 and December 2015. It was identified patients with potentially
pNx as no nodes were submitted. Furthermore, the accuracy of pN-staging operable NSCLC screened by CT and PET/CT and they were classified according
is reliant on the quality of intra-operative lymph node sampling. Although to tumour location in the inner third, middle third or outer third. The
significant improvements have been made in this timeframe at our centre prevalence of occult mediastinal lymph node metastases was analysed in
(published previously), any sub-optimal performance has the potential to relation to tumour location. Statistical analysis for best centrality definition
affect the validity of the results, particularly if multi-station N2 disease is was performed. Univariable analysis was performed using the Fisher exact
missed. test and multivarible analysis using logistic regression. Results: A total of 359
patients with clinical operable NSCLC were included in our study. Seventy-five
Keywords: Surgical staging, TNM classification, non small cell lung cancer (20.9%) tumours were located in the innerthird, 137 (38.2%) in the middlethird
and 147 (40.9%) in the outerthird. It was detected 23 patients with N2 disease
and negative TC and PET/CT, 8/38 (21.1%) in the innerthird, 6/121 (5.0%) in the
middlethird and 9/122 (7.4%) in the outerthird. Defining centrality as tumour
MA10: FACING THE REAL WORLD: NEW STAGING SYSTEM AND RESPONSE EVALUATION IN located in the innerthird of the hemithorax the incidence of occult N2 was
IMMUNOTHERAPY 21.1% and 6.2% for central and peripheral tumour respectively. And defining
centrality as tumour located in the inner twothirds the incidence of occult N2
was 8.8% for central tumours and 7.4% for peripheral. Univariable analysis
MA10.05 PROPOSALS FOR THE NOVEL CLINICAL T CATEGORIES shows statistical differences in occult N2 involvement between central
BASED ON THE PRESENCE OF GROUND GLASS OPACITY or peripheral defining central lesion as innerthird (p=0.002), but not for
COMPONENT IN LUNG ADENOCARCINOMA central definition of innternal twothirds (p=0.651). In multivariable analysis
considering centrality possible defenition, histology, Clinical T factor and
Aritoshi Hattori, Takeshi Matsunaga, Kazuya Takamochi, Shiaki Oh, Kenji
Clinical N1 affection, only innerthird as centrality definition was statistical
Suzuki
significance predictor factor for occult mediastinal lymph node involvement
General Thoracic Surgery, Juntendo University, Tokyo/Japan
(p= 0.027) Conclusion: Considering the results of our study the best definition
Background: In lung adenocarcinomas, the histologic lepidic growth for central tumour location is limited to the innerthird of the hemithorax.
pattern tends to correlate with the ground glass opacity (GGO) component, Given the low rate of occult N2 disease in the middle third location, the
while solid components correspond with invasive adenocarcinoma. The systematic evaluation of the mediastinum by ecobronchoscopy and/or
Eighth edition of the TNM staging system suggests that the tumor size be mediastinoscopy in this group of patients is not justified.
determined according to the invasive size excluding the lepidic component. Keywords: Staging, non small cell lung cancer, Centrality, occult N2
However, this new concept causes fatal confusion, i.e., tumors are classified
into a same T category despite the part-solid or pure-solid appearances
provided they showed a same solid component size. Methods: Between
2008 and 2012, we retrospectively evaluated 719 surgically resected cN0 MA10: FACING THE REAL WORLD: NEW STAGING SYSTEM AND RESPONSE EVALUATION IN
lung adenocarcinomas that measures 30mm or less in total dimension to IMMUNOTHERAPY
assess the prognostic impact on the presence of GGO among the Eighth TNM TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
classification. According to the new T category, it was defined based on the
solid component size as follow: Tis; 0 cm (pure-GGO), T1mi; ≤ 5 mm, T1a; 6-10
MA10.07 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION
mm, T1b; 11-20 mm, T1c; 21-30mm. Furthermore, all tumors were classified into
TOMOGRAPHY SCAN IN SOLID-TYPE STAGE-I PULMONARY
2 groups, i.e., GGO or Solid arms based on the presence of GGO component.
Results: Of the cases, 133 (18%) were categorized in Tis, 88 (12%) in T1mi, 121 ADENOCARCINOMAS: WHAT CAUSE FALSE-NEGATIVE CASES?
(17%) in T1a, 244 (34%) in T1b and 133 (19%) in T1c, respectively. Multivariate Filippo Lococo1, Carla Galeone2, Debora Formisano3, Salvatore Bellafiore4,
analysis revealed that both a presence of GGO and solid component were Angelina Filice5, Annunziata Tartaglione5, Alfredo Cesario2, Cristian
independently significant prognostic factors (p=0.007, 0.002). The 5y-overall Rapicetta2, Federica Fioroni6, Tommaso Ricchetti2, Massimiliano Paci2
1
survival (OS) was 99.2% in Tis, 95.8% in T1mi, 96.5% in T1a, 81.8% in T1b and Unit of Thoracic Surgery, IRCCS_Arcispedale Santa Maria Nuova, Reggio Emilia/
66.4% in T1c (p=0.038) with a median follow-up period of 56 months. When Italy, 2Cardio Thoracic and Vascular Surgery, Arcispedale -IRCCS Santa Maria Nuova
we evaluated the impact of T category based on GGO presence, the 5y-OS Di Reggio Emilia, Reggio Emilia/Italy, 3Department of Infrastructure Research and
was significantly different between GGO and Solid arm in each T categories Statistics, Arcispedale -IRCCS Santa Maria Nuova Di Reggio Emilia, Reggio Emilia/
Italy, 4Unit of Pathology, Arcispedale -IRCCS Santa Maria Nuova Di Reggio Emilia,
(T1a; 99.0% vs. 95.7%, p=0.045, T1b; 89.8% vs. 73.3%, p=0.004, T1c; 90.0% vs.
Reggio Emilia/Italy, 5Unit of Nuclear Medicine, Arcispedale -IRCCS Santa Maria
62.6%, p=0.046). Furthermore, clinical T categories significantly separated Nuova Di Reggio Emilia, Reggio Emilia/Italy, 6Medical Physics Unit, Arcispedale
the OS in Solid arm (p=0.015) (T1a vs. T1b; p=0.090, T1b vs. T1c; p=0.037). In -IRCCS Santa Maria Nuova Di Reggio Emilia, Reggio Emilia/Italy
contrast, the 5y-OS was approximately 90% or more in GGO arm despite their
T categories. Moreover, regarding radiological and pathological correlations, Background: False-negative 18F-fluorodeoxyglucose (FDG) uptake can be
the rates of AIS was only 65% in Tis, and 51% showed invasive adenocarcinoma divided into those cases related to technological limitations of positron-
even in T1mi. Conclusion: Clinical T category should be considered based on emission tomography (PET) and others related to inherent properties of
the presence of GGO on thin-section CT, and tumor size should be applied neoplasms. We aim to clarify possible factors causing false-negative (FN) PET
exclusively to radiological solid lung cancer. In contrast, oncological outcomes results in solid-type pulmonary adenocarcinomas (PAs). Methods: From
of the tumor with GGO component were excellent despite their T categories, 01/2007 to 12/2014, among 255 Stage-I NSCLCs we retrospectively review PET/
which should be described as Tis for pure-GGO, and T1a for part-solid tumor. CT-records, clinical information, preoperative thin-section CT-images, and
pathological features (classified by the IASLC/ATS/ERS subtyping criteria) of
Keywords: lung cancer, GGO component, TNM staging
94 consecutive solid-type Stage-I PA undergone surgical resection at Our blocking inhibitory signaling and therefore enhancing T-cell activity against
Institution. Univariate and multivariate logistic analysis were used to identify tumor cells; however, this peculiar mechanism of action might lead to many
and weigh the independent predictors of PET-findings: body weight, blood difficulties in evaluating clinical response with the usual CT imaging due to
glucose level, tumor-size, and histological classification. Results: There were inflammatory patterns that could confuse the evaluation. The aim of this
58 males and 36 females (mean age= 68.7 yrs, range 42-85). Seventeen lesions study was to assess the role of FDG-PET to support clinical decision based on
(18.1%) were judged as PET-negative and 77 lesions (81.9%) as PET-positive. CT scan. Methods: From May 2015 to April 2016, 74 patients with advanced
Overall, mean SUVmax was 8.0 (range 0-35) with higher SUVmax-values pretreated NSCLC received at least one dose of nivolumab (3 mg/Kg every
(p<0.001) in PA>2cm (mean SUVmax=10.6) than PA<2cm (mean SUVmax=4.8). 14 days) within a single-institutional translational research trial. Among
PET false-negative (FN) results were also differently distributed (27.9% in PA these, 58 patients were evaluable for response assessment. The patients
<2cm vs 9.8% in PA>2 cm, p=0.023). When clustering the PA in 2 histological underwent CT scan and FDG-PET every four cycles and, in case of progressive
classes (Class-A [“colloid/mucinous/lepidic”] vs Class-B [“micropapillary/solid/ disease, an additional evaluation was performed after two further cycles in
acinar/papillary”]), the radiometabolic patterns were significantly different order to confirm it. We evaluated the response to treatment by CT scan with
[mean SUVmax 3.8 in Class-A vs 9.9 in Class-B, p<0.001], as reported in Figure 1. RECIST criteria, Immuno-related Response Criteria (irRC), WHO criteria and
Similarly, a different distribution of PET FN-cases was observed (38.7% FN in immunoRECIST criteria, while the metabolic response has been determined
Class-A vs 7.9% FN in Class-B, p=0.001). Table 1 shows the results of with PERCIST criteria. Finally, we determined the concordance in terms of
multivariate logistic analysis. Both the tumor-size (cut-off=2cm) and IASLC/ response between CT evaluation criteria and metabolic response obtained
ATS/ERS aggregated clusters were clinically relevant factors for determining with PERCIST; concordance was calculated with kappa value. Results: Our
whether PET results were negative or positive, but only histology was findings showed a low concordance of all CT scan evaluation criteria to
statistically significant (OR:6.1, 95%CI: 1.85-20.15, p=0.003). PERCIST, the best concordance being between PERCIST and RECIST (K=0.500)
and the worst agreement being between PERCIST and irRC (K=0.295) . In
particular, PERCIST seems to underestimate the progressive disease (PD).
In fact, between 46% and 55% of patients, defined in progression with CT
evaluation criteria were considered in stable metabolic disease (SMD) by
PERCIST; among these, 50% of patients in the RECIST PD group and 80%
of RECIST SD patients were alive at 6 months. Furthermore, in our sample,
between 9% and 18% of patients were considered in progression with CT
evaluation criteria when they were in partial response with PERCIST; these
patients were still alive with a survival similar to those who defined in
partial response with RECIST (>9 months). Conclusion: FDG-PET evaluation
by PERCIST could not be helpful when SMD is reported, in fact, patients
that have a RECIST PD maintain a poor prognosis compared to RECIST SD
between the patients define as SMD. Conversely, PERCIST evaluation could be
informative when it define a partial response, specially when RECIST criteria
show a PD.
Keywords: response evaluation, Nivolumab, PERCIST, RECIST
IMMUNOTHERAPY
MA10.10 [18F]-FDG-PET/CT EARLY RESPONSE TO NIVOLUMAB IN

NSCLC
Dimitri Bellevre1, Gegory Petyt1, Guillaume Collet1, Claude Hossein-Foucher 1,
Simon Baldacci2, Anne Baranzelli2, Franck Semah1, Alexis Cortot 2
1
Nuclear Medicine Department, Lille University Hospital, Lille/France, 2Thoracic
Oncology, Lille University Hospital, Lille/France
Background: Nivolumab is approved for treatment of squamous and non-

squamous advanced NSCLC. Since nivolumab restores antitumor immunity,
it is not clear whether 18F-FDG-PET/CT is able to distinguish response from
tumor progression. We evaluated early metabolic patterns of response
to nivolumab in advanced NSCLC patients. Methods: We retrospectively
reviewed PET/CT scans and paired CT scans from 22 patients with advanced
NSCLC who received nivolumab 3mg/kg every 2 weeks and performed PET/
Conclusion: Among solid-type lung adenocarcinoma, tumor-size and CT before and after 4 infusions of nivulomab. Total Lesion Glycolysis (TLG)
histopathological findings were significantly associated with FDG-uptake. In and Metabolic Tumor Volume (MTV) of every lesion up to 5 per patient were
particular, it warrants attention that lesions ≤2cm and “colloid/mucinous/ measured on baseline and follow-up PET/CT. Percentage changes in MTV
lepidic” adenocarcinomas have a tendency for negative PET-findings. (ΔMTV) and TLG (ΔTLG) between the two PET/CT were calculated. Patients
were classified into responders (nivolumab for >6 months), non responders
Keywords: PET/CT, pulmonary adenocarcinoma, FDG uptake, false-negative
(nivolumab ≤6 months) or having pseudo-progression (PP, nivolumab and
result
clinical benefit >6 months despite initial progressive disease according to
RECIST criteria) Results: Among 22 patients, 6 (27%) were responders, 15
(68%) were non-responders and 1 (4.5%) had PP. Baseline MTV and TLG were
significantly lower in responders than in non-responders (medians 27 vs.
IMMUNOTHERAPY 63 mL, p=0.03 and 124 vs. 254 g, p=0.04, respectively). After 4 infusions of
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 nivolumab, metabolic parameters were significantly lower in responders than
in non-responders (median MTV : 2 vs. 148 mL, p=0.001 and median TLG : 6 vs.
835 g, p=0.002). Mean ΔMTV and ΔTLG were both -88% in responders, and
MA10.09 COMPARISON BETWEEN CT SCAN EVALUATION CRITERIA
+236% and +312% respectively in non-responders, which was significantly
AND PERCIST FOR EVALUATION OF IMMUNE CHECK-POINT different (p=0.0005). The only patient with PP had lower ΔMTV (+11%) and
INHIBITORS RESPONSE ΔTLG (+41%) than non-responders patients. Conclusion: In NSCLC, objective
Giovanni Rossi1, Carlo Genova1, Silvia Morbelli2, Erka Rijavec1, Giulia Barletta1, response and disease progression upon nivolumab usually translate into
Federica Biello1, Claudia Maggioni1, Simone Mennella3, Maria Giovanna Dal early and clear-cut patterns of change in PET/CT. Early PET/CT may help to
Bello1, Roberta Distefano1, Matteo Bauckneht2, Giuseppe Cittadini3, Franco distinguish progression from pseudo-progression.
Merlo1, Gianmario Sambuceti2, Francesco Grossi1
1
Lung Cancer Unit, San Martino Hospital - National Institute for Cancer Research, Keywords: FDG-TEP/CT, Immunotherapy, Nivolumab
Genova/Italy, 2Nuclear Medicine, San Martino Hospital - National Institute for MA10: FACING THE REAL WORLD: NEW STAGING SYSTEM AND RESPONSE EVALUATION IN
Cancer Research, Genova/Italy, 3Radiology, San Martino Hospital - National IMMUNOTHERAPY
Institute for Cancer Research, Genova/Italy TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
Background: Immune check-point inhibitors (ICPIs) exert their activity by

Hospital, Shanghai Jiao Tong University, Shanghai/China

MA10.11 COMPARISON AMONG DIFFERENT RADIOLOGICAL
CRITERIA FOR ASSESSING RESPONSE TO NIVOLUMAB IN Background: Conventionally, the classification of lung cancer and many
other malignancies is determined by the histology of a tumor. Large cell
ADVANCED NON-SMALL CELL LUNG CANCER
neuroendocrine carcinoma (LCNEC) is traditionally classified as a histological
Francesco Grossi1, Giovanni Rossi1, Erika Rijavec1, Giulia Barletta1, Federica variant of large cell carcinoma (LCC), which is a subtype of non-small cell
Biello1, Claudia Maggioni1, Simone Mennella2, Maria Giovanna Dal Bello1, lung cancer (NSCLC). However, LCNEC exhibits differential cytological,
Roberta Distefano1, Giuseppe Cittadini2, Franco Merlo3, Carlo Genova1 morphological, clinical and biological features than those of classic LCC,
1
Lung Cancer Unit, San Martino Hospital - National Institute for Cancer Research, thus rendering controversies regarding its classification. In 2015, with the
Genova/Italy, 2Radiology, San Martino Hospital - National Institute for Cancer integration of immunohistochemical analyses, the World Health Organization
Research, Genova/Italy, 3Clinical Trials Unit, San Martino Hospital - National
(WHO) has re-classified LCNEC under neuroendocrine tumors. Due to the
Institute for Cancer Research, Genova/Italy
rareness of LCNEC, few studies have been conducted on the molecular genetic
Background: Immune check-point inhibitors have dramatically changed the profiling of LCNEC. In this study, we characterized molecular signature
management of advanced non-small cell lung cancer (NSCLC); however, their associated with a cohort of LCNEC, SCLC and LCC using capture-based
mechanism of action creates concerns on the most appropriate method to targeted sequencing. Methods: We performed capture-based targeted
determine radiological responses to this drug class. The aim of this study is to sequencing on 30 surgically resected samples from patients with lung cancer
compare a set of different evaluation criteria for patients receiving nivolumab using BurningRock Biotech’s OncoScreen Panel. This panel, consisting of all
for advanced NSCLC. Methods: Patients with pre-treated advanced NSCLC exons and critical introns of 295 genes, covering multiple classes of somatic
were enrolled in a single-institutional translational research study in the mutations, including single nucleotide variation (SNVs), rearrangements, copy
San Martino Hospital – National Institute for Cancer Research, Genova, Italy number variations (CNVs) and insertions and deletions (INDELs), can be used
and received nivolumab (3 mg/kg every 14 days). Computed tomography to detect genetic alterations both qualitatively and quantitatively. Among
(CT) was performed at baseline and after every 4 administrations. The the 30 patients, 15 of them were diagnosed with LCNEC, 5 with LCC and 10
assessments were performed according to Immune-related response criteria with small cell lung cancer (SCLC). Results: While no statistically significant
(irRC), response evaluation criteria in solid tumors (RECIST 1.1), World Health difference was observed in total number of mutations among the three
Organization (WHO), and immune-related RECIST (irRECIST), which are subtypes, LCC carries the most number of somatic mutations followed by
recently proposed based on the original RECIST with the following differences LCNEC then SCLC. Overall, we identified 331 mutations with TP53 being the
derived by irRC: 1) new lesions do not automatically define progressive disease most frequently mutated gene in all three subtypes. Genes with recurrent
(PD), but are added to the target lesions count; 2) PD has to be confirmed somatic mutations detected in LCNEC, but not in LCC or SCLC include RUNX1,
with a subsequent CT-scan after 2 additional cycles. The concordance among ERBB4, BRCA1, and EPHA3. Copy number analysis revealed a higher prevalence
the different criteria was determined with Cohen’s kappa coefficient (K). of CNV in LCNEC, with 60% of cases harboring such alteration. There is no
Results: Fifty-two patients were eligible: median age= 70 years (44-85); male/ common CNVs shared among all three subtypes. NFкBIA amplification is the
female: 70%/30%; current or former smokers= 87%; non-squamous/squamous only common CNV found in both LCNEC and LCC; and AKT2 amplification is
histology= 79%/21%; median number of cycles= 6 (4-29). The following shared by LCNEC and SCLC. Most CNVs are subtype-specific. Interestingly, one
responses were observed: RET-fusion was discovered in one LCC sample and one EGFR exon 19 deletion
accompanied by EGFR copy number amplification was discovered in one
LCNEC sample. Conclusion: Targeted deep sequencing reveals distinct genetic
profile for LCNEC compared to LCC and SCLC. LCNEC harbors more CNV and
Partial Response Stable Disease Progressive Disease contains a panel of genes, including RUNX1, ERBB4, BRCA1 and EPHA3 that are
more frequently mutated comparing to LCC and SCLC.
First evaluation (4 cycles)
Keywords: LCNEC, NGS, molecular profiling
RECIST 1.1 4 (7.7%) 19 (36.5%) 29 (55.8%)
irRC 3 (5.8%) 23 (44.2%) 26 (50%)
WHO 3 (5.8%) 20 (38.5%) 29 (55.8%) MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS
irRECIST 4 (7.6%) 24 (46.2%) 24 (46.2%)
Best Response MA11.02 MUTATIONAL BURDEN IN PULMONARY

NEUROENDOCRINE TUMORS (PUNETS)
Partial Response Stable Disease Progressive Disease
Ivana Sullivan1, Myriam Kossai2, Gwénaël Le Teuff2, Marc Deloger2, Nicolas
RECIST 1.1 9 (17.3%) 14 (26.9%) 29 (55.8%) Dorvault2, Letizia Gianoncelli3, Vincent De Montpreville4, Bastien Job2, Maria
Bluthgen5, Benjamin Besse6, Jean-Charles Soria5, Julien Adam2, Jean-Yves
irRC 8 (15.4%) 19 (36.5%) 25 (48.1%) Scoazec2, Eric Baudin2, David Planchard2
1
WHO 7 (13.5%) 17 (32.7%) 28 (53.8%) Medical Oncology, Gustave Roussy, Villejuif/France, 2Gustave Roussy, Villejuif/
France, 3Istituto Clinico Humanitas, Rozzano/Italy, 4 Centre Chirurgical Marie-
irRECIST 11 (21.2%) 18 (34.6%) 23 (44.2%) Lannelongue, Le Plessis-Robinson/France, 5Medical Oncology Department,
Gustave Roussy, Villejuif/France, 6Department of Cancer Medicine, Gustave Roussy,
Generally, the concordance between first evaluation and best response was Villejuif/France
good for all the criteria (K ranging from 0.783 to 0.839); the concordance
between irRECIST and irRC was high (K= 0.828) and RECIST 1.1 had a good Background: Tumor mutational load (TML) by whole-exome sequencing
concordance with IRC (K= 0.734), irRECIST (K= 0.767), and WHO (0.766). (WES) is a potential determinant of response to immune checkpoint blockers.
Conclusion: The different response assessment methods were generally The use of PD-L1 as a predictive biomarker for use of PD-1/PD-L1 inhibitors is
concordant. Since response is more easily assessed with irRECIST than with limited. To date, there are few data concerning TML in puNETs. Methods: WES
irRC, the former might be proposed as an appropriate method of response was performed in fresh-frozen tumor-normal pairs from 35 typical carcinoid
evaluation. (TC), 4 atypical carcinoid (AC) and 9 large-cell neuroendocrine carcinoma
(LCNEC) consecutively collected. Exome enriched libraries were sequenced
Keywords: Response criteria, RECIST 1.1, immuno-related response criteria, on an Illumina HiSeq 2000 with a paired-end 2 x 100 bp protocol. Reads were
Nivolumab aligned to the reference hg19 using an implementation of the Burrows-
Wheeler Aligner, and a BAM file was produced for each tumor and normal
sample using the Picard pipeline. The MuTect algorithm was used to identify
SSNVs in WES data. We used a minimal allelic fraction cutoff of 0.1. Patients’
characteristics and TML were described (median and interquartile for
SESSION MA11: NOVEL APPROACHES IN SCLC AND NEU- quantitative variables and frequencies for qualitative variables). To evaluate
ROENDOCRINE TUMORS the effect of some factors on the TML, an analysis of variance was used. A log
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 transformation was performed according to the distribution of the TML. The
median follow-up was estimated using the Schemper’s method. The number
of relapses and deaths was reported. Results: Cohort included 24 male and
24 female. Median age at diagnosis was 57 [Q1= 46; Q3= 70] years, 38% of
MA11.01 MOLECULAR PROFILING OF LARGE CELL
carcinoids (TC+AC) and 89% of LCNEC were smokers, 26 (54%) stage I, 16 (34%)
NEUROENDOCRINE CARCINOMA USING CAPTURE-BASED
stage II, 3 (6%) stage III and 3 (6%) stage IV. All patients underwent surgery
TARGETED SEQUENCING and 5 (10%) received neoadjuvant treatment. Median follow-up was 32.6
Zhen Zhou1, Lei Zhu2, Shun Lu1, Jie Zhang2 (min= 4.4; max= 179.9) months; there were 8 (17%) relapses (6/9 LCNEC, 2/39
1
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai carcinoids) and 10 deaths. On average, 11.6 Gb of sequence were produced per
Jiao Tong University, Shanghai/China, 2Department of Pathology, Shanghai Chest sample, aiming a mean coverage of 72X. Overall median TML was 0.31/Mb [Q1=
0.22; Q3= 0.67], significantly lower in carcinoids tumors than LCNEC (0.28 [Q1= role in the detection of pre-clinical cancer. Small-cell lung cancer (SCLC)
0.20; Q3= 0.38]/Mb vs. 2.98 [Q1= 1.20; Q3= 4.84]/Mb, respectively, p<0.0001). is an excellent candidate for early detection given there are no successful
Similar findings were observed among smoker vs. non-smoker patients (0.28 therapeutic options for late-stage disease, and it displays universal
[Q1= 0.18; Q3= 0.38]/Mb vs. 0.60 [Q1= 0.28; Q3= 2.98]/Mb, respectively, p=0.04). inactivation of TP53 (Peifer and Fernandez-Cuesta et al., Nat Genet 2012;
Both variables were found to be independently correlated with TML within George et al., Nature 2015). Methods: We assessed the presence of TP53
the ANOVA test (p=0.0016). Conclusion: Our findings provide a unique portrait mutations in the cell-free DNA (cfDNA) extracted from the plasma of 51 SCLC
of puNETs, revealing different histotype mutational burden. Continued cases and 123 non-cancer controls. The results were further validated in an
work in harnessing immunological data in puNETs are needed for better independent series of 102 non-cancer controls. We identified mutations
understanding immunotherapy-treatment option in this orphan disease. using Needlestack (Delhomme et al., in preparation; https://github.com/
IARCbioinfo/needlestack), a pipeline specifically designed to accurately
Keywords: Tumor mutational load, whole-exome sequencing, pulmonary detect variants at very low allelic fractions (AF). Results: We detected TP53
neuroendocrine tumors mutations in the cfDNA of 49% of the SCLC patients (35.7% of the stage
I-II). While statistically significant in cases versus controls (p-value=6x10 -9),
TP53 mutations were also detected in the cfDNA of 11.4% of the non-cancer
controls, and these results were confirmed in the replication series (10.8%).
MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS The presence of TP53 mutations in controls was not correlated with age,
smoking, or alcohol-intake status. There was a statistically significant
difference between the mutational patterns found in cases versus controls
MA11.03 INSM1 IS A NOVEL BIOMARKER AND A CRUCIAL (p-value=0.008): within controls the fraction of nonsense, indel, or splicing
REGULATOR OF THE NEUROENDOCRINE DIFFERENTIATION mutations was lower than in cases. The median AF of the TP53 mutations
PATHWAY IN NEUROENDOCRINE TUMOURS OF THE LUNG detected in the five stage I-II SCLC (0.9%) was not significantly different
from that found in controls (1.2%; p-value=0.64), while it differed from
Fujino Kosuke 1, Kazuhiro Yasufuku2, Makoto Suzuki3, Takaaki Ito4
1
the median AF of stage III-IV SCLC tumors (8.2%; p-value=2x10 -6). Finally,
Division of Thoracic Surgery, University Health Network, Toronto/ON/Canada, we sequenced the DNA extracted from the white-blood cells (WBC) of 39
2
Division of Thoracic Surgery, Toronto General Hospital, University Health Network,
cfDNA TP53-positive patients, from which material was available (19 cases
Toronto/ON/Canada, 3Department of Thoracic Surgery, Graduate School of Medical
Science, Kumamoto University, Kumamoto, Japan, Kumamoto/Japan, 4Department and 20 controls). Four cfDNA TP53 mutations (1 case and 3 controls) were
of Pathology and Experimental Medicine, Kumamoto University, Graduate School detected in the WBC DNA, with similar AFs to those found in the cfDNA.
of Medical Sciences, Japan, Kumamoto/Japan These AFs, below 11%, are consistent with a somatic origin in both cfDNA
and WBC DNA. Conclusion: The detection of TP53 mutations in 11% of the
Background: Insulinoma-associated protein 1 (INSM1) is expressed 225 non-cancer controls suggests that somatic mutations in cfDNA among
predominantly in embryonic developing neuroendocrine (NE) tissues, and the individuals without any cancer diagnosis is a common occurrence, and poses
expression is significantly reduced/restricted in adult tissues. We previously serious challenges for the development of ctDNA screening tests for the
revealed that INSM1 is expressed exclusively in small cell lung cancer (SCLC) early diagnosis of cancer (Fernandez-Cuesta, Perdomo, and Avogbe et al.,
compared to non-small cell lung cancer (NSCLC). The significance of the EBioMedicine 2016). We will discuss these results as well as follow-up analyses
expression of INSM1 in lung cancer has been largely unknown. We investigated in retrospective and prospective series.
the utility of INSM1 as a novel immunohistochemical marker and researched
the biological significance in lung cancer cell lines. Methods: We compared Keywords: TP53, ctDNA, Early Detection, SCLC
INSM1 as an immunohistochemical marker for NE tumours of the lung to
conventional markers (chromogranin A (CGA), synaptophysin (SYP), and
CD56). To elucidate the biological function of INSM1 in the NE differentiation
MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS
pathway, we conducted INSM1 gene knockdown/overexpression experiments TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
using human lung cancer cell lines. Results: INSM1 was expressed in 100%
of SCLCs (44/44), Large cell neuroendocrine cell carcinomas (7/7), and
Carcinoids (11/11), but was not expressed in NSCLCs (90 adenocarcinomas MA11.06 SWOG 0124: PLATINUM-SENSITIVITY STATUS AND POST-
and 47 squamous cell carcinomas). This novel immnohistochemical marker PROGRESSION SURVIVAL IN PATIENTS WITH EXTENSIVE-STAGE
showed high sensitivity and specificity when compared to conventional NE SMALL CELL LUNG CANCER
markers. We demonstrated that knockdown of INSM1 expression resulted in Primo Lara1, Jieling Miao2, James Moon3, Mary Redman2, David R. Gandara4,
significant reduction of NE molecules in SCLC cell lines, and overexpression of Karen Kelly5
INSM1 induced NE differentiation in NSCLC cell lines. Conclusion: INSM1 was 1
UC Davis Comprehensive Cancer Center, Sacramento/CA/United States of
a superior NE immunohistochemical marker when compared to conventional America, 2 Swog Statistical Center, Seattle/WA/United States of America, 3Swog
markers. Furthermore, our biological molecular experiments revealed that Statistical Center, Seattle/United States of America, 4Division of Hem-Oncology,
INSM1 is a critical upstream regulator of the NE differentiation pathway in UC Davis Comprehensive Cancer Center, Sacramento/CA/United States of America,
5
SCLC cell lines. The elucidation of the significance of INSM1 expression in Hematology Oncology, UC Davis Comprehensive Cancer Center, Sacramento/CA/
lung cancer strongly supports the diagnosis of NE tumours of the lung and United States of America
promotes the understanding of the molecular biology of these tumours.
Background: Patients with extensive stage small cell lung cancer (ES-
Keywords: Insulinoma-associated protein 1, Neuroendocrine Tumours of the SCLC) who progress after frontline platinum-based chemotherapy are
Lung, small cell lung cancer often considered “platinum-sensitive” (progression ≥ 90 days from last
platinum dose) or “platinum-refractory” (progression < 90 days), as each
group reportedly has differential overall survival (OS) outcomes. In a pooled
analysis of recent SWOG trials of second and/or third-line targeted therapy,
MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS we showed that platinum-sensitivity status may no longer be as strongly
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 associated with OS (Lara et al, JTO 2015). We assessed post-progression
survival (PPS) following frontline platinum-based therapy in the context
of platinum sensitivity status in ES-SCLC patients treated on SWOG 0124, a
MA11.05 A CASE-CONTROL STUDY TO TEST THE USE OF CTDNA IN
phase III trial of Irinotecan/Cisplatin vs Etoposide/Cisplatin. Methods: Data
THE EARLY DETECTION OF SCLC REVEALS TP53 MUTATIONS IN
from 657 patients enrolled in S0124 were pooled. PPS was calculated as OS
NON-CANCER CONTROLS from the reported progression date. Crude PPS was evaluated according
Lynnette Fernandez-Cuesta1, Sandra Perdomo2, Patrice Avogbe1, Noémie to platinum-sensitivity status. Hazard ratios (HRs) for PPS accounting for
Leblay1, Tiffany Delhomme1, Valerie Gaborieau1, Behnoush Abedi-Ardekani1, platinum-sensitivity and baseline clinical covariates (i.e., measured at the
Estelle Chanudet1, Magali Olivier 1, David Zaridze3, Anush Mukeria3, Marta time of first line therapy) were calculated using single and multivariable Cox
Vilensky4, Ivana Holcatova5, Jerry Polesel6, Lorenzo Simonato7, Cristina Proportional Hazard models. Baseline covariates were included in a logistic
Canova7, Pagona Lagiou8, Christian Brambilla9, Elisabeth Brambilla9, Graham regression model to identify predictors of platinum-sensitivity. Recursive
Byrnes1, Ghislaine Scelo1, Florence Le Calvez-Kelm1, Matthieu Foll1, James partitioning analysis (RPA) was performed to define prognostic risk groups.
Mckay1, Paul Brennan1 Results: Of 657 patients, 534 had a progression date and thus included in
1
Genetic Cancer Susceptibility Group, International Agency for Research on Cancer the analysis: 162 (25%) were platinum-sensitive and 372 (75%) refractory.
(Iarc-Who), Lyon/France, 2Universidad El Bosque, Bogota/Colombia, 3Russian N.N. Fewer patients with PS 0 (32% vs. 41%) and more patients with weight loss
Blokhin Cancer Research Centre, Moscow/Russian Federation, 4Instituto Angel > 5% (40% vs. 31%) were seen in the refractory group. Crude unadjusted
Roffo, Buenos Aires/Argentina, 5Charles University, Praga/Czech Republic, 6Cro PPS was higher in platinum-sensitive vs refractory patients (median PPS
Aviano National Cancer Institute, Aviano/Italy, 7University of Padova, Padova/Italy,
8 7.5 vs. 4.3 months; HR=1.64, p <0.001, 95%CI 1.356, 1.981). A multivariable
University of Athens Medical School, Athens/Greece, 9 CHU de Grenoble, Grenoble/
France Cox model showed that baseline elevated serum lactate dehydrogenase
(LDH; HR=0.66, p<0.001) and platinum-sensitivity status (HR=1.54, p<0.001)
Background: Circulating-tumor DNA (ctDNA) is emerging as a key potential were independently associated with PPS. None of the baseline covariates
biomarker for post-diagnosis surveillance but it may also play a crucial predicted for platinum-sensitivity. Prognostic groups with differential PPS

based on platinum-sensitivity status, gender, and LDH were identified by

RPA. Conclusion: PPS was significantly higher for S0124 patients categorized MA11.09 PROGASTRIN-RELEASING PEPTIDE (PROGRP) TO RULE
as platinum-sensitive vs. refractory. Limitations of this work include lack of OUT PROGRESSIVE DISEASE IN PATIENTS WITH SMALL CELL LUNG
relevant clinical data at the time of progression and number and type of post- CARCINOMA (SCLC)
progression therapies. These data have implications for the development of
Thomas Muley1, Xiaotong Zhang 2, Stefan Holdenrieder3, Catharina Korse4,
ES-SCLC trials in the salvage setting. [Supported by NIH/NCI/NCTN grants to
Xiuyi Zhi5, Rafael Molina6, Zhongjuan Liu2, Gunther Hartmann3, Michel Van
SWOG: CA180888, CA180819, and in part by Pharmacia & Upjohn, a subsidiary
Den Heuvel4, Kun Qian5, Ramon Marrades6, Christine Engel7, Ying He7, Birgit
of Pfizer. ClinicalTrials.gov Identifier: NCT00045162]
Wehnl7, Farshid Dayyani8, Felix Jf Herth1
1
Keywords: platinum refractory, small cell lung cancer, post-progression Translational Research Unit (Stf), Translational Lung Research Center Heidelberg
survival, platinum sensitive (TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at
Heidelberg University Hospital, Heidelberg/Germany, 2Peking Union Medical
College Hospital (PUMCH), Beijing/China, 3University of Bonn, Bonn/Germany,
4
The Netherlands Cancer Institute, Amsterdam/Netherlands, 5 Xuanwu Hospital,
Capital Medical University, Beijing/China, 6Hospital Clinic, University of Barcelona,
MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS Barcelona/Spain, 7Roche Diagnostics GmbH, Penzberg/Germany, 8Roche
Diagnostics International, Rotkreuz/Switzerland
Background: For patients with SCLC, response to chemotherapy is monitored

MA11.07 IMPROVED SMALL CELL LUNG CANCER (SCLC) RESPONSE
by computed tomography (CT) scans, which can be costly and inconvenient.
RATES WITH VELIPARIB AND TEMOZOLOMIDE: RESULTS FROM A A previous study showed that baseline levels (>100 pg/ml) of the tumor
PHASE II TRIAL marker, ProGRP, were positively correlated with advanced SCLC, and a
Lauren Averett Byers 1, Lee Krug2, Saiama Waqar3, Afshin Dowlati4, Christine decline in ProGRP levels during treatment was associated with response.1
Hann5, Alberto Chiappori6, Taofeek Owonikoko7, Kaitlin Woo8, Yevgeniya However, the best approach to fully exploit ProGRP for monitoring treatment
Bensman2, Brenda Hurtado2, Robert Cardnell1, Lixia Diao9, Youhong Fan1, response is still unknown. The objective of this study was to determine if
Junya Fujimoto10, Jaime Rodriguez-Canales10, Lihong Long11, Erik Sulman12, progression could be ruled out solely by combining the changes in ProGRP
Ignacio Wistuba10, Jing Wang9, William Travis13, Alice Chen14, Charles Rudin15, levels over two chemotherapy cycles. Methods: Patients with SCLC receiving
Mark Kris16, Martin Fleisher2, John Heymach1, M Catherine Pietanza2 first-line platinum-based doublet chemotherapy or a single-agent cytotoxic
1
Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson in any subsequent treatment line were included from six centers in Europe
Cancer Center, Houston/TX/United States of America, 2Memorial Sloan and China. Samples were collected prospectively and ProGRP levels were
Kettering Cancer Center, New York/NY/United States of America, 3Washington measured in serum or plasma samples using a fully automated ProGRP assay
University, St Louis/MO/United States of America, 4University Hospitals Case at baseline and after chemotherapy cycles 1 and 2. Only patients with blood
Medical Center, Cleveland/OH/United States of America, 5The Sidney Kimmel samples taken at these time points and with elevated baseline ProGRP >100
Comprehensive Cancer Center at Johns Hopkins University, Baltimore/MD/United
pg/ml were eligible for this analysis. A logistic regression model was calculated
States of America, 6Moffitt Cancer Center, Tampa/FL/United States of America,
7
Hematology & Medical Oncology, Emory University School of Medicine, Atlanta/ to incorporate changes after the first cycle (i.e. from baseline to the end
GA/United States of America, 8Epidemiology and Biostatistics, Memorial Sloan of cycle 1) and in between cycles (i.e. end of cycle 1 to the end of cycle 2).
Kettering Cancer Center, New York/NY/United States of America, 9Bioinformatics & Progression was ascertained with CT scans. A non-progressor was defined as a
Computational Biology, University of Texas MD Anderson Cancer Center, Houston/ patient with complete response, partial response, or stable disease, according
TX/United States of America, 10Translational Molecular Pathology, The University to the RECIST v1.1 or WHO criteria. Progressors were patients with progressive
of Texas M.D. Anderson Cancer Center, Houston/TX/United States of America, disease only. Results: Overall, 123 patients (n=108 non-progressors, n=15
11
Pathology, University of Texas MD Anderson Cancer Center, Houston/TX/United progressors) satisfied the eligibility criteria. Median age was 62.0 years (range
States of America, 12Radiation Oncology, University of Texas MD Anderson Cancer
36.0–83.0), 56% were male, and 78% reported to be current or past smokers.
Center, Houston/TX/United States of America, 13Dept of Pathology, Memorial
Sloan Kettering Cancer Center, New York/NY/United States of America, 14Division of In this population, a decline in ProGRP from both baseline to cycle 1 and from
Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda/MD/United cycle 1 to cycle 2 was associated with non-progression (AUC 91.5%; 95% CI:
States of America, 15Medicine, Memorial Sloan Kettering Cancer Center, New York/ 85.3−97.8; sensitivity 100%; specificity 71%). All patients who experienced
NY/United States of America, 16Thoracic Oncology, Memorial Sloan Kettering Cancer a >25% relative decline in ProGRP levels after the first chemotherapy cycle,
Center, New York/NY/United States of America followed by any further decrease (>0%) after the second cycle, were found to
be non-progressors. Conclusion: By measuring the change in ProGRP levels
Background: PARP1 is overexpressed in small cell lung cancer (SCLC) at baseline and after each of the two subsequent chemotherapy cycles, we
and represents a novel therapeutic target for this disease. Preclinical were able to identify patients with non-progressive disease. This might reduce
data indicates that combining veliparib (an oral PARP-1/2 inhibitor) and the need for interim CT scans.References 1. Muley, et al. Journal of Thoracic
temozolomide (TMZ) results in synergistic tumor growth delay or regression. Oncology 2015; 10(9) Supplement 2:MINI27.13
In this study, we investigated whether adding veliparib to TMZ would improve
outcomes in patients with relapsed sensitive and refractory SCLCs. Candidate Keywords: SCLC, ProGRP
predictive biomarkers, including SLFN11, were then explored. Methods: SCLC
patients previously treated with 1 or 2 prior regimens were enrolled in the
trial and randomized 1:1 to receive oral TMZ 150-200mg/m2 /day (D1-5) with
either veliparib or placebo 40mg twice daily, orally (D1-7) (NCT01638546). MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS
Primary endpoint was 4-month progression free survival (PFS). Data were TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
analyzed in patients with platinum sensitive (progression >60 days after 1st
line therapy) or refractory disease (progression ≤60 days after 1st line therapy,
MA11.10 PROSPECTIVE STUDY OF GENOME-WIDE STREXOME AND
or in need of 3rd line treatment). Archived tissue was available for 53 patients
for biomarker analysis. Results: 104 patients were enrolled and 100 patients
TRANSCRIPTOME PROFILING IN PATIENTS WITH SMALL CELL LUNG
were treated. Baseline characteristics were balanced between treatment CANCER PROGRESSING AFTER 1ST LINE THERAPY
arms: 52% female; median age 62.5 (range, 31-84); 59% refractory disease; Glen Weiss 1, Ashish Sangal1, Heather Barilla1, Sara Byron2, Jeff Kiefer2, Jessica
33% needing 3rd-line therapy. Progression free survival at 4-months was Aldrich2, Timothy Whitsett2, John Carpten2, David Craig2
similar between the two arms, 36% vs. 27% (p=0.39). However, in 93 evaluable 1
Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear/
pts, response rate was significantly higher in pts treated with veliparib/TMZ AZ/United States of America, 2Translational Genomics Research Institute, Phoenix/
compared to TMZ alone (39% vs 14%, p =0.016). Median overall survival: 8.2 AZ/United States of America
mos (95% CI: 6.4-12.2) in veliparib arm and 7 mos (95% CI: 5.3-9.5) in placebo
Background: Small cell lung cancer (SCLC) that has progressed after 1st
arm, p = 0.50. Grade 3/4 thrombocytopenia and neutropenia more commonly
line therapy has few effective treatments and no new class of approved
occurred in the veliparib/TMZ arm: 50% vs 9% and 31% vs 7%, respectively.
therapies in over 20 years. Paired tumor-normal exome and transcriptome
Levels of SLFN11, a marker of SCLC response to PARP inhibition in preclinical
sequencing efficiency, coverage, cost, and analytics has improved over the
models, were assessed by immunohistochemistry. High SLFN11 in patient
last decade and has begun to be applied in the clinic. In this prospective study,
tumors (obtained at original diagnosis) was associated with a trend towards
we used genome-wide strexome (exome+structural variation) plus whole
better overall survival in the veliparib/TMZ arm, but no difference in outcome
transcriptome sequencing (NGS) to identify genomic events and associated
in the TMZ alone arm. Additional correlative studies are ongoing, including
expression changes in advanced SCLC and attempt to prescribe systemic
assessment of MGMT promoter methylation, and will be available at the time
therapy based on the results (NCT02297087, study was funded by SU2C).
of presentation. Conclusion: The combination of veliparib/TMZ increased
Methods: After informed consent a prospective fresh frozen tumor biopsy
response rates significantly, compared to TMZ alone. Hematologic toxicities
was obtained. Germline DNA was extracted from PBMC and reference normal
of the combination may have impacted PFS (which was not significantly
tissue RNA was obtained commercially. Strexome and RNA-seq libraries
different between the arms) by limiting dosing. Biomarkers such as SLFN11,
were prepped and NGS, data analysis, and reporting were performed in a
ATM, or MGMT promoter methylation could potentially help guide patient
CLIA-certified CAP accredited environment. Results: The study completed
selection in the SCLC population.
its accrual goal of 12 evaluable patients. There was one screen failure due to
Keywords: Temozolomide, SCLC, veliparib anticipated inadequate sample yield because of tumor location. The cohort
Copyright © 2016
TUESDAY, DECEMBER by- 14:15-15:45
6, 2016 the International Association for the Study of Lung Cancer S207
included 10 women, median age was 56.5 years and had 3 never smokers. All 1.1-137.4, p=0.045) and being younger than 65 years of age (OR: 4.8, 95% CI:
patients received prior platinum-based chemotherapy and were receiving 1-23.2, p=0.049) were found to be independent risk factors for HP metastasis.
>1st line systemic treatment while awaiting NGS results. The minimum tumor Conclusion: HP metastasis might be more common in SCLC patients. Reducing
content for successful NGS was 20%. The median turnaround time from the dose to the HP by HA-WBRT plan in SCLC may be risky for the development
sample collection to report was 27 days (range 21-38). Average strexome of HP metastasis compared with other malignant solid tumors.
coverage was 420X (tumor), 200X (germline), with an average of 277 million
RNA reads generated for tumors. All patients had ³2 clinically actionable Keywords: hippocampal avoidance, small cell lung cancer
targets identified (associated with a commercially available, FDA-approved
drug by predefined rules), median 4 targets (range 2-8). Three patients
received treatment identified by NGS. One has continuing partial response
by RECIST 1.1 >8 months on a clinical trial involving PD-1 inhibitor+irinotecan
(MLH1 mutation); treatment linked to NGS was already initiated prior to the SESSION MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY
report becoming available. One is too early to evaluate on olaparib (PARP1 TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
mutation), and one had disease progression on dasatinib (KIT overexpression)
as best overall response. One patient has not yet received NGS recommended
therapy, and the remaining 8 evaluable patients had clinical deterioration MA12.01 NEXT GENERATION SEQUENCING BASED CLINICAL
or died before NGS recommended therapy was initiated. Conclusion: SCLC FRAMEWORK FOR ANALYSES OF TREATMENT PREDICTIVE
after 1st line therapy tends to have more rapid progression and deterioration MUTATIONS AND GENE FUSIONS IN LUNG CANCER
making NGS application for systemic therapy challenging. Either applying
NGS earlier in the earlier stages of disease course or further improvements in Kajsa Ericson Lindquist1, Anna Karlsson2, Per Levéen1, Hans Brunnström1,
turnaround time may better address these challenges. Christel Reuterswärd2, Karolina Holm2, Mats Jönsson2, Karin Annersten2,
Frida Rosengren2, Karin Jirström1, Jaroslaw Kosieradzki3, Lars Ek 3, Åke Borg2,
Keywords: small cell lung cancer, clinical trials, whole transcriptome Maria Planck2, Göran Jönsson2, Johan Staaf2
1
sequencing, next-generation sequencing Pathology, Regional Laboratories Region SkÅne, Lund/Sweden, 2Oncology and
Pathology, Lund University, Lund/Sweden, 3Department of Respiratory Medicine
and Allergology, Skane University Hospital, Lund/Sweden
Background: The use of new, emerging techniques in the search of tailored

TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 patient therapies is rapidly becoming a reality. Here we describe the
optimization and implementation of next generation sequencing for
treatment predictive mutation screening in parallel with gene fusion
MA11.11 IS HIPPOCAMPAL AVOIDANCE DURING WHOLE BRAIN status of ALK, RET and ROS1 in non-small cell lung cancer (NSCLC) patients.
RADIOTHERAPY RISKY FOR SMALL CELL LUNG CANCER PATIENTS? Methods: The Illumina TruSight tumor 26-gene NGS panel was validated
Esra Kirakli1, Ozgur Oztekin2 in 81 clinical routine FFPE or cytology specimens and implemented in 533
1
Radiation Oncology, Dr. Suat Seren Göğüs Hastalıkları Ve Cerrahisi Eğitim Ve diagnostic NSCLCs during one year of clinical analysis. In parallel, a RNA-based
Araştırma Hastanesi, Izmir/Turkey, 2Diagnostic Radiology, Tepecik Education and NanoString method was evaluated in 169 cases for gene fusion status of
Research Hospital, Izmir/Turkey ALK, RET and ROS1. Results: We have successfully established a streamlined
workflow with a 5-day turnaround time from specimen arrival to mutation
Background: Hippocampal avoidance (HA) during whole brain radiotherapy report. The concordance in the validation cohort was 99% for comparable
(WBRT) is performed to prevent neural stem-cell injury causing decreased variants. In the 533 diagnostic samples, 1-2 variants were detected in 79% of
neurocognitive function. Nevertheless, the estimated risk for metastases in the cases. Most frequently mutated genes included TP53, KRAS, EGFR, STK11,
HA area in small cell lung cancer (SCLC) patients is unknown. The current study and BRAF, all with differences in mutational patterns between histological
aimed to characterize the metastatic distribution within the brain relative to subgroups. The RNA-based NanoString assay was successfully established
the hippocampus and estimate the incidence of hippocampal metastasis in and validated. The success rate in the 169 cases was 80% and 10 gene fusions
SCLC patients and also identify clinical and radiographic variables that may be were found (five ALK fusions, three RET fusions and two ROS1 fusions) all in
associated with the presence of metastases within the HA area. Methods: adenocarcinomas. Integration of mutation and gene fusion status revealed
SCLC patients treated with WBRT between January 2010 and December 2015 that 68% of adenocarcinomas, 13% of SqCCs and 56% of NSCLC-NOS harbored
were reviewed. T1-wighted, post-contrast axial MRI (1.5 or 3 Tesla) images ≥1 actionable alteration ALK, RET, ROS1, EGFR, KRAS, PIK3CA, BRAF, NRAS,
obtained just before therapeutic cranial irradiation were retrieved and MAP2K1, ERBB2 or AKT1. Specifically, in 13.2% of the adenocarcinomas
reviewed for each patient. The HA area was generated by expanding the where no EGFR or ALK alteration was detected emerging targeted therapy
hippocampal contour by 5 mm volumetrically to account for necessary dose may be considered in addition to the 15.3% of patients that was eligible for
fall-off between the hippocampus (HP) and the whole brain planning target EGFR or ALK inhibitors. The corresponding proportions for SqCCs were 5.5%
volume. Metastatic lesions within HP or HA area were defined as HP in addition to the 2.2%, and for NSCLC-NOS 2.5% in addition to the 11.2%
metastasis. HP metastasis rate was evaluated and characteristics of patients eligible for EGFR or ALK inhibitors. Conclusion: Next generation sequencing
with HP metastasis were analyzed and compared to patients without HP in combination with the NanoString technology is time- and cost efficient
metastasis. Results: 54 patients evaluated with cranial MRI were enrolled. HP in the diagnostic routine for treatment predictive mutation screening and
metastasis rate was 32% (17 patients). 4.4% of all metastases involved the HP gene fusion status detection. The techniques represent valuable tools for
and HA area (2.2% of metastases each) pinpointing patients eligible to standard targeted therapies in addition to
new emerging therapies.
Keywords: NGS, clinical routine, mutation, personalized medicine
MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY

MA12.02 MMP12 AND LMO7, TWO KEY PLAYERS ON OPPOSITE

SIDES OF EARLY LUNG SQUAMOUS CELL CARCINOMA
DEVELOPMENT
Angela Barrett 1, Sofia Lourenco1, Krishna Kolluri1, Bernadette Carroll2, Mary
Falzon2, Elaine Borg2, Jeremy George2, Sam Janes3, Vitor Teixeira1
1
Medicine, University College London, London/United Kingdom, 2University College
London Hospital, London/United Kingdom, 3Lungs for Living Research Centre, UCL
Respiratory, University College London, London/United Kingdom
Background: Our laboratory has a unique cohort of patients with pre-invasive

lung squamous cell carcinoma (SqCC) lesions, within which there is a clear
discrepancy between the prevalence of pre-invasive lesions and the incidence
of lung cancer, suggesting that not all pre-invasive lesions progress to cancer.
Using gene expression microarrays we identified 1846 genes significantly
differentially expressed between progressive and regressive pre-invasive
. The most common location of metastasis was frontal lobe followed by SqCC lesions. The macrophage metalloelastase MMP12 gene was found
cerebellum and temporal lobe. Having diabetes mellitus (OR: 12.1, 95% CI: to be highly expressed in progressive lesions, and we hypothesised that it

plays a role in epithelial-to-mesenchymal transition (EMT). Conversely, the PGAM5 and FUNDC1 may contribute to the pathogenesis of both COPD and
actin binding protein LIM-domain only 7 (LMO7) gene was highly expressed NSCLC, possibly through mitophagic processes.
in regressive lesions, and we postulated that it may be protective against
EMT due to its role in the maintenance of epithelial architecture. Initial Keywords: copd, mitochondrion, macrophages, Cancer
studies using three SqCC cell lines (A431, H357 and H376) with MMP12-
shRNA knockdown showed a significant decrease in migration and invasion
compared to non-silencing shRNA controls. LMO7-shRNA knockdown in
HBECs was found to significantly increase migration. The aim of this study MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY
is to further characterise the function and signalling of MMP12 and LMO7 in
lung SqCC development. Methods: Eight-week-old NOD/SCID mice were used
for tumorigenesis experiments. A431 and H357 MMP12-shRNA knockdown MA12.05 CAN TUMOR SPREAD THROUGH AIR SPACES (STAS)
and non-silencing shRNA cells were injected in a suspension of one million cells IN LUNG ADENOCARCINOMAS BE PREDICTED PRE- AND
in a total of 200μl, subcutaneously in the right and left flank, respectively. INTRAOPERATIVELY?
Tumours were measured every 2–5 days. Adhesion assays were carried out
Koji Kameda1, Shaohua Lu2, Takashi Eguchi1, Natasha Rekhtman2, Jason
to assess the roles of MMP12 knockdown or LMO7 overexpression on cell
Chang2, Joseph Montecalvo2, David Jones1, William Travis2, Prasad Adusumilli1
adhesion. Cell signalling mechanisms were assessed using western blotting, 1
qPCR and immunostaining. Results: We observed that MMP12 knockdown Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center,
New York/NY/United States of America, 2Department of Pathology, Memorial Sloan
decreases tumorigenicity in an immunocompromised mouse model. Both A431
Kettering Cancer Center, New York/NY/United States of America
and H357 MMP12 knockdown cells produced significantly smaller tumours
compared with non-silencing shRNA cells. We found that MMP12 knockdown Background: We and others have reported the prognostic impact of tumor
decreases cell adhesion, which is currently being further investigated along spread through air spaces (STAS) in lung adenocarcinomas. The goal of this
with effects on integrin signalling pathways. Levels of EMT markers were study is to investigate preoperative predicting factors for STAS and to
assessed in MMP12 knockdown and LMO7 overexpressing cells using qPCR, determine whether STAS can be detected by intraoperative frozen section
western blotting and immunostaining. Results indicate that higher MMP12 analysis. Methods: In a cohort of 874 patients with small (≤2cm) stage I
expression is associated with a mesenchymal phenotype, whereas higher adenocarcinoma (1995-2012), we reviewed preoperative computed
LMO7 expression is associated with an epithelial phenotype. Conclusion: tomography (CT) and positron emission tomography (PET) scans. According to
Our results suggest that MMP12 is a key driver of migration and invasion the 2016 Fleischner Society’s criteria, radiological whole tumor size,
in SqCC and its high expression may contribute to EMT, whereas LMO7 is a consolidation size, as well as C/T ratio (consolidation/whole tumor diameter)
putative tumour suppressor with a crucial role in maintaining epithelial cell were determined using thin slice (<3mm) CT scans where available (n=174).
architecture. MMP12 and LMO7 may be potential therapeutic markers for lung Clinico-radiological prediction of STAS was evaluated by logistic regression
cancer at an early stage. model. Using the frozen section slides with adequate adjacent lung
parenchyma surrounding tumor without artifact (n=48), the presence of STAS
Keywords: Matrix metalloproteinase, Lung Squamous cell carcinoma,
was evaluated by five pathologists who are unaware of the radiological
Epithelial-to-mesenchymal transition, pre-invasive lesions
findings or the pathological information on permanent slides. The kappa
statistic was calculated to measure the agreement between two pathologists.
Results: In univariable model for predicting STAS, current smoker, larger
consolidation tumor size, C/T ratio, and SUVmax were significant variables. In
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45 multivariable model, current smoker and C/T ratio were independent risk
factors for the presence of STAS (p=0.027 and p<0.001, respectively; Table 1a).
The sensitivity and the specificity of frozen section for prediction of STAS
MA12.04 MITOCHONDRIAL-RELATED PROTEINS, PGAM5 were 71% (95% confidence interval: 52-91%), 92.4% (81-100%) respectively, and
AND FUNDC1, IN COPD-ASSOCIATED NON-SMALL CELL LUNG the accuracy was 80% (71-89%). The kappa statistics were 0.40-0.74 (Table 1b)
CARCINOMA with 8/10 being moderate or substantial agreement. Conclusion: Smoking
Francois Kwong 1, Andrew Nicholson1, Ian Adcock2, Fan Chung 3 status and C/T ratio were independent predictors for the presence of STAS in
1 patients with small lung adenocarcinomas. Frozen section prepared with
Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London/
United Kingdom, 2National Heart and Lung Institute, London/United Kingdom,
adequate surrounding normal lung tissue may help identify STAS
3
Experimental Studies, National Heart and Lung Institute, London/United Kingdom intraoperatively.
Background: Patients with COPD and/or emphysema have an increased

risk of non-small cell lung cancer (NSCLC). COPD and lung cancer are both
characterised by increased oxidative stress associated with mitochondrial
dysfunction. We hypothesise that mitochondrial dysfunction is a driving
mechanism for the increased risk of NSCLC in COPD. We determined whether
there is dysregulated expression of mitochondrial-related proteins in NSCLC
arising in COPD, and if so, their clinical significance. Methods: To determine
the clinical relevance of mitochondrial related gene expression, we examined
a database containing transcriptomic data of more than 1, 000 human
NSCLC samples and with survival outcomes (https://precog.Stanford.edu/).
Immunohistochemistry for PGAM5 and FUNDC1 was performed on cancer and
background (‘normal’) tissue from lung cancer resections from non-smokers,
healthy smokers (without COPD) and COPD/ emphysema patients. Protein
expression was assessed using a semi-quantitative immunohistochemical
scoring system (H score). Specific gene expression was further correlated
with outcome in dataset GSE 72194, containing transcriptomic data of
NSCLC cases and patient survival. Results: 25 mitochondrial-related genes
were linked to survival in NSCLC. Of those 25, we chose to study further the
expression of PGAM5 and FUNDC1, which are regulators of mitochondrial
degradation (mitophagy). In background lung tissue, PGAM5 and FUNDC1,
only expressed in alveolar macrophages, were most highly expressed in COPD
(H score: 180 ± 58 and 23 ± 9, respectively) compared to healthy smokers (146
± 58 and 20 ± 8) and non-smokers (68 ± 48 and 3.3 ± 1.4) (p<0.05). In cancerous
tissue, only the malignant epithelial cells and associated macrophages, at
the periphery of the cancer, expressed PGAM5 and FUNDC1. PGAM5 was also
expressed in pre-neoplastic epithelium (squamous dysplasia and carcinoma
in situ). There was no difference in expression across the 3 groups, although
the macrophages, at the edge of cancer, from COPD patients tended to show
higher expression of PGAM5 and FUNDC1, compared to those from the other Keywords: smoking, diagnosis, computed tomography, radiology
groups. When the expression of PGAM5 was compared with that of 50 known
macrophage transcriptomic signatures within NSCLC samples, there was a
positive correlation between PGAM5 and 9 macrophage signatures (r= 0.27 -
0.44, p<0.05), with one a determinant of patient survival. Conclusion: PGAM5
expression in pre-neoplastic tissue and NSCLC, but not in normal epithelium,
suggests it plays a role in the transformation of malignant epithelial cells.
MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY Keywords: Lung cancer-specific death, Lung Squamous cell carcinoma,
invasion, Tumor spread through air spaces
MA12.06 TUMOR SPREAD THROUGH AIR SPACES (STAS) IN LUNG

SQUAMOUS CELL CANCER IS AN INDEPENDENT RISK FACTOR: A
COMPETING RISK ANALYSIS TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
Shaohua Lu1, Takashi Eguchi2, Kay See Tan3, Sarina Bains2, Kyuichi Kadota1,
Natasha Rekhtman1, Prasad Adusumilli2, William Travis4
1 MA12.08 CLINICOPATHOLOGICAL SIGNIFICANCE OF INCREASING
Department of Pathology, Memorial Sloan Kettering Cancer Center, New
York/NY/United States of America, 2Thoracic Service, Department of Surgery, PERCENTAGE OF HIGH-GRADE HISTOLOGICAL SUBTYPES IN LUNG
Memorial Sloan Kettering Cancer Center, New York/NY/United States of America, ADENOCARCINOMAS
3
Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New Shaohua Lu1, Takashi Eguchi2, Kay See Tan3, James Isbell2, David Jones2,
York/NY/United States of America, 4Dept of Pathology, Memorial Sloan Kettering
William Travis1, Prasad Adusumilli2
Cancer Center, New York/NY/United States of America 1
Department of Pathology, Memorial Sloan Kettering Cancer Center, New
Background: Tumor spread through air spaces (STAS) is a recently recognized York/NY/United States of America, 2Thoracic Service, Department of Surgery,
pattern of invasion in lung adenocarcinoma, however, the incidence of and Memorial Sloan Kettering Cancer Center, New York/NY/United States of America,
3
Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New
prognostic importance of STAS have not yet been defined in squamous cell
York/NY/United States of America
carcinoma (SCC). Methods: In a cohort of 445 patients with p-stage I-III lung
SCC, cumulative incidence of recurrence and lung cancer-specific death (LCSD) Background: In early-stage lung adenocarcinomas, high-grade micropapillary
was evaluated by competing risks analysis and overall survival (OS) by Cox (MIP) and solid (SOL) predominant pathology is known to be associated
models. Results: 76% of patients were >65 years of age. 273 patients died with worse prognosis. The aim of this study is, in addition to predominant
during follow up, one third (91, 33.3%) died of lung cancer whereas two thirds patterns, to investigate clinical impact of the presence of small amounts
died of competing events or unknown cause. STAS was present in 132 (30%). (≥5%) as well as increasing percentage of high-grade patterns. Methods:
The cumulative incidence of any, distant, and locoregional recurrence as well Invasive tumors from early-stage lung adenocarcinoma patients who
as LCSD were significantly higher in patients with STAS compared to those underwent curative-intent resection with no induction therapy were
without STAS (Figure), whereas there was no statistically significant investigated (N=2017; 1995-2012) (8th edition TNM pStage I=1390, II=357,
difference in OS. STAS was an independent predictor for both recurrence and III=270). In 388 cases, synchronous lymph node (LN) metastases were
LCSD in multivariable analysis (p=0.034 and 0.016, respectively, Table). available. Histological subtype (lepidic [LEP], acinar [ACI], papillary [PAP],
Conclusion: STAS was present in one third of resected lung SCC and it was an MIP, or SOL) percentages were stratified into 4 groups; 0-4%, 5-24%, 25-49%,
independent predictor of recurrence and LCSD, supporting our proposal that and 50-100%. The association between increasing percentage of patterns of
STAS is a clinically important pattern of invasion and not an artifact. primary tumor and the incidence of lymphatic/vascular invasion, necrosis,
tumor spread through air spaces (STAS) as well as estimated 5-year cumulative
incidence of recurrence (CIR) were analyzed. The differences in distribution
of each pathological variable between 4 groups was analyzed by Chi-square
test. The percentages of histological pattern were compared between primary
tumor and LN metastasis. Results: Increasing percentage of MIP pattern is
associated with increasing incidence of lymphatic/vascular invasion, STAS,
as well as 5-year CIR (Figure 1a, p<0.001). Increasing percentage of SOL
pattern is associated with increasing incidence of necrosis and 5-year CIR
(p<0.001). Presence (≥5%) of SOL pattern is associated with higher incidence
of lymphatic/vascular invasion and STAS (p<0.001) compared to the absence
(<5%) of SOL pattern, but no significant relationship between lymphatic/
vascular invasion and proportion of SOL pattern. The percentage of SOL
pattern in LN metastasis is higher than that in synchronous primary tumors
(Figure 1b). Conclusion: In early-stage lung adenocarcinomas, presence (≥5%)
of MIP or SOL patterns as well as increasing percentages is associated with
poor prognostic clinicopathological variables and incidence of recurrence.

Keywords: Extracapsular invasion, Metastatic lymph node, lung

adenocarcinoma, Micropapillary subtype
Keywords: micropapillary and solid, Histological subtypes, lymph node MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY
metastases, lung adenocarcinomas
MA12.10 HISTOLOGICAL SUBTYPING OF MATCHED PRIMARY AND

METASTASES SITES IN LUNG ADENOCARCINOMA: SIGNIFICANCE
OF SOLID PREDOMINANCE
Yusuke Takahashi1, Takashi Eguchi1, Shaohua Lu2, Robert Downey1, David
Jones1, William Travis2, Prasad Adusumilli1
MA12.09 COMPARATIVE HISTOLOGICAL SUBTYPE ANALYSIS OF 1
LUNG ADENOCARCINOMA TUMOR AND METASTATIC LYMPH New York/NY/United States of America, 2Department of Pathology, Memorial Sloan
NODES AND THE PROGNOSTIC IMPACT Kettering Cancer, New York/NY/United States of America
Shaohua Lu1, Takashi Eguchi2, Zachary Tano2, Daniela Molena2, David Jones2,
Background: Clinical significance of 2015 WHO classification histological
William Travis1, Prasad Adusumilli2
1
subtype of early-stage lung adenocarcinoma (LADC) has been well
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York/ documented; the incidence and significance of histological subtypes in
NY/United States of America, 2Thoracic Service, Department of Surgery, Memorial
autologous metastatic tumors is unknown. Methods: Histological subtyping
Sloan Kettering Cancer Center, New York/NY/United States of America
was performed on paired primary and metastatic LADC tumor samples from
Background: The goal of this study is to investigate comprehensive patients who underwent resection of metastases (N=203, 1996-2012). 57
comparative pathological analyses of both primary tumor and metastatic cases with inadequate tumor specimen and 4 cases diagnosed as local
lymph node (LN) and correlate with lung cancer-specific death (LC-death) recurrence were excluded. Results: Location of metastatic sites were – brain
in patients with LN-positive lung adenocarcinoma. Methods: PN1/2 lung 51 (35.9%), lung 48 (33.8%), lymph node 14 (9.9%), pleura 10 (7.0%), and
adenocarcinoma patients who underwent R0 resection without induction adrenal gland 5 (3.5%). Metastatic tumors demonstrated more frequent solid
therapy (n=402, 2000-2012) were included in the study. In primary tumor, histological pattern than primary tumors (first predominance: 51% vs. 24%;
lymphatic/vascular/pleural invasion, necrosis, tumor spread through second predominance 29% vs. 17%, Figure 1). Among all histological subtypes,
air spaces (STAS), as well as histologic subtypes according to 2015 WHO solid subtype showed the highest concordance between primary and
classification were evaluated. In metastatic LN, metastatic tumor size, metastatic tumors (Figure 2). In addition, analysis of all available
extracapsular invasion, histologic subtypes were evaluated. Recurrence clinicopathological factors showed significantly higher percentage of solid
and LC-death were analyzed by Cox model. Results: Micropapillary and subtype in both primary and metastatic tumors was observed in patients with
solid predominant subtypes were more frequent in LN metastases than in smoking history (p=0.003 and p=0.004, respectively). Conclusion: Analysis of
primary tumors (Figure). In multivariable analyses, adjuvant chemotherapy, a large cohort of primary and autologous metastatic LADC tumors
pleural invasion, extracapsular invasion of LN metastasis, micropapillary demonstrated a higher percentage of solid histological pattern metastases,
predominant subtype in LN metastasis were independent factors for even in cancers with a low solid component in the primary site of disease.
recurrence; adjuvant chemotherapy, pleural invasion, tumor STAS, and
extracapsular invasion were for LC-death (Table). Conclusion: In lung
adenocarcinoma lymph node metastases, predominant micropapillary
pattern and extracapsular invasion indicate high risk for recurrence and lung
cancer-specific death.
Results: Markerless tumour tracking successfully tracked tumours in all cases

at every imaging angle. The mean 3D tracking error ranged from 1.8-4.1mm for
Keywords: histological comparison, solid component the 11 CBCT scans, and was 3.0mm for the SABR case. Compared with the
current standard of care, i.e. a single estimation of tumour position prior to
treatment from the pre-treatment CBCT, markerless tumour tracking reduced
tumour localization error by 0.9-7.9mm. Tracking errors in the left-right,
superior-inferior, and anterior-posterior directions are shown in Figure1b.
SESSION MA13: MODERN TECHNOLOGIES AND BIOLO- Conclusion: A markerless tumour tracking method was developed and shown
to improve tumour localization accuracy in 12 lung cancer cases. This method
GICAL FACTORS IN RADIOTHERAPY can potentially enable wide access to motion-adaptive radiotherapy.
Keywords: Tumor tracking, Intrafraction monitoring, Real-time adaptive
radiotherapy, X-ray imaging
MA13.01 MARKERLESS TUMOUR TRACKING DURING LUNG
RADIOTHERAPY USING INTRAFRACTION X-RAY IMAGING
Chun-Chien (Andy) Shieh1, Vincent Caillet2, Michelle Dunbar 1, Paul Keall1,
MA13: MODERN TECHNOLOGIES AND BIOLOGICAL FACTORS IN RADIOTHERAPY
Nicholas Hardcastle2, Jeremy Booth2, Chen-Yu Huang1, Carol Haddad2, Thomas TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
Eade2, Ilana Feain1
1
Radiation Physics Laboratory, University of Sydney, Sydney/NSW/Australia,
2
Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards/NSW/ MA13.02 FIRST-IN-HUMAN CLINICAL EXPERIENCE WITH REAL-
Australia TIME TUMOR TARGETING VIA MLC TRACKING FOR STEREOTACTIC
RADIOTHERAPY OF LUNG CANCER
Background: Lung tumours often exhibit large and unpredictable motion that
Jeremy Booth1, Vincent Caillet1, Nicholas Hardcastle1, Carol Haddad1, Kathryn
can severely compromise radiotherapy outcomes. Markerless tumour tracking
Szymura1, Ricky O’Brien2, Benjamin Harris1, Thomas Eade1, Paul Keall2
can enable wide access to motion-adaptive radiotherapy, negating the risks 1
and costs associated with implanting markers. The main barrier to markerless Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards/NSW/
Australia, 2University of Sydney, Sydney/NSW/Australia
tumour tracking is the inferior tumor visibility on x-ray images due to
overlapping anatomic structures. The aim of this study is to develop a Background: MLC tracking is an emerging technology to improve tumor
markerless tumor tracking method for lung radiotherapy using intrafraction targeting and reduce normal tissue irradiation during radiotherapy. The
x-ray imaging. Methods: The markerless tumour tracking method (Figure1a) purpose of this work is to present the early clinical experience from the
consists of four steps: (1) Building a tumour and anatomic model from the first-in-human trial of real-time tumor targeting via MLC tracking for
cone-beam CT (CBCT) acquired prior to treatment, (2) Using the anatomic stereotactic ablative body radiotherapy (SABR) of lung cancer. Methods: Full
model to remove the contribution of anatomic structures on intrafraction ethics approval through an Australian ethics board has been received for
x-ray images, (3) Locating the tumour on the intrafraction 2D x-ray image via recruitment of 20 patients with stage 1 lung cancer or lung metastases into
template matching using the tumour model, (4) Determining the tumour 3D the MLC tracking clinical trial (NCT02514512). To date, seven recruited
position by a Kalman filter. The proposed method was retrospectively patients have each had three electromagnetic beacons inserted near the
validated on (i) 11 CBCT scans from four patients with central tumours, and (ii) tumor. An MLC tracking SABR plan was generated with planning target
a kV fluoroscopic scan during a stereotactic ablative radiotherapy (SABR) volume (PTV) expanded 5mm from end-exhale tumor volume (GTV). For
treatment from the Light SABR trial (NCT02514512). Tracking errors were comparison a conventional motion-encompassing SABR plan was generated
estimated using the motions of markers or beacons implanted near the with PTV expanded 5mm from a 4DCT-derived internal target volume.
tumours. Treatment was delivered using a standard linear accelerator using in-house
developed software to continuously adapt the MLC motion based on the
Calypso beacons’ movement. Tumor motion, treated volume and
reconstructed delivered dose were compared between MLC tracking and
conventional motion-encompassing treatment planning. Results: All seven
patients have been treated successfully with MLC tracking (29 successful
fractions). The MLC tracking PTV for all patients has been smaller than with
ITV based planning (range 12% to 41% reduction, or 2 to 18 cm3 with MLC
tracking). Subsequent reductions in normal lung dose were observed. Tumor
motion was seen to vary in motion range from the planning 4DCT during
treatment; significantly, larger motion was observed during treatment that
exceeded standard PTV boundaries. Reconstruction of delivered treatments
confirmed the accurate delivery of MLC tracking, with 100% prescribed dose
delivered to the GTV.
(See FIgure next page)

Radiation Oncology, The Netherlands Cancer Institute, Amsterdam/Netherlands
Background: Objectives: In lung cancer patients treated with image-

guided radiotherapy we use daily Cone-Beam CT (CBCT) guidance for setup
verification and to check on intra-thoracic anatomical changes (ITACs). ITACs
like tumor baseline shifts, the occurrence or dissolving of an atelectasis,
tumor progression or regression, pleural fluid- and infiltrative changes have
been reported in 72% of lung cancer patients (Kwint M R&O 2014) during the
course of irradiation. A traffic light protocol has been in use by the radiation
technologists since 2010 to classify anatomical changes seen on the CBCT
with anticipated different influences on the dose distribution using 4 action
levels. The purpose of this study was to quantify how often the ITACs occurred
in daily clinical practice and for which action level. Methods: All lung cancer
patients irradiated in 2015 (excluding stereotactic treatments) with a dose
>44 Gy were included. All patients had a daily CBCT guided online correction
protocol and the traffic light action level of each CBCT was recorded.
The following action levels have been defined: code red for immediate
consultation with the physician before beam-on, code orange for a decision
on the notification of the physician before the next fraction, code yellow to
inform the physician; no action is required- and green for no change so no
intervention necessary. We also analyzed the percentage of patients that
received a new planning-CTscan and/or a new treatment plan. Results: In 2015
a total of 299 lung cancer patients were conventionally irradiated with radical
intent and 5971 CBCT scans were made. Of these CBCTs 51% were scored as
code green, 24% as code yellow, 24% as code orange and code red in less than
1% of the CBCTs. Forty patients (13%) had a new treatment plan, of which
34 patients (11%) had a new planning CT-scan and 6 patients (2%) had a new
treatment plan on the original planning CT-scan. Conclusion: Image-guided
irradiation for 299 conventionally fractionated lung cancer patients (>44 Gy)
in 2015 revealed lTACs in 25% of the CBCT’s made and a physician’s decision on
the notification was necessary. A total of 13% of the patients treated received
an unscheduled adaptive treatment plan during the course of treatment.
The traffic light protocol in daily clinical workflow worked well as a tool to
prioritize a physician’s decision based on the ITACs seen on the CBCT images.
Keywords: image-guided radiotherapy, cone-beam CT, intra-thoracic

anatomical changes, adaptive radiotherapy

MA13.05 NIVOLUMAB IN NON-SMALL CELL LUNG CANCER (NSCLC):

THE REAL-LIFE DATA
Elizabeth Dudnik 1, Mor Moskovitz2, Sameh Daher3, Sivan Shamai4, Ekaterina
Hanovich5, Yelena Shechtman6, Mahmoud Abu-Amna6, Alona Zer 1, Mira
Wollner2, Jair Bar 7, Ofer Merimsky4, Arnold Cyjon5, Tzippy Shochat8, Nir Peled1
1
Thoracic Cancer Service, Davidoff Cancer Center, Petach Tiqwa/Israel, 2Rambam
Medical Center, Haifa/Israel, 3Oncology, Chaim Sheba Medical Center, Ramat Gan/
Israel, 4 Oncology, Souraski Medical Center, Tel Aviv/Israel, 5 Assaf Harofeh Medical
Center, Tzrifin/Israel, 6Medical Oncology, Rambam Medical Center, Haifa/Israel,
7
Thoracic Cancer Unit, Sheba Medical Center, Ramat-Gan/Israel, 8Rabin Medical
Center, Petach Tiqwa/Israel
Background: Nivolumab has been recently approved by the FDA as a 2nd -line
treatment of NSCLC. The data regarding its efficacy in the real-life setting is
lacking. Methods: 260 consecutive patients with advanced NSCLC treated
with nivolumab at five cancer centers in Israel between January 2015 and
March 2016 were observed for OS and toxicity. OS was analyzed by the
Cox proportional-hazards regression model. Results: Patient baseline
characteristics: median age 67y (range 41-99); males 68%; smokers 76%; ECOG
PS ≥2 46%; Non-sq/Sq/other 70%/23%/7%; KRASm/EGFRm/ALK+/other
genetic aberration/none/NA 7%/5%/0%/4%/42%/42%; brain metastases
21%; liver metastases 21%; treatment (Tx) line: 1st/2nd/3rd+-line/NA
6%/64%/26%/4%. Median duration of follow-up was 4.3 mo (range 0.1-13.8);
median Tx duration was 2.7 mo (range 0.1-15.5); median number of Tx cycles
delivered was 6 (range 1-26). 130 (50%) patients died; median OS comprised 6.6
Conclusion: The first treatments with MLC tracking have been successfully mo (95%CI 5.6-8.4). In univariate and multivariate analysis, the only variable
performed in seven lung cancer patients. Reductions in treated volumes were which significantly correlated with OS was ECOG PS (table 1). Median OS of
observed, which translated to reductions in delivered lung dose. patients with ECOG PS 0/1 and ECOG PS ≥2 comprised 8.6 mo and 3.5 mo,
respectively. Safety data is presented in table 2.
Keywords: lung radiotherapy, MLC tracking
(See Table next page)

MA13.03 ANALYSIS OF INTRA-THORACIC ANATOMICAL CHANGES

OBSERVED IN CLINICAL WORKFLOW OF CONE-BEAM CT GUIDED
RADIOTHERAPY FOR LUNG CANCER
José Belderbos, Maddalena Rossi, Margriet Kwint, Suzanne Beek, Jan-Jakob
Sonke
previously annotated by The Cancer Genome Atlas lung ACA dataset and all
hypermorphic mutations identified were located in the highly conserved
kinase domain. The majority of mutations have been known to enhance
kinase activity in melanoma in a fashion analogous to the well-known
BRAF V600E mutation. In line with these findings, we showed that kinase
domain mutations were hypermorphic as measured by MEK and ERK1/2
phosphorylation. We also showed that exposure of wild type BRAF cells to
radiation results only in a transient activation of MEK and ERK1/2. The MEK
inhibitor selumetinib selectively decreased the growth of cells with kinase
domain BRAF mutations and sensitized these cells to radiation. Conclusion:
BRAF mutations are associated with radiation resistance in lung ACA. Our
data nominates MEK inhibitors, a drug class currently in clinical use, as a
targeted therapeutic in select BRAF-mutant lung ACA. Further investigation
has the potential to yield an additional genotype-directed therapy that could
impact up to 4-6% of patients with lung ACA, a frequency comparable to that
of ALK rearrangements (4%) or EGFR mutations (10%).
Keywords: MEK inhibitors, precision medicine, radiogenomics, BRAF

MA13.07 TUMOR-TARGETED RADIATION PROMOTES ABSCOPAL

EFFICACY OF REGIONALLY ADMINISTERED CAR T CELLS: A
RATIONALE FOR CLINICAL TRIAL
Masha Zeltsman1, Jonathan Villena-Vargas1, Andreas Rimner2, Marissa
Mayor 1, David Jones1, Prasad Adusumilli1
1
New York/NY/United States of America, 2Radiation Oncology, Memorial Sloan
Kettering Cancer Center, New York/NY/United States of America
Background: Our laboratory has demonstrated the augmented anti-tumor

efficacy of intrapleurally administered cancer-antigen mesothelin (MSLN)-
targeted chimeric antigen receptor (CAR) T cells (Sci Transl Med 2014), and
translated the approach to a clinical trial (NCT02414269) for thoracic
malignancies. We hypothesized that regionally administered MSLN CAR T
cells can circulate systemically to achieve abscopal anti-tumor efficacy in an
antigen-specific manner, and the abscopal efficacy can further be promoted
by tumor-targeted radiation therapy (RT). Methods: Using optimized
protocols that would permit non-necrotic, well-vascularized tumor growth in
Conclusion: Nivolumab has reasonable efficacy and good safety profile in the pleura, chest wall, peritoneum and flank, tumors were established in
real-life setting. ECOG PS ≥2 is associated with poor prognosis. immunodeficient (NOD/SCID gamma) mice using mesothelioma or lung
adenocarcinoma (LAC) cells. Tumor burden progression, MSLN-targeted CAR
Keywords: Nivolumab, Anti-PD-1, ECOG PS, non-small cell lung cancer T-Cell accumulation at primary and distant tumors was monitored by
noninvasive bioluminescence imaging (BLI) and tumor volume measurements.
Results: A single dose of MSLN CAR T cells administered intrapleurally
proliferated (Figure 1A left panel), circulated extrapleurally and accumulated
MA13: MODERN TECHNOLOGIES AND BIOLOGICAL FACTORS IN RADIOTHERAPY at abscopal sites, including the lymph nodes, chest wall, peritoneum, and
flank within 3-5 days, with subsequent T-cell proliferation at abscopal sites
(Figure 1A right panel). Primary tumor-targeted, single-dose, thoracic RT prior
MA13.06 INTEGRATIVE GENOMIC PROFILING IDENTIFIES to T-cell administration augmented T-cell accumulation as demonstrated by
BRAF MUTATIONS AS NOVEL RADIOTHERAPEUTIC TARGETS IN BLI (Figure 1B) and tumor T-cell quantification (p<0.01). In a mouse model of
ADENOCARCINOMAS OF THE LUNG primary pleural, abscopal antigen-expressing and non-expressing flank
tumors (Figure 1C), a single, low-dose, non-cytotoxic thoracic RT enhanced
Eui Kyu Chie1, Priyanka Gopal2, Mohamed Abazeed2
1
abscopal site CAR T-cell accumulation that resulted in tumor regression
Radiation Oncology, Seoul National University College of Medicine, Seoul/Korea, (p=0.01; Figure 1D).
Republic of, 2Translational Hematology Oncology Research, Cleveland Clinic,
Cleveland/OH/United States of America
Background: Patients with non-small cell lung cancer (NSCLC) display a

wide spectrum of oncologic outcomes, suggesting significant underlying
biologic diversity. However, current radiotherapeutic management is largely
homogeneous for a given stage, To advance genotype-directed radiotherapy
in NSCLC, we sought to identify genetic determinants of radioresistance by
leveraging cancer genomic data with a recently developed high-throughput
platform for measuring radiation survival. Methods: We used our recently
validated high-throughput proliferation assay to profile 104 lung cancer
cell lines, including 89 NSCLC and 15 small cell lung cancer (SCLC) lines, for
radiation survival. Survival curve analyses permitted quantitative assessment
of radiosensitivity. Genomic correlates of radiosensitivity were explored
by calculating the information-based similarity metric and correlating
genomic parameters by accessing Oncomap data from the Cancer Cell Line
Encyclopedia, the COSMIC database of the Cancer Genome Project, and The
Cancer Genome Atlas. Results: Radiation survival across lineages reflected
clinical experience regarding differential response to fractionated radiation
inasmuch as lung squamous cell carcinoma and adenocarcinoma (ACA) had
similar radiosensitivity, whereas SCLC and carcinoid were, respectively,
more and less radiosensitive. Importantly, radiosensitivity varied more
within a lineage than across lineages, with a 6-fold difference in integral
survival among ACA lines. Correlation with cancer genomic data revealed
BRAF mutations within the most resistant ACA lines (P = 0.0097, FDR =
Conclusion: Regionally administered mesothelin-targeted CAR T cells
0.957). A majority of the mutations identified by our analysis have been
proliferate and eradicate the primary tumor, accumulate and demonstrate

anti-tumor efficacy at abscopal sites prior to eradication of the primary tumor radiation beam-holds whenever the target is outside a prespecified gating
in an antigen-specific manner. A single low-dose primary tumor-targeted window. The gating procedure is as follows: a 17 second inspiration breath-
radiation therapy promotes scopal and abscopal anti-tumor efficacy. These hold MR scan is performed for planning before each SABR fraction (resolution
results provide rationale to initiate a clinical trial of combination regional 1.6×1.6×3.0 mm). Image registration is performed, and contours adapted when
therapies with radiation therapy and CAR T cells. necessary. A 3mm PTV margin is added, and planned dose distribution
recalculated for the ‘anatomy of the day’, and reoptimized. A sagittal plane is
Keywords: CAR T-cell immunotherapy, Abscopal Effect, Radiation-Induced chosen for tumor tracking and gating, with a planning target margin of 3 mm.
Immunomodulation, radiation therapy The sagittal tracking view from the MRIdian console is projected on a MR-safe
monitor (Cambridge Research), and patients can continuously observe the
tracking image using a mirror inside the bore. Results: Since May 2016, 30
fractions of MR-guided gated delivery have been performed in 5 cancer
MA13: MODERN TECHNOLOGIES AND BIOLOGICAL FACTORS IN RADIOTHERAPY patients with 6 central tumors. All MR-based breath-hold PTV’s were smaller
(mean 19.8 ± 13.3 cc) than a conventional free-breathing, motion-
encompassing approach (mean 36.1 ± 21.9 cc). Plans of a single case are shown
MA13.09 SERIAL FDG AND FLT PET/CT DURING CURATIVE- in Figure 1. Video-assisted visual feedback achieved a breath-hold gating
INTENT CHEMO-RADIOTHERAPY FOR NSCLC IMPACTS PATIENT efficiency of 52% (range 27-88%).
MANAGEMENT AND MAY PREDICT CLINICAL OUTCOMES
David Ball1, Sarah Everitt2, Rodney Hicks3, Jason Callahan3, Alan Herschtal4,
Tomas Kron5, Nikki Plumridge1, Michael Mac Manus1
1
Radiation Oncology, Peter MacCallum Cancer Centre, Parkville/VIC/Australia,
2
Radiation Therapy, Peter MacCallum Cancer Centre, Parkville/VIC/Australia,
3
Molecular Imaging, Peter MacCallum Cancer Centre, Parkville/VIC/Australia,
4
Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Parkville/
VIC/Australia, 5Medical Physics, Peter MacCallum Cancer Centre, Parkville/VIC/
Australia
Background: FDG-PET/CT is the gold-standard for non-small cell lung

cancer (NSCLC) diagnosis, staging and tumour delineation prior to chemo-
radiation therapy (CRT). FDG-PET is superior to CT for subsequent response
assessment. Sequential interim metabolic and proliferative tumour response
assessment with FDG and 3’-Fluorothymidine (FLT) respectively, prior to
and during CRT is novel and may predict outcome. Methods: Patients with
FDG-PET-stage I-III NSCLC who were prescribed radical chemo-RT (60 Gy in 30
fractions @ 5/wk) were enrolled. FDG and FLT PET/CT scans were performed at
baseline and at weeks 2 and 4 of CRT. Intra-treatment tumour response judged
by reduction in FDG and FLT uptake was categorised as complete (CR)/partial
response (PR), stable (SD) or progressive disease (PD) using EORTC criteria.
Overall Survival (OS) and Progression Free Survival (PFS) were measured
relative to intra-treatment scan dates and plotted using Kaplan-Meier curves.
Univariate Cox regressions were used to calculate associations between 1.
SUVmax of baseline FDG and FLT GTV and 2. intra-treatment FDG and FLT
response with patient outcomes (OS and PFS). Results: Sixty patients were
recruited between 2009-13; male 62%; median age 66 years, adenocarcinoma
(42%). Two-year OS and PFS were 0.51 and 0.26 respectively. Of 332 PET/CT
scans analysed, study scans provided additional information to FDGBL in 21
(35%) patients. Distant metastasis was detected in 3 patients on FLTBL and
in 2 patients on FDG/FLTwk2 changed treatment intent to palliative. Loco-
regional progression during RT was observed in 5 (8%) patients, prompting
larger RT fields. FLTwk2 response (SD vs CR/PR vs PD) was associated with OS
[HR (95%CI) 1 vs 2.02 (0.87, 4.65) vs 20.09 (4, 114), p=0.012] and PFS [1 vs 2.01
(0.92,4.37) vs 32.41 (3,348), p=0.024]. Associations between the baseline
FDG and FLT SUVmax and patient outcomes were not significant, including OS
where FDG SUVmax HR [95% CI] was 1.04 [0.98, 1.10], p=0.25 and FLT SUVmax
HR [95% CI] was 1.07 [0.93, 1.22], p=0.33. Conclusion: Tumour response on
FLTwk2 was associated with OS and PFS. The possible association between
worse clinical outcomes and early suppression of FLT uptake during CRT may
be a result of repair of tumour DNA damage. Baseline FLT, FLTwk2 and FDGwk2
detected rapid distant and loco-regional progression in 10 (17%) patients
prompting changes in treatment intent and RT fields.
Keywords: PET/CT, FDG, FLT, NSCLC

TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 Conclusion: For high-risk SABR cases, use of MR-guided, video-assisted
breath-hold gated SABR delivery constitutes a novel treatment method,
allowing for minimization of mobility- and setup margins, and for improved
MA13.10 MAGNETIC RESONANCE IMAGING-GUIDED DELIVERY verification of SABR delivery. Data from additional patients undergoing
OF LUNG STEREOTACTIC RADIOTHERAPY USING PATIENT- treatment will be presented.
CONTROLLED VISUAL GUIDANCE
Keywords: Stage I NSCLC, SABR, central tumors, MRI-guided delivery
Shyama Tetar 1, Frank Lagerwaard1, Miguel Palacios1, Niels Haasbeek2, Omar
Bohoudi2, Berend Slotman2, Anna Bruynzeel2, Suresh Senan2
1
VU University Medical Center, Amsterdam/Netherlands, 2Radiation Oncology, VU
University Medical Center, Amsterdam/Netherlands MA13: MODERN TECHNOLOGIES AND BIOLOGICAL FACTORS IN RADIOTHERAPY
Background: Treatment-related toxicity is more common following
stereotactic ablative radiotherapy (SABR) for central lung tumors, than is the
case for peripheral tumors [Tekatli 2015]. Further reductions in doses to MA13.11 INVESTIGATING THE FEASIBILITY OF ESTABLISHING A
critical central structures are possible using respiration-gated SABR delivery, PROSPECTIVE COHORT OF LUNG CANCER PATIENTS FOLLOWING
but insertion of fiducial markers for gating is also associated with toxicity. We RADIOTHERAPY WITH CURATIVE INTENT
describe a novel approach for clinical delivery of breath-hold gated SABR
Lynn Calman1, Sophia Taylor 1, Rebecca Foster 1, Alison Richardson1, Peter
under continuous MRI-guidance. Methods: The MRIdian® system permits
Smith1, Janis Baird1, John Edwards2, Corinne Faivre-Finn3, Claire Foster 1
tumor visualization at 4 frames/second during treatment delivery, with 1
University of Southampton, Southampton/United Kingdom, 2 Sheffield Teaching
Hospitals NHS Foundation Trust, Sheffield/United Kingdom, 3The Christie, was 7.6 for all LC cases (TMB ≥15 in 24% of cases), compared to 4.5 for 80,000+
Manchester/United Kingdom samples of diverse tumor types in the database. Of LCs assessed 0.3% were
MSI-H, of which 30/31 were TMB-high; however, 24% of MSS-stable cases
Background: Worldwide lung cancer is the biggest cause of cancer mortality
were also TMB-high. PD-L1 amplification and DNA repair pathway mutation
(Cancer Research UK, 2012) and is the UK’s second most commonly diagnosed
(MLH1, MSH2, POLE) were found in 1.0% and 1.1% of LC cases analyzed,
malignancy (Macmillan Cancer Support, 2013). Early detection and treatment
respectively. Tumors harboring known drivers (ALK, ROS1, EGFR, BRAF V600E,
significantly improves five year survival rates but curative treatments can
MET splice) had low TMB (median: 2.5, 3.6, 3.8, 3.8, 4.5), whereas tumors with
impact on patients’ health and wellbeing. To date little research has been
KRAS mutation, non-V600E BRAF mutation, PD-L1 amplification, or DNA
conducted to establish the support needs and recovery patterns of health
repair alterations were more likely to be TMB-high (median: 9.0, 10.8, 14.4,
and wellbeing among lung cancer patients treated with curative intent
21.6). Conclusion: High TMB may be a predictive biomarker of response to
radiotherapy. This limits our ability to identify those most at risk of poorer
ICPIs. Several factors including lack of a known driver, MSI-H status, PD-L1
health and wellbeing outcomes and target services effectively to support
amplification, and DNA repair mutation correlated with high TMB (P<0.0001
patients better. This study assesses the feasibility of collecting patient
for all cases). However, 95% of TMB-high cases assessed were MSS and lacked
reported outcomes measures (PROMs) and clinical details to understand
both PD-L1 amplification and DNA repair mutation, and thus would likely
recovery after curative intent radiotherapy treatment for lung cancer.
not be selected for immunotherapy by assessment of individual genomic
Methods: This mixed methods study used a prospective, longitudinal cohort
alterations or MSI status alone. A validation cohort of NSCLC patients
design. Eligible patients awaiting curative intent radiotherapy were recruited
treated with anti-PD-1/PD-L1 therapies including analysis of clinical outcome,
from six UK sites between October 2015 and June 2016. Questionnaires
TMB, genomic profile, and available clinicopathologic characteristics will be
were completed before undergoing radiotherapy and 3 months later. The
presented. CGP of LC to simultaneously determine TMB, MSI status, PD-L1
questionnaires included validated patient reported outcome measures,
amplification, and the presence of driver alterations may provide clinically
including quality of life, symptoms, social support, wellbeing and socio-
useful predictors of response to ICPI and other targeted therapies using a
demographic details. Participants’ medical details were collected by
single platform, but prospective clinical trials are needed to confirm these
healthcare professionals (HCPs) including cancer type, stage, treatment,
observations.
and comorbid conditions. Study procedures were evaluated in a qualitative
process evaluation. Results: Of 229 eligible patients, 136 consented to the Keywords: NSCLC, tumor mutational burden, comprehensive genomic
study with 73% uptake of those approached. A further 13 patients provided profiling
reduced consent to collect demographic and medical information only.
Preliminary results: response rates 76% at baseline and 65% at 3 months.
Of baseline responders: 59% were male; the median age was 70 years; 29%
lived alone; 61% were home owner-occupiers and 20% were current smokers. MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
Baseline EORTC-QLQ-C30 results showed a mean global health status score TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
of 56.6 and patients were most affected by dyspnoea and fatigue with
mean scores of 48.8 and 45.0. These are in line with expected scores based
MA14.02 EVALUATION OF PD1/PDL1 EXPRESSION ON PERIPHERAL
on reference data. To date 9 HCPs, 7 patients and 2 stakeholders have been
interviewed as part of the process evaluation, study processes and procedures
BLOOD CELLS SUBPOPULATIONS IN PATIENTS WITH NON-SMALL
are deemed acceptable to participants. Conclusion: This study demonstrates CELL LUNG CANCER
it is feasible to recruit a cohort of lung cancer patients prospectively to Oscar Arrieta, Edgar Montes-Servín
assess wellbeing and patterns of recovery following radiotherapy. This novel Unidad Funcional de Oncología Torácica Y Laboratorio de Medicina Personalizada,
approach to understanding lung cancer patients’ experiences of survival will National Cancer Institute, Mexico City/Mexico
enhance our ability to target appropriate and timely support to those most at
risk of poorer health and wellbeing. Background: Currently the immune system is considered an important target
of study within the therapeutic alternatives for many tumors that have
Keywords: quality of life, Feasibility, Radiotherapy developed resistance in lung cancer. Many molecules called checkpoints
regulate antitumor immunity as PD-L1 it is expressed in tumour cells and is a
biomarker for anti PD-L1/PD-1 therapy. PD-1 / PD-L1 is expressed on exhausted
activated T cells. This signaling pathway is involved in tumor evasion of the
immune system. It has recently been demonstrated that the blockade of
SESSION MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: PD-1 or its ligand PD-L1 and PD-L2, restore the antitumor immune response
BIOMARKERS AND COSTS leading to a durable tumor regression. However, the expression of PD-1/PD-L1
in T cells from peripheral blood of patients with non-small cell lung cancer has
not been widely studied. Methods: We investigated the expression of PD-1
and its ligands PD-L1 and PD-L2 on peripheral blood T cells subpopulations
(CD3+ CD4+ / CD8+) of patients with non-small cell lung cancer. We included
MA14.01 UPDATED DATASET ASSESSING TUMOR MUTATION 50 NSCLC patients (stage IIIB and IV) naive to treatment and 10 healthy
BURDEN (TMB) AS A BIOMARKER FOR RESPONSE TO PD-1/PD-L1 subjects. Immunophenotyping was performed using multiparametric flow
TARGETED THERAPIES IN LUNG CANCER (LC) cytometry. Analyzing its prognostic significance regarding outcome analysis
Alexa Schrock1, Neelesh Sharma2, Nir Peled3, Jose Bufill4, Gordan Srkalovic5, as well as its potential biomarker. Results: Our results showed that the
David Spigel6, David Fabrizio1, Garrett Frampton1, Caitlin Connelly1, Mary Beth percentage of PD-1, PD-L1 and PD-L2 expression in peripheral blood cells in
Lipka2, Anna Belilovski3, Jun Lo1, Yali Li1, James Sun1, Kyle Gowen1, Gregory NSCLC patients was lower compared to healthy subjects [P<0.005] and the
Kalemkerian7, Luis Raez8, Sai-Hong Ou9, Jeffrey Ross1, Philip Stephens1, Siraj Mean Fluorescence Intensity (MFI) was higher in patients compared to the
Ali1, Vincent Miller 1 control group [P<0.001]; The expression of PD-1 in T-helper or CD4+ of NSCLC
1
Foundation Medicine, Cambridge/United States of America, 2Hematology patients was significantly higher than in cells from control subjects [P<0.001].
and Oncology, University Hospitals, Cleveland/OH/United States of America, Similarly, the expression of PD-1 in T cytotoxic cells or CD8+ patients was
3
Davidoff Cancer Center, Petach Tikva/Israel, 4 Michiana Hematology-Oncology, significantly higher than in controls [P<0.001]. In the clinical analysis, we
Pc, Mishawaka/IN/United States of America, 5Sparrow Regional Cancer Center, found that a higher percentage of PD-1+ CD3+ cells was statistically associated
Lansing/AL/United States of America, 6Sarah Cannon Research Institute, Nashville/ with tobacco exposure [P=0.0160], and de MFI was associated with the non-
United States of America, 7University of Michigan Cancer Center, Ann Arbor/MI/ adenocarcinoma histology [P=0.0001] additionally, the presence of 3 or more
United States of America, 8 Memorial Cancer Institute, Miami/FL/United States of
metastases was associated to a higher MFI of PD-1 on CD3+ CD8+ [P=0.0490].
America, 9University of California Irvine School of Medicine, Orange County/CA/
In the overall survival (OS) analysis the percentage of CD3+/CD4+/PD-1+
≤20.91 was associated with a higher median OS [P= 0.045]. Conclusion: Several
Background: Immune checkpoint inhibitors (ICPIs) nivolumab and studies demonstrate the importance of infiltrating PD-1+ T cells within
pembrolizumab have been FDA-approved in non-small cell LC (NSCLC). Current tumors; however these results showed that the PD-1/PD-L1/PDL-2 expression
IHC based diagnostics are challenged by assay and slide scoring issues and in peripheral blood cells could be used also as a potential biomarkers in NSCLC
modest predictive value, and more robust and comprehensive biomarkers patients.
of ICPI efficacy are needed. A discovery set of 64 NSCLCs treated with ICPIs
Keywords: PD-1, PD-L1, NSCLC, biomarker
suggested that high TMB (≥15 mutations/Mb) significantly correlated with
longer time on drug (Spigel et al., ASCO 2016, Abstract:9017). Methods:
Comprehensive genomic profiling (CGP) was performed during the course
of clinical care. TMB was assessed as the number of somatic, coding, base
MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
substitution and indels per Mb of genome. Microsatellite instability-high TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
(MSI-H) or stable (MSS) status was determined using a proprietary algorithm.
Results: 15,529 LCs: 66% adenocarcinoma, 1% sarcomatoid, 14% NSCLC NOS,
11% squamous, 5% small cell, and 2% large cell were assessed. TMB was similar MA14.03 THE IMPACT OF GENOMIC LANDSCAPE OF EGFR MUTANT
across all lung histologies (median: 6.3, 8.1, 9.0, 9.9, 9.9, and 10.8); the median NSCLC ON RESPONSE TO TARGETED AND IMMUNE THERAPY

Yasir Elamin1, Waree Rinsurongkawong2, Hai Tran3, Kathryn Gold4, Jeff Lewis2, to be 8.2 months (6.4, 10.7) and 14.9 months (10.4, NA) for docetaxel and
Emily Roarty5, Andrew Futreal6, Jianjun Zhang7, John Heymach8 pembrolizumab, respectively (HR= 0.54 (0.38, 0.77)). Model-based projections
1
Thoracic/head and Neck Medical Oncology, MD Anderson Cancer Center, Houston/ show that should all patients be treated with docetaxel, expected mean
TX/United States of America, 2MD Anderson Cancer Center, Houston/TX/United lifetime is 1.0 years. For patients receiving a PD-L1 biomarker test per KN010
States of America, 3Thoracic/head and Neck Medical Oncology, MD Anderson 28.49% will be identified as PD-L1 strong positive (TPS≥50%). PD-L1 (TPS
Cancer Center, Houston/United States of America, 4 Moores Cancer Center, ≥50%) predicts a life expectancy with biomarker directed pembrolizumab of
University of California San Diego, La Jolla/United States of America, 5Thoracic, 2.25 years on average. Conclusion: Use of PD-L1 biomarker identification can
Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer significantly improve OS prognoses for patients considering pembrolizumab
Center, Houston/TX/United States of America, 6The University of Texas MD
and docetaxel with advanced NSCLC based on both clinical trial results and
Anderson Cancer Center, Houston, Hx/United States of America, 7Department of
Thoracic/head and Neck Medical Oncology, The University of Texas MD Anderson model-based projections from KN010.
Cancer Center, Houston/AL/United States of America, 8Thoracic/head and Neck
Medical Oncology, MD Anderson, Houston/TX/United States of America
Keywords: PD-L1
Background: EGFR mutations define a distinct subset of NSCLC characterized

by clinical benefit from tyrosine kinase inhibitors. The impact of genomic
alterations that coexist with EGFR mutations is not fully understood. In MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
addition, the responsiveness of EGFR mutant NSCLC to immune checkpoint
blockade is not well defined. Methods: We queried our prospectively collected
MD Anderson Lung Cancer Moon Shot GEMINI Database to identify EGFR MA14.06 NIVOLUMAB IN NEVER SMOKER PATIENTS WITH
mutant NSCLC patients. We analyzed the genomic landscape of these tumors ADVANCED SQUAMOUS NSCLC: RESULTS FROM THE ITALIAN
derived from next generation sequencing, performed as part of routine
EXPANDED ACCESS PROGRAMME (EAP)
clinical care, to comprehensively describe the concurrent genomic aberrations
in EGFR mutant NSCLC and their impact on clinical outcomes. We used log Giuseppe Lo Russo 1, Lucio Crinò2, Domenico Galetta3, Andrea Ardizzoni4,
rank and Fisher’s exact tests to identify associations between co-concurrent Enrico Cortesi5, Frederico Cappuzzo6, Paola Bordi7, Luana Calabrò8, Fausto
mutations and clinical outcomes. Results: 1958 non-squamous NSCLC Barbieri9, Antonio Santo10, Giuseppe Altavilla11, Giacomo Cartenì12, Enrico
patients were identified in the GEMINI database. The frequency of EGFR Mini13, Enrico Vasile14, Floriana Morgillo15, Alessandro Scoppola16, Carmelo
mutations was 14.1% (n=276). Among EGFR mutant patients, 188 underwent Bengala17, Gianpiero Fasola18, Natale Tedde19, Francovito Piantedosi20
1
targeted next generation sequencing of a minimum of 46 cancer related Fondazione IRCCS - Istituto Nazionale Dei Tumori, Milano/Italy, 2Division of
genes. The majority of EGFR mutant patients (77.6%, n=146) had at least one Medical Oncology, Santa Maria Della Misericordia Hospital, Perugia/Italy,
3
National Cancer Research Centre, Istituto Tumori “Giovanni Paolo Ii” Bari, Italy,
coexisting mutation. The most frequent co-mutations identified were TP53
Bari/Italy, 4 Medical Oncology, S. Orsola-Malpighi University Hospital, Bologna/
(47%, n=88), CTNNB1 (7.5%, n= 14) and PIK3CA (6.5%, n=12). ALK and ROS1 Italy, 5Sapienza University, Rome/Italy, 6 Ausl Romagna, Ospedale Santa Maria
translocations were found to coexist with EGFR mutations in one patient Delle Croci, Department of Oncology and Hematology, Ravenna/Italy, 7Medical
each. Of patients treated with a first or second generation TKI, concurrent Oncology Unit, University Hospital of Parma, Parma/Italy, 8 Medical Oncology
TP53 mutations were associated with a shorter progression free survival (HR= and Immunotherapy, University Hospital of Siena, Siena/Italy, 9University
1.81, P= 0.039). Eight patients with EGFR/CTNNB1 co-mutations developed Hospital Policlinico of Modena, Oncology Unit, Modena/Italy, 10 Givop (Gruppo
acquired TKI resistance with T790M secondary mutation being the resistance Interdisciplinare Veronese Oncologia Polmonare), Azienda Ospedaliera
mechanism in six (75%) of them suggesting that coexisting mutation can Universitaria Integrata Di Verona, Verona/Italy, 11Department of Human Pathology,
Oncology Unit, University of Messina, Messina/Italy, 12Division of Medical
dictate emerging resistance mechanisms. Twenty patients were treated with
Oncology, A.Cardarelli General Hospital, Napoli/Italy, 13University of Florence,
anti PD1/PD-L1 agents (nivolumab n= 18, pembrolizumab n=2). Only two (10%) Department of Experimental and Clinical Medicine, Firenze/Italy, 14 Azienda
patients achieved confirmed radiological response, one lasting for 6 months Ospedaliero Universitaria Pisana Istituto Toscano Tumori, Pisa/Italy, 15Oncologia
and the second ongoing at 6 months. Both patients were never smokers, one Medica, Dipartimento Di Internistica Clinica E Sperimentale “f. Magrassi E A.
with EGFR exon 20 insertion and no concurrent mutations, and the other Lanzara”, Seconda Università Degli Studi Di Napoli, Napoli/Italy, 16Divisione Di
with EGFR exon 19 deletion and TP53 mutation. Sixteen patients developed Oncologia, Idi-IRCCS, Roma/Italy, 17Division of Medical Oncology, Misericordia
confirmed progressive disease. Finally, one patient with 17 pack-year smoking General Hospital, Grosseto/Italy, 18Department of Medical Oncology, University-
history, EGFR G719/S768I double mutation and concurrent PIK3CA mutation Hospital Santa Maria Delle Grazie, Udine/Italy, 19 Oncologia Medica Asl2, Olbia/
Italy, 20 Department of Medical-Surgical Oncology and Thoracic Disease, Napoli/
achieved stable disease lasting for four months. The median progression free
Italy
survival for the cohort treated with immunotherapy was 2 months (range:
1-not reached). Conclusion: Concurrent genomic aberrations may predict Background: Nivolumab is the first checkpoint inhibitor approved for the
response duration to TKIs and may be associated with particular emerging treatment of Sq-NSCLC to show a survival benefit vs the standard of care
resistance mechanisms to TKIs in EGFR mutant NSCLC. Immunotherapy docetaxel in the randomised, phase III, CheckMate 017 study. In the nivolumab
results in durable clinical benefit in a subset of EGFR mutant NSCLC patients. development program, a greater clinical benefit was shown in current and
former smokers than in never smokers. Nevertheless, no data are available in
Keywords: Targeted therapy, Immunotherapy, EGFR mutant NSCLC
this respect from a real world setting. For this reason, we decided to use the
data collected in the EAP in order to assess the effectiveness and tolerability
of nivolumab treatment in the never smoker patient population. Methods:
Nivolumab was provided upon physician request for patients aged ≥18 years
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 who had relapsed after a minimum of one prior systemic treatment for stage
IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously
every 2 weeks for <24 months. Patients included in the analysis had received
MA14.05 IMPLICATIONS OF IMPLEMENTATION OF A PD-L1 ≥1 dose of nivolumab and were monitored for adverse events using Common
BIOMARKER-BASED STRATEGY FOR TREATMENT OF ADVANCED Terminology Criteria for Adverse Events. Results: Of 372 patients with
NSCLC Sq-NSCLC participating in the EAP in Italy, 38 (10.2%) were never smokers,
Min Huang1, James Pellissier 1, Thomas Burke 2, Ruifeng Xu1 a proportion very similar to the one observed in Checkmate 017 (10%). With
1 a median number of doses of 8 (range, 1–22) and a median follow-up of 5.6
Center for Observational and Real-World Evidence, Merck & Co., Inc, North Wales/
PA/United States of America, 2Center for Observational and Real-World Evidence, months, the disease control rate in this group was 50%, including 9 patients
Merck & Co., Inc., Lebanon/NJ/United States of America with a partial response and 10 with stable disease. Eight patients were treated
beyond RECIST-defined progression, with 4 of them achieving disease control.
Background: The KEYNOTE-010 (KN010) clinical trial, a multi-center, As of April 2016, median progression-free survival and overall survival were
worldwide, randomized Phase II/III trial of pembrolizumab 2m/kg every 3 3.5 months and not reached, respectively. 17 patients (44.7%) discontinued
weeks and docetaxel 75mg/m2 every 3 weeks in patients with previously treatment for any reason except toxicity and 5 (13.1%) discontinued due to AE.
treated advanced NSCLC with PD-L1 positive tumors showed a significant Conclusion: These preliminary results, although obtained from a small sample
overall survival (OS) advantage for patients receiving pembrolizumab. We size, suggest that nivolumab is effective and well tolerated in a never smoker
examined the improvement in prognoses for patients who elect to learn their group of patients with advanced Sq-NCLCS in the real life and warrant further
PD-L1 biomarker results using extrapolative survival modeling. Methods: investigation in this area.
Partitioned survival models to project long-term outcomes were developed
using data from patients enrolled in KN010, with treated patients in the Keywords: nivolumab, Squamous NSCLC, never smokers
pembrolizumab 2m/kg and docetaxel 75mg/m2 arms included in these
analyses. As OS for docetaxel patients is not dependent on PD-L1 status,
KN010 results were assumed to represent docetaxel efficacy in all patients
irrespective of PD-L1 status.The model projected expected lifetime using MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
Kaplan Meier estimates of PFS and OS from the trial with extrapolation
based on parametric functions and long term registry data. Results: Results
directly from KN010 showed for patients with TPS≥50%, median survival MA14.07 REAL LIFE EXPERIENCE WITH IMMUNOTHERAPY IN THE
NETHERLANDS (NSCLC). Methods: We used The Health Economics Medical Innovation

Robert Schouten, Paul Baas, Michael Van Den Heuvel Simulation (THEMIS) alongside available clinical trial data to estimate the
anticipated increase in NSCLC patient survival post-diagnosis resulting from
Thoracic Oncology, Netherlands Cancer Institute / Antoni Van Leeuwenhoek,
Amsterdam/Netherlands the introduction of IO therapy. THEMIS is an established microsimulation
with a 50-year time horizon that tracks a representative sample of patients
Background: Randomized phase III trials have shown that the PD-1 blocking aged ≥51 years to project longevity. These outcomes were estimated for
monoclonal antibody Nivolumab is effective in advanced NSCLC. Nivolumab is metastatic NSCLC patients under a pre-IO scenario and compared to a post-
registered by the FDA and EMA for treatment of NSCLC. However, approval in IO scenario where IO is available for either first- or second-line treatment.
The Netherlands was put on hold because of Nivolumab’s high price per Patients were classified as either heavy, medium, or light responders,
quality adjusted life year (QALY). From August 2015, Nivolumab was provided corresponding to reductions in mortality hazards of 96.5%, 64.4%, and 0%,
through a compassionate use program. Here we present our experience in respectively, based on extrapolations of clinical trial results for nivolumab
treating NSCLC patients with Nivolumab in real life. Methods: Efficacy and (see table). Health state transitions probabilities and medical expenditures
safety of Nivolumab was assessed in patients with advanced NSCLC, were estimated from nationally representative datasets. Mortality and
previously treated with at least one line of platinum-based chemotherapy and disease stage were estimated using the Surveillance and Epidemiology End
an ECOG-PS of ≤2. Nivolumab was administered 2-weekly at a dose of 3 mg/kg Results (SEER) database. Results: In the pre-IO simulation, metastatic NSCLC
intravenously. Response evaluation took place according to RECIST 1.1 at 12 patients lose 11.3 years of life (comparable with the published 11.8 years). The
and 24 weeks after start of treatment. Results: In the 10-month period in a results from the post-IO scenarios are shown in the table. For comparison,
single center 189 patients started treatment with Nivolumab, with a mean SEER data suggest that survival in metastatic NSCLC patients has only
follow up time of 106 days after start of treatment. Mean age was 62 years increased by 0.3 years since 1998.
(range 29–83), 57% male, 18,5% never smoked, 68% had adenocarcinoma, 20%
had squamous histology and 12% were other, mixed or unspecified types. Heavy Light Re-
Medium Medium
Heavy Respond- sponder Addition-
Respond- Responder
Population Responder er Hazard Hazard al Life
er Preva- Hazard
Prevalence Reduc- Reduc- Years
lence Reduction
tion tion
Second-line
monother-
20% 30% 96.5% 64.4% 0% 2.1
apy, All
patients
First-line
monother-
30% 40% 96.5% 64.4% 0% 3.25
apy, PD-L1
>1%
First-line
monother-
50% 40% 96.5% 64.4% 0% 4.72
apy, PD-L1
>50%
First-line
combination
60% 30% 96.5% 64.4% 0% 4.22
therapy,
PD-L1 >1%
First-line
combination
100% 0% 96.5% N/A N/A 7.06
therapy, PD-
L1 >50%
Conclusion: Current IO therapies represent a significant step towards

extending life expectancy for metastatic NSCLC patients.
Keywords: immuno-oncology, non-small cell lung cancer, survival, Life

Twenty-four percent of patients experience immunotherapy related toxicity, expectancy
most toxicities were short-term or easily manageable. No grade 5 toxicities,
one grade 4 hepatitis and one grade 3 hypophysitis were observed.
Hypothyroidism was most frequently observed (gr.1-2; 9,5%), followed by
skin-reactions (gr.1-3; 3,8%) and colitis (gr.1-2; 3,2%). Other immune related MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
toxicities were hepatitis (gr.1-4; 2,5%), infusion reactions (gr.1; 2,5%),
pneumonitis (gr.2; 1,9%), hyperthyroidism (gr.1; 1,3%), arthritis (gr.2; 0,6%),
hypophysitis (gr.3; 0,6%) and diabetes mellitus type 1 (gr.3, 0,6%). Conclusion: MA14.10 RELATIVE IMPACT OF DISEASE MANAGEMENT COSTS IN
Although follow up is short and response data not yet mature, real-life THE ECONOMICS OF PEMBROLIZUMAB IN PREVIOUSLY TREATED
efficacy and safety data from Nivolumab are comparable to phase III trial PD-L1 POSITIVE ADVANCED NSCLC
data.
Min Huang1, Yanyan Lou2, James Pellissier 1, Thomas Burke 3, Frank Liu1,
Keywords: Immunotherapy, Safety, efficacy, NSCLC Vamsidhar Velcheti4
1
Center for Observational and Real-World Evidence, Merck & Co., Inc, North Wales/
PA/United States of America, 2Hematology/Oncology, Mayo, Jacksonville/FL/
United States of America, 3Center for Observational and Real-World Evidence,
Merck & Co., Inc., Lebanon/NJ/United States of America, 4Solid Tumor Oncology,
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 Cleveland Clinic, Cleveland/OH/United States of America
Background: This study aimed to understand the impact on disease

MA14.09 DEMONSTRATING LIFE EXPECTANCY GAINS WITH management costs beyond drug acquisition costs in the context of an
IMMUNO-ONCOLOGY (IO) THERAPIES economic evaluation of pembrolizumab compared with docetaxel in
patients in patients with previously treated PD-L1 positive (TPS>=50%)
Jeffrey Sullivan1, Alison Sexton Ward1, Beata Korytowsky2, Desi Peneva1,
advanced NSCLC. The analysis was conducted from a US third-party payer
Jennifer Benner 1, Darius Lakdawalla3, Bjorn Bolinder2, Robert Figlin 4, Anupam
perspective. Methods: A partitioned-survival model was developed using
Jena5
1 data from patients from the KEYNOTE-010 (KN010) clinical trial. The model
Precision Health Economics, Los Angeles/CA/United States of America, 2Bristol-
used KM estimates of PFS and OS from the trial for patients treated with
Myers Squibb, Princeton/NJ/United States of America, 3University of Southern
California, Los Angeles/CA/United States of America, 4 Cedars-Sinai Medical Center, pembrolizumab 2mg/kg and docetaxel 75kg/m2 with extrapolation based
Los Angeles/CA/United States of America, 5Harvard Medical School, Boston/MA/ on fitted parametric functions and long-term registry data. Costs of clinical
United States of America management of advanced NSCLC along with drug acquisition/administration
and adverse event management costs were included in the model. The base-
Background: Immuno-oncology (IO) therapies offer the possibility of long- case analysis used a time horizon of 20 years. Costs and health outcomes were
term survival to metastatic cancer patients. Prior analyses have shown that discounted at a rate of 3% per year. Results: Base case results project for PD-
lung cancer reduces life expectancy by an average of 11.8 years (Burnet NG, L1 positive (TPS>=50%) patients treated with pembrolizumab a mean survival
et al. Br J Cancer. 2005;92:241-245.). We aimed to investigate the impact of of 2.25 years. For docetaxel, a mean survival time of 1.07 years was estimated.
IO therapies on life extension of patients with non-small cell lung cancer

Weekly disease management costs observed in KN010 for the progression-

free state were $866 and $1,298 for pembrolizumab and docetaxel, MINI ORAL ABSTRACT SESSIONS -
respectively. Weekly disease management costs for the progressive disease WEDNESDAY, DECEMBER 7, 2016
state were $1,938 based on a US healthcare claim database. Results projected
total disease management costs to be $166K per patient treated with
pembrolizumab compared with $93K for docetaxel because of extended
SESSION MA15: IMMUNOTHERAPY PREDICTION
progression-free and post-progression survival with pembrolizumab. Nearly WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
half (45%) of total expected cost differences between pembrolizumab and
docetaxel are due to the incremental disease management costs. Further
analyses that exclude drug treatment costs show that the additional disease MA15.01 IMMUNOGRAM FOR CANCER-IMMUNITY CYCLE TOWARDS
management costs associated with extended progression-free and overall PERSONALIZED IMMUNOTHERAPY OF LUNG CANCER
survival exceed $50,000 per LY gained ($61,864). Conclusion: Pembrolizumab Takahiro Karasaki1, Kazuhiro Nagayama1, Hideki Kuwano1, Jun-Ichi Nitadori1,
improves outcomes compared to docetaxel in PD-L1 positive (TPS>=50%) Masaaki Sato1, Masaki Anraku1, Akihiro Hosoi2, Hirokazu Matsushita2,
pre-treated advanced NSCLC patients in the US. The improved overall survival Yasuyuki Morishita3, Kosuke Kashiwabara4, Masaki Takazawa5, Osamu
with pembrolizumab is accompanied by the economic reality of additional Ohara5, Kazuhiro Kakimi2, Jun Nakajima1
non-pembrolizumab costs that represent their own substantial economic 1
Thoracic Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo/
burden. Japan, 2Immunotherapeutics, The University of Tokyo Hospital, Tokyo/Japan,
3
Molecular Pathology, Graduate School of Medicine, the University of Tokyo,
Keywords: Cost-effectiveness, PD-L1, advance NSCLC Tokyo/Japan, 4Biostatistics, School of Public Health, the University of Tokyo, Tokyo/
Japan, 5Technology Development, Kazusa Dna Research Institute, Kisarazu/Japan
Background: The interaction of immune cells and cancer cells shapes the
MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS immunosuppressive tumor microenvironment. For successful cancer
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30 immunotherapy, comprehensive knowledge of anti-tumor immunity as a
dynamic spacio-temporal process is required for each individual patient.
MA14.11 AN ESTIMATE OF THE ECONOMIC IMPACT OF To this end, we developed an “immunogram for the cancer-immunity cycle”
using next-generation sequencing. Methods: Whole-exome sequencing
IMMUNOTHERAPY RELATIVE TO PD-L1 EXPRESSION IN BRAZIL
and RNA-Seq were performed in 20 non-small cell lung cancer patients (12
- AN UPDATE WITH BRAZILIAN COSTS
adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine
Pedro Aguiar Jr 1, Ramon De Mello2, Hakaru Tadokoro1, Hani Babiker3, Gilberto carcinoma). Mutated neoantigens and cancer-germline antigens expressed in
Lopes 4 the tumor were assessed for predicted binding to patients’ HLA molecules.
1
Universidade Federal de SÃo Paulo, SÃo Paulo/Brazil, 2Universidade Do Algarve,
Faro/Portugal, 3Honor Health, Scottsdale/AZ/United States of America, 4HCOR
Cancer Center, SÃo Paulo/Brazil
Background: Delivering high quality cancer care at an affordable cost is one of

the main challenges for health care professionals and policy makers, especially
in low- and middle-income countries. The objective of our study is to assess
the economic impact of nivolumab and pembrolizumab with and without
the use of PD-L1 as a biomarker in Brazil. Methods: We developed a decision-
analytic model to determine the cost-effectiveness of PD-L1 assessment and
the second-line treatment with NIVO or PEMBRO versus docetaxel. The model
used outcomes data from randomized clinical trials and drug acquisition costs
were estimated using current prices in Brazil. Thereafter, we used Brazilian
epidemiologic data to estimate the economic impact. Results: We included
three RCTs (two with NIVO and one with PEMBRO). The estimated number of
cases eligible for therapy with immune checkpoint inhibitors is 4,733. Treating
all patients with NIVOLUMAB would cost US$ 173 million dollars each year,
representing an increase of 21% in current Brazilian expenses for cancer drugs
acquisition. Treating only patients with PD-L1 > 1% with NIVOLUMAB would
cost 93 million dollars every year, leading to an increase of 11.3% in expenses
for cancer drugs acquisition. However, with such selection, up to 46% of cases
would not be treated and 315 years of life would be lost compared to treating
all patients regardless of PD-L1 expression. The cost of each year-of-life saved
was improved by PD-L1 selection (from US$ 196,000 to US$ 164,000). Table 1
summarizes our findings for five different scenarios of treatment. The results
were similar with NIVOLUMAB and PEMBROLIZUMAB.
IMPACT
YEARS ON
LIFE- OF TOTAL TOTAL COST/
QALY ICER % NOT
SCENARIO YEARS LIFE COST CANCER LYS
GAIN (US$) TREATED
SAVED NOT (US$) DRUG (US$)
SAVED EXPEND-
ITURE
NIVO ALL 173
0.148 129 K 885 0 0% 21.1% 196 K
COMERS Million
NIVO PD- 108
0.201 570 315 46% 93 11.3% 164 K
L1 > 1% K
PEMBRO
PD-L1 > 0.138 137 K 666 NA 34% 100 12.1% 150 K
1%
NIVO ALL
SQ/ > 1% 0.216 99 K 738 147 35% 116 14.0% 157 K
NSQ
PEMBRO
PD-L1 > 0.164 116 K 285 NA 72% 43 5.2% 151 K
50%
Conclusion: The use of PD-L1 expression as a biomarker for treatment with

immune checkpoint inhibitors decreases the overall economic impact and the
cost per life-year saved. Further study and societal discussion is needed in
order to find the optimal strategy for patient selection.
Keywords: Pharmacoeconomy, Policy Maker, Immunotherapy, biomarker
mutation load (p = 0.047) and patients with a longer smoking history tended
to have longer PFS although this trend did not reach statistical significance
(p = 0.07). Expression of PD-L1 in either tumor cells or ICs was not associated
with NSM burden (p = 0.47) or PFS (p = 0.92). PD-L1 expression in the tumor
microenvironment was associated with increased numbers of tumor-
associated macrophages (p = 0.0002), and non-regulatory and regulatory
T cells (p = 0.0038 and 0.01 respectively). Conclusion: The non-synonymous
mutation burden in lung carcinoma as assessed by targeted next generation
sequencing is associated with increased PFS and durable clinical benefit to
immune checkpoint inhibitors. In this limited cohort, PD-L1 expression using
clone E1L3N does not predict response to these therapies. We add to growing
evidence that increased somatic mutations in carcinomas influence response
to immune checkpoint blockade.
Keywords: Mutation burden, Immunotherapy, next generation sequencing
The expression of genes related to cancer-immunity was assessed and MA15: IMMUNOTHERAPY PREDICTION
normalized; immunogram was drawn in a radar chart composed of 8 axes WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
reflecting 7 steps of cancer-immunity cycle. Results: Distinctive patterns of
immunogram were observed in lung cancer patients: T-cell-rich and T-cell-poor.
Patients with T-cell-rich pattern had gene signatures of abundant T cells, Tregs MA15.03 THE PREDICTIVE VALUE OF MUTATION/NEOANTIGEN
and MDSCs, checkpoint molecules and immune-inhibitory molecules in the BURDEN FROM CTDNA ON THE EFFICACY OF PD-1 BLOCKADE IN
tumor, suggesting the presence of counter regulatory immunosuppressive ADVANCED NSCLC
microenvironment. Unleashing of counter regulations, i.e. checkpoint Weijing Cai1, Caicun Zhou1, Chunxia Su1, Feng Ying Wu1, Shengxiang Ren1,
inhibitors, may be indicated for these patients (Figure A). Immunogram of Xiaoxia Chen1, Fred R. Hirsch2
T-cell-poor phenotype reflected lack of anti-tumor immunity, inadequate DC 1
Medical Oncology, Shanghai Pulmonary Hospital, Shanghai/China, 2Division of
activation, and insufficient antigen presentation in the tumor (Figure B). Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora/CO/
When the immunograms were overlaid within each tumor histology, no typical United States of America
pattern was elucidated. Both T-cell-rich and T-cell-poor phenotypes were
present in each histology, suggesting that histology cannot necessarily Background: Immune checkpoint, PD-1, inhibitors, have been approved to
reflect the cancer-immunity status of the tumor (Figure C,D). These results treat advanced NSCLC patients without oncogenic driver in the second-line
were consistent with previous studies showing that clinical responses of setting based on durable clinical benefit. It has been demonstrated that the
checkpoint blockade were not easily predicted by the histology. overall mutational burden in tumor tissue was significantly associated with
progression free survival (PFS) of advanced NSCLC patients treated with PD-1
Conclusion: Utilizing the immunogram, the landscape of the tumor inhibitor. However, tumor tissue may not be available from all patients at any
microenvironment in each patient can be appreciated. Immunogram for the time during PD-1 blockade therapy. Therefore, the purpose of this study was
cancer-immunity cycle can be used as an integrated biomarker and thus may to explore the predictive value of mutation/neoantigen burden from ctDNA
become a helpful resource toward optimal personalized immunotherapy. on efficacy of PD-1 inhibitors. Methods: We treated advanced NSCLC patients
without oncogenic drivers with PD-1 inhibitor in the second or more line
Keywords: cancer-immunity cycle, neoantigen, immunogram, transcriptome setting. The whole-exome of tumor tissues and ctDNA at baseline and ctDNA
at every time of efficacy evaluation from these patients were sequenced by
NGS. The hybrid-capture-enriched libraries were sequenced on the Illumina
HiSeq 4000 platform with 75-base paired-end reads, sequencing depth was
MA15: IMMUNOTHERAPY PREDICTION 300 for ctDNA whole-exome sequencing. We compared the results of whole-
exome sequencing between patients who achieved objective response to
PD-1 inhibitor and patients who experienced disease progression. Besides,
MA15.02 NON-SYNONYMOUS MUTATION BURDEN IN LUNG we also compared the results of whole-exome sequencing between baseline
CARCINOMA IS ASSOCIATED WITH DURABLE CLINICAL RESPONSE ctDNA and ctDNA extracted at efficacy evaluation. Results: Up to now, a
TO IMMUNE CHECKPOINT BLOCKADE total of 23 patients treated with PD-1 inhibitor received efficacy evaluation
at least once in this study. Of them, 4 patients achieved partial response (PR),
Navin Mahadevan1, Anika Adeni2, Peter Hammerman2, Mark Awad3, Leena
3 patients achieved stable disease (SD). Of 4 patients with PR, 3 patients
Gandhi2, Lynette Sholl4
1
were found to harbor high mutation burden (more than 400 nonsynonymous
Pathology, Brigham and Women’s Hospital, Boston/United States of America,
2 mutations) from ctDNA and only 1 patient harbored mutation burden of
Medical Oncology, Dana-Farber Cancer Institute, Boston/MA/United States
less than 100 from ctDNA at baseline. We found the mutation or neoantigen
of America, 3Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute,
Boston/MA/United States of America, 4Pathology, Brigham and Women’s Hospital, burden from ctDNA changed during PD-1 blockade therapy. The efficacy of
Boston/MA/United States of America PD-1 inhibitor appeared to be more significantly associated with neoantigen
burden rather than mutation burden. Only one ctDNA sample was found
Background: Recent evidence indicates that efficacy and durability of positive for MSH6 mutation (C1337X) and all baseline ctDNA samples were
responses to immune checkpoint inhibitors in lung carcinomas correlate with negative for microsatellite instability (MSI) status. Conclusion: Evaluating
increased nonsynonymous mutation (NSM) burden, putative neoantigen nonsynonymous mutation burden/neoantigen burden from ctDNA was
number, and in some tumor types, PD-L1 protein expression. In this study, we feasible in advanced NSCLC patients treated with PD-1 inhibitors. The
retrospectively analyzed the relationship of lung carcinoma mutation burden, predictive value of neoantigen burden from ctDNA on the efficacy of PD-1
PD-L1 expression and immune infiltrates with clinical response in patients inhibitor may be better than that of mutation burden in advanced NSCLC. It
receiving immune checkpoint blockade. Methods: Tumor nonsynonymous may not be feasible to determine the status of mismatch-repair deficiency and
mutation data derived from clinical targeted next generation sequencing (309 MSI using ctDNA samples in advanced NSCLC. An expanded study is ongoing.
genes) of lung carcinomas from 94 patients treated with immune checkpoint More details will be presented in the conference.
inhibitors was correlated with clinical outcomes, including durable clinical
benefit (DCB; >6 months partial or stable response) and progression-free Keywords: neoantigen burden, ctDNA, PD-1 blockade, Mutation burden
survival (PFS). PD-L1 immunohistochemistry (clone E1L3N, Cell Signaling
Technology, Envision+ detection, Dako) was considered positive if ≥1% of
tumor cells and/or tumor-infiltrating immune cells (IC) stained. PU.1, CD3,
and FOXP3 immunohistochemistry was used to highlight tumor-associated MA15: IMMUNOTHERAPY PREDICTION
macrophages and non-regulatory and regulatory T cell populations, which
were manually quantified per mm2. Results: The mean patient age was 62
years (range: 32-91 years). Lung tumor types included 69 adenocarcinomas, 11 MA15.05 PD-L1 IMMUNOHISTOCHEMISTRY AS BIOMARKER IN NON-
squamous cell carcinomas, 5 small cell carcinomas, and 9 of other/combined SMALL CELL LUNG CANCER (NSCLC)
histology. Therapies included PD1 inhibitors (82), a PD-L1 inhibitor (5)
Dagmar Krenbek 1, Barbara Weidinger 1, Christa Jarius1, Sophia Holzer2,
and multiple agents (7). Across all tumor types, patients with DCB had a
Hannah Fabican2, Andrea Mohn-Staudner2, Maximilian Hochmair2, Andreas
significantly higher number of NSM (range: 1-42) than patients who showed
Chott1, Ulrike Setinek1
no durable benefit (NDB) [DCB: 12; NDB: 8, p = 0.0027]. Patients with greater 1
Otto Wagner Hospital, Department of Pathology, Vienna/Austria, 2Otto Wagner
than the median number of NSM (9) had significantly longer PFS than
Hospital, Department of Respiratory and Critical Care Medicine, Vienna/Austria
those with ≤9 (p = 0.015). Increasing smoking history correlated with higher

Background: Anti-PD1 (programmed cell death 1) therapeutic antibodies 67/Granzyme-B in CD3 predicted longer survival after PD-1 axis blockade than
have recently become available as a promising option in the treatment of high CD3/high Ki-67/Granzyme-B in CD3, or low T-lymphocyte infiltration.
patients with NSCLC in Austria. Several clinical studies suggested PD-L1 Conclusion: Increased somatic mutations are associated with smoking and
(programmed cell death ligand 1) protein expression in tumor cells to be a response to PD-1 agents, but not with tumor T-cell infiltration/activation
useful prognostic biomarker using several antibodies and different cutoffs. and overall survival. Regardless of the mutational load, increased T-cell
We studied PD-L1 expression in our NSCLC patient cohort and compared the infiltration using QIF is significantly associated with longer survival after PD-1
performance of different antibodies. Furthermore we aimed to investigate axis blockade in NSCLC. The subgroup of NSCLC with the highest potential of
the value of PD-L1 expression as a biomarker in a subset of patients treated benefit to immune reinvigoration using PD-1 axis blockade comprise tumors
with Anti-PD1 immunotherapy. Methods: PD-L1-Imunohistochemistry with elevated lymphocyte infiltration but low in situ activation/proliferation.
(IHC) was performed in 437 lung cancer specimens (316 adenocarcinomas,
77 squamous cell carcinomas and 44 NSCLC NOS) using the clones SP263 Keywords: Immunogenomics, Immunoprofiling, PD-1 axis blockers, non-small
(Ventana), 28.8 (Abcam) and EL1L3N (Cell Signaling) on the VENTANA IHC cell lung cancer
platform. The percentages of tumor cells (TC) with membranous staining
were determined - irrelevant of staining intensity; TC-counts of less than 1
% were interpreted as negative. Staining with at least two of the antibodies
was available in 378 specimens (SP263/28.8 in 320 and 28.8/E1L3N in 117). 60 MA15: IMMUNOTHERAPY PREDICTION
specimens were stained with three antibodies. From 58 patients receiving
Nivolumab clinical information about response to therapy was available.
Results: PD-L1 was expressed in 244 specimens (54.84%). 112 (25.63%) showed MA15.07 MOLECULAR DETERMINANTS OF LACK OF TUMOR
TC counts ≥50%, and 132 (30.21%) were <50%. 193 (44.16%) were negative. IMMUNE INFILTRATION IN NSCLC
SP263 showed stronger staining intensity than 28.8 and E1L3N. Differences
Sope Olugbile1, Riyue Bao1, Thomas Hensing 2, Yusuke Nakamura1, Everett
in TC-percentage were seen in 67 of 378 specimens, with major changes in 16
Vokes1
specimens (negative to positive in 4 and <50% to ≥50% in 12 cases). Higher 1
University of Chicago, Chicago/IL/United States of America, 2Northshore
TC percentages were seen with SP263. In the 58 treated patients complete
University Health System, Chicago/IL/United States of America
remission was seen in 6 (4 ≥50%, 2 negative), partial remission in 14 (10
≥50%, 3 <50%, 1 negative), stable disease in 4 (2 <50%, 2 negative), paradox Background: Non-small cell lung cancer (NSCLC) make up the majority of
reaction in 7 (1 ≥50%, 3 <50%, 3 negative) and progressive disease in 27 (4 all lung cancer cases and is associated with very poor prognosis. Immune
≥50%, 14 <50%, 9 negative). Conclusion: PD-L1 is expressed in the majority checkpoint blockers have now been shown to induce unprecedented durable
of NSCLC patients. Despite minor differences in expression levels all three response in a fraction of NSCLC patients with pre-existing T cell infiltration
tests provided reliable results. Furthermore PD-L1-IHC showed to be a useful within their tumor. However in order to improve their efficacies beyond
biomarker in NSCLC especially concerning the good response to Anti-PD1 this subset of patients, a detailed molecular characterization to identify
therapy in tumors with PD-L1 expression ≥50%. However as some PD-L1 factors associated with lack of T cell infiltration is needed. A recent analysis
negative tumors also responded, negative test results cannot definitely in metastatic melanoma identified Wnt/B-catenin pathway activation as
exclude patients from immunotherapy. a mechanism for lack of T cell infiltration. We pursued similar analyses of
immunologic gene signatures and molecular associations in squamous cell
Keywords: non-small cell lung cancer, PD-L1 immunohistochemistry,
lung cancer (SCC) and lung adenocarcinoma (LA). Methods: We analyzed
Immunotherapy
RNAseq data from two lung cancer datasets of The Cancer Genome Atlas
(TCGA) (N = 499 for SCC and N = 514 for LA). Samples were categorized into
non-T cell inflamed and T cell-inflamed groups using unsupervised consensus
clustering based on the expression of 160 immune-related genes. Ingenuity
MA15: IMMUNOTHERAPY PREDICTION
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 pathway analysis was utilized to identify molecular pathways activated in
non-T cell-inflamed tumors. Results: A similar proportion of non-T cell-
inflamed tumors were identified in the two cohorts (SCC: 34%; LA: 31%). 47%
MA15.06 PREDICTIVE VALUE OF MEASURING SOMATIC MUTATIONS of the SCC tumors were identified as T cell-inflamed, as compared to 37% in
AND TUMOR INFILTRATING LYMPHOCYTES FOR PD-1 AXIS THERAPY LA. A positive correlation was observed between CD8A and PD-L1, IDO1, LAG3
IN NON-SMALL CELL LUNG CANCER (NSCLC) and TIM3 (p<0.00001). Total of 1,216 genes are significantly up-regulated in
Scott Gettinger 1, Jungmin Choi2, Nikita Mani3, Ila Datar4, Edward Kaftan5, non-T cell-inflamed SCC tumors and 596 in LA with at least 1.5-fold change and
Sarah Goldberg6, Daniel Zelterman7, Katerina Politi4, Richard Lifton2, David FDR-adjusted p<0.05. Among these, a total of 194 genes are up-regulated in
Rimm8, Roy Herbst9, Kurt Schalper4 both SCC and LA, with the rest being specific for each subtype (SCC: 84%; LA:
1 67%). Pathway analysis suggested 35 upstream regulators were activated
Yale Cancer Center, New Haven/CT/United States of America, 2Genetics, Yale School
of Medicine, -/United States of America, 3Pathology, Yale University, New Haven/
in SCC and 32 in LA (activation z-score≥2.0). Among these, 10 upstream
United States of America, 4Pathology, Yale University, New Haven/CT/United States regulators are activated in both datasets (ATF4, CTNNB1, KAT6A, KLF4, MYC,
of America, 5Yale Cancer Center, New Haven/United States of America, 6Medical NFE2L2, PI3K, SCAP, SP1, SREBF2). Finally, we performed the same gene
Oncology, Yale Cancer Center, New Haven/CT/United States of America, 7Yale School expression analysis on RNAseq data from matched normal tissues (N = 51 for
of Medicine, New Haven/United States of America, 8Department of Pathology, Yale SCC and N = 59 for LA) and confirmed that the T-cell inflamed gene signature
University School of Medicine, New Haven/CT/United States of America, 9Medical is a property of the tumor rather than normal lung tissue. Conclusion: Our
Oncology, Yale Cancer Center, New Haven, Ct/CT/United States of America analyses successfully identified genes and associated pathways that are
enriched in NSCLC subtypes with no immune infiltration. Rational strategies
Background: Diverse factors have been associated with clinical benefit
to improve the efficacy of immune checkpoint blockers beyond the current
to PD-1 axis blockers in NSCLC including PD-L1 protein expression by
subset of responders should be based on targeting these pathways.
immunohistochemistry and increased mutation load/predicted class-I
neoantigens. However, the association and predictive value of the tumor Keywords: biomarker, non-small cell lung cancer, immunotherapy biomarker
genomic landscape, composition of the tumor immune microenvironment
and T-cell function remain unclear. Methods: We performed whole exome
DNA sequencing and multiplexed quantitative immunofluorescence
(QIF) for T-cells in pre-treatment FFPE samples from 45 NSCLC patients MA15: IMMUNOTHERAPY PREDICTION
treated with PD-1 axis blockers (alone or in combination) in our institution. WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
Genomic analysis was used to evaluate the mutational load and predicted
class-I neoantigens. Multiplexed QIF-based immunoprofiling was used to
measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell MA15.09 RESPONSE TO THE TREATMENT IMMEDIATELY BEFORE
proliferation (Ki-67 in CD3+ cells) and T-cell activation (Granzyme-B in CD3+ NIVOLUMAB MONOTHERAPY MAY PREDICT CLINICAL RESPONSE
cells). We studied the association between the tumor somatic mutations, TO NIVOLUMAB
predicted neoantigens, T-cell infiltration/function and clinical benefit / Haruki Kobayashi1, Shota Omori2, Kazuhisa Nakashima2, Kazushige Wakuda2,
survival. Results: Increased mutational load was positively associated Akira Ono2, Hirotsugu Kenmotsu2, Tateaki Naito2, Haruyasu Murakami2,
with predicted class-I neoantigens, variants in DNA-repair genes, smoking Masahiro Endo2, Toshiaki Takahashi2
and absence of activating mutations in EGFR; but not associated with the 1
Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka/Japan, 2 Shizuoka
level of CD3+ T-cells, T-cell proliferation (Ki-67 in CD3+ cells) and function Cancer Center, Shizuoka/Japan
(Granzyme-B in CD3+ cells). Increased mutations and candidate class-I
neoantigens were significantly associated with response to therapy (P=0.02 Background: Nivolumab was approved in Japan on December 17, 2015 for
and 0.03, respectively), but not with overall survival at 3-years (median cut- previously treated non-small cell lung cancer (NSCLC). The expression of
point, log rank P=0.92 and 0.80, respectively). Higher CD3 positivity was not programmed death-ligand 1 (PD-L1) in tumor tissue is considered a predictive
associated with response to therapy (P=0.17), but was significantly associated factor for clinical response to nivolumab. However, in Japan, there are no
with overall survival (median cut-point, log rank P=0.03). Regardless of the commercially available diagnostic kits for evaluating PD-L1 expression. In
mutational load and candidate neoantigen content, elevated CD3 with low Ki- addition, little is known regarding other predictive factors of response to
nivolumab monotherapy in patients with NSCLC. Therefore, we examined

the relationships between the response to nivolumab monotherapy and
clinical parameters in patients with NSCLC. Methods: Between December
2015 and April 2016, we performed a retrospective analysis of 50 patients
with NSCLC treated with nivolumab monotherapy (3 mg/kg, every 2 weeks)
at our Institution in the clinical setting. Results: Baseline characteristics of
patients who received nivolumab monotherapy were: median age, 65 years
[range:39–76]; 60% male; 26% ECOG-PS 0, 64% ECOG-PS 1; 38% smoker; 58%
stage IV disease, 22% postoperative recurrence; 80% non-squamous (SQ)
NSCLC; 36% non-SQ NSCLC patients had active EGFR mutations; 20% second-
line, 18% third-line. The objective response rate (ORR) for all patients treated
with nivolumab monotherapy was 18% (95%CI 10–31). Univariate analysis
revealed that predictive factors of response to nivolumab monotherapy
were associated with “SQ”, “response to the treatment immediately before
nivolumab monotherapy”, “therapeutic line of nivolumab (second-line and
third-line treatment)” and “smoker” categories (Table 1). In the multivariate
logistic regression analysis, the independent predictive factors were “SQ”
(P = 0.0069) and “response to the treatment immediately before nivolumab
monotherapy” (P < 0.0001) (Table 1).
Conclusion: This work provides evidence that TP53 and KRAS mutation in
lung adenocarcinoma may be served as a pair of potential predictive factors in
guiding PD-1 blockade immunotherapy.
Conclusion: “Response to the treatment immediately before nivolumab
monotherapy”, other than “SQ” histology may be predictors of clinical Keywords: programmed cell death protein-1 (PD-1) blockade, KRAS, lung
response to nivolumab in patients with NSCLC. adenocarcinoma, TP53
Keywords: Nivolumab, a predictive factor, non-small cell lung cancer

MA15.11 ACQUIRED RESISTANCE MECHANISMS TO EGFR KINASE
MA15.10 POTENTIAL PREDICTIVE VALUE OF TP53 AND KRAS INHIBITORS ALTER PD-L1 EXPRESSION STATUS IN LUNG CANCER
MUTATION STATUS FOR RESPONSE TO PD-1 BLOCKADE Kenichi Suda1, Leslie Rozeboom1, Christopher Rivard1, Hui Yu1, Mary Ann
IMMUNOTHERAPY IN LUNG ADENOCARCINOMA Melnick2, Trista Hinz3, Kim Ellison1, Daniel Chan1, Katerina Politi4, Lynn
Heasley3, Tetsuya Mitsudomi5, Fred R. Hirsch1
Zhong-Yi Dong, Wen-Zhao Zhong, Si-Yang Liu, Zhi Xie, Si-Pei Wu, Yi Long Wu
1
Division of Medical Oncology, University of Colorado Anschutz Medical Campus,
Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou/China
Aurora/CO/United States of America, 2Department of Pathology, Yale University,
New Haven/CT/United States of America, 3Department of Craniofacial Biology,
Background: Although clinical studies have shown promise for targeting
University of Colorado Anschutz Medical Campus, Aurora/CO/United States of
programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in
America, 4Pathology, Yale University, New Haven/CT/United States of America,
non-small cell lung cancer (NSCLC), the factors that predict which subtype 5
Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of
patients will be responsive to checkpoint blockade remains elusive. This study Medicine, Osaka-Sayama/Japan
was sought to identify the potential biomarkers that predicted response to
PD-1 blockade immunotherapy in lung adenocarcinoma. Methods: We Background: Immunotherapies that target PD-1/PD-L1 exploit the primary
performed an integrated analysis on the multiple-dimensional data types roles of cytotoxic agents in lung cancers. However, tyrosine kinase inhibitors
including genomic, transcriptomic, proteomic and clinical data from cohorts (TKIs) are still considered to be the first choice in lung cancer patients with
of both lung adenocarcinoma public database including The Cancer Genome EGFR mutations. Although immunotherapies may be applied as second line or
Atlas (TCGA), GEO repository (GSE72094) and Broad dataset, and clinical later therapeutic approaches in these patients, after acquisition of resistance
immunotherapeutic patients in our center. Gene Set Enrichment Analysis to EGFR-TKIs, it is unclear if acquired resistance mechanisms alter PD-L1
(GSEA) was used to determine potentially relevant gene expression signatures expression status that is employed as an important predictive biomarker
between specific subgroups. Results: We observed distinct function of TP53 for PD-1/PD-L1 targeting agents. Methods: Lung cancer cell lines with EGFR
and KRAS mutation in regulating immune tumor microenvironment (TME). It mutations (HCC827, HCC4006, PC9, and H1975) and their isogenic descendants
is TP53 mutation but not KRAS mutation in lung adenocarcinoma that with acquired resistance to various EGFR-TKIs were examined in this study. The
significantly increased expression of immune checkpoints, facilitated CD8+T resistance mechanisms of descendants include T790M secondary mutation,
cell infiltration and activated T-effector and interferon-γ (IFN-γ) signature. MET gene amplification, epithelial to mesenchymal transition (EMT), and
Interestingly, TP53 and KRAS co-mutated subgroup manifested exclusive loss of amplified EGFR mutant allele. PD-L1 expression status was analyzed
increased expression of PD-L1 and a highest proportion of PD-L1+/CD8A+. by immunohistochemistry (IHC) and immunoblotting. Effects of acquired
More importantly, TP53 or KRAS mutated tumors showed prominently resistance mechanisms on PD-L1 expression were also evaluated by shRNA
increased mutation burden and specifically enriched in the transversion-high mediated knockdown of candidate molecules, and co-localization analysis
(TH) cohort. Further analysis focused on the potential molecular mechanism using fluorescent imaging. IFN-gamma was used to mimic immune cell attack.
revealed that TP53 or KRAS mutation altered a group of genes involved in cell Published microarray data of cells with acquired resistance to EGFR-TKIs
cycle regulating, DNA replication and damage repair. Finally, clinical were also employed to evaluate our findings. Results: PD-L1 expression was
immunotherapeutic data were further confirmed that TP53 or KRAS mutation upregulated in several resistant cells and correlated with EGFR activation.
lung adenocarcinoma patients, especially those with co-occurring TP53/KRAS In addition, we found that the phosphorylation of EGFR tyrosine (Y) 992
mutations, showed remarkable clinical benefit to PD-1 blockade site, but not Y845, Y1068, or Y1173, was correlated with increased expression
immunotherapy. of PD-L1. We also observed that TKI-resistant cells with marked E-cadherin
downregulation (HCC4006 erlotinib resistant cells and H1975 osimertinib
resistant cells), one of hallmarks of EMT, showed decreased expression of
PD-L1. However, one cell line (853#10), displaying EMT-like phenotype but only
slight E-cadherin downregulation, showed PD-L1 upregulation. Published

microarray data from three TKI-resistant lines with EMT-like features also
support the correlation of low E-cadherin and reduced PD-L1 expression.
ShRNA mediated knockdown of E-cadherin decreased the expression of PD-L1
in parental cell lines. IFN-gamma treatment upregulated PD-L1 expression in
both parental and in resistant cells with E-cadherin downregulation, however
PD-L1 expression in resistant cells was still lower and localized mainly in the
cytoplasm rather than the cell membrane. Conclusion: We observed a dramatic
change of PD-L1 expression status in lung cancers with EGFR mutation
after acquisition of resistance to EGFR-TKIs, depending on the resistance
mechanisms. These results support the importance of re-biopsy after
acquisition of resistance to EGFR-TKIs, not only for the resistance mechanisms
but also for the evaluation of PD-L1 expression status.
Keywords: EGFR mutation, epithelial to mesenchymal transition, T790M

mutation, EGFR-TKIs
Remarkably, aerosol-delivered shRab25 significantly decreased the
expression level of Rab25 and other prominent apoptosis related proteins in
SESSION MA16: NOVEL STRATEGIES IN TARGETED female A/J mice. The apoptosis in these mice were determined by detecting
THERAPY the expression level of Bcl-2, PCNA, Bax and further confirmed by TUNEL
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 assay. Conclusion: Our results strongly confirm the tumorigenic role of Rab25
in tobacco carcinogen induced-lung cancer and hence demonstrate aerosol
delivery of shRab25 as a therapeutic target for lung cancer treatment.
MA16.01 TARGETED GENE THERAPY FOR TOBACCO CARCINOGEN- Keywords: Lung cancer, Aerosol delivered shRab25, NNK, Gene therapy
INDUCED LUNG CANCER
Nomundelger Gankhuyag 1, Chong-Su Cho2
1
Veterinary Medicine, Seoul National University, Seoul/Korea, Republic of,
2
Agricultural Biotechnology and Research Institute for Agriculture and Life Science, MA16: NOVEL STRATEGIES IN TARGETED THERAPY
Seoul National University, Seoul/Korea, Republic of
Background: Rab25, a member of Rab family of small GTPases, is associated

MA16.02 MUTATIONAL LANDSCAPE OF TKI NAÏVE AND RESISTANT
with progression of various types of human cancer including lung cancer that
is the leading cause of cancer-associated deaths around the globe. Methods: EGFR MUTANT LUNG ADENOCARCINOMAS
In this study, we report the gene therapeutic effect of short hairpin Rab25 Katherine Hastings1, Jungmin Choi1, Anna Wurtz1, Zenta Walther 1, Guoping
(shRab25) on 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced Cai1, Isabel Oliva2, Ziming Zhao2, Stephen Gaffney2, Atila Iamarino2, Siming
lung tumorgenesis in female A/J mice. Initially, Mice (six-week-old) were Zhao1, Mark Bi1, Sarah Goldberg1, Anne Chiang1, Zongzhi Liu3, Jeffrey
injected with single dose of NNK (2 mg/0.1 ml saline/mouse) by intraperitoneal Townsend2, Joseph Schlessinger 1, Richard Lifton1, Roy Herbst1, Scott
injection to induce the tumor. 8 weeks later, shRab25 was delivered with Gettinger 1, Katerina Politi3
1
GPT-SPE (glycerol propoxylate triacrylate (GPT) and spermine) complex into Yale University, New Haven/CT/United States of America, 2Yale School of Medicine,
tobacco-induced lung cancer models through a nose-only inhalation system New Haven/CT/United States of America, 3Pathology, Yale University, New Haven/
twice a week for 2 month. CT/United States of America
Background: The identification and development of tyrosine kinase

inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR)
have revolutionized and greatly improved the treatment of EGFR-mutant
non-small cell lung cancer (NSCLC). Unfortunately, acquired resistance (AR)
to these agents remains a major clinical problem hindering durable responses.
Although significant work has been done to identify particular mechanisms of
acquired resistance, little is known regarding the global mutational landscape
of EGFR mutant tumors before therapy or at the manifestation of acquired
resistance. Methods: Using specimens obtained in the IRB approved, Yale
Lung Rebiopsy program, we completed whole exome sequencing of 15 EGFR
mutant tumors with paired tissue obtained pre-treatment and at the time
of AR to EGFR TKIs. An additional 5 unpaired AR samples were also analyzed.
The mutational burden and copy number profile of the specimens were
studied. Results: We found that the mutational burden of pre-treatment
EGFR mutant tumors varies widely between tumors. TKI treatment, however,
does not significantly alter the overall or non-synonymous mutation load
at AR. Interestingly, EGFRL858Rtumors had a significantly higher mutation
burden at acquired resistance to EGFR TKIs than EGFR Δ19 tumors. The higher
mutation burden in EGFRL858R tumors compared to those harboring EGFR Δ19
mutations was further confirmed through analysis of TCGA data. Recurrently
altered genes shared in the pre- and AR specimens include TP53, EGFR and
AKT1. Alterations in EGFR (T790M), MYCBP2, WHSC1L1, AXL, MET, HGF, MYC
and NTRK1 were found at exclusively at AR. Conclusion: Collectively, these
data provide valuable insight into the mutational landscape of EGFR mutant
NSCLCs as they evolve on TKIs and identify potential resistance candidate
genes for further investigation.
Results:
Keywords: Resistance, Targeted therapy, EGFR
MA16: NOVEL STRATEGIES IN TARGETED THERAPY

MA16.03 GLOBAL RET REGISTRY (GLORY): ACTIVITY OF RET-

DIRECTED TARGETED THERAPIES IN RET-REARRANGED LUNG
CANCERS
Oliver Gautschi1, Julie Milia-Baron2, Thomas Filleron3, Jürgen Wolf4, David
Carbone5, Dwight Owen6, D. Ross Camidge7, Vighesh Narayanan7, Robert
Doebele8, Benjamin Besse9, Jordi Remon10, Pasi Jänne11, Mark Awad11, Nir
Peled12, Chul-Cho Byoung13, Daniel Karp14, Michael Van Den Heuvel15, Heather
Wakelee16, Joel Neal17, Tony Mok18, James Chih-Hsin Yang19, Sai-Hong Ou20,
Georg Pall21, Patrizia Froesch22, Gérard Zalcman23, David R. Gandara24, of Korea, Suwon/Korea, Republic of, 2Medical Oncology, Seoul St. Mary’S Hospital,
Jonathan Riess24, Vamsidhar Velcheti25, Kristin Zeidler 1, Joachim Diebold1, the Catholic University of Korea, Seoul/Korea, Republic of, 3Pulmonology, Seoul
Martin Früh26, Sebastian Michels4, Isabelle Monnet27, Sanjay Popat28, Rafael St. Mary’S Hospital, the Catholic University of Korea, Seoul/Korea, Republic of,
4
Pathology, Seoul St. Mary’S Hospital, the Catholic University of Korea, Seoul/
Rosell29, Niki Karachaliou30, Sacha Rothschild31, Jin-Yuan Shih32, Arne Warth33,
Korea, Republic of
Thomas Muley34, Florian Cabillic35, Julien Mazieres36, Alexander Drilon37
1
Medical Oncology, Lucerne Cantonal Hospital, Luzern/Switzerland, 2Oncologie Background: EGFR tyrosine kinase (TKI) showed better progression free
Thoracique, Hopital Larrey, Toulouse/France, 3Institut Claudius Regaud, Institut survival (PFS) in EGFR-mutant non-small cell lung cancer (NSCLC), but the
Universitaire Du Cancer Toulouse, Toulouse/France, 4 Oncology, Cio, Cologne/ overall survival (OS) benefit were not clear so far. Treatment sequence may
Germany, 5Medical Oncology, Ohio State University Comprehensive Cancer Center,
contribute to OS, but there are little data so far. We aimed to analyze the
Columbus/OH/United States of America, 6Ohio State University Comprehensive
impact of treatment sequence of EGFR TKI and chemotherapy on outcomes
Cancer Center, Columbus/OH/United States of America, 7Medicine, University of
Colorado, Denver/United States of America, 8Division of Medical Oncology, University in EGFR-mutant NSCLC. Methods: Among NSCLC patients who had EGFR
of Colorado, Aurora/CO/United States of America, 9Department of Cancer Medicine, exon 18–21 mutation test results between 2009 and 2014 at Seoul St. Mary’s
Gustave Roussy, Villejuif/France, 10 Department of Medical Oncology, Gustave Hospital, 114 patients who had recurrent or metastatic disease, EGFR mutation
Roussy, Paris/France, 11Lowe Center for Thoracic Oncology, Dana-Farber Cancer positive excluding T790M mutation, and received both EGFR tyrosine
Institute, Boston/MA/United States of America, 12Thoracic Cancer Unit, Davidoff kinase inhibitor (TKI) and chemotherapy as the 1st or 2nd line of treatment
Cancer Center, Petach Tiqwa/Israel, 13Yonsei Cancer Center, Seoul/Korea, Republic were included. Patients were categorized into two groups according to the
of, 14University of Texas MD Anderson Cancer Center, Houston/TX/United States of
treatment sequence: 1st line EGFR TKI followed by chemotherapy (group A),
America, 15Netherlands Cancer Institute, Amsterdam/Netherlands, 16Department
1st line chemotherapy followed by EGFR TKI (group B). The median follow-up
of Medicine, Division of Oncology, Stanford University, Stanford/CA/United States
of America, 17Medicine (Oncology), Stanford Cancer Intitute/Stanford University, duration was 64.6 (15.8–202.8) months. Results: Among total 114 patients, 69
Stanford/CA/United States of America, 18Princess of Wales Hospital, The Chinese patients received EGFR TKI first and then chemotherapy (group A), and the
University of Hong Kong, Hong Kong/Hong Kong Prc, 19Department of Oncology, remaining 45 patients received vice versa (group B). Group A was younger (P =
National Taiwan University Hospital, Taipei/Taiwan, 20University of California at 0.029) and less frequently received platinum-doublet agents than Group B (P
Irvine, Orange/CA/United States of America, 21Fachkliniken Wangen, Wangen Im <0.001). Performance status and EGFR mutation status were not different.
Allgäu/Germany, 22Eoc, Bellinzona/Switzerland, 23University Hospital Bichat, Paris/ Overall response or disease control rate were significantly better for EGFR TKI
France, 24University of California Davis Cancer Center, Sacramento/CA/United States
comparing to chemotherapy regardless of treatment sequence. However, PFS
of America, 25Cleveland Clinic, Pepper Pike/United States of America, 26Kantonsspital
on both treatment were longer in group B (P = 0.008), especially for patients
St. Gallen, St. Gallen/Switzerland, 27Centre Hospitalier Intercommunal de Creteil,
Creteil/France, 28Royal Marsden Hospital, London/United Kingdom, 29Hospital with exon 19 deletion (P = 0.002). On multivariate analyses, performance status
Germans Trias I Pujol, Catalan Institute of Oncology, Barcelona/Spain, 30 Instituto (P = 0.006 for PFS, P <0.001 for OS) and treatment sequence [hazard ratio (HR)
Oncológico Dr Rosell (IOR), Hospital Universitario Quirón-Dexeus, Barcelona/Spain, = 0.027, P = 0.027 for PFS; HR = 0.64, P = 0.065 for OS] were related to prognosis.
31
Medical Oncology, University Hospital Basel, Basel/Switzerland, 32National Taiwan Conclusion: For exon 19 deletion subtype of EGFR-mutant NSCLC patients,
University Hospital, Taipei/Taiwan, 33Heidelberg University Hospital, Heidelberg/ the sequence of cytotoxic chemotherapy followed by EGFR TKI showed better
Germany, 34Translational Research Unit, Thoraxklinik at University of Heidelberg and PFS comparing with the reverse sequence, EGFR TKI followed by cytotoxic
Translational Lung Research Center (TLRC), Heidelberg/Germany, 35Université de
chemotherapy . We will present the data from larger cohorts the WCLC meeting.
Rennes 1, Rennes/France, 36University Hospital, Toulouse/France, 37Memorial Sloan
Kettering Cancer Center, New York/NY/United States of America Keywords: non-small cell lung cancer, EGFR mutation, treatment sequence
Background: GLORY is a global registry of patients with RET-rearranged non-
small cell lung cancer (NSCLC). In order to complement ongoing prospective
studies, the registry’s goal is to provide data on the efficacy of RET-directed
targeted therapies administered outside the context of a clinical trial. We
previously reported results from our first interim analysis (Gautschi, ASCO MA16: NOVEL STRATEGIES IN TARGETED THERAPY
2016). Following additional accrual into the registry, updated results are WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
presented here, with a focus on an expanded efficacy analysis of various RET
inhibitors. Methods: A global, multicenter network of thoracic oncologists MA16.06 PHASE I/II STUDY OF AC0010, MUTANT-SELECTIVE EGFR
identified patients with pathologically-confirmed NSCLC harboring a RET
INHIBITOR, IN NON-SMALL CELL LUNG CANCER (NSCLC) PATIENTS
rearrangement. Molecular profiling was performed locally via RT-PCR,
WITH EGFR T790M MUTATION
FISH, or next-generation sequencing. Anonymized data including clinical,
pathologic, and molecular features were collected centrally and analyzed by Yi Long Wu1, Qing Zhou1, Xiaoqing Liu2, Li Zhang 3, Jianying Zhou4, Lin Wu5,
an independent statistician. Response to RET tyrosine kinase inhibition (TKI) Tongtong An6, Ying Cheng7, Xin Zheng8, Bei Hu8, Ji Jiang8, Xin Fang9, Wanhong
administered off-protocol was determined by RECIST1.1 (data cutoff date: Xu9, Xiao Xu9
1
April 15, 2016). In the subgroup of patients who received RET TKI therapy, the Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH)and
objectives were to determine overall response rate (ORR, primary objective), Guangdong Academy of Medical Sciences, Guangzhou/China, 2 Affiliated Hospital
progression-free survival (PFS), and overall survival (OS). Results: 165 patients of Academy of Military Medical Science, Beijing/China, 3Department of Respiratory
Diseases, Peking Union Medical College Hospital, Peking Union Medical College and
with RET-rearranged NSCLC from 29 centers in Europe, Asia, and the USA were
Chinese Academy of Medical Sciences, Beijing, China, Beijing/China, 4Department
accrued. The median age was 61 years (range 28-89 years). The majority of of Respiratory Disease, Thoracic Disease Center, the First Affiliated Hospital,
patients were female (52%), never smokers (63%), with lung adenocarcinomas College of Medicine, Zhejiang University, Hangzhou/China, 5Department of
(98%) and advanced disease (91%). The most frequent metastasic sites were Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer
lymph nodes (82%), bone (51%) and lung (32%). KIF5B-RET was the most Hospital and Institute, Beijing/China, 6Department of Thoracic Medicine, the
commonly identified fusion (70%). 53 patients received at least one RET-TKI Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University,
outside of a clinical protocol, including cabozantinib (21), vandetanib (11), Changsha/China, 7Jilin Province Cancer Hospital, Changchun/China, 8 Clinical
sunitinib (10), sorafenib (2), alectinib (2), lenvatinib (2), nintedanib (2), Pharmacology Research Center, Peking Union Medical College Hospital, Peking
Union Medical College and Chinese Academy of Medical Sciences, Beijing/China,
ponatinib (2) and regorafenib (1). In patients who were evaluable for response 9
Acea Pharmaceutical Research, Hangzhou, China, and Acea Biosciences Inc. San
(n=50), the ORR was 37% for cabozantinib, 18% for vandetanib, and 22% for Diego, USA, Hangzhou/China
sunitinib. Median PFS was 3.6, 2.9, and 2.2 months and median OS was 4.9,
10.2, and 6.8 months for cabozantinib, vandetanib, and sunitinib, respectively. Background: AC0010 was designed specifically to inhibit EGFR active mutations
Responses were also observed with nintedanib and lenvatinib. Among and the T790M acquired resistant mutation. The purpose of the study is to
patients who received more than one TKI (n=10), 3 partial responses were determine the safety, antitumor activity and recommended phase II dose of
achieved after prior treatment with a different TKI. Conclusion: RET inhibitors AC0010 in T790M-postitive NSCLC patients after the first generation EGFR TKIs
are active in individual patients with RET-rearranged NSCLC, however, novel treatment. Methods: This is a dose escalation and expansion phase I/II study.
therapeutic approaches are warranted with the hope of improving current Oral AC0010 was administered on a 28-day cycle with the starting dose at 50 mg
clinical outcomes. GLORY remains the largest dataset of patients with RET- BID. In any given dose cohort, if 1 out of 3 patients was evaluated as PR at the
rearranged NSCLC, and continues to accrue patients. first cycle, and no DLT determined, up to 20 patients will be enrolled. Plasma
samples were collected to evaluate pharmacokinetics of AC0010. T790M in
biopsy samples was detected by a central laboratory. NCT02330367. Results: As
of 10 Jul 2016, 136 patients have been treated across 7 cohorts (50, 100, 150, 200,
MA16: NOVEL STRATEGIES IN TARGETED THERAPY 250, 300, and 350 mg BID). At the 30 Jun 2016 cutoff, 124 pts were evaluable.
MTD has not been reached. The most common adverse events (AE) regardless of
study drug relationship were diarrhea (38%), rash (26%) and ALT/AST elevation.
MA16.05 FOR EGFR MUTANT NON-SMALL CELL LUNG CANCER, Most AEs were grade 1 and 2. The most common Grade 3/4 drug-related AE was
TREATMENT SEQUENCE MATTERS? diarrhea (2%) rash (2%) and ALT/AST elevation (4%, 2%). All patients with AEs of
the grade 3/4 were recovered after either stopped the treatment or reduced the
Ho Jung An1, Yuneyoung Shin1, Sook Hee Hong2, Young Kyoon Kim3, Seung
dose. As of the cutoff date, there is no Grade 2,3 hyperglycemia, and grade 3 QTc
Joon Kim3, Kyo-Young Lee4, Jin Hyoung Kang2
prolongation. RECIST responses were observed at all dose levels except 50 mg
1
Department of Medical Oncology, St. Vincent’S Hospital, the Catholic University BID. Amongst 124 evaluable patients in all cohorts, ORR (including unconfirmed

responses) and disease control rate (DCR) was 44% and 85% respectively. In the America, 4University of Colorado Cancer Center, Aurora/CO/United States of America,
5
dose cohorts between 150 mg BID and 300 mg BID (n=95 pts), the ORR and DCR University of Pittsburgh Medical Center, Pittsburg/PA/United States of America,
6
were 51% and 89%. PK shows rapid absorption with a Tmax of 2-4h and a median Unc Lineberger Comprehensive Cancer Center, Chapel Hill/NC/United States of
America, 7Peter MacCallum Cancer Center, Melbourne/VIC/Australia, 8 Massachusetts
T1/2 of 8 h. At 300 mg BID, total 32 patients were treated and ORR and DCR are
General Hospital, Boston/MA/United States of America, 9Dana-Farber Cancer
53% and 90% respectively. Based on the efficacy, safety and PK results, the
Institute, Boston/MA/United States of America, 10 Pfizer Oncology, La Jolla/CA/United
300 mg BID was selected as RP2D. The phase II, AEGIS-1 study has started.The States of America, 11Rho Inc, Chapel Hill/NC/United States of America
Phase II result will be presented. Conclusion: AC0010 shows a safe profile and
antitumor activity against T790M mt NSCLC. Phase II, AEGIS-1 study is ongoing Background: MET alterations leading to exon 14 skipping occur in ~4% of non-
to evaluate therapeutic outcomes as a second line treatment for T790M squamous nonsmall cell lung cancer (NSCLCs) and 20–30% of sarcomatoid lung
positive NSCLC patients. Clinical trial information: NCT02330367 carcinomas, resulting in MET activation and sensitivity to MET inhibitors in
vitro.1–4 Crizotinib, initially developed as a MET inhibitor, is currently approved
Keywords: Phase I/II study, NSCLC, T790M, AC0010 for the treatment of ALK-rearranged and ROS1-rearranged advanced NSCLC.
We present crizotinib antitumor activity and safety data in patients (pts) with
MET exon 14-altered advanced NSCLC. Methods: Advanced NSCLC pts positive
for MET exon 14-alteration status determined locally by molecular profiling
MA16: NOVEL STRATEGIES IN TARGETED THERAPY were enrolled into an expansion cohort of the ongoing phase I PROFILE 1001
study (NCT00585195) and received crizotinib at a starting dose of 250 mg
BID. Objective responses were assessed using RECIST v1.0. Results: As of the
MA16.07 DRUG REPURPOSING TO OVERCOME DE NOVO data cut-off of Feb 01, 2016, 21 pts with MET exon 14-altered NSCLC received
RESISTANCE OF NON-TRADITIONAL EGFR MUTATIONS crizotinib treatment (18 response-evaluable, 3 not yet evaluable). Median
age was 68 y (range: 53−87). Tumor histology was: 76% adenocarcinoma,
Jacqulyne Robichaux 1, Zhi Tan2, Monique Nilsson1, Shuxing Zhang2, Kwok-Kin
14% sarcomatoid adenocarcinoma, 5% adenosquamous carcinoma, and 5%
Wong 3, John Heymach4
1 squamous cell carcinoma. Sixty-two percent (62%) of pts were former-smokers,
Thoracic/head and Neck Medical Oncology, University of Texas MD Anderson
38% never-smokers, and there were no current smokers. Duration of treatment
Cancer Center, Houston/TX/United States of America, 2Experimental Therapeutics,
University of Texas MD Anderson Cancer Center, Houston/TX/United States of ranged from 0.2 to 12.2 mo, with 76% of pts (16/21) still ongoing. Five pts
America, 3Medical Oncology, Dana Farber Cancer Institute, Boston/MA/United discontinued treatment (1 due to AE, 3 due to clinical or disease progression,
States of America, 4Thoracic/Head & Neck Medical Oncology, University of Texas and 1 preferred alternative treatment formulation). PRs were observed in 8
MD Anderson Cancer Center, Houston/TX/United States of America pts, for an objective response rate of 44% (95% CI: 22–69); 9 pts had stable
disease. Median time to response was 7.8 weeks (range: 7.0–16.3), which was
This abstract is under embargo until December 3, 2016 at 07:00 CET. the approximate time of the scheduled first on treatment tumor scans for
patients. Median progression-free survival could not be calculated. The most
common (≥25%) treatment-related AEs (TRAEs) were edema (43%) diarrhea
(33%), nausea (33%), vision disorder (33%), and vomiting (29%). Most TRAEs
were grade 1/2 in severity and consistent with the known safety profile of
crizotinib. Four grade 3 TRAEs (edema, bradycardia, anemia, and weight
increased) and no grade 4 or 5 TRAEs were reported. Enrollment of pts with
MET exon 14-altered NSCLC continues, and updated data will be available
at the time of presentation. Conclusion: Crizotinib has clinically meaningful
antitumor activity in pts with MET exon 14-altered advanced NSCLC. The drug
has a tolerable AE profile, consistent with that previously reported for pts
with ALK-rearranged or ROS1-rearranged advanced NSCLC. Further study of
crizotinib in this pt population is warranted.
Keywords: non-small cell lung cancer, crizotinib, MET
MA16: NOVEL STRATEGIES IN TARGETED THERAPY

MA16.10 LUNG-MAP (S1400) LUNG MASTER PROTOCOL: ACCRUAL

AND GENOMIC SCREENING UPDATES
Vassiliki Papadimitrakopoulou1, Mary Redman2, David R. Gandara3, Fred
R. Hirsch4, Philipp Mack5, Hossein Borghaei6, Corey Langer 7, James Wade8,
Martin Edelman9, Kathy Albain10, Primo Lara5, Charu Aggarwal11, Mark
Socinski12, Scott Gettinger 13, Lyudmila Bazhenova14, Shakun Malik15, Vincent
Miller 16, Shannon Mcdonough17, Ellen V. Sigal2, Karen Kelly18, Roy Herbst19
1
MD Anderson Cancer Center, Houston/TX/United States of America, 2Friends of
Cancer Research, Washington/DC/United States of America, 3Division of Hem-
Oncology, UC Davis Comprehensive Cancer Center, Sacramento/CA/United States
of America, 4Other, Univ. of Colorado Cancer Center, Aurora/CO/United States of
America, 5UC Davis Comprehensive Cancer Center, Sacramento/CA/United States
of America, 6Medical Oncology, Fox Chase Cancer Center, Philadelphia/PA/United
States of America, 7Hematology/Oncology, University of Pennsylvania Health System,
Philadelphia/PA/United States of America, 8Heartland Ncorp, Decatur/IL/United
States of America, 9University of Maryland Medical Center, Baltimore/MD/United
States of America, 10Dept of Medicine, Division of Hematology/Oncology, Loyola
Univ Chicago Stritch School of Medicine, Maywood/IL/United States of America,
11
Hematology/Oncology, University of Pennsylvania, Philadelphia/PA/United
States of America, 12Medicine, University of Pittsburgh, Pittsburgh/United States
of America, 13Yale Cancer Center, New Haven/CT/United States of America, 14Moores
MA16: NOVEL STRATEGIES IN TARGETED THERAPY Cancer Center, University of California San Diego, La Jolla/United States of America,
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 15
Ctep, NCI/NIH, Rockville/MD/United States of America, 16Clinical Development,
Foundation Medicine, Inc, Cambridge/MA/United States of America, 17Swog Statistical
Center, Seattle/WA/United States of America, 18Hematology Oncology, UC Davis
MA16.09 ANTITUMOR ACTIVITY AND SAFETY OF CRIZOTINIB IN
Comprehensive Cancer Center, Sacramento/CA/United States of America, 19Medical
PATIENTS WITH MET EXON 14-ALTERED ADVANCED NON-SMALL Oncology, Yale Cancer Center, New Haven, Ct/CT/United States of America
CELL LUNG CANCER
Alex Drilon1, Sai-Hong Ou2, Jeffrey Clark 3, D. Ross Camidge4, Mark Socinski5, Background: Lung-MAP (S1400), is a master protocol that incorporates
Jared Weiss6, Benjamin Solomon7, Gregory Riely1, Rebecca Heist8, Geoffrey genomic testing of tumors through a next generation sequencing (NGS)
Shapiro9, Sherry Wang10, Maria Winter 10, Katherine Monti11, Keith Wilner 10, platform (Foundation Medicine) and biomarker-driven (matched) therapies
Paul Paik1 for patients with squamous cell lung cancer (SCCA) after progression on first-
1 line chemotherapy. Methods: The Lung-MAP trial, activated June 16, 2014,
Memorial Sloan Kettering Cancer Center, New York/NY/United States of
America, 2University of California at Irvine, Irvine/CA/United States of America,
includes 3 matched- and 1 non-match study. Matched studies include: S1400B
3
Massachusetts General Hospital Cancer Center, Boston/MA/United States of evaluating taselisib, a PI3K inhibitor, S1400C evaluating palbociclib, a CDK
4/6 inhibitor and, S1400D evaluating AZD4547, an FGFR inhibitor. The non- not reached (95% CI: not calculable [NC], NC). The estimated percentage of
match study S1400I tests nivolumab + ipilimumab vs. nivolumab. Two studies patients remaining in response at 9 months was 75% (95% CI: 53, 88). CNS
have closed: S1400E evaluating rilotumumab an HGF monoclonal antibody + disease control rate (DCR) was 92% (46/50; 95% CI: 81%, 98%). Median time
erlotinib closed 11/26/2014 and S1400A evaluating MEDI4736 in non-match to first response was 5.7 weeks (range: 5.6–6.6). Median best percentage
pts, closed 12/18/2015. Results: From June 16, 2014 to June 15, 2016, 812 pts change from baseline in CNS target lesion size was 53% (range: -100% – +80%).
were screened and 292 pts registered to a study: 116 to S1400A, 27 to S1400B, Median follow up for CNS progression-free survival (PFS) was 11 months; the
53 to S1400C, 32 to S1400D, 9 to S1400E and 55 to S1400I. Demographics: median CNS PFS was not reached (95% CI: 7, NC). At 12 months, 56% (95%
Screening was successful for 705 (87%) of screened eligible pts. Median age CI: 40%, 70%) of patients were estimated to remain on study, alive and CNS
67 (range 35-92); male 68%; ECOG PS 0-1 88%, PS 2 10%; Caucasian 85%, Black progression-free. CNS response was observed regardless of prior radiotherapy
9%, other 5%; never/former/current smokers 4%/58%/36%. Table 1 displays to the brain. Conclusion: Osimertinib demonstrates durable efficacy in
biomarker prevalence; 39% of pts matched; 33.9%, 4.8%, and 0.3% with 1, patients with T790M NSCLC and measurable CNS metastases, with a CNS
2, and all 3 biomarkers, respectively. Tumor mutation burden (TMB) was response rate of 54% and a DCR of 92%.
available for 636 (90.4%) of eligible pts. The distribution of TMB is: 126 (19.8%)
low (≤5 mutations Mb), 415 (65.1%) intermediate (6-19 mutations/Mb), and Keywords: brain metastases, AZD9291, osimertinib, T790M
96 (15.1%) high (≥20 mutations/Mb). The median TMB was 10.1. Conclusion:
Genomic screening is feasible as part of this master protocol designed to
expedite drug registration, confirm anticipated prevalence of targeted
alterations in SCCA and reveal intermediate or high TMB in most (80.2%) pts.
Treatment results are not yet available as patients continue to accrue. Clinical SESSION MA17: GENETIC DRIVERS
trial information: NCT02154490 WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
Total FGFR CDK PIK3CA
FGFR MA17.01 MICROARRAY IDENTIFICATION OF GENETIC DRIVERS OF
12.9% 2.4% 0.6%
(15.9%) BRAIN METASTASIS IN LUNG ADENOCARCINOMA
CDK Gavitt Woodard1, Vivianne Ding1, Matthew Rosenblum1, Fleur Leguay1, Clara
14.6% 1.8%
(18.8%) Zoon-Besselink1, Kirk Jones2, Tasha Lea3, Michael Mcdermott4, Il-Jin Kim1,
PIK3CA David Jablons1
6.4% 1
Surgery, University of California, San Francisco, San Francisco/CA/United States
(8.8%)
of America, 2Pathology, University of California, San Francisco, San Francisco/
Biomarker United States of America, 3Pathology, University of California, San Francisco, San
prevalence Francisco/CA/United States of America, 4Neurosurgery, University of California,
and overlap. San Francisco, San Francisco/United States of America
Keywords: genomic screening, umbrella trial, S1400, Squamous cell lung Background: Brain metastasis in non-small cell lung cancer (NSCLC) develop
cancer in 20-40% of all patients and represent a major cause of NSCLC morbidity and
MA16: NOVEL STRATEGIES IN TARGETED THERAPY mortality. The mechanisms driving metastatic potential across the blood-
brain-barrier remain poorly understood. Methods: Affymetrix microarray
was performed on RNA extracted from 75 pairs of snap-frozen primary lung
MA16.11 CNS RESPONSE TO OSIMERTINIB IN PATIENTS WITH adenocarcinoma and matched normal lung tissue. Changes in gene expression
T790M-POSITIVE ADVANCED NSCLC: POOLED DATA FROM TWO from the primary lung adenocarcinomas that did not ever metastasize to brain
over up to 15 years of follow up were compared to the lung adenocarcinomas
PHASE II TRIALS
that ultimately seeded a brain metastasis. From these 75 patients, tissue
Glenwood Goss 1, Chun-Ming Tsai2, Frances Shepherd3, Myung-Ju Ahn4, from 5 paired snap-frozen brain metastases was also available and gene
Lyudmila Bazhenova5, Lucio Crinò6, Filippo De Marinis7, Enriqueta Felip8, expression changes between the primary lung adenocarcinomas and matched
Alessandro Morabito9, Rachel Hodge10, Mireille Cantarini11, Tetsuya brain metastases were investigated to identify genes and pathways of
Mitsudomi12, Pasi Jänne13, James Chih-Hsin Yang14 interest in the development of brain metastasis. Affymetrix Transcriptome
1
Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Analysis Console software was used for data analysis and interpretation
Ottawa/ON/Canada, 2Taipei Veterans General Hospital and School of Medicine, with fold changes >2.0 and p-value of <0.05 for significance. Results: From
National Yang-Ming University, Taipei/Taiwan, 3University Health Network,
the 75 patients 20 (27%) ultimately developed a brain metastasis from
Princess Margaret Cancer Centre, Toronto/Canada, 4 Medicine, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul/Korea, Republic their primary lung adenocarcinoma and 55 (73%) were followed long term
of, 5Uc San Diego Health, Moores Cancer Center, San Diego/CA/United States of without development of brain metastasis. Microarray identified 71 genes
America, 6Santa Maria Della Misericordia Hospital, Azienda Ospedaliera Di Perugia, that were differentially expressed in lung adenocarcinomas that later
Perugia/Italy, 7Thoracic Oncology Division, European Institute of Oncology, Milan/ produced brain metastasis. S100 calcium binding protein, RAP1GAP, GPR160,
Italy, 8Vall D’Hebron Institute of Oncology, Barcelona/Spain, 9Instituto Nazionale and immunoglobins were among the upregulated genes in primary lung
Tumori Di Napoli, Naples/Italy, 10 Astrazeneca, Cambridge/United Kingdom, adenocarcinomas that developed brain metastasis. Within the matched
11
Astrazeneca, Macclesfield/United Kingdom, 12Thoracic Surgery, Kindai University sets of brain metastasis, hierarchical clustering showed clear distinction in
Faculty of Medicine, Osaka-Sayama/Japan, 13Lowe Center for Thoracic Oncology,
expression patterns comparing brain metastasis verses normal lung, as well
Dana-Farber Cancer Institute, Boston/United States of America, 14 Cancer Research
Center, National Taiwan University, Taipei/Taiwan as primary adenocarcinomas verses normal lung. 267 genes were identified
to be significantly differentially expressed between paired brain metastasis
Background: Brain metastases develop in 25–40% of patients with NSCLC. and primary lung adenocarcinomas. Significant changes in focal adhesion,
Osimertinib is an oral, potent, irreversible EGFR-TKI, selective for both angiogenesis, matrix metalloproteinase pathways, and immunoglobulins were
sensitising (EGFRm) and T790M resistance mutations. Preclinical and early found in the brain metastasis compared with the paired primary lung tumor.
clinical evidence support central nervous system (CNS) penetration and Conclusion: This study represents the largest microarray analysis of snap
activity of osimertinib. Two Phase II studies (AURA extension [NCT01802632] frozen pairs of primary lung adenocarcinoma and brain metastasis to date.
and AURA2 [NCT02094261]) evaluating the efficacy and safety of osimertinib S100 calcium binding protein, RAP1GAP, GPR160 genes, immunoglobulins,
are ongoing. We present a pre planned subgroup analysis assessing pooled and focal adhesion, angiogenesis, and matrix metalloproteinase pathways
CNS response from these two studies; data cut-off (DCO) was 1 November were among the upregulated genes in primary lung adenocarcinomas that
2015. An earlier pooled analysis from these two studies (1 May 2015 DCO) developed brain metastasis.
showed the objective response rate (ORR) in patients with CNS metastases
was consistent with ORR in the overall patient population. Methods: Patients Keywords: Metastasis pathways, lung adenocarcinoma, RNA microarray,
with advanced NSCLC who progressed following prior EGFR-TKI therapy Brain metastasis
with centrally-confirmed T790M positive status (cobas® EGFR Mutation
Test) received osimertinib 80 mg once daily (n=411). Patients with stable,
asymptomatic CNS metastases were eligible for enrolment. CNS efficacy
MA17: GENETIC DRIVERS
was assessed in an evaluable for CNS response analysis set, which included WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
patients with at least one measurable CNS lesion on baseline brain scan
(RECIST v1.1) by blinded independent central neuroradiology review (BICR).
Effect of prior radiotherapy on CNS response was assessed. Results: As of MA17.02 GENOME-WIDE COPY NUMBER AND MUTATIONAL
1 November 2015, 50/192 patients with baseline brain scans had at least ANALYSIS IN LONGITUDINAL BIOPSIES OF MATCHED PRIMARY AND
one measurable CNS lesion identified by BICR. Baseline demographics were METASTATIC PULMONARY ADENOCARCINOMAS
broadly consistent with the overall patient population. Confirmed CNS
Thomas Lorber 1, Noemi Andor2, Tanja Dietsche1, Valeria Perrina1, Darius
ORR was 54% (27/50; 95% CI: 39%, 68%), with 12% complete CNS response
Juskevicius1, Arthur Krause1, David Müller 1, Didier Lardinois3, Michael Barrett4,
(6/50 patients). The median CNS duration of response (22% maturity) was
Christian Ruiz1, Lukas Bubendorf 1

1
University Hospital Basel, Institute for Pathology, Basel/Switzerland, 2Division Methods: 94 tumor samples originating from 45 clinically considered multiple
of Oncology - Department of Medicine, Stanford University School of Medicine, primary lung cancer patients (including multiple solid tumors and multifocal
Stanford/United States of America, 3University Hospital Basel, Thoracic Surgery, tumors) were available for genomic alteration analysis (NCT02833467). DNA
Basel/Switzerland, 4 Mayo Clinic, Scottsdale/AZ/United States of America and RNA were extracted from fresh tumor tissue or formalin-fixed, paraffin-
embedded tissue. 143 cancer-related genomic alterations including single
Background: There are still limited data on the extent of intratumoral
nucleotide variations (SNVs), short insertions and deletions (InDels), copy
heterogeneity of cancer gene mutations and genome-wide copy number
number variations (CNVs) and gene rearrangements were identified by
aberrations between primary tumors and metastases in non-small cell lung
Oncomine Comprehensive Panel (OCP), Ion Torrent techniques. High
cancers (NSCLC). Deconvolution of the intermixture of tumor and stromal
frequency clinical relevant mutations (EGFR, KRAS, BRAF, PIK3CA) were
components remains a major challenge for such analysis. To overcome these
identified in circulating tumor DNA by droplet digital PCR (ddPCR). Results:
limitations, we applied a refined nuclei flow sorting approach on matched
The median age of the patients was 61 years and 71% were female. 91%
longitudinal biopsies (primary/metastasis) from pulmonary adenocarcinomas.
patients were stage I. Molecular analysis performed with a good quality. One
Methods: Multiparameter Ploidy Profiling (MPP) comprises the isolation of
hundred and thirty-six mutations and twenty four fusions were detected.
nuclei from frozen or formalin-fixed and paraffin embedded (FFPE) tissues,
Alterations were found in 81 of the 94 lesions (86%), involving EGFR (50.0%),
followed by multiparameter flow sorting by DAPI for DNA content (ploidy)
TP53(10.6%), KRAS (8.5%), BRAF (4.3%), ERBB2 (4.3%),
and TTF1 as a lineage marker to enrich for tumor cell nuclei. Homogenous TTF1
PIK3CA(2.1%),PTEN(2.1%),ALK (2.1%),ROS1 (1.1%), RET (7.4%), NF2(2.1%),
expression was ascertained by immunohistochemistry. Sorted populations
CDKN2A(2.1%), APC(5.3%), ATM(5.3%),etc. Forty-two (93.3%) patients
were subjected to genomic profiling by high resolution aCGH and NGS with
harbored discordant gene distribution between multiple tumors. CNVs were
the Ion Torrent™ Comprehensive Cancer Panel. This approach allows for the
much higher in patients with more than 2 lesions. Forty-eight lesions
detection of genome-wide copy number aberrations and provides all exon-
harbored detectable somatic mutations by ddPCR, in which 30(62.5%) lesions
coverage of 409 well-known cancer genes. Sequencing was performed with
were identified positive in circulating tumor DNA. 76.9% (20/26) solid
a mean depth of 965x. Results: MPP was successfully applied on 44 frozen
dominant lesions were positive, which is significantly higher than ground
or FFPE tissue specimens from 19 patients. Clonally unrelated secondary
glass opacity(GGO) dominant lesions(45.5%, 10/22, p=0.037). Conclusion:
primaries were found in three patients, defined by the absence of both
Targeted NGS by OCP is feasible to detect multiple mutations simultaneously
shared copy number (CN) transition and somatic mutations. The concordance
in early stage multiple primary lung cancers. Circulating tumor DNA has the
rate between primary tumor and corresponding metastases was 65.2% and
ability to detect discordant somatic mutations and may represent of the
reached 85.5% for mutations and copy number amplifications/deletions in
overall mutational load and inter-tumor heterogeneity in multiple solid lung
the top 12 affected genes (including CDKN2A, KRAS, ATM, KEAP1, EGFR and
tumors.
STK11). The correlation of the allele frequencies between primary tumors
and metastases was linear (r=0.87, p<0.001), irrespective of the time interval Keywords: Circulating Tumor DNA, lung cancer, multiple primary lung cancer
between the tissue resections. Overall, ploidy was not different between
primary tumors and metastases. Additionally, the metastases did not bear a
higher burden of private events (CN transitions and somatic mutations) than
the primary tumors. Conclusion: MPP is a powerful method to increase the
precision of downstream analysis due to unprecedented purity of tumor DNA.
Our data argue for a high concordance rate of mutations and CN transitions
between primary tumors and their corresponding metastases. Intriguingly,
the ploidy remains remarkably stable during progression even after long
time-periods, which suggests chromosomal stability with a limited degree of
macroevolutionary shifts over time and space. Taken together, our data suggest
the presence of at least two evolutionary patterns: 1) early/branched and 2)
late/linear progression, with a continuum from high to low genetic divergence
of the primary tumor and metastases to their most recent common ancestor.
Keywords: flow sorting, longitudinal, genomic, aCGH

MA17.03 IDENTIFYING GENOMIC ALTERATION AND INTER-TUMOR

HETEROGENEITY OF MULTIPLE PRIMARY LUNG CANCERS BY
TARGETED NGS OF TUMOR TISSUE AND CTDNA
Kezhong Chen1, Jingbo Zhang2, Wei Chen2, Fan Yang1, Jiangqiao Cai1, Feng
Lou2, Xun Wang1, Mingyu Zhao2, Jay Zhang2, Jun Wang1
1
Thoracic Surgery, Peking University People’S Hospital, Beijing/China, 2 San Valley
Biotechnology Inc, Beijing/China
Background: Evidence supports the existence of genomic discrepancy in

multiple primary lung cancers (MPLC). This study identified genomic
alterations of MPLC by targeted next-generation sequencing (NGS) and
assessed whether inter-tumor heterogeneous somatic mutations could be
detected in circulating tumor DNA (ctDNA).
MA17: GENETIC DRIVERS Background: Morphological and genetic heterogeneity predict prognostics,
impede continuous responses to systemic regimens and foster inevitable
treatment failure. But how morphological and genetic features evolve in
MA17.05 EVOLUTIONARY TRAJECTORIES OF MOLECULAR tumorigenesis still remains controversial. Methods: Single(n=1112) and
PROGRESSION IN DIFFERENT SUBTYPES OF PRIMARY LUNG multiple(n=91) primary adenocarcinoma patients receiving surgeries with
specific prominent subtypes were screened. Six patients with mixed ground
ADENOCARCINOMAS
glass opacities and maximum cross-sections of primary tumors were randomly
Hao-Ran Zhai1, Shiyong Li2, Bing Liao3, Lixu Yan4, Jian Su5, Zhi-Yong Chen5, selected. Intra-tumoral regions with different subtypes and imaging densities
Shuang Gao2, Song Dong5, Ben-Yuan Jiang5, Xue-Ning Yang5, Qing Zhou5, Jin-Ji related to relative distributions, were resected for target region sequencing
Yang5, Xu-Chao Zhang5, Mao Mao2, Wen-Zhao Zhong5, Yi Long Wu5 and further molecular evolutionary analyses. Results: Clinical data revealed
1
Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong certain preferences of driver gene mutations and discrepant survival benefits.
Academy of Medical Sciences; Southern Medical University., Guangzhou/China, Driver gene heterogeneity was higher in multiple primary lung cancers(51.7%,
2
The Bgi-Shenzhen, Shenzhen/China, 3Department of Pathology, The First
15/29) than single ones(1.4%, 1/70). Copy number alterations implied more
Affiliated Hospital, Sun Yat-Sen University, Guangzhou/China, 4Department of
consistence within the same subtype and tended to be higher in lepidic
Pathology, Guangdong General Hospital, Guangdong Academy of Medical Sciences,
Guangzhou/China, 5Guangdong Lung Cancer Institute, Guangdong Provincial Key subtype. Somatic nucleotide variants revealed highest homogeneity between
Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital different regions within the same tumor lesion. Sequencing data indicated
& Guangdong Academy of Medical Sciences, Guangzhou/China larger fractions of geographically ubiquitous mutations than pathologically
ones, and higher mutation frequencies of shared mutations in the lepidic than
acinar subtype. Phylogenetic trees exhibited higher
geographically private mutation burdens of lepidic
than acinar region in lesions with mixed subtypes;
while in lesions with the same subtype, the central
region bore higher mutation burdens than in the
periphery, implying a linear accumulation of genetic
mutations. Functional analyses of private mutations
verified that lepidic subtypes promoted intracellular
organism and structure development, promoting
growth and proliferation. Acinar subtypes lead to
metabolic and signaling transduction pathway.
Preferences of divergent pathway alterations
delineated branched evolutions from low to higher
grade subtypes.
Conclusion: We propose a model that the same

morphological subtype evolves with a linear
accumulation and mixed subtypes in branched
evolutionary trajectories with preferences to
pathway alterations. Couple with relatively
geological distributions of different subtypes, tumor
microenvironment might contribute more to genetic
instability and thus tumor evolutions.
Keywords: pulmonary adenocarcinoma, morphology,

Genetic evolution, Predominant subtypes

MA17: GENETIC DRIVERS quantitation by CAPP-Seq. Twenty-one (61.8%) patients were treated with
conventionally fractionated radiotherapy, 8 (23.5%) with hypofractionated
radiotherapy, 3 (8.8%) with surgery, and 2 (5.9%) with both surgery and
MA17.06 LANDSCAPE OF SOMATIC MUTATIONS INVOLVING LUNG radiotherapy. Twenty-five (73.5%) patients received platinum-based doublet
CANCER ASSOCIATED GENES IN NON-SMALL CELL LUNG CANCER chemotherapy. Following treatment completion, patients underwent disease
surveillance by CT scans and CAPP-Seq every 3-6 months. CT scans were
(NSCLC) PATIENT-DERIVED XENOGRAFTS
evaluated using RECIST v1.1. CAPP-Seq was performed at each time point
Vibha Raghavan1, Shirley Tam1, Nhu-An Pham1, Ming Li1, Frances Shepherd2, as previously described (Newman et al, Nature Medicine 2015 and Nature
Geoffrey Liu2, Ming Tsao3 Biotechnology 2016). Results: A total of 222 scans and 107 plasma samples
1
Princess Margaret Cancer Centre, Toronto/ON/Canada, 2Dept of Medical Oncology were analyzed. Median follow-up time was 21.1 months and median overall
and Haematology, Princess Margaret Cancer Centre and University of Toronto, survival was 30.0 months. Eighteen (52.9%) patients progressed based on
Toronto/ON/Canada, 3Departments of Pathology, Princess Margaret Cancer Centre
RECIST criteria and CAPP-Seq detected ctDNA at or before the time of RECIST
and University of Toronto, Toronto/ON/Canada
progression in all patients (18 of 18; 100%) with a lead-time of 121 +/- 39 days
Background: Patient-derived tumor xenografts (PDXs) have high fidelity (mean +/- SEM). For 13 of 16 (81.3%) evaluable patients who progressed, ctDNA
to their histological origins, and maintain the molecular heterogeneity was detected at the first time-point after completion of all treatment (median
and genetic aberrations of the donor patient tumors more faithfully than 2 months post treatment), indicating detection of minimal residual disease.
established in non-small cell lung cancer (NSCLC) cell lines. This study Two-year overall survival for patients with detectable post-treatment ctDNA
evaluated whether our panel of PDX models recapitulate known cancer- was 25.3% versus 92.9% for those with no detectable post-treatment ctDNA
related gene mutations. Methods: Whole-exome sequencing was completed (p=0.0003, HR=6.8, 95% CI=2.6-17.9). This difference remained significant
on 103 NSCLC PDX models, 47 adenocarcinoma (AdC) and 56 squamous (SqCC), in multivariate models controlling for stage, age, sex, and tumor volume
with a mean coverage of 84x. After filtering for contaminating mouse reads, (P=0.01). Conclusion: We found that noninvasive ctDNA profiling appears to
the exome data were aligned using the Burrows-Wheeler Aligner, processed be useful for evaluating response to lung cancer treatment. Quantitation of
using the standard GATK pipeline, and mutations were identified using ctDNA allowed identification of minimal residual disease, which was strongly
MuTect. Additional filtering using dbSNP, ExAC and ESP was performed for associated with outcome. These results suggest that ctDNA assessment after
cases without corresponding normal adjacent lung exome data (n = 80). The definitive intent treatment could potentially be used to guide risk-adapted
identified mutations were compared to 1260 frequently mutated cancer- treatment strategies for localized lung cancer.
related genes, which were compiled from a panel of cancer-related mutated
Keywords: biomarker, Genomics, Circulating Tumor DNA, minimal residual
genes (555) and a panel of lung cancer-specific mutated genes (1082). Results:
disease
High rates of somatic mutations were observed in both AdC (mean of 12.4
mutations/megabase) and SqCC (mean of 11.7 mutations/megabase) PDX
models. Compared to the rates observed in primary lung cancers in The
Cancer Genome Atlas studies (mean of 8.9 mutations/megabase in AdC;
8.1 mutations/megabase in SqCC), these values appear higher, but may be WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
inflated due to the lack of data from corresponding normal tissues. AdC
models had a total of 953 mutated genes (median: 57 genes/model; range:
5-307), while SqCC models were characterized by 1007 mutated genes MA17.09 PREMATURE FIBROBLAST SENESCENCE IN LARGE CELL
(median: 55 genes/model; range: 21-354). Specific mutation frequencies CARCINOMA PROVIDES ENHANCED GROWTH AND INVASIVE
were compared to those determined in a recent study involving genomic ADVANTAGES TO CANCER CELLS IN CULTURE AND IN VIVO
alterations in human primary lung AdC and SqCC (Nature Genetics 2016; 48; Roberto Lugo1, Marta Gabasa1, Francesca Andriani2, Marta Puig1, Federica
607–616). This comparison, based on mutated genes common in both studies, Facchinetti2, Josep Ramírez3, Abel Gómez-Caro4, Pere Gascón5, Albert
demonstrated significant correlation of the frequencies in 791 genes in AdC Davalos6, Noemi Reguart5, Luca Roz2, Jordi Alcaraz1
(ρ=0.78; p<2.2×10 -16), as well as in 799 genes in SqCC (ρ=0.73; p<2.2×10 -16). 1
Dept of Biomedicine, Facultat de Medicina, Universitat de Barcelona, Barcelona/
Three genes that were reported as significantly mutated in both AdC and SqCC Spain, 2Tumor Genomics Unit, Department of Experimental Oncology and
primaries, and had higher mutation frequencies in SqCC, were also observed Molecular Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori Int, Milano/
to be higher in our SqCC PDX models (TP53: 48.9% in AdC vs. 55.4% in SqCC; Italy, 3 Anatomopathology Unit, Hospital Clínic de Barcelona, Barcelona/Spain,
4
CDKN2A: 4.3% vs. 7.1% and PIK3CA: 2.1% vs. 23.2%); however, the statistical Thoracic Surgery Unit, Hospital Clínic de Barcelona, Barcelona/Spain, 5Medical
significance of these differences needs to be tested. Conclusion: Mutation Oncology, Hospital Clinic, Barcelona University, Barcelona/Spain, 6Buck Institute
landscapes in cancer genes are recapitulated in AdC and SqCC PDX models. The for Age Research, Novato/CA/United States of America
fidelity of these landscapes in matched patient primary tumour samples is
Background: Tumor-associated fibroblasts (TAFs) are increasingly regarded as
being investigated.
essential co-conspirators for tumor progression in all solid tumors including
Keywords: Somatic mutations, PDX, whole-exome sequencing, NSCLC non-small cell lung cancer. While most TAFs exhibit activation markers
indicative of a myofibroblast-like phenotype, senescence markers have been
reported in a growing list of selected cancer types only. However, the presence
of senescent TAFs in lung cancer remains undefined. Assessing senescence in
MA17: GENETIC DRIVERS lung TAFs is important because previous studies have reported that senescent
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45 TAFs enhances tumor growth, which is in marked contrast with the widely
accepted tumor-suppressive role of senescence in cancer cells. Methods: We
examined common senescence markers in patient derived lung TAFs from
MA17.07 CIRCULATING TUMOR DNA DETECTS MINIMAL RESIDUAL the 3 major non-small cell lung cancer (NSCLC) subtypes: adenocarcinoma
DISEASE AND PREDICTS OUTCOME IN LOCALIZED LUNG CANCER (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Given
Aadel Chaudhuri1, Alexander Lovejoy1, Jacob Chabon1, Aaron Newman2, the difficulties in gathering LCC-TAFs owing to the lower prevalence of LCC
Henning Stehr 1, Carmen Say1, Justin Carter 1, Li Zhou1, Robert West3, Joseph compared to the other subtypes, primary fibroblasts from 2 independent
Shrager4, Joel Neal5, Heather Wakelee5, Billy Loo1, Ash Alizadeh5, Maximilian fibroblast collections were used. Senescence markers included senescence-
Diehn1 associated beta-galactosidase, permanent growth arrest and spreading.
1
Radiation Oncology, Stanford University, Stanford/CA/United States of America, Results: We found an enrichment of the myofibroblast-like phenotype in TAFs
2
Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, regardless their histologic subtype, yet senescence was observed in LCC-TAFs
Stanford/CA/United States of America, 3Pathology, Stanford University, Stanford/ only regardless their neuroendocrine status. Likewise, co-culturing normal
CA/United States of America, 4Division of Thoracic Surgery, Stanford University, lung fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient
Stanford/CA/United States of America, 5Department of Medicine, Division of
to induce senescence, and this induction was prevented in the presence
Oncology, Stanford University, Stanford/CA/United States of America
of an antioxidant, indicating that it is mediated through oxidative stress.
Background: CT imaging is standard-of-care for surveillance following Remarkably, senescent fibroblasts provided growth and invasive advantages
definitive lung cancer therapy but is complicated by difficulties in to LCC cells in culture and in vivo beyond those effects provided by control
distinguishing recurrence from treatment-related fibrosis and inability to (non-senescent) fibroblasts. Conclusion: Our findings expand recent evidence
detect microscopic disease. CAPP-Seq is a novel blood-based assay that uses that challenges the common assumption that lung TAFs are a heterogeneous
next-generating sequencing to quantitate circulating tumor DNA (ctDNA). We myofibroblast-like cell population regardless their histologic subtype. Of
performed a prospective study to compare disease surveillance by CAPP-Seq note, because LCC often distinguishes itself in the clinic by its aggressive
to CT imaging after definitive treatment for localized lung cancer. Methods: nature, our findings support that senescent or senescent-like TAFs may
We prospectively enrolled 34 patients treated definitively for non-metastatic contribute to the selective aggressive behavior of LCC tumors.
primary lung cancer at Stanford University between June 2010 and September
Keywords: cancer associated fibroblasts, large cell carcinoma, senescence,
2015. Our cohort included 22 (64.7%) patients with stage III, 6 (17.6%) patients
tumor microenvironment
with stage II and 6 (17.6%) patients with stage I disease. All patients received
pre-treatment evaluation by thoracic CT and PET/CT scans as well as ctDNA

MA17.10 YES1 Kinase is a New Therapeutic Target in Non-small Cell Lung Cancer
Jackeline Agorreta1, Irati Garmendia1, Maria Pajares1, Daniel Ajona1, Daniel

Alameda1, Carmen Behrens2, Ignacio Wistuba3, Ruben Pio1, Luis Montuenga4
1
Program in Solid Tumors and Biomarkers, Cima-University of Navarra, Pamplona/
Spain, 2Translational Molecular Pathology, MD Anderson, Houston/TX/United
States of America, 3Translational Molecular Pathology, The University of Texas MD
Anderson Cancer Center, Houston/United States of America, 4Solid Tumors and
Biomarkers Program, Cima. University of Navarra, Pamplona/Spain
Background: Next-generation sequencing techniques have allowed the

discovery of driver mutations in non-small cell lung cancer (NSCLC) that can
be translated into advances in cancer diagnosis and treatment. However,
specific oncogenic alterations are still unknown in a high proportion of
NSCLC patients, that therefore cannot benefit from targeted therapies.
The challenge is to identify new genetic alterations that allow the use of
molecular-targeted therapies. In previous studies from our group (Aramburu
et al. BMC Genomics 2015), the analysis of tumor molecular profiles
from patients with NSCLC allowed us to identify the DNA copy number
amplification of YES1 kinase (v-YES-1 Yamaguchi sarcoma viral oncogene
homolog 1) as a prognostic marker in lung cancer. YES1 kinase is member of
the Src family of non-receptor protein tyrosine kinases that are involved in Conclusion: Our study demonstrates that knockdown of Akt2 suppresses
the regulation of cell growth, apoptosis, cell-cell adhesion, cytoskeleton tumorigenesis by attenuating cell proliferation, increasing apoptosis and
remodeling, and differentiation. The aim of this project is to evaluate if YES1 is interfering cell cycle in non-small cell lung cancer. Raf1 overexpression partly
a driver gene in NSCLC, and if targeting its activation may be a potential new offsets these effects by enhancing cell proliferation, suppressing apoptosis
therapeutic strategy. Methods: We first evaluated the prognostic role of YES1 and affecting downstream proteins. Thus, there may be existing Akt2/Raf1
protein expression in two independent series of 76 and 234 NSCLC patients, pathway in NSCLC, which plays an important role in tumorigenesis.
respectively. In both series, the multivariate analysis revealed that high
YES1 expression is an independent poor prognostic factor for overall survival Keywords: Akt2, Raf1, Cell signal pathways, NSCLC
(CUN series HR: 3.416 [0.933-12.508]; MD Anderson series HR: 1.570 [1.032-
2.391]). We next evaluated the effect of YES1 knockdown in 5 NSCLC cell
lines with YES1 amplification and overexpression, and in 3 cell lines without
YES1 amplification and with low protein expression. YES1 downregulation
by two specific siRNAs decreased proliferation and cell survival only in those
cells overexpressing YES1. Congruently, YES1 inhibition led to apoptosis
only in those cells. Results: Consistent with these results, constitutive
overexpression of YES1 in cells with low YES1 expression significantly
enhanced cell proliferation. We next evaluated the effect of the multitarget
Src kinase inhibitor dasatinib on the proliferation of NSCLC cell lines with
high (8 cell lines) or low (4 cell lines) YES1 expression. Dasatinib dramatically
inhibited proliferation in high YES1-expressing cell lines, whereas low YES1
cell lines were more resistant to dasatinib treatment (GI50s were four orders
of magnitude higher in resistant cells). Conclusion: In conclusion, our results
indicate that YES1 is a promising therapeutic target in NSCLC. Furthermore,
amplification and high expression of YES1 may define a subset of patients who
may potentially benefit from dasatinib treatment.

MA17.11 KNOCKDOWN OF AKT2 SUPPRESSES TUMORIGENESIS

AND RAF1 OVEREXPRESSION OFFSETS THIS EFFECT IN NON-SMALL
CELL LUNG CANCER
Shuang Zhao 1, Wei Min Li2
1
Department of Respiratory Medicine, West China Hospital, Sichuan University,
Chengdu 610041, China., Chengdu/China, 2West China Hospital, Chengdu/China
Background: Akt2 (Protein Kinase B isoform 2) is an essential protein, which

is involved in tumor cell proliferation, differentiation, motility, and cell death
in non small cell lung cancer (NSCLC). Raf1 is also a key protein regulating the
functions in NSCLC. However, the relationships between Akt2 and Raf1 are
unknown. This study aimed to investigate the influence of Akt2 knockdown
and its interaction with overexpression Raf-1 in non-small cell lung cancer
cells. Methods: Small interfering RNA was used to knockdown Akt2 and
lentivirus was introduced to overexpress Raf1 in H1299, A549, Sk-mes and
H460 cell lines. Western blot was performed to investigate expression levels
of relevant proteins in the pathway. Cell survival, proliferation and apoptosis
were evaluated in vitro and vivo. Then we examined Akt2 and Raf1 expressions
via immunohistochemistry (IHC) in 65 NSCLC patients. Results: Knockdown
of Akt2 suppressed cell proliferation, arrested tumor cells in G0/G1 phase and
induced apoptosis in all cell lines distinctively. Raf1 phosphorylation was also
inhibited after Akt2 knockdown in the cell lines. When Raf1 overexpression
combined with Akt2 knockdown in these cell lines, cell proliferation was
enhanced, and apoptosis rates was decrease compared with Akt2 knockdown
alone. These trends were also observed in vivo experiments. Furthermore,
the downstream proteins of Raf1, such as MEK, ERK, p-MEK and p-ERK were
observed decrease in Akt2 knockdown groups. Of all NSCLC specimens,
Akt2(+)/Raf1(+) patients had the worst prognosis of 5-year overall survivals.

tobacco smoke (ETS) might provide some explanation to the presence of

POSTER SESSION 1 - MONDAY, DECEMBER 5, 2016 such genetic traits. Furthermore, ETS exposure might have a different effect
should occur at home in adult life, during childhood, or at work. We aim to
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO know if ETS exposure is associated with EGFR mutations or ALK alterations
in a huge sample of never smoking lung cancer cases. Methods: We recruited
CONTROL AND CESSATION/PREVENTION never smoking lung cancer cases diagnosed consecutively in 9 Spanish
Tobacco, Radon, Air Pollution, Other Risk Factors – Hospitals since 2011. We collected extensive information on different lifestyle
MONDAY, DECEMBER 5, 2016 activities and also measured residential radon exposure. Cases had to be
older than 30 years with no upper age limit and with no previous history of
cancer. A never smoker was defined as: 1) an individual who smoked less than
P1.01-001 REDUCTION OF CIGARETTE CONSUMPTION THROUGH A 1 daily cigarette for no more than 6 months or, 2) no more than 100 cigarettes
NATIONAL POLICY FOR TOBACCO CONTROL IN BRAZIL smoked in lifetime. EGFR mutations and ALK alterations were determined
using standard procedures. Logistic regressions were performed to analyze
Ana Paula Teixeira, Tânia Cavalcante
the influence of exposure to ETS in different settings (adult life at home, at
Executive Secretariat of the National Commission for Implementation the work or during childhood). The dependent variables were EGFR mutation
Framework Convention on Tobacco Control, National Cancer Institute-Ministry of
(of any type) or not, or ALK translocation (present/absent). Results were
Health, Rio de Janeiro/Brazil
adjusted by age, gender and residential radon exposure. Results: We included
Background: According to WHO, “approximately one person dies every six 389 never smoking lung cancer cases. 80.5% were females and the median
seconds due to tobacco, accounting for one in 10 adult deaths. Up to half of age was 71 and the interquartilic range 61-78 years. 246 patients had EGFR
current users will eventually die of a tobacco-related disease”, which can be determined (63.2% of the total) and of them, EGFR was mutated in 43%.
lung cancer (87%), pulmonary disease (61%) and coronary heart disease (32%), ALK status was determined in 97 patients (24.9% of the total), and was
considering secondhand smoke exposure too as says the Surgeon General´s positive in 16 patients (16.5%). Living at home with a smoker for more than 20
Report. To protect the health of the Brazilian population, the government years was not associated with EGFR mutation or ALK translocation, and the
has been applying measures, since the 90 years, to reduce the harm caused by same occurred for being exposed to ETS at work. When exposure to ETS in
tobacco use. Brazil is also committed to reduce the premature mortality from childhood (before 16) was considered, we observed that those exposed to ETS
tobacco use in 30% from 2013 to 2025, to achieve one of the nine voluntary had an OR of EGFR mutation of 0.57 (95%CI 0.31-1.05; p= 0.07). No association
WHO Global NCD´s Targets. Methods: Quantitative secondary data analysis was observed for ALK translocation. Conclusion: These results suggest that
confronting the cigarette prevalence rates found in Risk and Protective exposure to environmental tobacco smoke in childhood might reduce the
Factors Surveillance for Chronic Diseases Telephone Survey (VIGITEL) and the chance of EGFR mutation in never smokers with lung cancer. This observation
National Policy for Tobacco Control measures. Results: Before ratifying the would add more evidence to avoid exposure to ETS in any time of life. Funding:
WHO Framework Convention on Tobacco Control, in 1996 the government ISCIII/PI13/01765/Cofinanciado FEDER
started promoting smoke-free places, banning the advertising, promotion
Keywords: EGFR, ALK, Environmental tobacco smoke
and sponsorship, that were finally regulated in 2014. In 2011, the Secretariat of
Federal Revenue developed a new system for cigarette taxation to establish
a minimum price for a pack of twenty cigarettes and raise the cigarette´s
excise tax gradually. In May,2016 the total taxation represents 76% of the
cigarette price and will bring to 81% afther December 2016. This is one of the POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
measures of the Framework Convention for Tobacco Control/WHO more cost- PREVENTION
TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS –
effective in the country: Article 6, which deals with the rising prices and taxes MONDAY, DECEMBER 5, 2016
on tobacco products to reduce demand. Several surveys and studies point
to a reduction in smoking prevalence. Every year, since 2006, the VIGITEL
report has shown prevalence rates collected in the entire adult population of P1.01-003 NOVEL ASSOCIATIONS BETWEEN LUNG CANCER-
the 27 state capitals. In 2015 the frequency of smokers decreased to 10.4%, RELATED GENES AND INDOOR RADON EXPOSURE
compared to 2006 which were 15.7% for both sexes. The report also reiterated Jung Ran Choi1, Seong Yong Park2, Hye Run Kim3, Dae Ryong Kang4
the effectiveness of the prices and taxes measure, when you compare the 1
Institute of Genomic Cohort, Yonsei University Wonju College of Medicine, Wonju/
frequency of former smokers with lower education, those representing people Korea, Republic of, 2Thoracic and Cardiovascular Surgery, Ajou University School
with lower income. In 2006 they were 25.6%, and in 2015 they increased to of Medicine, Suwon/Korea, Republic of, 3Internal Medicine, Division of Medical
29.1%. Conclusion: The present study shows a prevalence decline as a positive Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/
result coming from the National Policy for Tobacco Control implementation Korea, Republic of, 4 Ajou University School of Medicine, Suwon/Korea, Republic of
between the years of 2006 and 2015. To achieve the WHO Global NCD´s Target
we still have too much work to do, specilally protect the National Policy from Background: Although the most important risk factor for lung cancer is
the tobacco industry interference. smoking, lung cancer in never smokers (LCINS) is being increasingly reported.
Thus, studies of other risk factors for lung cancer are needed. Recently, radon
Keywords: WHO FCTC, Tax and Price, Consumption, Tobacco Control (Rn), a natural, noble gas, was recognized as the second most common risk
factor for lung cancer. OBJECTIVES
To identify variations in genes associated with lung cancer in never smokers

exposed to radon gas. Methods: We conducted an optimized next generation
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ sequencing analysis of lung cancer-related genes in normal and tumor tissues
PREVENTION
from Korean LCINS patients who had been exposed to radon gas indoors.
MONDAY, DECEMBER 5, 2016 A total of 926 SNPs showing genome-wide statistical significance were
analyzed. Results: Several genes commonly associated with lung cancer,
EGFR and TP53 in chromosomes 7 and 17, respectively, showed significant
P1.01-002 ENVIRONMENTAL TOBACCO SMOKE EXPOSURE AND correlations with LCINS. Others included ERG in chromosome 21, RIT1 in
EGFR MUTATIONS/ALK TRANSLOCATION IN NEVER SMOKERS. A chromosome 1, and BIRC6 in chromosome 2. Meanwhile, several additional
MULTICENTRE STUDY IN SPANISH NEVER-SMOKERS loci showed novel associations with LCINS as a result of exposure to radon
Mónica Pérez-Ríos 1, Alberto Ruano-Ravina2, Maruxa Zapata1, María Torres- gas, including PDK1, VHL, WHSC1L1, CHD4, MBD2, ATRX, CCND1, and PTPRD.
Durán3, Virginia Leiro-Fernández3, Isaura Parente-Lamelas4, Iria Vidal-García5, Conclusion: Using next generation sequencing, we found several lung
Olalla Castro-Añón6, Margarita Amenedo7, Mariano Provencio-Pulla8, Antonio cancer-related genes to be associated with tumors in never smokers exposed
Golpe Gómez9, Rosirys Guzmán-Taveras10, María José Mejuto-Martí11, Ángeles to radon. Most of the noted loci have not been shown to be associated with
Rodríguez12, Juan Barros-Dios1 lung cancer, and provide new insights into the development of LCINS. Our
1
University of Santiago de Compostela, Santiago de Compostela/Spain, 2Preventive findings may serve as a reference for replication and validation studies on
Medicine & Public Health, University of Santiago de Compostela, Santiago the prevention and treatment of LCINS as a result of exposure to radon gas.
de Compostela/Spain, 3Neumology, Alvaro Cunqueiro Hospital, Vigo/Spain, ACKNOWLEDGMENTS: This study was supported by the Korean Ministry of
4
Pulmonary Medicine, Ourense Hospital Complex, Ourense/Spain, 5University Environment as part of the “Environmental Health Action Program” (grant
Hospital Complex of A Coruna, A Coruña/Spain, 6Lucus Augusti Hospital, Lugo/ number 2015001350002).
Spain, 7Oncologic Center of Galicia, A Coruña/Spain, 8Puerta de Hierro University
Hospital, Madrid/Spain, 9Santiago de Compostela University Hospital Complex, Keywords: Radon, next generation sequencing, lung cancer in never smoker,
Santiago de Compostela/Spain, 10 Central University Hospital of Asturias, Oviedo/ genetic variation
Spain, 11 Arquitecto Marcide Hospital, Ferrol/Spain, 12Pontevedra Hospital Complex,
Pontevedra/Spain
Background: Mutations or translocations in driver genes of lung cancer such as

EGFR or ALK are important treatment targets for advanced lung cancer. These
alterations are present mainly in never-smokers. Exposure to environmental
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ alters pattern of tobacco-use, especially smoking. Findings are expected to
PREVENTION
be strategically significant to inform future policies. Methods: Questionnaire
MONDAY, DECEMBER 5, 2016 of Global Adult Tobacco Survey-India(2010), developed by WHO,CDC and
Govt. of India was modified to answer research questions and accommodate
retrospective-cohort study design. Through 2-step randomization process,
P1.01-004 IS THERE ANY ROLE OF RESIDENTIAL RADON IN NON 500 households were sampled from Delhi. Participants were adults and
SMALL CELL LUNG CANCER (NSCLC) PATIENTS HARBORING interviewed during March-June,2016 comprehensively, including tobacco-
MOLECULAR ALTERATIONS? use currently and before gutka-ban. Inbuilt mechanisms in standardized
Laura Mezquita1, Amparo Benito2, Maria Eugenia Olmedo3, Pablo Reguera3, questionnaire cross-validated self-report and minimised recall bias. Data
Ainhoa Madariaga3, Maria Villamayor3, Silvia Patricia Cortez3, Luis Gorospe4, was entered into SPSS and statistically analysed. Results: 94% of 500
Almudena Santon2, Sagrario Mayoralas5, Raul Hernanz6, Alberto Cabanero7, households visited agreed to participate. 73.4%of pre-ban gutka-users
Alfredo Carrato3, Pilar Garrido3 switched to twin-sachet (pan-masala and chewing-tobacco sold separately by
1
Medical Oncology Department, Gustave Roussy, Villejuif/France, 2Pathology gutka-manufacturers to circumvent law). Delhi’s order bans all ST products.
Department, University Hospital Ramon Y Cajal, Madrid/Spain, 3Medical Oncology But, except premixed gutka, remaining ST products are freely available and
Department, University Hospital Ramon Y Cajal, Madrid/Spain, 4Radiology consumed. 21.8%switched to khaini or other ST products. A large fraction
Department, University Hospital Ramon Y Cajal, Madrid/Spain, 5Pulmonary switched from singledose sachets to multidose sachet. Interestingly,
Department, University Hospital Ramon Y Cajal, Madrid/Spain, 6Radiation 96.2%respondents believed tobacco as very harmful(84.6%) or somewhat
Oncology Department, University Hospital Ramon Y Cajal, Madrid/Spain, 7Thoracic harmful(11.6%). However, only 18.6%gutka users attempted quitting after
Surgery Department, University Hospital Ramon Y Cajal, Madrid/Spain
ban. 4.8%successfully quitted. In our sample, we DIDNOT find anyone
Background: Radon gas is the first cause of lung cancer in non-smoking switching to smoking due to gutka unavailability. On an opposite thought,
population. The World Health Organization (WHO) recommends radon one may expect, ban on an ST product(Gutka) will increase awareness
concentration lower than 100 Bq/m3. In recent years, most of the and motivate smokers to quit as spillover effect. But it wasn’t observed
advances in personalized therapy in NSCLC patients also occurred in non- either. Conclusion: In absence of strong quitting promotion campaign, ban
smokers. Furthermore, limited information is available about the clinical on selective tobacco products has limited role in changing prevalence of
and pathological characteristics in patients exposed to radon gas. We tobacco use. If selective ST products are banned, ST users preferably switch
hypothesized that residential radon could be associated to some specific to other available ST products, BUT NOT to smoking. As majority ST users
pathological and molecular alterations in NSCLC patients. Methods: switched instead of quitting (after gutka-ban without simultaneous quitting
Prospective study of a cohort of NSCLC patients harbouring molecular campaign), we may logically conclude that effective ban on all ST products
alterations (EGFR, BRAF mutations (m), ALK and ROS1 rearrangements may lead ST users to switch to less favourable option of smoking. This is,
(r)) in our centre, between September 2014 and October 2015. A radon however, subject to verification by similar study if there is ever effective ban
detector alpha-track was given to each patient to measure residential radon on all ST products.
concentration for 3 months; it was analysed using optical microscopy. Keywords: Smokeless Tobacco, Gutka ban, smoking, GATS
We collected demographic information, smoking history, environmental
exposure and clinical characteristics. The pathologic characteristics were
prospectively revised by a lung cancer pathologist, including histology
pattern, grade and inflammatory infiltrate. EGFR and BRAF mutation (m)
were analyzed using quantitative real-time polymerase chain reaction (PCR) POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
and ALK and ROS1 rearrangement by fluorescence in situ hybridization PREVENTION
(FISH). Data was analyzed using IBM SPSS v.20. Results: 60 detectors were MONDAY, DECEMBER 5, 2016
delivered (10% missing), 48 patients were evaluated (89.6% living in Madrid).
Median age 66.5 (29- 82); 33 (68.8%) females; 33 non-smokers (31.3% passive
smokers and 35.4% childhood exposure) and 3 (6.3%) light smokers. 100% P1.01-006 INTERSTITIAL LUNG DISEASES ARE AN ANTECEDENT OF
adenocarcinoma (35.4% mixte, 18.8% acinar, 10.4% solid, 8.3% papillary, LUNG CANCER
8.3% micropapilllary, 8.4% others and 10.4% unknown); EGFRm 36 patients, Wonil Choi
ALKr 10 patients and BRAFm 2 patients. Home characteristics measured: Department of Internal Medicine, Keimyung University School of Medicine, Daegu/
79.2% flat (89.1% measurement at bedroom); building material: 89.6% bricks. Korea, Republic of
Median length of stay was 28 years (2-55). Median height of house 2 floors
(0-15). Median of radon concentration: 104 Bq/m3 (42- 915); 60.42% over Background: Diffuse pulmonary fibrosis may progress into lung cancer
WHO recommendation. By molecular alteration: EGFRm median 96 Bq/m3 through continuous accumulation and rapid proliferation of fibroblasts and
(42-915), ALKr median 116 (64-852) and BRAFm median 125 (125). A significant repeated epithelial injury. Repetitive injury and repair can lead to multiple
association was observed between non-EGFR mutation and concentration genetic alterations affecting cellular growth, differentiation, and survival,
over the WHO recommendation (p=0.044). In univariant analysis, radon which may elicit malignant potential in the injured area. Diffuse pulmonary
concentration was associated with non-mucinous histology and low tumoral fibrosis appears on chest images through expression of bilateral reticular
grade (p=0.033 and p=0.023, respectively). Conclusion: Our final results have or reticulonodular opacities, called interstitial lung diseases. The clinical
shown no consistent association between residential radon and molecular significance of these diseases remains poorly understood. To investigate
alterations in NSCLC patients, but a trend has been suggested in ALKr and whether interstitial lung diseases increase lung cancer incidence in a cohort of
BRAFm. Large multicenter studies are needed to confirm this hypothesis. patients from a national population. Background: Diffuse pulmonary fibrosis
may progress into lung cancer through continuous accumulation and rapid
Keywords: Radon, molecular alteration, NSCLC proliferation of fibroblasts and repeated epithelial injury. Repetitive injury
and repair can lead to multiple genetic alterations affecting cellular growth,
differentiation, and survival, which may elicit malignant potential in the
injured area. Diffuse pulmonary fibrosis appears on chest images through
expression of bilateral reticular or reticulonodular opacities, called interstitial
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION lung diseases. The clinical significance of these diseases remains poorly
TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS – understood. To investigate whether interstitial lung diseases increase lung
cancer incidence in a cohort of patients from a national population. Results: A
nationwide retrospective cohort study using Korean Health Insurance Review
P1.01-005 FIRST OF ITS KIND STUDY IN INDIA FINDS THAT and Assessment Service data, including 13,666 patients with interstitial lung
GOVERNMENT’S BAN ON GUTKA (HIGHLY POPULAR SMOKELESS disease (6.4% with concomitant idiopathic pulmonary fibrosis) diagnosed
January–December 2009. The end of follow-up was June 31, 2014. Up to four
TOBACCO PRODUCT) DID NOT INCREASE SMOKING AT ALL
matching chronic obstructive pulmonary disease controls with and without
Gaurav Kumar 1, Pradeep Kumar2 concomitant interstitial lung disease (8,012 cases) were selected to compare
1
Community Medicine, Gmers Medical College, Ahmedabad/India, 2Gmers Medical the lung cancer high-risk group. Lung cancer was counted after diagnosis of
College, Ahmedabad/India interstitial lung disease, idiopathic pulmonary fibrosis, or chronic obstructive
pulmonary disease. Conclusion: The incidence of lung cancer was 126.9
Background: India with 11.2%(111.9 million) of world’s smokers has 2nd largest
cases per 10,000 person-years (2,732 cancers) in the chronic obstructive
population at elevated risk of lung cancer. Almost twice, 206 million(GATS,
pulmonary disease group, 156.6 (809 cancers) in the interstitial lung disease
2010), are Smokeless tobacco(ST) users in India, highest globally. Supreme
group, and 370.3 (967 cancers) in the chronic obstructive pulmonary disease
Court of India observed that gutka and pan-masala are food products.
with interstitial lung disease group. Among various interstitial lung disease
Beginning in 2012, almost all state governments in India banned gutka and
definitions, idiopathic pulmonary fibrosis showed the highest lung cancer
pan-masala containing tobacco. APPREHENSION was raised that ban on ST
incidence. A total of 112 of the 879 patients with idiopathic pulmonary fibrosis
products will cause switching to smoking by huge ST user population vastly
developed lung cancer, an incidence of 381 cases per 10,000 person-years.
increasing risk of lung-cancer in India. This ban provided natural experiment
Interstitial lung diseases have high potential to develop into lung cancer even
on which this observational research studied how ban on popular ST products

when combined with chronic obstructive pulmonary disease. response was recorded. Random sampling method was used and data was
collected from a cross-sectional survey. The surveywas conducted between
Keywords: lung cancer, Incidence, interstitial lung disease January and February 2015. Statistical analysis was done using SPSS version
17 and Logistic regression model was used to identify possible associations
with tobacco smoking status. The level of significance was Results: A total
of 259answered the questionnaire of which 29% declared to be smokers.
About 53% of the males have smoked at least once in their life and the age
PREVENTION of cigarette initiation was 16-17 years for 28% of the sample.76%considered
TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS – health professionals as behavioural models for patients, and 96% affirmed
that health professionals have a role in giving advice or information about
smoking cessation. Although 87% heard about smoking related issues during
P1.01-007 A CROSS-SECTIONAL STUDY ON TOBACCO CONSUMPTION undergraduate courses, only 17% received specific smoking cessation training
PATTERN AMONG AUTO RICKSHAW DRIVERS IN CHENNAI CITY, during specialization. 93% of the sample agreed that health professionals
should receive specific training on smoking cessation according to while 6%
TAMIL NADU, INDIA
were of the opposite opinion. Conclusion: The present study highlights the
Delfin Lovelina Francis importance of focusing attention on smoking cessation training, given the
Public Health Dentistry, Tagore Dental College and Hospital, Chennai/India high prevalence of smokers among physicians specializing in medicine and
dentistry, their key role both as advisers and behavioural models, and the
Background: Tobacco use is a major preventable cause of premature death
limited tobacco training offered in the curriculum. In the field of public health,
and diseases, currently leading to five million deaths worldwide which are
tobacco screening, and intervention is one of the most effective clinical
expected to raise over eight million deaths worldwide by 2030. India is the
preventive services.
second largest consumer of tobacco in the world. Tobacco use is a leading
cause of deaths and disabilities in India as well, killing about 1.2 lakh people Keywords: Medical students, smoking habits, oral cancer
in 2010. About 29% of adults use tobacco on a daily basis and an additional
5% use it occasionally. This study is contemplated with an aim to assess the
prevalence of tobacco consumption and the associated factors involved in
its consumption, as this group of the population is under constant pressure
and account for the workforce of the country. So through this study we could POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
be able to know * The reasons of consumption. * Amount of consumption TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS –
*Awareness of ill effect of tobacco consumption* Out of Pocket expenditure. MONDAY, DECEMBER 5, 2016
Methods: ACross sectional descriptive study was conducted among Auto
Rickshaw Drivers in Chennai City.Auto drivers who were working for more
than two years and present on the day of examination and who were willing P1.01-009 SMOKING AND LUNG CANCER: DATA FROM THE SINGLE
to participate in the study were included.Cluster random sampling technique CENTER IN ALBANIA
was used. 400 samples were selected from 40 auto stands of various parts of Daniela Xhemalaj1, Fatmir Caushi2, Ilir Peposhi3, Elona Hila3, Gisela Pumo1,
Chennai City.Data was collected using a Survey Proforma which comprised Asela Hasa1, Hasan Hafizi3
of a Questionnairewhich can assess the frequency of consumption, age of 1
Pathology, University Hospital of Lung Diseases, Sauk/Albania, 2Thoracic Surgery,
initiation, the amount of consumption, mental stress, economic factors, any University Hospital of Lung Diseases, Tirana/Albania, 3Thoracic Surgery, University
past history of disease and most importantly the awareness towards oral Hospital of Lung Diseases, Tirana/Albania
cancer.The data recorded was transferred and analysed using SPSS version
20.Chi- square test was used to test the significance between groups. Results: Background: Albania is a country with a high prevalence of smoking but a
Prevalence among auto rickshaw drivers for consumption of tobacco products national cancer registry has not been initiated yet and data on lung cancer
was very high (87%). Auto rickshaw drivers were mostly used tobacco in the are scarce. Methods: Aim - Methods: In 2010-2014, 1254 patients presented
form of Gutkha (72%) and bidi (40%) in comparison to other products. In the to our hospital with either symptoms or an abnormal finding in their chest
opinion of auto rickshaw drivers increase in tax may reduce it consumption X-ray and were diagnosed with lung cancer. This is a descriptive retrospective
and the majority of drivers (70%) think that tobacco must be banned. study, reporting data on the histological type of cancer and smoking history
Conclusion: Prevalence of tobacco use among auto rickshaw drivers was very Results: Results: Of the 1254 patients, 79% (n= 1001) were men and 21%
high. Mostly they use tobacco products to reduce stress, to be awake or to (n=253) women . Age range was (16-89), with mean age in men 62.4 ±8,5 and
remove nervousness but a large number of participants also use them without in women 58±10,2. Diagnosis was confirmed by histology [table 1] : Regarding
any reason. Almost one half of the study population was suffering from NSCLC, 78% of patients had an advanced stage (III and IV). Only 268 patients
tobacco related diseases like cough, ulcer on mouth, lung disorder. They are in were non-smokers, 126 were ex-smokers and the remaining 67 % (n=860) were
definite need of tobacco cessation activities. current smokers with high exposure (92 pack/years). Day hospital avarage is
7 day,and day range was(1-21) with SD± 6.4. Performance status was:60.2%
Keywords: Tobacco, Awareness, Prevalence, Addiction. improved,35.2% idem,3.3% dead in hospital.
Squamous
Adeno-
cell Small cell others Total
carcinoma
carcinoma
PREVENTION 56% 22% 7% 100%
TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS – men 15%(n=150)
(n=560) (n=220) (n=71) (n=1001)
11% 72% 5% 12% 100%
women
(n=27) (n=183) (n=13) (n=30) (n=253)
P1.01-008 KNOWLEDGE, ATTITUDES, AND SMOKING BEHAVIOURS
AMONG DENTAL AND MEDICAL STUDENTS IN CHENNAI, TAMIL Conclusion: In Albania,lung cancer is an increasing pathology (p<0.005)
NADU, INDIA and there is a high prevalence of squamous cell carcinoma especially in
Delfin Lovelina Francis men,probably associated with the heavy history of smoking and most
Public Health Dentistry, Tagore Dental College and Hospital, Chennai/India patients are diagnosed at a late stage.Policies for smoking cessation should
be strengthened and a lung cancer screening program should be initiated.
Background: Tobacco use continues to be the leading cause of preventable
disease and it is responsible for more than 5 million deaths each year
worldwide. Despite this, there are still 650 million smokers in the world. The
prevalence of smoking among adults accounts for approximately 25% deaths
annually. smoking remains the main cause of mortality and morbidity in the PREVENTION
developing nations. Healthcare professionals have an important role to play TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS –
both as advisers influencing smoking cessation and as role models. However, MONDAY, DECEMBER 5, 2016
many of them continue to smoke. Several studies have demonstrated the
efficacy of smoking cessation programs and the importance of physician’s
P1.01-010 AWARENESS OF LUNG CANCER RISK FACTORS AMONG
advice to their patients. The aims of the present study are as follows: (i)
LAY PERSONS AND PHYSICIANS
to evaluate smoking prevalence, knowledge and attitudes, and tobacco
cessation training (ii) to examine the difference between smokers and Laurent Greillier 1, Jean-François Morere2, Jérôme Viguier3, Chantal Touboul4,
nonsmokers; Methods: A structured questionnaire consisting of 14 questions Jean-Yves Blay5, François Eisinger6, Christine Lhomel7, Xavier Pivot8, Alexis
related to tobacco/smoking habits, cessation training and role of health Cortot9, Sébastien Couraud10
professionals in tobacco control were asked to the study population and their 1
Hôpital Nord, Marseille/France, 2Hôpital Paul Brousse, Villejuif/France, 3Hôpital
Bretonneau, Tours/France, 4Kantarhealth, Paris/France, 5Centre Léon Bérard, POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
Lyon/France, 6Institute Paoli Calmettes, Marseille/France, 7Roche, Boulogne- PREVENTION
Billancourt/France, 8 CHU Besançon, Hôpital Jean Minjoz, Besançon/France, MONDAY, DECEMBER 5, 2016
9
Hôpital Calmette, Lille/France, 10Service de Pneumologie, Centre Hospitaliser Lyon
Sud, Pierre Bénite/France
P1.01-012 KAVA EFFECTS ON THE METABOLISM OF TOBACCO-
Background: Tobacco consumption, and more specifically active smoking,
SPECIFIC CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-
remains the main risk factor for lung cancer (LC) and continues to be the
target of awareness campaigns worldwide. However, in recent decades, other BUTANONE (NNK) IN HUMANS
risk factors have been identified, including passive smoking, atmospheric Drew Oostra, Naomi Fujioka, Chengguo Xing, Sreekanth Narayanapillai,
pollution and occupational exposure. This analysis focuses on awareness Jordan Paladino, Hannah Alves
of LC risk factors among the lay population and physicians. Methods: The University of Minnesota, Minneapolis/MN/United States of America
4th French nationwide observational survey, EDIFICE 4, was conducted by
phone interviews of a representative sample of 1602 subjects, aged between Background: Kava is extracted from the roots of piper methysticum and is
40 and 75 years, from June 12 to July 10, 2014. A mirror survey was also consumed by South Pacific Islanders as a relaxing beverage. Epidemiologic
conducted by phone among physicians between July 9 and August 8, 2014. evidence points to a protective effect of kava against tobacco-induced lung
Both surveys were conducted using the quota method on representative cancer. NNK is a potent tobacco-specific carcinogen indisputably linked to
samples of 1602 lay persons and 301 physicians. The following analyzes were lung cancer formation. Kava reduced NNK-induced lung adenoma formation
conducted amongst 1463 lays persons with no history of cancer and 301 in the A/J mouse model. Data also suggest that enhanced NNAL detoxification
physicians. Interviewees were asked to cite the five main risk factors for LC. may be a potential mechanism by which kava exerts a chemopreventive
Results: LC risk factors associated with tobacco in general were widely cited effect. In humans, urinary NNAL is a validated biomarker of NNK uptake.
in first position by both physicians and the lay population (100% and 96%, We conducted a clinical trial in smokers to assess the effect of kava on
respectively; P≤0.01), with the role of active smoking (100% vs 94%, P≤0.01) NNK metabolism. The primary objective was to compare urinary total
and passive smoking (77% vs. 68%, P≤0.01) clearly identified. Twice as many NNAL before and after kava administration. Secondary objectives included
physicians cited asbestos as a risk factor, ranking it in second place, compared comparing the NNAL-gluc/NNAL-free ratio, determining the safety of kava,
with the lay population (77% vs. 30%, P≤0.01). Atmospheric pollution was and quantifying O6 -methylguanine adducts. The hypothesis was that kava
cited to the same degree by physicians and the lay population (49% vs. 43%, administration would result in increased levels of NNAL in the urine (and
P=0.05), the latter ranking it second. Heredity and family history came increased NNAL-gluc/NNAL-free ratio), reflecting increased elimination and/
fourth (32% vs. 13%, P≤0.01) and alcohol fifth (13% vs. 10%, not statistically or increased detoxification of NNK. Additionally, we hypothesized that
significant), in both populations. Infections and other respiratory disorders kava could reduce O6 -methylguanine adducts. Methods: We conducted
were cited by less than one person in ten (7%). Poor dietary habits were very a single-arm, open-label clinical trial in adult healthy smokers, in which
rarely cited by either physicians or the lay population (<1% vs 4%, respectively, subjects took a commercial kava supplement three times daily for seven
P≤0.01). Conclusion: The awareness of risk factors for lung cancer is broadly days. Twenty-four hour urine collections were collected at baseline, days
consistent with the established risk factors, among both physicians and the 4-5, and days 6-7 of the kava intervention for NNAL quantification. Blood
lay persons in our survey. As expected, tobacco was ranked first, followed samples were collected at baseline, day 4, and day 7 of the kava intervention
by atmospheric pollution and asbestos, though the latter is less present in for safety monitoring and for DNA adduct analysis. Subjects also completed
the mind of the lay population compared to physicians. It is noteworthy that a detailed tobacco questionnaire, food diary, smoking diary, and cigarette
even among physicians, a history of respiratory disorders was only marginally evaluation scale (CES) questionnaire. To date, 17 subjects (goal = 18) have
acknowledged. completed the study. Results: The results and statistics are being finalized.
Short-term kava administration was safe with no evidence of hepatotoxicity.
Keywords: risk awareness, lay population, history of respiratory disorders, Subjects experienced less of the reinforcing effects of smoking after short-
risk factors term kava administration as determined by the CES scores. The total CES
score decreased on average by 4.47, from 45.53 to 41.06 (p=0.053, 95% CI
-0.06-9.01). Notably, the smoking “satisfaction” scores decreased by 0.607
(p=0.024, 95% CI 0.09-1.12). Conclusion: This is the first study investigating
the effect of kava on NNK metabolism in humans and is the first step to gain
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ a more sophisticated mechanistic understanding of kava’s role in potentially
PREVENTION
TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS – modulating tobacco-related lung cancer risk. Short-term kava administration
MONDAY, DECEMBER 5, 2016 is safe in healthy adult smokers. Kava holds potential as a possible
chemopreventive agent for smokers or tobacco cessation aide.
P1.01-011 ROFLUMILAST ATTENUATES BENZO(A)PYRENE-INDUCED Keywords: Kava, NNK, NNAL, Tobacco smoke
LUNG CANCER VIA SUPPRESSION OF AIRWAY INFLAMMATION IN
MURINE MODEL
Chang Dong Yeo, Hyonsoo Joo
Catholic University of Korea, Seoul/Korea, Republic of
PREVENTION
Background: Chronic airway inflammation has been emerging targets for lung TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS –
cancer chemoprevention as well as treatment of COPD. The aim of the present MONDAY, DECEMBER 5, 2016
study was to determine the role of roflumilast and aerosolized budesonide
in benzo(a)pyrene-induced lung cancer in mice and to elucidate the possible
P1.01-013 EMPHYSEMATOUS CHANGES AND PULMONARY
their mechanisms. Methods: Female A/J mice were given a single dose of
FUNCTION FOR ASBESTOS-RELATED LUNG CANCER IN JAPAN
benzo(a)pyrene. Intraperitoneal administration of roflumilast (1mg/kg, 5mg/
kg) began 2 weeks post-carcinogen treatment and continued tri-weekly for Takumi Kishimoto
28 weeks. Aerosolized budesonide was administered by aerosol delivery for 2 Asbestos Research Cnter, Okayama Rosai Hospital, Okayama/Japan
min/day and 5 days/week. Tumor load was determined by averaging the total
tumor volume in each group. Results: Benzo(a)pyrene induced an average Background: Smoking accelerates the incidence of asbestos-related lung
tumor size of 9.4 ± 1.8 tumors per mouse, with an average tumor load of 19.5 cancer. We evaluated emphysematous changes by chest CT and pulmonary
± 3.8mm3. Roflumilast treatment at 1 and 5 mg/kg did not inhibit tumor function for asbestos-related lung cancer in Japan. Methods: Two hundred
number, however, reduced tumor load, an average of 8.8 ± 2.0 mm3 at 5mg/ and twenty-two patients of asbestos-related lung cancer compensated by
kg treatment, significantly. Aerosolized budesonide administration did not Japanese compensation law were evaluated as age, gender, smoking index,
show reductions of tumor number or load. The decreased expressions of histology, survival, therapy and occupational history including first asbestos
cyclic AMP and protein kinase A caused by benzo(a)pyrene were increased exposed age, asbestos exposing terms and latency from the first asbestos
by roflumilast treatment. NF-κB expression in tumor tissues was lower in exposure to lung cancer. Radiographic evaluation was done by chest CT
the roflumilast group than the place group. Conclusion: In vivo experiments using Goddard classification of emphysema. Pulmonary function test was
in the benzo(a)pyrene-induced model of lung cancer show that roflumilast done by spirometry and flow-volume curve. Results: Ages range from 49
significant inhibits tumorigenicity via suppression of inflammation. Possible to 92 years with a median of 75 years. Male occupied 97.7%. Non-smoker
mechanisms between cAMP pathway and lung cancer development will is only 13 patients and other 209 are smokers with Brinkman Index ranges
needed to be determined. from 45 to 3000 of a median of 900. For histology of lung cancer, 60.4% are
adenocarcinoma and 22.4% of squamous cell carcinoma, 12.6 %of small cell
Keywords: Roflumilast, budesonide, lung cancer carcinoma and 1.8 of large cell carcinoma and 2.6 % of pleomorphic carcinoma
et al. Eighty seven patients were operated and other 87 patients performed
chemotherapy. Best supportive therapy is 34 patients. Median survival was
15.8 months. For asbestos histories, median first exposed age was 23 years,
asbestos exposing term was 32 years and the latency of lung cancer was 50

years. For Goddard score of emphysematous changes, 28% showed 0 point Microbiology and Immunology, and Surgery, Dalhousie University, Halifax/NS/
and 33% of 1~4 points and more than 21 points occupied only 4%, which Canada, 3Beatrice Hunter Cancer Research Institute, Halifax/NS/Canada
means very low percentages of emphysematous changes for these asbestos-
Background: Diets rich in polyphenols are well-known to reduce lung cancer
related lung cancer, nonetheless of high percentages of heavy smokers. For
risk among high-risk populations. We analyzed the efficacy of polyphenols-
pulmonary function test, FEV1.0% is 70.5%±11.3% and %FEV1.0 is 85.6±22.2%.
rich Haskap (Lonicera caerulea L.) fruit extracts in preventing tobacco specific
More than half patients are normal pulmonary function except more than
nitrosamine (TSNA)-induced DNA damage in BEAS-2B lung epithelial cells.
1,000 of Brinkman index or more than 15 points of Goddard score. From the
Methods: Monomeric polyphenols of Haskap fruits were extracted in ethanol
classification of GOLD criteria, 54.1% are normal, stage 1 is 20.7%, stage 2
and water, and profiled. TSNA, 4-(methylnitrosamino)-1-(3-pyridyl)-1-
is 22.5 % stage 3 is 1.8% and stage 4 is only 0.9%. Conclusion: Almost all of
butanone (NNK) and 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1-
asbestos-related lung cancer in Japan are heavy smoker, but 61% showed none
butanone (NNKOAc) were used (at sub-lethal concentrations) independently
or low grade of emphysematous changes by chest CT and only 2.7% had severe
to induce the carcinogenesis process in BEAS-2B cells. Cell viability assay was
pulmonary dysfunction.
confirmed that the tested concentrations of Haskap extracts were not
Keywords: Asbestos, smoking, emphysema lung cancer cytotoxic to BEAS-2B cells. Results: The Haskap extracts contain diversity of
polyphenols including phenolic acids and flavonoids, however, cyanidin-3-O-
glucoside was the most predominant. Pre-treatment of cells with the Haskap
extracts could significantly reduce the NNK- and NNKOAc-induced DNA
double strand breaks, DNA fragmentation and intracellular reactive oxygen
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ species, compared to non-treated cells. Immunocytochemistry for H2AX-
PREVENTION
TOBACCO, RADON, AIR POLLUTION, OTHER RISK FACTORS – phosphorylation (Serine 139, red) A. NNKOAc 100 µM, 3 h; B. Haskap ethanol
MONDAY, DECEMBER 5, 2016 extract (50 µg/mL, 3 h)+NNKOAc (100 µM, 3 h). DNA counter-staining was
performed with 4,6-diamino-2-phenylindole (blue).
P1.01-014 THE ROLE OF HEREDITARY FACTOR, PROFESSION

AND THE HABIT OF CIGARETTE SMOKING IN DEVELOPING LUNG
CANCER
Irina Pavlovska1, Nikola Orovcanec2, Biljana Tausanova2, Beti Zafirova2
1
Department of Epidemiology, Institute of Epidemiology and Biostatistics,
Skopje/Macedonia, 2Department of Epidemiology, Institute of Epidemiology and
Biostatistics, Medical Faculty, Skopje/Macedonia
Background: Lung cancer (LC) is the most common and deadliest cancer
in the world. In the Republic of Macedonia, within the period 2002-2012,
the LC took the first place according to the frequency of appearing in men,
while it was on the fourth place in women. The number of the risk factors is
great being connected with the occurrence of LC. The aim of this study was
to analyze the role of genetic factor, professional exposure and the habit of
cigarette smoking in occurrence of lung cancer. Methods: The research was
conducted as a case-control study. It included 185 patients diseased of LC
(investigated group-IG) and the same number of persons without malignant
disease (control group-CG). In the study were included only interviewees
with pathohistologically confirmed LC. Through calculating the risks of the
Odds ratio (OR), the risk-factors, which had a role in occurrence of the disease,
were quantified, while with the Confidence intervals (CI), the statistical
significance for the error level less 0,05 (p) was defiend. Results: According Conclusion: The polyphenols-rich Haskap extracts could prevent TSNA-
to the investigation results, malignant disease of two members in one family induced DNA damage in lung epithelial cells in vitro. Protective effects of
was found in 13,5% of the IG, 9,4% of the CG, respectively. Current smokers Haskap polyphenols against DNA damage are being investigated in vivo using
(CS) with present hereditary factor had almost 4 times (OR=3,95; 95%CI, 1,78- A/J mice.
8,77), greater risk to become ill compared to the never smokers (NS) without
hereditary factor. The risk was greater when the same would be compared Keywords: DNA damage, Haskap, Nitrosamine, BEAS-2B cells
to the NS with present hereditary factor (OR=8,76; 95%CI, 1,80-42,68).In
the diseased, the professional exposition was present in 68,6% from IG,
versus 67% in the CG. The highest risk for LC was found in transport workers
(OR=2,50;95%CI, 1,01-6,15) and automehanics (OR=2,31;95%CI, 0,76-7,07).
CS represented 67% of diseased individuals versus 40,5% of the CG. The POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
risk for them to develop LC was 5,54 (95%CI, 3,0-10,23), times significantly PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
greater compared to the NS. The risk for the disease was significantly MONDAY, DECEMBER 5, 2016
greater in individuals who were smoking >20years (y), >20cigarettes/day (c/
day), compared to those, who, in the same time period, smoked <20c/day
P1.01-016 AN INTERNATIONAL EPIDEMIOLOGICAL ANALYSIS OF
(OR=3,78;95%CI, 2,04-7,01). The risk to develop LC in former smokers (FS), who
>20y smoked >20c/day was 2,40 (95%CI, 0,94-6,14), times greater compared
YOUNG PATIENTS DIAGNOSED WITH NSCLC (ADUJOV - CLICAP)
to those, who smoked >20y, <20c/day. Conclusion: This disease developed Luis Corrales-Rodriguez 1, Oscar Arrieta2, Luis Mas3, Omar Castillo-
twice more commonly in the examined individuals, exposed to professional Fernandez4, Normand Blais5, Claudio Martin6, Ludwing Bacon7, Allan
carcinogens. The LC is multifactor disease for which development, besides Ramos-Esquivel8, Mauricio Cuello9, Leonardo Rojas10, Melissa Juárez1, Andrés
smoking, as a main determinant, in mutual interaction are the genetic and Cardona11
1
other factors of the surrounding and the way of living. Medical Oncology, Cimca / Hospital San Juan de Dios, San José/Costa Rica,
2
Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto
Keywords: lung cancer, hereditary factor, cigarette smoking, occupation Nacional de Cancerologia, Mexico City/Mexico, 3Medical Oncology, Instituto
Nacional de Enfermedades Neoplasicas, Lima/Peru, 4 Medical Oncology, Instituto
Oncologico Nacional, Panama City/Panama, 5Hematology and Medical Oncology,
Hôpital Notre Dame - CHUM, Montreal/QC/Canada, 6Department of Clinical
Oncology, Instituto Alexander Fleming, Buenos Aires/Argentina, 7Oncology
Department, Hospital Roberto Calderón, Managua, Nicaragua, Managua/
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO Nicaragua, 8 Medical Oncology, Hospital San Juan de Dios, San José/Costa Rica,
9
CONTROL AND CESSATION/PREVENTION Medical Oncology Department, Udelar, Montevideo/Uruguay, 10 Centro Javeriano
de Oncología, Hospital Universitario San Ignacio, Bogotá/Colombia, 11Medical
Protective Factors, Risk Reduction, Smoking Cessation – Oncology, Clinical and Traslational Oncology Group, Institute of Oncology, Clínica
MONDAY, DECEMBER 5, 2016 Del Country, Bogota/Colombia
Background: Eventhough lung cancer remains a disease of a median age at

diagnosis of 70y, a proportion of patients are diagnosed at 40y or younger.
P1.01-015 POLYPHENOLS-RICH FRUIT EXTRACTS PREVENT
Patients diagnosed before the age of 40 tend to be never-smokers, are
TOBACCO SPECIFIC NITROSAMINE-INDUCED DNA DAMAGE IN stage IV adenocarcinoma, and tend to have an EGFR activating mutation
LUNG EPITHELIAL CELLS or a EML4-alk translocation. It is crucial to determine the epidemiological
D.I.M. Amararathna1, D.W. Hoskin2, M. Johnston3, H.P.V. Rupasinghe1 characteristics of patients younger than 40y. Our study groups the largest
1
Environmental Sciences, Dalhousie University, Truro/NS/Canada, 2Pathology, population of patients less than 40y diagnosed with NSCLC. Methods: In this
epidemiological retrospective study, 249 patients (Argentina=6, Canada=19, population among 30-40 years old peoples; 3.4 fold higher in 40-50 yo and 1.4
Colombia=29, Costa Rica=9, Mexico=89, Nicaragua=2, Panama=19, and fold higher in 50-60 and 60+ yo categories. Conclusion: There is a dramatic
Peru=76) with a histologically confirmed NSCLC aged 40 years or less at shift of lung cancer toward young peoples in prisons. However, presentation,
diagnosis were included. Data included age, gender, histology, stage, EGFR management and prognosis are similar in prisoners compared to controls. These
and alk mutation analysis, and date of death or last follow-up. Progression finding should justify a specific screening policy in that high-risk population.
free survival (PFS) and overall survival (OS) were also recorded. Results:
NSCLC patients aged 40 years or less accounted around a 4% of the total Keywords: lung cancer, epidemiology, prison, case control study
NSCLC population. Median age was 34.5 years (range 14-40), 137 (55%) were
women, and 192 patients (77.1%) were non-smokers. Adenocarcinoma was the
most frequent histological subtype with 203 patients (81.6%) and 24 patients
(9.6%) were squamous. 214 patients (85.9%) were stage IV and 23 patients
(9.2%) were stage III at diagnosis. The site(s) of metastasis was obtained in PREVENTION
203/214 stage IV patients where 39.9% (n=81) had lung, 35.6% (n=72) had PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
SNC, and 31.7% (n=64) had bone metastasis. EGFR mutation (EGFRm) analysis
was determined in 103 patients with 40 patients (38.8%) having an EGFRm.
EML4-alk analysis was determined in 165 patients with 11 patients having P1.01-018 TOBACCO USE AND PERCEPTIONS ABOUT CESSATION
a positive translocation (6.7%). The OS for all patients was 14.4 months TRAINING AMONG HEALTH PROFESSIONS STUDENTS: ESTIMATES
(95%CI=11.2-17.6), PFS was 5.7 months (95%CI=4.9-6.5), and there was no
BY COUNTRIES AND WHO REGIONS
significant difference according to histological subtype. OS for EGFRm(+) was
42 months (95%CI=30.8-54.0) and for EGFRm(-) was 19.4 months (95%CI=14.8- Chandrashekhar Sreeramareddy 1, N Ramakrishnareddy2, Mahbubur
24.0) (p=0.002); PFS for EGFRm(+) was 11.9 months (95%CI=6.3-17.5) and for Rahman3
1
EGFRm (-) was 7.1 months (95%CI=5.3-8.9) (p=0.005). OS for alk(+) was 28.0 Family Medicine and Population Health, International Medical University, Kuala
months (95%CI=15.4-40.6) and for alk(-) was 10.6 months (95%CI=6.9-14.3) Lumpur/Malaysia, 2Community Medicine, Bangalore Medical College and Research
Institute, Bangalore/India, 3Institute of Epidemiology, Disease Control & Research
(p=0.065). Conclusion: NSCLC patients aged 40 years or less constitute a small
(Iedcr), Dhaka/Bangladesh
but important proportion of patients with this diagnosis. Other risk factors
may be involved in the pathogenesis of the disease in this population due to Background: Health professionals play an important role in cessation
a low smoking history found. SNC metastasis at diagnosis seems to be more and prevention of tobacco use by providing a brief counseling or even a
frequent in this population. EGFR mutation and EML4-alk translocation simple advise to their patients. Smoking habit among health professionals
frequency is higher than the frequency reported in the general population. themselves may deter them from providing cessation advice and counseling to
their patients. Using GHPSS data, we aim to provide updated global, regional,
Keywords: NSCLC, 40 years or less, EGFR, young
country-level estimates on prevalence tobacco use among medicine, dentistry,
nursing and pharmacy students and describe their attitudes towards tobacco
cessation training. Methods: The Global Health Professions Student Survey
collects data on cigarette smoking and use of other tobacco products,
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ training received to provide patient counselling on cessation techniques
PREVENTION etc. We analysed country-wise aggregate data on current cigarette smoking’
PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
(smoking cigarettes ≥1 days during the past 30 days), and ‘current use of
tobacco products other than cigarettes’ (chewing tobacco, snuff, bidis, cigars,
or pipes ≥1 days during the past 30 days), indicators on ‘health professionals’
P1.01-017 THE DRAMATIC SHIFT OF LUNG CANCER TOWARD YOUNG role’ and ‘cessation training’. We calculated aggregate rates for each World
IN PRISONS Health Organization regions using ‘metaprop’ command in Stata-11. Results:
Luc Renault 1, Eric Pradat2, Emmanuel Perrot1, Christophe Bartoli3, Laurent In 236 surveys from 2005 to 2011 from 70 (medical), 56 (dental), 56 (nursing)
Greillier4, Anne Remacle-Bonnet5, Norbert Telmon6, Laurent Molinier 7, Julien and 54 (pharmacy) countries 107,527 students (68,809, girls and 37,886 boys)
Mazières8, Sébastien Couraud9 were surveyed. Overall, in all courses smoking was highest in Europe (20%,
1 medical to 40%, dental students) followed by the Americas (13%, pharmacy
Unité Hospitalière Sécurisée Interrégionale, Hospices Civils de Lyon, Hôpital Lyon
Sud, Pierre Bénite/France, 2Département D’Information Médicale, Hospices Civils
to 23%, dental students). Other tobacco use rates were higher in the eastern
de Lyon, Hôpital Lyon Sud, Pierre Bénite/France, 3Unité Hospitalière Sécurisée Mediterranean (10-23%) and Europe (7-13%) countries. Tobaccco use among
Interrégionale, Service de Médecine En Milieu Pénitentiaire, Hôpital Nord, female students was lowest in Asian and African countries. In countries
Assistance Publique - Hôpitaux de Marseille, Marseille/France, 4Service Oncologie survyed ≥70% of students agreed that medical professionals are role models
Multidisciplinaire Et Innovations Thérapeutiques, Hôpital Nord, Assistance and have a role in advicing and information about smoking cessation to their
Publique - Hôpitaux de Marseille, Marseille/France, 5Service D’Information patients and public. In the countries surveyed in all the regions, only about
Médicale, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Marseille/ 9.2-36.9% of students (except 80% among dental students in the eastern
France, 6Service de Médecine Légale Et Pénitentiaire, Hôpital Rangueil, CHU
Mediterranean) reorted that they have received formal training on smoking
Toulouse, Toulouse/France, 7Département D’Information Médicale, Hôtel-Dieu
Saint-Jacques, CHU Toulouse, Toulouse/France, 8Service de Pneumologie, Hôpital
cessation approaches. and ≥80% of all students agreed they should receive a
Larrey, CHU Toulouse, Toulouse/France, 9Service de Pneumologie Et Cancérologie formal cessation training. Conclusion: Health professions students ready to
Thoracique, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre Bénite/France receive cessation training. Tobacco control experts should work with medical
educators to discourage tobacco use among health professional students
Background: Although prisoners could be at higher risk for lung cancers, very and implement integrated smoking cessation training into their medical
few studies focused on that particular population. In a previous cohort study curricula. Implications: Our results provide a global snapshot and regional
(Carbonnaux et al. Oncology 2013;85:370–377), we found an early onset of estimates of tobacco use among health professions students and cessation
lung cancer in imprisoned patients. The aim of the CARCAN study was to training. Results highlight the need for cessation advice/assistance to health
assess epidemiological characteristics, management, prognosis and incidence professions students currently using tobacco and the need for introducing
of lung cancer among prisoners compared to general population. Methods: cessation training particularly in developing Afro-Asian countries.
We designed a multi-centric observational case-control study. Cases were
lung cancer diagnosed in prison in 3 penitentiary medical units (PMU) of Keywords: Tobacco Use; Smoking Cessation; Health Professions Education;
France from 2005 to 2013 (Lyon / Marseille / Toulouse). Up to 3 controls were Epidemiology; Surveys
selected for each case from hospital databases. Controls were randomly
matched to cases for center, sex, and year of diagnosis. Overall and age-specific
cumulated incidences were calculated in the penitentiary area covered by the
3 participating PMU and in the French population using national statistics.
Results: Overall, 170 controls and 72 cases met the inclusion criteria and were PREVENTION
analyzed. Cases were mainly men (99%). Mean age at diagnosis was 52.9 (±11.0) PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
in prisoners and 64.3 (±10.1) in controls patients (P<10-4). Most of prisoners MONDAY, DECEMBER 5, 2016
were current smokers compared to controls (83% vs 53%; P<10-4). We did not
find significant difference in histologic type or TNM stage at diagnosis between P1.01-019 INTEGRATION OF TOBACCO CESSATION COUNSELING IN A
the two groups. Also, there was no significant difference in first-line treatment
LUNG SCREENING PROGRAM
type in both groups; especially there was no difference in the rate of patient
undergoing supportive care only. Median time from first symptoms to first Patricia Franklin1, Anna Gladfelter2, Mary Meek 3, Matthew Steliga4
1
treatment was 3.3 months [2.7-3.9] in controls compared to 3.6 months [2.7-4.4] Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical
in prisoners (P=0.947). We found no significant difference in progression free Sciences, Little Rock/United States of America, 2College of Medicine, University
of Arkansas for Medical Sciences, Little Rock/AR/United States of America,
and overall survival between the two groups. Cumulated incidence (2008-2013) 3
Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock/
in men was dramatically increased in prisons in each age category compared to AR/United States of America, 4Winthrop P. Rockefeller Cancer Institute, University
the French incidence. Incidence was 4.5 fold higher in prisons than in the general of Arkansas for Medical Sciences, Little Rock/AR/United States of America

Background: In the lung screening population, the prevalence of lung cancer Keywords: Catechin hydrate, aldehyde dehydrogenase 1, carcinoembryonic
is typically a small percentage (2.3% (10/440) in our institution’s program). antigen, chemoprevention
A much more common, treatable, and potentially overlooked condition in
the lung screened patient population is nicotine addiction. The National
Lung Screening Trial contained 49% current smokers. A review of our lung
cancer screening program showed 70.2% (309/440) of patients were active
smokers at the time of lung screening. Methods: Our lung screening program is POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
designed so that all scheduling would be done by a coordinator who is a Nurse PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
Practitioner and a Certified Tobacco Treatment Specialist. A telephone call to MONDAY, DECEMBER 5, 2016
schedule the scan was done by the coordinator and basic tobacco cessation
intervention was integrated into every call. Futher follow up as face-to-face
P1.01-021 THE IMPACT OF SMOKING STATUS ON OVERALL
counseling was offered. We reviewed institutional data to determine what
proportion of active smokers would agree to individualized counseling when
SURVIVAL IN A POPULATION-BASED NON-SMALL CELL LUNG
it would be conveniently offered at the point of the scan, by the person CANCER (NSCLC) SURGICAL RESECTION COHORT
coordinating the program. Results: Over a consecutive 26 month period, 440 Nicholas Faris 1, Yu-Sheng Lee2, Meghan Meadows2, Matthew Smeltzer2,
patients underwent lung screening. The majority of patients (70.2%, 309/440) Meredith Ray2, Kenneth Ward2, Carrie Fehnel1, Cheryl Houston-Harris3,
were actively smoking. Telephone intervention reached 100% (309/309). Raymond Osarogiagbon3
The telephone intervention consisted of an Ask, Advise, Refer strategy 1
Thoracic Oncology Research Group, Multidisciplinary Thoracic Oncology Program,
which offered further resources including: a quitline referral, a weekly group Baptist Cancer Center, Memphis/TN/United States of America, 2 School of Public
counseling session referral, and an indepth personal counseling session which Health, University of Memphis, Memphis/TN/United States of America, 3Thoracic
would be provided at the time and place of the screening scan. The same Oncology Research Group, Multidisciplinary Thoracic Oncology Program, Baptist
Cancer Center, Memphis/United States of America
tobacco treatment specialist who provided telephone intervention, met
face-to-face with 80.6% (249/309) of active smokers for in depth counseling Background: Surgical resection is the optimal treatment modality for NSCLC,
and development of a cessation plan. Conclusion: Our lung screening while smoking has been shown to have a negative survival impact. We
program detected lung cancer in a minority of participants (2.3%, 10/440) evaluated smoking’s impact on overall survival within a population-based
but encountered nicotine addiction in the majority of participants (70.2%, cohort of patients with surgically-resected NSCLC. Methods: We examined all
309/440). Positioning Certified Tobacco Treatment Specialists as coordinators patients who had a curative-intent NSCLC resection from 2009-2016 in 4
of lung screening programs ensure that all participants receive at minimum contiguous Dartmouth Hospital Referral Regions of the US. We compared
a telephone intervention. The initial telephone intervention coinciding with patient and clinical characteristics among never, former (stopped >1 year
scheduling the screening scan allowed a relationship to develop between prior), and active smokers using the Chi-square and ANOVA tests. Survival
the patient and the coordinator (who is tobacco cessation specialist). Most analyses were conducted with the Kaplan-Meier method and Cox Proportional
participants who were smoking (80.6%, 249/309) agreed to in depth counseling Hazards models. Results: Of 2,202 patients, 206 (9%) were never, 846 (38%)
which was conveniently provided at the point of service with the screening were former, and 1,150 (52%) were active smokers. Significant demographic
scan. Without integration of the resources, few patients would have sought and clinical differences between cohorts included age, sex, race, insurance,
out cessation counseling. As lung screening will recur annually, this will provide comorbidities, pulmonary function, method of detection, ASA status, extent,
longitudinal support. Further data about acceptance of counseling and data primary site and length of resection, histology, and histologic grade (all
about long term cessation in a lung screening program will be gathered. p<0.05). Short-term post-operative mortality (at 30-, 60-, 90-, 120-days) rates
Keywords: Screening, tobacco, nursing for never smokers were 1%, 2%, 4%, 4%; for active smokers, 4%, 6%, 7% and
8%; and for former smokers, 5%, 7%, 9%, and 11%; and differed significantly
by smoking status (p=0.0539, p=0.0316, p=0.0187, p=0.0017). At 5 years,
overall survival was 69% for never smokers, 55% for active, and 49% for
former smokers (p=0.0002) (Figure 1). Controlling for age, sex, race, insurance,
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ histologic grade, extent of resection, and length of surgery, and compared
PREVENTION with never smokers, active smokers had 1.3 times (p=0.05) the hazard of death
MONDAY, DECEMBER 5, 2016 and former smokers had 1.4 times the hazard of death (p=0.04).
P1.01-020 CHEMOPREVENTIVE EFFECT OF CATECHIN HYDRATES

AGAINST BENZO(A)PYRENE INDUCED LUNG CARCINOGENESIS IN
MICE: PLAUSIBLE ROLE OF ALDH1
Ayaz Shahid, Sarwat Sultana
Medical Elementology and Toxicology, Jamia Hamdard University, New Delhi/India
Background: Lung cancer is a devastating disease with a poor prognosis.

Chemoprevention has came out as a very promising protective strategy
against cancer and numerous natural compounds in diet have shown their
curative potential on lung cancer. Catechin is mainly found in green tea and
possess anti-oxidative, anti-inflammatory and antiproliferative activity.
The present study was designed to investigate the mechanism-based
chemopreventive nature of catechin hydrate (CH) against B(a)P induced
lung carcinogenesis in Swiss albino mice and possible role of aldehyde
dehydrogenase 1 (ALDH1). Methods: B(a)P was administered orally (50 mg/
kg body weight) twice a week for four successive weeks to induce lung cancer
in mice. CH was supplemented to mice at doses of 20 and 40mg/kg b. wt. The
body weight, lung weight, lactate dehydrogenase (LDH), lipid peroxidation
(LPO), xanthine oxidase (XO), carcinoembryonic antigen (CEA), antioxidants
armory activities (SOD, CAT, QR, GPx, GR, GST and GSH) were estimated.
Further, histopathological analysis of lung tissue and Immunohistopathology Conclusion: In this population-based cohort, smoking is negatively associated
analysis of ALDH1, VEGF, PCNA, NF-kB, COX-2, caspase-3 and Bcl-2 were also with post-operative mortality and long-term overall patient survival;
carried out Results: Administration of B(a)P resulted in increased XO, LPO, although active smokers had better survival outcomes than former smokers.
LDH, and CEA with subsequent decrease in activities of tissue anti-oxidant
Keywords: non-small cell lung cancer, Surgical resection, survival, tobacco
armory. It also resulted in up-regulation of VEGF, PCNA, NF-kB, COX-2,
control and cessation
caspase-3 and down regulating Bcl-2. ALDH1 expression was also increased
in B(a)P-induced lung cancer group. Pre-treatment with CH at a dose of
20 and 40 mg/kg b. wt. significantly decreased in XO, LDH, LPO, CEA and
increased anti-oxidant armory. Moreover, assessment of protein expression
revealed that CH pre-treatment effectively regulated hyperproliferation, POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
inflammation and apoptosis in lung of mice. Immunohistochemical analysis PREVENTION
also revealed that CH pre-treatment showed significantly reduced in ALDH1 PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
expression. Further, the antiproliferative effect of CH was confirmed by
histopathological analysis. Conclusion: Overall, Our findings suggest that
catechin hydrate inhibits B(a)P-induced lung tumor formation by modulating P1.01-022 SMOKING CESSATION RELATED TO LUNG RESECTION
hyperproliferation, inflammation, apoptosis and ALDH1 expression. Bruno Sarana1, Indrek Benno1, Piret Kibur 1, Ragnar Toomas Kibur2, Triin Kütt2,
Mait Raag 3, Tanel Laisaar 1 POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
1
PREVENTION
Thoracic Surgery Department, Tartu University, Tartu/Estonia, 2Tartu University, PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION –
Tartu/Estonia, 3Public Health, Tartu University, Tartu/Estonia MONDAY, DECEMBER 5, 2016
Background: Smoking cessation interventions are often ineffective,

although negative health effects of smoking are well established. However, P1.01-024 UNIVERSITY STUDENTS’ PERCEPTIONS ABOUT
evidence suggests that diagnosis of a severe medical condition or a surgical EFFECTIVENESS OF MPOWER POLICIES ON TOBACCO CONTROL IN
intervention may force people to quit smoking without any counseling. Aim PANAMA CITY PANAMA
of this study was to determine the smoking cessation rate among patients Omar Castillo-Fernandez 1, Maria Lim1, Yamileth Pereira2, Doris Bellido1, Olivia
undergoing lung resection and factors associated with perioperative smoking El Achtar2, Lilian Montano1, Roberto Lopez1
cessation. Methods: All lung resection patients in one thoracic surgery 1
Medical Oncology, Instituto Oncologico Nacional, Panama City/Panama, 2 Surgical
department in 6 years were included. A phone-interview was conducted with Oncology, Instituto Oncologico Nacional, Panama City/Panama
all (accessible) patients aged > 16. Wilcoxon rank-sum test, and chi-squared
or Fisher exact test were used for statistical analysis. Results: In 6 years 970 Background: Tobacco use is a leading preventable cause of disease, disability
patients were operated on; 406 (229 male, 177 female; mean age 56.4 [range 16 and death worldwide. To expand the fight against the tobacco epidemic,
to 85] years) were available for the study. At the time of surgery 155 patients WHO has introduced the MPOWER package of six proven policies:1.- Monitor
(38.2%) were non-smokers, 82 (20.2%) ex-smokers, and 169 (41.6%) current tobacco use and prevention policies, 2.- Protect people from tobacco smoke,
smokers. 56.3% of males and 22.6% of females were smokers (p<0.0001). 145 3.- Offer help to quit tobacco use 4.-Warn about the dangers of tobacco
patients had lung cancer and 261 patients other causes for lung resection, 5.-Enforce bans on tobacco advertising, promotion and sponsorship, and
with different smoking distribution in these 2 groups (p<0.0001). Sixty nine 5.-Raise taxes on tobacco. The aim of this study was to evaluate the student´s
patients (40.8%) quit smoking before the operation: 22 due to the planned perception about the effectiveness of each intervention. Methods: Students
operation, 23 due to the newly diagnosed disease, and 24 for other reasons. from public and private universities in Panama city were surveyed. Students
Seventy two patients (42.6%) did not smoke after hospital discharge including were asked to evaluate each policy in a binary answer (less effective or very
66 (39.1%) also a year later. An additional 40 (23.7%) patients had tried to effective). Chi squared test was used to compare answers between smokers
stop, and 57 (33.7%) continued smoking. The quit rate was higher among lung and never smokers Results: 302 students answered the questionnaire: 157
cancer patients versus others (uncorrected p=0.007), and patients operated females (52%) and 145 males (48%). Median age was 21 years. There were
through thoracotomy versus VATS (uncorrected p=0.0295); and was not 73 smokers (24.2%) and 229 never smokers (75.8%). Median age of start
influenced by age, gender or duration of smoking before quitting. Conclusion: smoking was 16 years (10-25), median of cigarettes per week was 6 (1-48).
Almost 40% of patients undergoing lung resection stopped smoking without There were not discrepancies in effectiveness between the two groups in
special counseling, with very few restarting. Smoking cessation rate was monitoring tobacco use policies (p=0.31). 56% of never smokers and 28% of
higher among patients with lung cancer and patients operated through smokers considered that protect people from tobacco smoke is very effective
thoracotomy. (p<0.001). Offer help to quite tobacco is considered very effective in 31% of
smokers versus 52% of never smokers (p=0.003). To require effective package
Keywords: Smoking Cessation, Thoracic Surgery warning labels is very effective in 24.6% of smokers and 48% of never smokers
(p<0.0001). Implement counter-tobacco advertising is equally effective for
half of both groups (p=0.06). To obtain free media coverage of anti-tobacco
activities is very effective in 53% of never smokers and 32% of smokers (p=
0.002). To enforce bans on tobacco advertising promotion and sponsorship is
PREVENTION very effective in 46% of never smokers and 52% of smokers (p=0.34). Increase
PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION – tax rates for tobacco products and ensure that they are adjusted periodically
to keep pace with inflation and rise faster than consumer purchasing power
is very effective for 46% of smokers and 57% of never smokers (p=0.09).
P1.01-023 SMOKING CESSATION BEFORE INITIATION OF Strengthen tax administration to reduce the illicit trade in tobacco products
CHEMOTHERAPY IN METASTATIC NON-SMALL LUNG CANCER: did not show difference in effectiveness of both groups (p=0.15). Conclusion:
INFLUENCE ON PROGNOSIS MPOWER policies are useful to prevent smoking. The perception of the
effectiveness of each intervention varies according tobacco use.
Ana Linhas, Sérgio Campainha, Sara Conde, Ana Barroso
Centro Hospitalar Vila Nova de Gaia/espinho, Vila Nova de Gaia/Portugal Keywords: tobacco, policy, student
Background: The association between cigarette smoking and lung cancer

mortality is well known. Some studies have shown a decreased overall survival
(OS) in early stage non-small cell carcinoma (NSCLC) patients that continue
to smoke after diagnosis. It is documented that in patients with metastatic POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
disease, continued smoking increases resistance to systemic therapies but PREVENTION
the impact of smoking cessation during treatment on outcomes for these MONDAY, DECEMBER 5, 2016
patients is not well defined. Objective: To evaluate the impact of smoking
cessation, before initiation of chemotherapy (CT), on survival in advanced
NSCLC. Methods: Patients referred to our centre, between January 2010 and P1.01-025 MASS MEDIA AND TOBACCO IN BANGLADESH: AN
June 2016, and diagnosed with metastatic NSCLC were analysed. Patients INVESTIGATION ON THE ROLE OF MASS MEDIA IN THE LIGHT OF
defined as smokers at diagnosis and treated with at least one cycle of TOBACCO CONTROL
chemotherapy were included. Clinical characteristics and survival outcome Tahsina Sadeque 1, Kapil Ahmed2
were reviewed and compared between patients who quit smoke before and 1
News & Current Affairs, Somoy Television, Dhaka/Bangladesh, 2Research and
after the initiation of chemotherapy. Results: A total of 113 patients were Evaluation, Bangladesh Centre for Communications Programs (Bccp), Mirpur/
included [mean age 59±10 years; 89.4% (n=101)]. The histological type more Bangladesh
predominant was adenocarcinoma (70.8%) and the most common sites of
metastasis were lung, bone and brain (35.4%, 23.9% and 23%, respectively). Background: The tobacco epidemic is one of the biggest public health threats
The majority of patients had performance status 1 and no weight loss at the world has ever faced.Tobacco used is a widespread phenomenon in
time of diagnosis (53.1% and 58.4%, respectively) and the comorbidity most Bangladesh and that causes numerous deaths and disabilities in a year. The
prevalent was hypertension (19.5%). The average number of cigarettes studues conducted elsewhere have strengthened the evidence that mass
smoked was 51±23pack-years and 81.4% of patients smoked >30pack-years. media campaigns conducted in the context of comprehensive tobacco control
The most used CT regimen was platinum combined with pemetrexed (63.7%). programs can promote quitting and reduce smoking as well as smokeless
Patients who quit smoking before CT showed a better median OS although tobacco prevalence.Awareness building campaigns in mass media against
not statistical significant (8 vs. 7 months; p=0.478). This was also seen in tobacco use should be prioritized more and this paper will be an initiative
heavy smokers ≥30 pack-years, with a median OS of 8 vs. 6.5 months (p=0.674). towards enhancing mass media’s role in controlling tobacco in Bangladesh.
The multivariate analysis only showed an influence of type of CT on survival. Methods: This is a qualitative study and both primary, as well as secondary
Conclusion: Although not significant differences in OS between groups were data were used where information gathered through the Key Informant
observed in our sample, the median survival was better in patients that Interviews (KIIs) and media contents. The employees of media houses (five
quit smoking before the initiation of CT, even in heavy smokers. Continued national papers, two online news portals and six TV channels) were selected as
smoking after CT initiation is known to adversely affect treatment response study respondent. Media Content Analysis is used through the broad range of
and quality of life and efforts to encourage smoking cessation even among ‘texts’ from transcripts of interviews and discussions along with the materials
this population of patients should be made. like reports, footages, advertisements, talk-shows, articles etc. Results: The
study result documented several opinions of discussants where Mass media
Keywords: advanced NSCLC, Smoking Cessation, chemotherapy, survival was found to play a strong role in support of the amended tobacco control
law and its implication that could be created public support against tobacco

farming, exposing to companies’ tactics and other tobacco control activities. Center, Petach Tiqwa/Israel
The study results also revealed that in controlling tobacco supply and demand
effectively, media has been assisting the government and anti-tobacco Background: Background: Screening for lung cancer is recommended among
activities productively. Majority of the Key Informants opined spontaneously heavy current or former smokers at age 55-80. Transitional Cell Carcinoma
on tobacco control program publicity, organizational interference, and of the Bladder (TCC) and lung cancer share same risk factors, however the
influence of other activities on media. They also emphasized role of media existence of TCC is not indicated as a reason for screening for lung cancer.
for activities of anti-tobacco organizations, awareness building actions, Patients with invasive TCC undergo full staging and therefore lung cancer is
popularization of tobacco control law and its amendment. Conclusion: The usually detected if it co-exists. However, in superficial TCC, lung evaluation is
study shows evidence that mass media coverage of tobacco control issues not routinely done and may be missed. Here, we have studied the incidence
is influencing the context of comprehensive tobacco control programs. To of lung cancer among low stage bladder cancer patients aiming to evaluate
reduce tobacco consumption, along with strict enforcement efforts, media if this can be defined as a population at risk. Methods: Methods: The SEER
should be used to assist with the implementation of the tobacco control law. (Statistics, Epidemiology and End Results) database was used to determine
A sustained nationwide campaign to educate the masses against the dangers the Incidence and standardized incidence ratio (SIR), and the average time to
of smoking and smokeless tobacco is needed and media can play an important discovery of lung cancer in Patients with localized TCC of the bladder (AJCC 6
role in creating further awareness about the dangers associated with tobacco stages T0 through T 1a2) in years 2000-2013, stratified by age and gender, and
consumption. compare them to the SIR for all solid tumors. Results: Results: based on 89691
patients (F:M ratio 1:3.3), the SIR for all solid tumors was 1.95[CI95%:1.87-2.04]
Keywords: Mass Media and Tobacco, Tobacco control in Bangladesh, Role of for women and 1.87[1.83-1.9] for men. The SIR for lung cancer in women was
Mass Media significantly higher, 2.40[2.19-2.62], with significance persisting among all
age groups >50y. The SIR for men was 1.81[1.73-1.9], not significantly different
from the risk for all solid tumors in any age group. The median latency period
until discovery of lung cancer was 5.41, 3.54, 2.74 and 0.08 years in women,
and 4.41, 3.59, 2.96 and 0.96 in men, for age groups 50-59, 60-69, 70-79 and
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ 80+, respectively. Conclusion: Conclusion: Incidence of lung cancer is higher in
PREVENTION
PROTECTIVE FACTORS, RISK REDUCTION, SMOKING CESSATION – localized TCC patients than among the general population, and among women
MONDAY, DECEMBER 5, 2016 it appears to be significantly higher than the general risk of solid tumors. Early
stage TCC patients may therefore stand to gain from lung cancer screening,
and should be considered as potential screening candidates.
P1.01-026 TOBACCO USE, AWARENESS AND CESSATION AMONG
MALAYALI TRIBES, YELAGIRI HILLS, TAMIL NADU, INDIA Keywords: TCC, lung cancer, Bladder, Women
Delfin Lovelina Francis
Public Health Dentistry, Tagore Dental College and Hospital, Chennai/India
Background: Health is a state of complete wellbeing free from any discomfort

and pain. Despite remarkable world-wide progress in the field of diagnostic, POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
curative and preventive medicine, still there are large populations of people LUNG CANCER SCREENING, DIAGNOSIS –
living in isolation in natural and unpolluted surroundings far away from MONDAY, DECEMBER 5, 2016
civilisation, maintaining their traditional values, customs, beliefs and
myths. India has the second largest tribal population of the world next to
P1.01-028 HIGH RISK OLDER SMOKERS’ PERCEPTIONS, ATTITUDES
the African countries. About half of the world’s autochthonous people live in
India, thus making India home to many tribes which have an interesting and
AND BELIEFS ABOUT LUNG CANCER SCREENING
varied history of origins, customs and social practices. The present study was Janine Cataldo
conducted to assess the tobacco use, awarness and its effect on health among Physiological Nursing, University of California, San Francisco, San Francisco/CA/
Malayali tribes, Yelagiri Hills, Tamil nadu, India. Methods: The inhabitants of United States of America
the 14 villages of the Yelagiri hills, who have completed 18years and residing
Background: The US Preventive Services Task Force recommends that
for more than 15years present on the day of examination and who were
smokers aged 55-80 should be screened annually with low dose computed
willing to participate in the study were included. Data was collected from a
tomography (LDCT). Successful implementation of lung cancer screening
cross-sectional survey, using a Survey Proforma, clinical examinationand a
depends on being able to reach high-risk individuals. This study identified
pre-tested questionnaire which included Demographic data, tobacco habits.
demographic, smoking history, health risk perceptions, knowledge, and
An intra-oral examination was carried out by a single examiner to assess
attitude factors of older smokers related to LDCT agreement. Using binary
the Oral Health Status using WHO Oral Health Surveys – Basic Methods
logistic regression we produced a predictive model of factors to explain
Proforma (1997).SPSS version15 was used for statistical analysis. Results:
LDCT agreement. Methods: As part of a larger Tobacco Attitudes and Beliefs
Results showed that among 660 study population, 381(57.7%) had no formal
Study, we conducted a cross-sectional, national, online survey of 549 older
education. Among the study population 75%) had the habit of alcohol
(≥ 45 years) current and former smokers. Univariate differences between
consumption. Of those who had the habit of smoking, 26% smoked beedi,
groups for agreement and non-agreement for LDCT was conducted. Using all
10.9% smoked cigarette, 65% chewed raw tobacco, 18% chewed Hans and
variables that demonstrated a significant association with LDCT agreement,
28% had a combination of smoking and smokeless tobacco usage. The reason
a binary logistic regression analysis was conducted to predict agreement to
for practicing these habits were as a measure to combat the cold, relieving
have an LDCT. Results: Almost 80% of the sample believed that a person who
stress and body pain after work, and the lack of awareness of the hazards of
continues to smoke after the age of 40 has at least a 25% chance of developing
the materials used. Prevalence of oral mucosal lesions in the study population
lung cancer and if asked, 79.4% would agree to a LDCT. Using Chi Square
was due to tobacco usage and alcohol consumption and lack of awareness
analyses, nine variables that were significant at the 0.10 level were selected
regarding the deleterious effects of the products used. Conclusion: From
for inclusion in model development. Four of the independent variables made a
the results of this study it may be concluded that the Malayali tribes were
unique statistically significant contribution to the model: Believes that early
characterized by a lack of awareness about oral health, deep rooted dental
detection of lung cancer will result in a good prognosis; Perceives accuracy of
beliefs, high prevalence of tobacco use and limited access to health services.
LDCT as an important factor in the decision to have a LDCT scan; Believes that
Keywords: Malayali tribes, Tobacco usage, oral health status, WHO oral health they are at high risk for lung cancer; and Believes that a negative LDCT result
proforma, Beliefs. would decrease worry without encouraging continued smoking. Conclusion:
Older smokers are aware of the risks of smoking, are interested in smoking
cessation, and most are interested in and positive about LDCT. Cognitive
aspects of participation in screening are key to increasing the uptake of lung
cancer screening and smoking cessation among high-risk smokers.
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO Keywords: LDCT, Attitudes and Beliefs, Smoking Cessation, older smokers
CONTROL AND CESSATION/PREVENTION
Lung Cancer Screening, Diagnosis –
PREVENTION
LUNG CANCER SCREENING, DIAGNOSIS –
P1.01-027 INCREASED RISK OF LUNG CANCER AMONG WOMEN MONDAY, DECEMBER 5, 2016
WITH SUPERFICIAL TCC: A POTENTIAL RISK COHORT FOR LUNG
CANCER SCREENING
P1.01-029 PERSONAL AND HOSPITAL FACTORS ASSOCIATED WITH
Yaakov Tolwin1, Eli Rosenbaum2, Nir Peled2
1 2 LIMITED SURGICAL RESECTION, IN-HOSPITAL MORTALITY AND
Sackler School of Medicine, Tel Aviv University, Tel Aviv/Israel, Davidoff Cancer
COMPLICATIONS IN NEW YORK STATE States of America, 8 Cardiothoracic Surgery, St. Bernard’s Regional Medical Center,
Wil Lieberman-Cribbin1, Bian Liu1, Emanuele Leoncini2, Raja Flores3, Jonesboro/AR/United States of America, 9North Mississippi Medical Center, Tupelo/
MS/United States of America
Emanuela Taioli4
1
Department of Population Health Science and Policy and Institute for Background: Incomplete resection of NSCLC has a negative impact on survival.
Translational Epidemiology, ICAHN School of Medicine at Mount Sinai, New York/ We evaluated risk factors associated with positive margins within a
NY/United States of America, 2 Section of Hygiene, Institute of Public Health,
comparative observational population-based cohort study. Methods: We
Università Cattolica Del Sacro Cuore, Milan/Italy, 3Thoracic Surgery, ICAHN School
analyzed curative-intent resections from 2009-2016 from 4 contiguous
of Medicine at Mount Sinai, New York/NY/United States of America, 4Department
of Population Health Science and Policy, ICAHN School of Medicine at Mount Sinai, Dartmouth Hospital Referral Regions in 3 US states. Statistical analyses were
New York/NY/United States of America preformed using univariate and multiple logistic regression models. Results:
Among the 2,275 NSCLC-resected patients, 52% were male, 78% white, 45%
Background: Lung cancer represents 13.4% of all newly diagnosed US cancers Medicare insured, and 36% privately insured, with a median age of 67 years.
and 27.1% of all cancer deaths. Early stage lung cancer is generally treated with Factors associated with a higher margin positivity rate included male sex,
surgical resection. Many patient- and hospital-level factors influence the large cell histology, undifferentiated tumor grade, neo-adjuvant therapy,
selection of appropriate surgical procedures and their outcome. We identified clinical stage IIIA and IIIB, bilobectomy extent of resection, patients with
patient- and hospital-level characteristics influencing the type of lung cancer abnormal diffusing capacity of the lungs for carbon monoxide (DLCO), use of
surgical approach utilized in New York State and assessed in-hospital bronchoscopic biopsy for diagnosis greater than 1 day before surgery, left lung
complications and mortality. Methods: Patients were selected from the resection, and tumor size >7cm (all p<0.15, Table 1). American Society of
Statewide Planning and Research Cooperative System, SPARCS (1995-2012) Anesthesiologists (ASA) score, prior lung cancer, smoking status, Charlson
based on ICD-9-CM codes of diagnosis (162 and 165) and procedures score, FEV1, PET/CT, brain scan, bone scan, mediastinoscopy, blood
(32.0-32.9). Surgery was categorized into: limited resection (LR: 32.2-32.3), transfusion, and hospital were not associated with positive margins in
lobectomy (L: 32.4), and pneumonectomy (P: 32.5-32.6). Statistical analyses univariate analyses (all p>0.15). Controlling for sex, histology, tumor grade,
were performed in SAS v9.4 and ArcMap v10.3.1. Results: There were 36,460 tumor size, neo-adjuvant therapy, clinical stage, extent of resection, DLCO,
patients (age 60-75 years); 56% underwent L, 37% LR, and 7% P. LR patients pre-operative bronchoscopic biopsy, and primary resection site in the multiple
were more likely to be older (ORadj 1.01, 95%CI [1.01-1.02]), female (ORadj 1.10 variable analysis, sex (p=0.0134), clinical stage (p<0.001), extent of
[1.06-1.15]), Black (ORadj 1.24 [1.15-1.34]), with comorbidities (ORadj 1.10 resection(p=0.0461), DLCO (p=0.0431), and bronchoscopic biopsy (p=0.0029)
[1.04-1.16]) than L patients. Opposite trends were observed among P patients, were independently associated with risk for positive margins (Table 1).
except for race. Over time, the odds of P decreased, while those of LR Conclusion: This detailed evaluation in a large regional cohort indicates
significantly increased (ORadj 1.22 [1.16-1.29] for years 2007-2012 vs 1995-2000). patient-level characteristics are associated with positive surgical resection
Teaching hospitals were less likely to perform LR over L (ORadj 0.82 [0.75- margins. Our recently published evaluation of the National Cancer Database
0.88]), while the opposite was true for hospitals with larger surgery volumes also identified institutional factors that impact the rates of positive margins.
(ORadj 1.07[1.03-1.11]). In-hospital complications were significantly less after LR Patient-level, surgeon-level, and institutional-level factors should be
than L (ORadj 0.66 [0.62-0.69]), while in-hospital mortality was similar (ORadj considered jointly to fully understand factors impacting margin positivity
0.93 [0.84-1.03]). In-hospital mortality was directly associated with age, rates.
length of stay, urgent/emergency admission, and inversely associated with
female gender, private insurance, and surgery volumes.
Conclusion: There is a growing trend towards LR, which is still more likely to be
performed in older patients with co-morbidities. In-hospital outcomes were
affected by patients’ clinical and personal characteristics, and were better
after LR than L or P.
Keywords: Limited Surgical Resection, In-hospital mortality, In-hospital

complications, Personal and Hospital characteristics

PREVENTION
P1.01-030 FACTORS ASSOCIATED WITH MARGIN POSITIVE

RESECTIONS FOR NON-SMALL CELL LUNG CANCER (NSCLC) IN THE
MID-SOUTH REGION OF THE US
Yu-Sheng Lee1, Matthew Smeltzer 2, Nicholas Faris3, Meredith Ray1, Carrie
Fehnel3, Cheryl Houston-Harris3, Meghan Meadows1, Paul Levy4, Chris
Mutrie5, Brad Wolf6, Lawrence Deese7, Lynn Wiggins8, Vishal Sachdev9, Sam
Signore5, Edward Robbins5, Raymond Osarogiagbon3
1
Epidemology and Biostatistics, University of Memphis School of Public Health,
Memphis/TN/United States of America, 2Epidemiology and Biostatistics, University
of Memphis School of Public Health, Memphis/TN/United States of America,
3
Thoracic Oncology Research Group, Multidisciplinary Thoracic Oncology Program,
Baptist Cancer Center, Memphis/TN/United States of America, 4 Cardiothoracic
Surgery, Nea Baptist, Jonesboro/AR/United States of America, 5Cardiothoracic
Surgery, Baptist Memorial Hospital, Memphis/TN/United States of America,
6
Cardiothoracic Surgery, Baptist Memorial Hospital, Desoto/MS/United States of Keywords: Surgical resection, Non-small cell, Postivive margins
America, 7Cardiothoracic Surgery, Baptist Memorial Hospital, Oxford/MS/United

POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ medical care due to acute unbearable symptoms and lifethreatening
PREVENTION
conditions, there are limited data on them at the emergency departments
MONDAY, DECEMBER 5, 2016 (ED). National Emergency Department Information System Database (NEDIS)
collects information about ED visits in Korean population. We aimed to
determine the frequency and main causes of emergency consultations and
P1.01-031 DOES MALIGNANT PLEUAL MESOTHELIOMA (MPM) the predicting factors for hospital admissions and deaths. Methods: In this
BEHAVIOUR DIFFER AMONG DECADES? retrospective observational study, we reviewed all the cases of ED visit for
Fatma Abou Elkasem1, Mohamed Rahoma2, Iman Abou El Khir3 six months, from July 2014 to December 2014, in three university hospitals:
1
Medical Oncology, National Cancer Insititute, Cairo/Egypt, 2 Surgical Oncology, Hanyang University Hospital and Chung-Ang University Hospital in Seoul,
National Cancer Insititute, Cairo/Egypt, 3Pathology, National Cancer Insititute, and Chungbuk National University Hospital in Cheongju. By reviewing all
Cairo/Egypt the medical records including NEDIS database, we identified cases with lung
cancer and performed descriptive statistics and logistic regressions analysis.
Background: MPM is extremely aggressive and has a long-latency period. Results: Of all 62,369 ED visits, there were 292 ED visit (0.5%) by 216 patients
Hence, detected at advanced stages resulting in an unfavorable prognosis with lung cancer. Among them, 76.4% had only one ED visit in study period.
(1-2years). However, MPM prognosis has been improving over the past few The main reasons for consultation were respiratory symptoms (36.8%) and
years with availability of better diagnostic and treatment regimens. We aim fatigue/alteration of the general state (12.7%), and pain (12.4%). ED visit leads
to compare clinico-pathologic characteristics of old-MPM cases referred to to hospital admission in 74.9% and hospital death in 25.1% of lung cancer
National Cancer Institute(NCI)-Cairo university between (2002-2003)and patients. In multivariate analysis, the main independent predictor factors
new MPM cases (2012-2015) Methods: Retrospective review of MPM cases of hospitalization are diagnostic phase of lung cancer (odd ratio 9.3) and
presented to NCI..Data regarding demographics, histology, symptoms and the transfer from another hospital (odd ratio 4.9). The palliative phase with
signs, tumor staging and CT-findings were obtained from all patients’ records. best supportive care alone (odd ratio 5.2) and abnormal heart rate at the
Pearson’s Chi(X2)and Fisher’s Exact t-tests were used for statistical analysis. time of ED visit (odd ratio 2.4) are statistically associated with death during
Results: 1) Old cohort (n=100): 100 patients were encountered. Median age hospitalization. Conclusion: Our study shows that ED visit is a frequent but
was 46 years. Males were 59% of cases. 30% has PS1. Asbestos exposure was clinically important event for patients with lung cancer. We might consider
documented in 74 cases. 44 cases were smokers, 25 cases were industrial- certain risk factors indicating hospitalization and death in lung cancer
workers. Family history was positive in 12 cases. Dyspnea was the presenting patients visiting ED to improve delivery of quality cancer care.
symptom in 92 cases, chest pain in 83% and tuberculous pleuritis in 2 cases,
effusion in all cases, pleural thickening in 80%, tracheal shift to the opposite- Keywords: Emergency Departments, Hospitalization, Death, lung cancer
side in 23%, T2 represented 41%. Epithelioid subtype 46.6%. Pathological
T2= 34%. 2) New cohort (n=194): 194 patients were encountered.Median age
was 53 years. Males and females were nearly equally distributed. Epithelioid
subtype was 63.4%. Rt-sided lesions were evident in nearly two-thirds of the
cases. Pleural thickening was nodular in 131 (69.7%) cases. Inter-lobar fissure POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
was thickened in 29.4%. Mediastinal Pleura was affected in 37.1%. Nearly, half LUNG CANCER SCREENING, DIAGNOSIS –
of our cases had effusion. Ossification & calcification were detected in 8 (4.1%) MONDAY, DECEMBER 5, 2016
cases. Contraction of hemithorax was identified in 77 (39.7%) cases. Chest
wall invasion (CWI) was present in 18 (9.3%) cases. Pulmonary nodules were
P1.01-033 EGFR MUTATION AND ALK: ARE PATIENTS BEING
detected in one-fifth of the cohort. Metastases were detected in 9 (4.6%)
cases (Figure). ADEQUATELY TESTED IN BRAZIL?
Gilberto Lopes 1, Maria Fernanda Simões1, Oddone Braghiroli1, Edna Prado2
1
Núcleo de Oncologia Da Bahia, Salvador/Brazil, 2Close-Up International, São
Paulo/Brazil
Background: Lung cancer is one of the most common malignancies in the

world. In Brazil, it is estimated that 28,200 new cases will be diagnosed in
2016. This cancer affects more men and is usually caused by tobacco exposure.
The most common histology is adenocarcinoma and many of these patients
have driver mutations which help guide therapeutic choice. The aim of this
study was to delineate the epidemiological profile of patients with NSCLC
in Brazil and to evaluate the prevalence of testing for ALK translocations
and EGFR mutations in patients in the public and private settings in Brazil.
Methods: Observational, descriptive, retrospective, multicenter study
involving 230 public and private institutions in Brazil. We obtained data from
a commercial database with 1642 Non Small Cell Lung Cancer (NSCLC) patients
treated in the country between January and December 2015. Variables
analyzed: age, sex, smoking, presence of EGFR and ALK mutation. Results:
Out of 1642 patients, 814 were treated in the public service (49.57%) and 828
in private services (50.42%). Most patients were men (58.28% vs. 41.71%
female). The mean age at diagnosis was 61.8 years (median 62 years), 32.58%
were former smokers, 31.12% current smokers, 19.48% never smoked and
Conclusion: By comparing both groups, we found that more lymph node data were not available for 16.8% of subjects. Most patients had metastatic
involvement(N+), less metastasis(M+),older median age,more females, more disease at diagnosis (65.04%), 23.20% had stage III, 9.31% stage II and 2.43%
epithelial subtype, less pleural effusion presentation, more pleural thickening stage I. 68.57% had adenocarcinoma, 27.52% squamous cell cancers, 1.4%
were detected in group 2(new cases) reflecting better staging ( large cell and 2.67% had other histological types. Among the 534 patients
mediastinoscopy& PET-CT),early detection, more incidence in females and with non-squamous histology treated in public settings, 244 patients were
better treatment modalities. tested for EGFR (46,69%) and only and only 36 were tested for ALK (6,74%).
In private services, of 656 patients with non-squamous subtypes, 454 were
Keywords: comparison, mesothelioma, clinicopathological, decades tested for EGFR (69,2%) and 77 for ALK (11,73%). Conclusion: Overall, testing
for EGFR mutations was below ideal, especially in the public setting. More
worryingly, and likely due to the lack of availability of crizotinib in Brazil until
2016, very few patients were tested for ALK translocations in 2015. Much work
needs to be done in education and advocacy to improve testing patterns in
PREVENTION the country.
MONDAY, DECEMBER 5, 2016 Keywords: PREVALENCE, lung cancer, EGFR, ALK
P1.01-032 EMERGENCY DEPARTMENT VISITS BY LUNG CANCER

PATIENTS IN KOREA
Dong Won Park, Gun Woo Koo, Tai Sun Park, Ji-Yong Moon, Sang-Heon Kim, POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
Tae-Hyung Kim, Dong Ho Shin, Ho Joo Yoon, Jang Won Sohn LUNG CANCER SCREENING, DIAGNOSIS –
Department of Internal Medicine, Hanyang University College of Medicine, Seoul/ MONDAY, DECEMBER 5, 2016
Korea, Republic of
Background: Although lung cancer patients frequently require emergency P1.01-034 ECOG SCALE OF PERFORMANCE STATUS IN LUNG
CANCER AT THE FIRST CONSULTATION AT A NATIONAL CANCER pts in SP and 697,709 pts in DN groups were included in the analysis, which
INSTITUTE IN A DEVELOPING COUNTRY IN LATIN AMERICA accounted for 22% and 74% of all NSCLC pts respectively. Pt characteristics
(SP/DN %): median age 72/68, male 53/53, white 89/84, stage IV 28/41,
Silvia Josefina Ayala Leon1, Cinthia Viviana Gauna Colás1, Miguel Antonio
treated at academic centers 33/32, government insured 72/57, mean tumor
Agüero Pino1, Miguel Ayala León2
1
size (cm) 3.5/4.4. An increasing trend in incidence of SP was observed (19.5%
Capiata, National Cancer Institute Prof.Manuel Riveros, Capiata/Paraguay,
2 in 2004 to 24% in 2012) vs. a decreasing trend in DN (75.6% in 2004 to 73%
Mexico DF, National Institute of Cardiology Ignacio Chavez, Mexico DF/Mexico
in 2012). About 12% in SP and 15% in DN received chemotherapy as part of
Background: This article reviews ECOG scale values at the first consultation their treatment. Surgery was performed in 39% of SP group vs. 28% in DN.
in our Institute, we review demographic and other related variables. ECOG Radiation was given to 43% of the pts in DN vs. 36% in SP. On UV and MV
at first consultation is related to treatment options. Methods: Between analysis, SP was associated with better survival than DN (HRs 0.84 and 0.93
January 2004 and December 2013, all patients diagnosed with a pathology of respectively; p<0.001). The SP group had higher 5-year OS (23% vs. 19.6%,
SCLC and NSCLC at National Institute of Oncology at Paraguay were analyzed p<0.001) and a higher median survival (17 vs. 11.5 months) compared to DN.
retrospectively. ECOG performance status, were recorded. SPSS 20 was used On stratifying by stage, DN had inferior survival in stage IV pts (HR 1.12,
to analyze. Results: We studied 478 subjects. At age mean 60,40 [95% CI 59,45 p<0.001) compared to SP but better survival in stage I and II pts (HRs 0.86
to 61,34] years and ECOG performance status mean 2,13 [95% CI 2,06 to 2,20] and 0.93, p<0.001). No difference in OS was seen in stage III pts (HR 1.01, p=
points. Frequency of ECOG was to 2: 48.1%, to 3:31.3%, to 1: 19 %, to 4:1.1%, to 0.4). Conclusion: The incidence of second primary has increased over the past
0: 0,6% of our population. Place of living predominant ECOG at Rural place: decade. Second primary NSCLC is diagnosed at an earlier stage, smaller tumor
ECOG 2: 50%, ECOG 3: 30.6%. At Urban places ECOG 2:44.9% and ECOG 3:32.4% size, and is associated with a better survival, compared to de novo NSCLC.
(P>0.05) ECOG and occupational relation was unemployed ECOG 2: 54.2%,
Keywords: second primary, NCDB, de novo nsclc, trend analysis
Other professions ECOG 2: 46.9%, Farmers ECOG 2: 43.3,6%, homemakers
ECOG 3: 50% (P= 0.008). Most of patient were smokers ECOG 4: 100%, ECOG
2: 86%, ECOG 3: 81%, ECOG 1: 76,1%, (P=0,000). Clinical severity and ECOG
relation was predominant at ECOG 0 to Stage IIIB:66.7% and ECOG 1 to Stage
IIIB:43.5%. And predominant at ECOG 2 was Stage IV: 54.7%, ECOG 3 and 4 was POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
Stage IV: 60%, both (P=0,000). ECOG 1: 33,8% accept to chemotherapy ,ECOG PREVENTION
2: 46.6% Reject any treatment, ECOG 3: 43.9% Reject any treatment, ECOG 4: PROGNOSTIC FACTORS, TREATMENT –
40% accept to radiotherapy (P=0,000). Non-Small cell carcinoma predominant
ECOG 2: 48.2% Small cell carcinoma: predominant ECOG 2: 48.1%(P>0.05).
Conclusion: Our mean ECOG was 2.13 but predominance in our populations is P1.01-036 LUNG CANCER SCREENING PROGRAM IS COST EFFECTIVE
ECOG 2 with 48% and ECOG 3 with 31%. Prevalence of ECOG 2 and 3 at first IN FRENCH SETTING: A MODEL BASED STUDY
consultation was found at Rural and Urban Places. Statistical significance Christos Chouaid1, Juliette Vella-Boucaud1, Jean Claude Pairon2, Anne
was found at work and ECOG performance with prevalence to ECOG 2 except Duburcq3, Bruno Detournay3, Laurent Boyer4, Bruno Housset4, Pascal
to homemakers who had prevalence to ECOG 3. Association with smoking Andujar2, Isabelle Monnet1
prevalence was ECOG 4 at first consultation. Is important to conclude that 1
Chest Departement, Grc Oncoest Creteil, Creteil/France, 2Inserm U955, Ist, Creteil/
at ECOG 0 and 1 clinical stage IIIB was predominant and to ECOG 2 to 4 was France, 3Cemka, Bourg La Reine/France, 4Inserm U905, Creteil/France
clinical stage IV, which shows relation between clinical severity and ECOG
performance, but multivariate analysis will be required. Relation between Background: The National Lung Screening Trial (NLST) showed that
treatment show a high rejection to treatment at ECOG 2 and 3. With this screening with low-dose computed tomography (CT) as compared with
analysis we need to seek a logistic regression model to search relation with chest radiography reduced lung cancer-mortality. There is no data’s on the
ECOG performance and other variables. faisability and cost-effectiveness of CT lung cancer screening program in the
French setting. Methods: We estimated mena life-years gaineds, costs and
Keywords: Lung neoplasms, quality of life, Neoplasm Staging incremental cost-effectiveness ratio (ICER) for screening with low-dose CT
compare to no screening. Estimations of life-years gained were based on the
efficacy of NLST trail applied to the general french population using the same
inclusion criteria’s that NLST trail (age of 55 to 74 years with a minimum of
30 pack-years of smoking and no more than 15 years since quitting) adjusted
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO to sex, age and smoking status. Costs were limited to directs costs from the
CONTROL AND CESSATION/PREVENTION payers perspective. We also performed sensitivity analysis based on several
Prognostic Factors, Treatment – asssumptions of program efficacy. Results: The target population was 5 551
141 subjects. Compared with no screening, screening with low-dose CT, over
a period of 2 years, will have an additional cost of 941 978 €, will provide 52.4
additional year of life with a corresponding ICER of 17 969 € per year gained.
Sensititiviy analysis showed that this result is sensitive to program efficacy
P1.01-035 TRENDS, PATTERNS OF TREATMENT AND OUTCOMES IN (number, stage and survival of lung cancer diagnosed by the program) and to
NON-SMALL CELL LUNG CANCER (NSCLC) AS A SECOND PRIMARY: subjects compliance rate to the program. Conclusion: Cost effectiveness of
A NATIONAL CANCER DATA BASE (NCDB) ANALYSIS CT lung cancer screening program in a French population using the same main
Madhusmita Behera1, Theresa Gillespie1, Yuan Liu2, Yaqi Jia2, Kristin Higgins2, inclusion criteria and outcomes of NLST trial appears as acceptable from the
Conor Steuer3, Nabil Saba2, Dong Shin2, Suchita Pakkala4, Rathi Pillai5, french health system
Taofeek Owonikoko6, Walter Curran7, Chandra Belani8, Fadlo Khuri3, Suresh
Keywords: model study, lung cancer screening, cost effectiveness
Ramalingam9
1
America, 2Winship Cancer Institute, Emory University, Atlanta/United States of
America, 3Emory University, Atlanta/United States of America, 4Hematology/
Medical Oncology, Winship Cancer Institute of Emory University, Atlanta/GA/
United States of America, 5Hematology and Medical Oncology, Winship Cancer PREVENTION
Institute, Emory University, Atlanta/GA/United States of America, 6Hematology/ PROGNOSTIC FACTORS, TREATMENT –
Medical Oncology, Emory University, Atlanta/GA/United States of America, MONDAY, DECEMBER 5, 2016
7
Radiation Oncology, Emory University Winship Cancer Institute, Atlanta/GA/
United States of America, 8Penn State Hershey Cancer Institute, Hershey/PA/
United States of America, 9Winship Cancer Institute, Emory University, Atlanta/GA/ P1.01-037 BASELINE DEMOGRAPHICS AND COMORBIDITIES OF
United States of America PATIENTS WITH ADVANCED NSCLC COMPARED TO THE GENERAL
POPULATION FROM TWO REGIONS IN SWEDEN
Background: The prevalence of NSCLC as a second primary tumor has been
increasing over the past decades, though very little data are available in Stephan Linden1, Ana Banos Hernaez2, Josefine Reding2, Jonas Nilsson2, Nahila
the literature. We analyzed the NCDB, an oncology outcomes database Justo2, Jukka Montonen1, Patrice Verpillat 1
1
administered by the American College of Surgeons and the American Cancer Global Epidemiology, Boehringer Ingelheim, Ingelheim/Germany, 2Mapi Group,
Society, to study the outcomes and patterns of treatment of patients (pts) Stockholm/Sweden
diagnosed with NSCLC as a second or subsequent primary (SP). Methods:
Background: Lung cancer is the most commonly diagnosed cancer in men and
The NCDB was queried from 2004 to 2012 for NSCLC pts. Pts diagnosed with
the third most common in women. However, detailed analyses of patient
NSCLC as SP were compared with pts with de novo (DN) NSCLC as defined
newly diagnosed with advanced non-small cell lung cancer (NSCLC) in routine
by sequence number in the database. Univariate (UV) and multivariable
clinical care, compared to the general population, is limited. Methods: This
analyses (MV) with overall survival (OS) were conducted by Cox proportional
non-interventional study is based on existing data from the population-based
hazards model. Kaplan-Meier plots were produced to compare the survival
national Swedish Cancer Registry. All adult patients diagnosed with advanced
curves by subgroups along with log-rank p-values. Results: A total of 207,518
NSCLC between 2006 and 2013 receiving care in the regions of Skåne and

Västra Götaland counties (about 37.6% of NSCLC patients in Sweden) were Variable HR 95%CI P
included and matched (1:4) by age at diagnosis, gender and region of residence
to a sample from the general population (controls). In- and outpatient visit BMI (group)
data was extracted from regional databases in order to assess prevalence of 3 1
selected baseline comorbidities detected in the year before diagnosis. Results:
1 1.06 0.96-1.17 0.26
In total, 4,758 patients with advanced NSCLC were identified and matched
to 18,996 controls. At the date of the initial NSCLC diagnosis, the median age 2 1.03 0.85-1.23 0.789
was 69.0 (range 22-97; 96.2% above 50), and 52.7% were men. The stage of 4 0.92 0.85-0.99 0.036
disease was IIIb in 19.8% (n=944) or IV in 80.2% (n=3,814) of the patients. When 5 0.9 0.81-1.01 0.061
specified, adenocarcinoma was the most frequent histology (70.4%) followed Age (years)
by squamous cell carcinomas (25.4%). A total of 50.9% of the NSCLC patients
had recorded morbidities in the year preceding the diagnosis compared to <=40 1
34.8% of the controls (Odds Ratio (OR) 1.94; P<0.001)). Patients with advanced 41-50 1.07 0.74-1.54 0.714
NSCLC had significantly more often (P<0.001) respiratory disorders (16.4% vs.
51-60 1.02 0.72-1.46 0.899
3.2%; OR 6.02), infections (13.4% vs 6.1%; OR 2.37), anaemia (3.4% vs. 1.7%; OR
61-70 1.05 0.74-1.49 0.796
2.08), musculoskeletal disorders (3.7% vs. 2.5%; OR 1.51), and cardiovascular
disease (27.8% vs. 22.7%; OR 1.31). No significant difference was observed in 71-80 1.11 0.78-1.59 0.553
prevalence of gastro-intestinal disorders, metabolic disorders or skin disorders. >80 1.54 1.07-2.22 0.02
Regarding disorders of the central nervous system, while depression was more Sex
frequently present among NSCLC patients (3.8% vs. 2.8%; OR 1,38) dementia
was more prevalent among controls (0.6% vs. 1.2%; OR 0.48). As expected, brain Men 1
metastasis was diagnosed overwhelmingly more for NSCLC patients (53 cases, Women 0.81 0.74-0.88 <0.001
vs. 2 cases; OR 107.0). Conclusion: The present study suggests that patients
Smoking
diagnosed with advanced NSCLC have a significantly higher morbidity burden
than the general population in these regions in Sweden. Never-smoker 1
Keywords: non-small cell lung cancer, NSCLC, epidemiology, Comorbidities Former-smoker 1.19 1.06-1.35 0.004
Current-smoker 1.27 1.13-1.44 <0.001
PS
PS0 1
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ PS1 1.58 1.45-1.73 <0.001
PREVENTION
PROGNOSTIC FACTORS, TREATMENT – PS2 2.66 2.4-2.95 <0.001
PS3 5.6 4.95-6.34 <0.001
PS4 10.61 8.62-13.05 <0.001
P1.01-038 PROGNOSIS VALUE OF BODY MASS INDEX (BMI) AND Stage
WEIGHT LOSS AT DIAGNOSIS IN PRIMARY LUNG CANCER: RESULTS
OF KBP-2010-CPHG STUDY <=IIB 1
Didier Debieuvre 1, Hugues Morel2, Bruno Raynard3, Jean-Philippe Oster4, IIIA 1.89 1.61-2.21 <0.001
Acya Bizieux5, Antoine Lévy6, Jean-Pierre Mathieu7, Patrick Dumont8, Étienne IIIB 3 2.56-3.52 <0.001
Leroy-Terquem9, Bernard Asselain10, François Blanchon11, Michel Grivaux11 IV 4.71 4.13-5.38 <0.001
1
Service de Pneumologie, Groupe Hospitalier Régional Mulhouse Sud Alsace
(Ghrmsa) - Hôpital Emile Muller, Mulhouse/France, 2 Service de Pneumologie, Conclusion: In 2010, in France, in real life conditions, 1-year survival was low
Centre Hospitalier Régional, Orleans/France, 3Unité Transversale de Diététique Et in lung cancer patients with low BMI at diagnosis and recent weight loss.
de Nutrition, Institut Gustave Roussy, Villejuif/France, 4Service de Pneumologie, Overweight appeared to be a protective factor in particular for stage IIIA and
Hôpitaux Civils de Colmar - Hôpital Pasteur, Colmar/France, 5Service de IIIB cancers.
Pneumologie, Centre Hospitalier Départemental de La Roche-Sur-Yon, La
Roche-Sur-Yon/France, 6Service de Pneumologie, Centre Hospitalier Jacques Keywords: mortality, risk factors, Body mass index, weight
Cœur, Bourges/France, 7Service de Pneumologie, Centre Hospitalier de La Côte
Basque, Bayonne/France, 8Service de Pneumologie, Centre Hospitalier de Chauny,
Chauny/France, 9Service de Pneumologie, Chi de Meulan-Les-Mureaux, Meulan-
Les-Mureaux/France, 10Université de Paris-Sud Orsay, Paris/France, 11Service de
Pneumologie, Centre Hospitalier de Meaux, Meaux/France POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
Background: We studied the relationship between 1-year mortality and PROGNOSTIC FACTORS, TREATMENT –
weight at diagnostic in 6,965 adult patients followed for primary lung cancer MONDAY, DECEMBER 5, 2016
in 104 general hospitals. Methods: Patients were classified into 5 groups:
Group 1, underweight with recent weight loss; Group 2, underweight without P1.01-039 DOES DISTANCE BETWEEN CHEST AND SURGERY
recent weight loss; Group 3, normal weight; Group 4, overweight; Group 5,
DEPARTMENTS IMPACT OUTCOME IN LUNG CANCER PATIENTS?
obese. Kaplan-Meier method (1-year mortality) and Cox multivariate analysis
RESULTS OF KBP-2010-CPHG STUDY
(independent risk-factors) were used. Results: Respectively, 11%, 4%, 45%,
29%, and 12% of patients belonged to Groups 1, 2, 3, 4, and 5. One-year survival Didier Debieuvre 1, Violaine Frappat2, Stéphanie Dehette3, Jacky Crequit4,
was lower in Group 1 (27% [24%-30%]) and higher in Group 4 (50% [48%-52%]) Michel Carbonnelle5, Patricia Barre6, Daniel Coëtmeur 7, François Goupil8,
or 5 (53% [50%-57%]) than in Group 2 (47% [41%-53%]) or 3 (43% [42%-45%]) Olivier Molinier8, Michel Grivaux9
1
(Fig. 1). As compared with normal weight, overweight was an independent Service de Pneumologie, Groupe Hospitalier Régional Mulhouse Sud Alsace
protective factor. Independent protective/risk factors are presented in Table (Ghrmsa) - Hôpital Emile Muller, Mulhouse/France, 2 Service de Pneumologie, Centre
1. Interaction analyses showed that overweight was a significant independent Hospitalier de Chambery, Chambery/France, 3Service de Pneumologie, Centre
Hospitalier de Compiegne, Compiegne/France, 4Service de Pneumologie, Centre
protective factor for stage IIIA and IIIB cancer (HR=0.77 [0.6-0.99], p=0.038;
Hospitalier Laënnec, Creil/France, 5Service de Pneumologie, Hôpital Auban Moet,
HR=0.75 [0.59-0.97], p=0.029, respectively). Epernay/France, 6Service de Pneumologie, Centre Hospitalier de Cahors, Cahors/
France, 7Service de Pneumologie, Centre Hospitalier Saint-Brieuc - Hôpital Yves Le
Foll, Saint-Brieuc/France, 8Service de Pneumologie, Centre Hospitalier Du Mans,
Le Mans/France, 9Service de Pneumologie, Centre Hospitalier de Meaux, Meaux/
France
Background: We studied the impact of the distance between chest and

thoracic surgery departments on the outcome of patients followed, for
primary lung cancer diagnosed in 2010, in the chest department of 104 French
general hospitals participating in KBP-2010-CPHG study. Methods: 6,083
patients with non-small-cell lung cancer (NSCLC) participated in this study.
Univariate and multivariate analyses were performed to identify independent
factors for surgery and 1-year mortality. Distance from the usual thoracic
surgery department in 2010 was collected for each chest department and
included in the model as a 4-class variable: 0 km (same hospital), 1-34 km, 35-
79 km, and ≥80 km. Results: Overall, 23% of hospitals had a thoracic surgery
department; otherwise, mean distance between the hospital and the surgical not impair outcome in NSCLC patients managed in the chest departments of
center was 65 km. 1,157 patients (19%) were operated on; vital status was French general hospitals.
known for 5,876 patients (97%). Distance was not an independent factor for
surgery and for mortality. Independent factors for surgery and mortality are Keywords: non small cell lung cancer, thoracic surgery department, mortality,
presented in Tables 1 and 2. Table 1- Surgery (multivariate analysis: adjusted Surgery
odd-ratios)
OR 95% CI p
Distance (km) PREVENTION
PROGNOSTIC FACTORS, TREATMENT –
0 1 MONDAY, DECEMBER 5, 2016
1-34 0.97 [0.74-1.27] 0.833

35-79 0.88 [0.66-1.18] 0.399 P1.01-040 LONG-TERM SURVIVAL IN METASTATIC NON-SMALL-
>=80 1.02 [0.78-1.32] 0.91 CELL LUNG CANCER: AN INVESTIGATION USING SURVEILLANCE,
EPIDEMIOLOGY AND END RESULTS DATA
Age (year)
Eva Szabo 1, Erin Prophet2, Ho-Lan Peng 3, Hwa Lee3, Shine Chang 3, Jennifer
Continuous 0.95 [0.94-0.96] <0.001 Davis3
Stages 1
Division of Cancer Prevention, National Cancer Institute, Bethesda/MD/United
States of America, 2Rice University, Houston/TX/United States of America, 3MD
IV 1 Anderson Cancer Center, Houston/TX/United States of America
I 248.18 [172.48-357.11] <0.001
Background: The introduction of new effective modalities for the treatment
II 155.78 [107.70-225.32] <0.001 of metastatic non-small cell lung cancer (NSCLC), such as targeted therapies
IIIA 34.23 [24.80-47.25] <0.001 and immunotherapy, has resulted in reports of long-term survival in small
IIIB 2.33 [1.40-3.89] 0.001 sub-groups of patients treated with these therapies. It is therefore important
to understand the frequency and characteristics of long-term survivors in
Histology large cohorts of advanced-stage lung cancer patients who were diagnosed
Adenocarcinoma 1 and treated prior to the advent of these new therapies. Methods: A survival
analysis of data from the Surveillance Epidemiology and End Results database
Squamous-cell carcinoma 0.77 [0.61-0.96] 0.023 was performed. The cohort was limited to patients diagnosed with stage
PS IV NSCLC, squamous and adenocarcinoma histology only, between 1991
and 2007, with follow-up through 2012. Outcomes and factors associated
PS0 1 with extended survival were evaluated in the 10% of patients with longest
PS1 0.58 [0.47-0.71] <0.001 survival (long-term survivors, ≥21 months) vs. 90% short-survival patients (<
PS2 0.12 [0.08-0.17] <0.001 21 months). Patients surviving ≥ 5 years were compared with those surviving
<5 years and ≥21 months. Demographic, tumor characteristic, and treatment
PS3 0.08 [0.04-0.16] <0.001
differences between long-term and short-survival patients were compared
PS4 0.07 [0.02-0.32] <0.001 using chi-square and Student’s T-test for categorical and continuous variables,
respectively. For descriptive analyses unadjusted for confounders, Kaplan
Meier curves and log-rank tests were used to compare survival by histology
and long-term survival status. Results: Among the 44,387 patients diagnosed
Table 2- Mortality (multivariate analysis: adjusted hazard-ratios)
at stage IV, long-term survivors (4,544) are distinguishable from short-survival
patients (39,843) by younger age, female sex, Asian/ Pacific Islander race,
HR 95% CI p lower tumor grade, adenocarcinoma histology, upper lobe site, and treatment
with surgery. Among only long-term survivors (≥ 21 months), predictors
Distance (km)
of longest survival are younger age, lower tumor grade, and treatment by
0 1 surgery and radiation. Median survival increased over time from 3 to 4 months
for short-survival patients versus 30 to 36 months for long-term survivors.
1-34 1.02 [0.94-1.11] 0.661
Notably, 1.5% of patients survived >5 years even prior to modern combination
35-79 1.00 [0.91-1.10] 0.985 chemotherapy regimens, targeted therapies, and immunotherapy.
>=80 1.01 [0.93-1.09] 0.887 Conclusion: Despite the poor overall survival of patients diagnosed with stage
IV NSCLC, the top 10% of survivors have significantly longer survival than
Age (year)
the rest and a sub-population of individuals with extraordinary survival is
Continuous 1.01 [1.01-1.01] <0.001 identifiable. The discrepancy in median survival between long-term survivors
Sex and the rest suggests that long-term survivors comprise a disproportionate
percentage of clinical trial participants and provides a rationale for more
Men 1 detailed clinical and molecular analyses in order to improve therapeutic
Women 0.86 [0.80-0.94] <0.001 targeting and future study design.
Stages Keywords: SEER, epidemiology, NSCLC long-term survival
IV 1
I 0.15 [0.13-0.18] <0.001
II 0.29 [0.25-0.34] <0.001
IIIA 0.41 [0.37-0.46] <0.001 PREVENTION
IIIB 0.65 [0.58-0.72] <0.001 MONDAY, DECEMBER 5, 2016
PS
PS0 1 P1.01-041 QUANTITATIVE IMAGING FEATURES PREDICT RESPONSE

OF IMMUNOTHERAPY IN NON-SMALL CELL LUNG CANCER
PS1 1.58 [1.45-1.73] <0.001
PATIENTS
PS2 2.79 [2.52-3.09] <0.001
Ilke Tunali1, Jhanelle Gray2, Jin Qi3, Mahmoud Abdullah3, Yoganand
PS3 5.75 [5.11-6.48] <0.001 Balagurunathan3, Robert Gillies3, Matthew Schabath4
PS4 10.2 [8.52-12.20] <0.001 1
Biomedical Engineering, Namik Kemal University, Tekirdag/FL/Turkey, 2Thoracic
Oncology, Moffitt Cancer Center, Tampa/FL/United States of America, 3Radiology
Smoking
and Cancer Imaging, Moffitt Cancer Center, Tampa/FL/United States of America,
4
Never-smoker 1 Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa/
FL/United States of America
Former-smoker 1.18 [1.05-1.33] 0.005
Current-smoker 1.33 [1.18-1.49] <0.001 Background: Although immunotherapy has revolutionized the field of
cancer treatment, response rates are only ~20% in non-small cell lung cancer
Conclusion: In 2010, the absence of an on-site thoracic surgery department did (NSCLC) patients and cost of this therapy is high. Predictive biomarkers

are needed to identify patients likely to benefit. Converting digital medical There were no statistically significant differences with respect to PD-L1
images into high-dimensional data (‘Radiomics’) contains information that expression for patient characteristics, overall survival (OS), or progression-
reflects underlying pathophysiology and that can be revealed via quantitative free survival (PFS). Additionally, there were no statistically significant
analyses. We extracted radiomic imaging features from baseline CT scans differences with respect to PD-L1 expression by EGFR (WT/PD-L1<25% =
(prior to initiation of immunotherapy) and identified features that predict 74.4% vs. WT/PD-L1≥ 25% = 88.5%), KRAS (WT/PD-L1<25% = 74.7% vs. WT/
response to immunotherapy in NSCLC patients. This work is an initial test of PD-L1≥ 25% = 69.2%), and ALK status (Neg/PD-L1<25% = 98.5% vs. Neg/PD-
the hypothesis that radiomic data may predict who will respond favorably L1≥ 25% = 100%). However, mutation load (total number of non-synonymous
and who will not. Methods: We curated a subset of data and images from 13 mutations) was statistically significantly correlated with PD-L1 expression
different institutional immunotherapy clinical trials. Patients were stage (correlation coefficient = 0.23; P = 0.03). Conclusion: In this study of NSCLC
III/IV NSCLC and received PD-1, PD-L1, or doublet checkpoint inhibitors. patients treated with 2 or more lines of standard of care chemotherapy, PD-L1
All target nodules were identified on the CT prior scan prior to initiation expression (high vs. low and as a continuous covariate) was not statistically
of immunotherapy. RECIST guidelines 1.1 were used to measure patient significantly associated with OS or PFS. We did observe a novel positive
response from baseline to last follow-up scan. Based on last follow-up, 43 correlation between PD-L1 expression and mutational load.
patients had progressive disease (PD) and 28 patients with partial response
(PR) or complete response (CR). Since we focused on extreme responses, Keywords: PD-L1, lung cancer, epidemiology, Immunotherapy
stable disease (SD) patients were not included in the current analyses. We
extracted 219 radiomic features including size, shape, location, and texture
information from a total of 210 target nodules (lung, lymph nodes, or other).
Backward-elimination analyses were utilized to generate parsimonious
radiomic models associated with objective responses (PD vs. PR/CR) and PREVENTION
post estimation computed performance statistics. Results: There were no PROGNOSTIC FACTORS, TREATMENT –
significant differences for the patient characteristics between patients
with PD vs. CR/PR. Analysis of the radiomic features for all target nodules
to differentiate PD patients vs. PR/CR patients resulted in a final model P1.01-043 COMPARISON OF GENDER, RACE DISTRIBUTION, AND
containing 2 features that provided an AUROC of 0.64 (95% CI 0.56–0.72). SURVIVAL IN THE 1990S TO 2010S IN LUNG CANCER PATIENTS AT A
When we analyzed features for only lung target nodules, we identified a final
SINGLE INSTITUTION
model with 4 features that produced an AUROC of 0.79 (95% CI 0.68–0.89).
When we analyzed the imaging features for lymph node target nodules, Bahar Laderian1, Diana Saravia2, Ali Laderian3, Adrian Ishkanian4, Mohammad
we found that a final model with 1 feature yielded an AUROC of 0.67 (95% Jahanzeb5
1
CI 0.51–0.82). Conclusion: Radiomic features of lung target nodules have Internal Medicine, University of Miami, Miller School of Medicine, Miami/FL/
better performance statistics for predicting response to immune therapies United States of America, 2Internal Medicine, University of Miami, Miller School
of Medicine, Miami/United States of America, 3Suffolk County Community
compared to target nodules from other organ sites. With this model, cutoffs
College, Selden/NY/United States of America, 4University of Miami Miller School of
can be chosen to reduce non-responders with high confidence. Change feature Medicine, Miami/United States of America, 5University of Miami Miller School of
analyses following therapy are underway. Medicine, Miami/FL/United States of America
Keywords: Imaging Epidemiology, Radiomics, Immunotherapy, Quantitative Background: In the United States, lung cancer occurs in about 225,000
imaging patients and causes over 158,000 deaths annually. Due to a shift in smoking
patterns between the genders that started decades ago, the incidence of
lung cancers appeared to have shifted accordingly. Thus, we analyzed our
institutional data as described below. Methods: This is a retrospective study
that compares two populations of lung cancer patients in two different
PREVENTION five-year periods a decade apart: one from 1996 to 2000 consisting of 1355
PROGNOSTIC FACTORS, TREATMENT – lung cancer patients and the other from 2011 to 2015 consisting of 2220 lung
cancer patients from our institutional tumor registry data. We included lung
cancers that have been associated with smoking such as adenocarcinoma,
P1.01-042 MOLECULAR EPIDEMIOLOGY OF PROGRAMMED CELL squamous cell carcinoma, and small cell lung cancer. The two populations were
DEATH 1-LIGAND 1 (PD-L1) PROTEIN EXPRESSION IN NON-SMALL compared in category of gender; race and marital status were also included to
examine any major population shifts during these time periods. Crude survival
CELL LUNG CANCER
at two-year follow up period was also examined. The results were analyzed
Matthew Schabath1, Tapashi Dalvi2, Hongyue Dai3, Alan Crim3, Anita Midha4, using Excel as well as Matlab. This project is IRB approved. Results: From 1996
Norah Shire2, Jill Walker5, Danielle Greenawalt6, David Lawrence5, James to 2000, the percentage of male population with lung cancer associated with
Rigas7, Robert Brody2, Danielle Potter2, Naveen Kumar3, Shane Huntsman3, smoking was 63%. This number decreased significantly to 51% in the period
Jhanelle Gray8 2011-2015 (p-value < 0.00001). The percentage of African American patients
1
Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa/ in 1996-2000 was 14% and decreased to 11% in 2011-2015 (p-value 0.0039). The
FL/United States of America, 2 Astrazeneca, Gaithersburg/MD/United States of number of divorced patients increased from 8.1% to 11% (p-value 0.0025).
America, 3M2Gen, Tampa/FL/United States of America, 4 Astrazeneca, Cheshire/
The number of widowed patients decreased from 12.3% to 9.8% (p-value
United Kingdom, 5 Astrazeneca, Hertfordshire/United Kingdom, 6 Astrazeneca,
Waltham/MA/United States of America, 7Astrazeneca, Hanover/NH/United States
0.0096). For patients with stage IV lung cancer diagnosed from 1996 to 1998,
of America, 8H. Lee Moffitt Cancer Center and Research Institute, Tampa/FL/United the crude survival rate at 2-year follow up was 17%, which increased to 29%
States of America in patients diagnosed from 2011 to 2013 (p-value < 0.00001). Conclusion: Our
results demonstrate that the proportionate incidence of lung cancer in males
Background: Expression of programmed death-ligand 1 (PD-L1) in non-small has decreased significantly from the late 90s to the early 2010s. The change
cell lung cancer (NSCLC) patients might identify patients who would benefit in race and marital status, while statistically significant, is less dramatic. The
from PD-L1 blocking antibodies. In a retrospective cohort of NSCLC patients, percentage of African American population has also decreased significantly.
we characterized PD-L1 expression and other biomarkers to determine if PD-L1 The crude survival rate at 2 year follow up for those with stage IV lung cancer
expression is a prognostic biomarker and whether patient characteristics significantly increased. While this could, in part, be due to stage migration,
could be identified to determine those associated with high expression. a real prolongation due to improvements in systemic therapy is likely. More
Methods: This was a retrospective analysis of 136 NSCLC patients diagnosed attention should be drawn to the fact that nearly twice as many women die
between 1997 and 2015 with stage IIIB and IV disease and treated at Moffitt from lung cancer compared to breast cancer, for a more proportionate support
Cancer Center and affiliated institutions. All patients had at least 2 lines of research efforts.
of standard of care chemotherapy and sufficient archival tumor tissue for
PD-L1 testing by the Ventana SP263 validated assay and mutation status Keywords: lung cancer, gender distribution
testing by targeted DNA sequencing with the TumorCare Panel. High PD-L1
expression was defined as ≥ 25% of tumor cells with membrane positivity for
PD-L1 at any intensity above background staining. Statistical analyses were
performed comparing PD-L1 expression by patient characteristics. Survival
analyses were performed using Kaplan-Meier survival curves and the log-rank PREVENTION
statistic. All statistical tests were two-sided; P-value of less than .05 was PROGNOSTIC FACTORS, TREATMENT –
considered statistically significant. Results: Of the 136 tissues tested for PD- MONDAY, DECEMBER 5, 2016
L1 expression, 116 (85.3%) were collected by surgical resection and 20 (14.7%)
were collected by biopsy. Mean sample age was 7.2 years (SD=2.8 years). 82 P1.01-044 ACCELEROMETER-DETERMINED PHYSICAL ACTIVITY
of the 136 samples also underwent targeted DNA sequencing. In this patient
AND SEDENTARY TIME AMONG LUNG CANCER SURVIVORS
cohort, 51.5% were male, 83.1% were ever smokers, 90.4% were White, 39%
were stage IV at time of tissue collection, 71.3% had adenocarcinoma, 28.7% Adrijana D’Silva1, Gwyn Bebb2, Terry Boyle3, Steve Johnson4, Jeff Vallance4
1
had four or more lines of therapy, and 24.2% had high-expression for PD-L1. Oncology, University of Calgary, Calgary/AB/Canada, 2University of Calgary and
Alberta Health Services, Calgary/Canada, 3Curtin University, Perth/WA/Australia,

4
Athabasca University, Athabasca/AB/Canada
Background: Physical activity is an effective way to positively influence

health outcomes among cancer survivors. Few studies have examined physical
activity and sedentary behaviour among lung cancer survivors. Further,
these studies have used self-report measures of physical activity, which may
bias results (e.g., overestimation) and lead to incorrect conclusions. Only
one study to date has reported on objectively-assessed sedentary behaviour
among lung cancer survivors. The primary aim of this currently ongoing study
is to determine the prevalence of objectively-assessed physical activity and
sedentary time among lung cancer survivors. Methods: Lung cancer survivors
in Southern Alberta diagnosed between 1999 and 2014 are currently being
recruited to participate. Eligibility criteria include: confirmed non-small cell
lung cancer, completed treatment, and not living in hospice/palliative care.
Consenting participants wear an Actigraph® GT3X+ accelerometer on their hip
for seven days. Time spent sedentary, in light and in moderate-to-vigorous
intensity physical activity are derived from the accelerometer data and
processed using 60-second epochs. Physical activity and sedentary behaviour
accumulated in 10 minute and 30 minute continuous bouts will be examined.
Results: Recruitment began in June, 2016. A total of 660 survivors were invited
and 113 have agreed to participate. Of the 374 survivors that did not respond,
most indicated they were not interested (n=115). Others denied having lung
cancer (n=6) or had invalid contact information (n=27). Six were deceased. Conclusion: Significant differences exist in P-H and patient/hospital
Currently the response rate is 18.2%. Of the 113 that consented, eight characteristics, which may affect type of surgery and outcome. P-H should be
participants withdrew due to health concerns (n=4), time constraints (n=2), incorporated to improve health disparities in accessing surgical care.
and loss of interest in the study (n=2). Of the 105 participants, the median
Keywords: Surgery, lung cancer, Patient-Hospital Distance
age at diagnosis was 66 years, and 72 years at recruitment, the majority were
female (n=62), and 85 had a smoking history. Adenocarcinoma was the most
common diagnosis (n=65). The majority of participants were diagnosed stage I
(n=53) with others diagnosed at stage II (n=23), III (n=18), and IV (n=11). Overall,
65 survivors underwent a lung resection while 18 of those received adjuvant POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
therapy. Other treatments included concurrent chemotherapy and radiation PREVENTION
(n=11) and radical radiation alone (n=23). Conclusion: This study will be the PROGNOSTIC FACTORS, TREATMENT –
first to report on objectively assessed physical activity and sedentary time
among a population-based sample of lung cancer survivors. Despite inherent
difficulties of this type of research (e.g., older population), the positive P1.01-046 HETEROGENEITY OF NSCLC SURGERY EXISTS IN
response rate suggests high participation interest. We expect to reach our TREATMENT PATTERNS AND HOSPITAL COSTS AMONG DIFFERENT
recruitment target of 140 patients by September, 2016, with data analysis CENTERS OF CHINA, A STUDY OF 5060 PATIENTS
completed in November, 2016.
Jian Zhou1, Yanguo Liu2, Fan Yang 3, Jun Wang 3
1
Keywords: Lung cancer survivors, sedentary behavior, health-related quality Thoracic Surgery, Peking University People’s Hospital, Beijing/China, 2Peking
of life, physical activity University People’s Hospital, Beijing/China, 3Thoracic Surgery, Peking University
People’s Hospital, Beijing/China
Background: Lung cancer is the leading cause of death of all tumors in China.
But due to imbalanced development of different provinces, the surgical
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ treatments of Non-small cell lung cancer in different areas of China diverse.
PREVENTION The Chinese National NSCLC outcome registry was founded in 2013, which
PROGNOSTIC FACTORS, TREATMENT – covers 17 provinces across China. We analyze the data of 5060 NSCLC patients
retrieved from this registry to reveal the imbalanced circumstances. Methods:
Data of stage I-III patients were obtained from the NSCLC surgical outcome
P1.01-045 PATIENT TO HOSPITAL DISTANCE IN ACCESS TO CARE registry, which included 5060 patients who underwent lung resection
AND LUNG CANCER SURGICAL TREATMENT surgeries from 17 tertiary hospitals nationwide in 2013-2014. Baseline data,
surgical treatment pattern parameters, pathology, number of lymph nodes
Wil Lieberman-Cribbin1, Bian Liu1, Raja Flores2, Emanuela Taioli1
1
dissected, and total hospital costs. Heterogenity of quantitative data was
Department of Population Health Science and Policy and Institute for
analyzed using Kruskal-Wallis test. Results: Among the 5060 patients, the
Translational Epidemiology, ICAHN School of Medicine at Mount Sinai, New York/
NY/United States of America, 2Thoracic Surgery, ICAHN School of Medicine at mean age was 59.7, while 3204 were male. Mean pre-op forced expiratory
Mount Sinai, New York/NY/United States of America volume in 1 second (FEV1) was 2.23L (P<0.01), FEV1/FVC was 81.8%(P<0.01).
64.6% patients combined with at least one comorbidity. The average diameter
Background: Lung cancer represents 13.4% of all newly diagnosed US cancers of the tumor was 3.28cm(P<0.01). Mean operation time was 181.2 minutes.
and 27.1% of all cancer deaths. Health disparties exist in accessing proper care (P<0.05).The post-operative pathology confirmed 59.8% as adenocarcinoma
and receving surgical treatment. We examined the role of Patient to Hospital while 30.2% as squamous carcinoma. Based on the data submitted by
distance (P-H) in access to care. Methods: Patients were selected from the different centers, 88.4%(mean,0 to 98.41) patients who were confirmed
New York State Statewide Planning and Research Cooperative System as stage III patients received adjuvant therapy before surgery(P<0.01). The
(1995-2012) based on ICD-9-CM diagnosis (162 and 165) and procedures rate of minimally invasive surgery was 48.1(mean, 8.1 to 94.7)% in different
(32.0-32.9). Surgery was categorized into: limited resection (LR: 32.2-32.3), regions(P<0.01). The number of stations of lymph nodes harvested was
lobectomy (L: 32.4), and pneumonectomy (P: 32.5-32.6). Distance calculations 5.8(mean, 4.3 to 7.4)(P<0.05). Mean hospital cost was 55070 (mean, 43051 to
(ArcMap 10.3.1) and linear regressions (SAS v9.4) were performed to determine 69686 ) RMB(P<0.01).
the factors influencing P-H. Results: There were 36,460 patients (age 60-75
years); 56% underwent L, 37% LR, and 7% P; 95% of patients underwent No. of lymph Adjuvant
surgery at a hospital < 70 kilometres (km) from their home (mean±SD Cost VATS No. of patients
Center nodes in therapy of
20.49±30.24 km; median 11.10 km). P-H was shorter in LR (19.10±27.71 km) than (CNY) % submitted
lobectomy Stage III%
L (21.00±30.96 km) and P (23.87±36.56 km; p < 0.001). At multivariable
analysis, P-H was positively associated with teaching hospitals (β: 3.33, p < 1 6.3 46861 90.2 99.3 838
0.001), admitted during 1995-2000 (β: 1.08, p < 0.001) and 2001-2006 (β: 1.23, p 2 6.4 52891 27.5 98.8 788
< 0.001), and P (β: 1.57, p < 0.001), and inversely associated with female gender
(β: -0.49, p = 0.016), age at admission (β: -0.17, p < 0.001), black race (β: -8.22, p < 3 4.5 47516 59.0 84.8 729
0.001), Medicaid (β: -3.37, p < 0.001), private insurance (β: -0.79, p = 0.004), rural 4 5.6 70875 60.3 50.3 676
hospitals (β: -2.80, p < 0.001), LR (β -0.81, p < 0.001), and mortality (β -1.05, p =
0.081). Similar associations were found in the L subgroup; among LR patients 5 5.3 51742 78.9 98.6 392
there was no statistically signficant association between P-H and female 6 7.4 65409 26.1 100 387
gender.
7 6.8 50696 8.5 100 293

was worst, with SS, for age ≥65 years (158.5x61.5 months; p=0.018), staging
8 4.8 42206 8.3 98.6 265
≥2 (NRx75.7 months; p=0,027), ECOG ≥1 (158.5x35.2 months; p=0.001), node
Total 5.9 57757 50.07 88.45 5060 positive disease (N0xN≥1: NRx33.9; p=0.001). Same tendencies were observed
for TC, also with SS, but not for AC. Median overall survival (mOS) retained the
Conclusion: The heterogenity of surgical treatment is quite huge in different same tendency: 5-year OS was 74% for TC and 55% for AC and 10-year OS was
centers of China. The baseline status before surgery, pre-operative therapy 74% for TC and 47% for AC. mOS was not reached. Age ≥ 65 years (p=0.001),
strategy, surgical technique, and health economic data submitted to the ECOG ≥1 (p=0.001) and staging ≥ 2 (p=0.001) also were predictable for worst
registry showed imbalanced development of NSCLC surgical treatment in mOS. Conclusion: This study demonstrates an epidemiologic descriptive
different regions of China. outlook of neuroendocrine LC in a Brazilian population. Older age, worst
performance and higher staging were prognostic for poor outcomes in
Keywords: registry study, health economic, surgical treatment pattern,
survival.
Chinese NSCLC surgical outcome
Keywords: Atypical Carcinoid, epidemiology, Neuroendocrine Lung Cancer,
Typical Carcinoid

PREVENTION
MONDAY, DECEMBER 5, 2016 POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
P1.01-047 CLINICAL PRESENTATION AND OUTCOME OF
NEUROENDOCRINE LUNG TUMORS IN A BRAZILIAN COHORT FROM
2000 TO 2016 P1.01-048 FACTORS CONTRIBUTING DELAYS DURING
Marcelo Corassa, Vladmir Cordeiro De Lima, Aldo Dettino, Diego Silva, Thiago MANAGEMENT OF LUNG CANCER: A STUDY FROM TERTIARY LEVEL
De Oliveira, Helano Freitas HOSPITAL IN NEPAL
Medical Oncology, A.C.Camargo Cancer Center, São Paulo/Brazil Sandhya Acharya1, Rashmey Pun2, Susmita Sharma1
1
Clinical Oncology, National Academy of Medical Sciences, Bir Hospital,
Background: Neuroendocrine lung tumors (NET) are rare and heterogeneous Kathmandu/Nepal, 2Nepal Medical College and Teaching Hospital, Kathmandu/
neoplasms. Typical carcinoids (TC) and atypical carcinoids (AC) have better Nepal
prognosis and their treatment is mainly focused on surgery. Large cell
neuroendocrine carcinomas (LCNLC) are commonly widespread at diagnosis. Background: Lung cancer is the leading cause of cancer related morbidity
Here we present clinical characteristics and outcome of patients with TC, and mortality in both the sexes in Nepal. It accounts for 15.4 % of total
AC and LCNLC treated at AC Camargo Cancer Center (ACCCC). Methods: We cancer as per hospital based Cancer Registry in Nepal. Majority of patients
selected 114 consecutive patients with TC, AC or LCNLC treated at ACCCC from are diagnosed and treated at advanced stage. This can be partly contributed
2000 to 2016. Demographic variables included individual data, diagnostic and to long lag period between the onset of symptoms and the initiation of
treatment patters. Data was collected and processed to obtain outcomes cancer treatment. This study tries to evaluate the factor contributing
and survival information. It was intended to obtain not only epidemiologic delays in various steps in lung cancer diagnosis and treatment. Methods:
characteristics, but also to determine and confirm selected variables as This retrospective cross-sectional observational study was conducted at
prognostic. Results: Main demographic results are described in the Table Department of Clinical Oncology, Bir Hospital, National Academy of Medical
below: Sciences (NAMS), Nepal. We reviewed the record of the all registered,
histologically diagnosed lung cancer patient during the year 2012 and 2013
Results: A total of 123 patient’s were diagnosed as Lung cancer and their
VARIABLES TC AC TOTAL
records were evaluated. Out of these 123 patients, 60% of the cases were
NUMBER OF males. The mean age was 63.93 years with the youngest being 35 and the
64(56.1%) 24(21.1%) 88(100%) eldest was 83 years. Significant number of patient was in stage III (59%)
PATIENTS
and IV (33%). About 89% of the patients were smokers. Non-small cell lung
SEX MALE 53.1% 41.7% 45.5%
cancer (NSCLC) accounted 83% and small cell lung cancer was (SCLC) 17%.
FEMALE 46.9% 58.3% 54.5% A total of 17% (21) of patient were on empirical Anti-tubercular treatment
(ATT) since the onset of current symptoms. While analyzing delay with
MEDIAN AGE YEARS 56.35 53.74 57.48 independent T test showed mean delay of 25.01 days (-/+ SD 6.17) in patient
without ATT and with ATT delay was 57.09 days (-/+ SD 8.05) (p=<0.01). Thirty
CLINICAL STAGING I 83.9% 55.0% 76.8%
five percentage (43) of patient received treatment within 1 month from
II 4.8% 20.0% 8.5% the first hospital visit, 28% (34) within two months and 37%(46) within 3-4
months of the first hospital visit. The delay in specialist visit was shorter in
III 6.5% 0.0% 4.9% advanced cancer and small cell cancer may be because of the acute presenting
symptoms. Conclusion: Various factors contributing for the delays are lag
IV 4.8% 25.0% 9.8% time from symptom onset to first visit with primary physician, delay due to
investigation and symptomatic treatment under primary physician care,
ECOG 0 71.7% 84.6% 76.4%
delay further aggravated by empirical but inappropriate ATT, further delay
≥1 20.3% 15.4% 25.4% due to diagnostic procedure to establish the cancer diagnosis. Thus proper
and timely referral to the specialist from primary physician will reduce these
COMORBIDITIES YES 56.9% 65.2% 59.3% delays and help to avoid situation where curable disease become incurable
and significantly alters the prognosis.
NO 75.4% 66.7% 73.1%
Keywords: Anti-tubercular treatment, Lung Cancer, Treatment delay,
SMOKING HISTORY YES 24.6% 33.3% 26.9%
NO 75.4% 66.7% 73.1%
OTHER
YES 32.8% 4.2% 25% POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
MALIGNANCIES
PREVENTION
NO 67.2% 95.8% 75% MONDAY, DECEMBER 5, 2016
FAMILY HISTORY YES 59.4% 66.7% 61.4%
NO 40.6% 33.3% 38.6%

P1.01-049 PREDICTORS OF HIGH GRADE TOXICITY OF
CHEMOTHERAPY AMONG MALIGNANT PLEURAL MESOTHELIOMA
SURGERY YES 92.2% 79.2% 88.6% PATIENTS
NO 7.8% 20.8% 11.4% Fatma Abou Elkasem1, Mohamed Rahoma2, Iman Abou El Khir3
1
Medical Oncology, National Cancer Insititute, Cairo/Egypt, 2 Surgical Oncology,
For the entire population, median progression free survival (mPFS) was 158.5 National Cancer Institute, Cairo/Egypt, 3Pathology, National Cancer Institute,
months. mPFS was not reached (NR) for TC and AC, with 5-year PFS 81% for Cairo/Egypt
TC and 84% for AC and 10-year PFS 69% for TC and 59% for AC; no Statistical
Background: Malignant pleural mesothelioma is an aggressive thoracic
Significance (SS) was found between TC and AC in mPFS (p=0,549). mPFS
malignancy associated with exposure to asbestos, and its incidence is
anticipated to increase during the first half of this century. Chemotherapy is higher ECOG values. Methods: Between January 2004 and December 2013, all
the mainstay of treatment, yet sufficiently robust evidence to substantiate patients diagnosed with a pathology of SCLC and NSCLC at National Institute
the current standard of care has emerged only in the past 5 years. Methods: of Oncology at Paraguay were analyzed retrospectively. ECOG performance
A retrospective cohort study of 100 MPM patients referred to NCI, Cairo status were recorded and SPSS 20 was used to analyze with logistic Binary
University in 3 years. Detailed data, Pearson’s Chi (x2) square and Logistic regression Results: We studied 478 subjects. At age mean 60,40 [95% CI 59,45
regression model were used for statistical analysis. Results: We found a to 61,34 ] years and ECOG performance status mean 2,13 [95% CI 2,06 to 2,20]
statistical significant relation between age ( 0.005), male gender (0.002), points. Bivariate correlations show no relation with age, gender, living place,
endemic area residence( 0.001), industrial workers ( 0.018), duration of work, smoking, alcohol consumption, histopathology of lung cancer only with
exposure (0.04), smokers (0.009), Simian virus ( 0.019), P53 ( 0.001), RbP motive of consultation and clinical severity. In our model of predicting a ECOG
(0.001), PS ( 0.0.16) and development of high grade toxicity of platinum based 3 to 5 adding first motive of consultation show a Nagelkerke R2: 0.14, Hosmer
chemotherapy. y Lemeshow P: 0.95. Adding to the model clinical severity Nagelkerke R2: 0.07
Hosmer y Lemeshow P: 1.0. Variables in our predicting model show at clinical
Median age = 46 years, only 17% of cases developed high grade toxicity severity IIB stage OR:6,62 [95% CI 1,13 to 38,52 P=0.035], clinical severity IIIA
complications of platinum based chemotherapy. Males were 59% of cases. stage OR: 3.85 [95% CI 1,18 to 12.51 P=0.025],clinical severity IIIB stage OR:4,49
PS, residence, smoking, occupation, history of asbestos exposure, family [95% CI 1,87 to 10,78 P=0.001]. At limited-stage SCLC clinical severity OR: 10,12
history, simian virus, P53, Rbp, dyspnea, chest pain, cough, expectoration, [95% CI 1,88 to 54,34 P=0.007]. At first motive of consultation chest paint OR:
haemoptysis, weight loss, fatigue, metastatic symptoms, chronic lung 3,13 [95% CI 1,38 to 7,11 P=0.006]. Cough OR: 2,30 [95% CI 1,11 to 4,76 P=0.024].
infection, Tuberculous pleuritic, effusion, pleural thickening, Tracheal shift, Palpable Tumoral mass OR: 8,35 [95% CI 1,65 to 42,07 P=0.010]. Conclusion:
TNM staging, surgical operations, pathological staging, radiotherapy ,cause Regardless our expectations about relation of disability of patient with lung
of death and chemotherapy toxicity are assessed in our patients. Conclusion: cancer about place of living, work, gender, age this variables show no relation
Many factors predict high grade chemotherapy toxicity. So, search for target with ECOG at 3 to 5. In Our review we found a prediction model with clinical
therapy and immunotherapy instead of chemotherapy in this selected group severity adding 7% to prognostic of limited self-care and by adding to the
can improve both quality of life and response rate. model first motive of consultation a 14% of prognostic of worst ECOG status.
If first consultation motive is chest pain, cough or palpable tumoral mass,
this are strongly related with worst ECOG values. As a conclusion most of our
patients are diagnostic in advance clinical stages with a bad performance
status which will limited our options to treatment. All of these can be related
PREVENTION with a late consultation or a late detection of the disease.
MONDAY, DECEMBER 5, 2016 Keywords: Lung neoplasm, quality of life, Neoplasm Staging
P1.01-050 OVERALL SURVIVAL IN ADVANCED LUNG CANCER

PATIENTS TREATED AT ONCOSALUD-AUNA
Alfredo Aguilar 1, Claudio Flores2, Luis Mas1, José María Gutierrez1, Luis POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO
Pinillos3, Carlos Vallejos1
1 2 CONTROL AND CESSATION/PREVENTION
Department of Medical Oncology, Oncosalud - Auna, Lima/Peru, Dirección
Científica Y Académica, Oncosalud - Auna, Lima/Peru, 3Radioncología - Auna, Lima/ Descriptive Epidemiology –
Peru MONDAY, DECEMBER 5, 2016
Background: Lung cancer still remains as the principal death cause in many
regions around the world. Unfortunate, between 60-70% of patients are
diagnosed with advanced disease (clinical stage IIIB-IV). We report the overall P1.01-052 LUNG CANCER MORTALITY IN MEXICO, 1990-2014
survival of advanced lung cancer in patients treated at a private institution Laura Tirado1, Laura-Alejandra Ramírez-Tirado2, Oscar Arrieta2
1
(Oncosalud – AUNA). Methods: We analyzed data of 75 patients with Public Health, Faculty of Medicine, National Autonomous University of Mexico,
advanced lung cancer and treated at Oncosalud-AUNA between 2013-2014. Mexico City/Mexico, 2Thoracic Oncology Unit and Laboratory of Personalized
Overall survival was determinate using Kaplan-Meier method and survival Medicine, Instituto Nacional de Cancerología, Mexico City/Mexico
curves comparison were performed using logrank test. Results: The median
Background: Mortality from lung cancer ranks first in men and third in
age was 70 years (range: 39-91) and 49% of patients were women. In patients
women in Mexico. We aim to assess the mortality rate from lung cancer in
with clinical stage IV, the metastatic sites were generally brain (28%),
the Mexican population during the period from 1990 through 2014. Methods:
osseous (18%), cervical and supraclavicular (14%). The 66.7% of patients
In this longitudinal study we analyzed the mortality rate of lung cancer,
received chemotherapy with/without radiotherapy, 9% radiotherapy only
adjusted for age, sex and degree of marginalization. The mortality rate was
and 24% non-treatment. In patients previously treated with chemotherapy,
adjusted applying the direct method. In adittion, we used the 2010 Mexican
52% received targeted therapy. The 77% of patients hab died, the follow-up
Population,which was taken from the Population and Housing Census.
median of survivors was 23 months (CI95%: 17-29), survival median was 9.6
Deaths were taken from the mortality database of the Ministry of Health
months (CI95%. 5.6-13.5) and 1 and 2 years survival rate were 38% and 23%,
of Mexico. The degree of marginalization of the population was made based
respectively. The survival rate at 1 and 2 years in those receiving targeted
on the marginality index established by the National Population Council,
therapy ware 65% and 43%, and those who did not receive were 35% and 10%.
it includes five categories of marginalization: Very low, low, medium, high
The overall survival present a difference regarding to ECOG scale (p = 0.015)
and very high. The 33 states of the Mexican Republic are divided into these
and CYFRA 21.2 (p = 0.04). Conclusion: Overall survival for our patients is
categories, approximately being six to seven in each. Finally, the annual
similar to other series. Patients under ECOG scale <2 and CYFRA 21.1 < 3.3ng/
percentage change was calculated. Results: During the study period a
ml had a relatively better prognostic.
decrease we observed a decrease in the lung cancer mortality rate adjusted
Keywords: Lung cancer, overall survival for age and gender. Thus, the rate in 1990 was higher (110 deaths per 100,000
population), which decreased to 90 per 100,000 in 2014, representing a
decrease of more than 15%. In relation to gender we observed a decrease in
the mortality rate for both genders. In addition, the mortality rate in women
was three times lower from that among men througout the whole period of
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ study. Nonetheless, we observed a slight increasing trend for women in the
PREVENTION
last years. Regarding the marginalization index we observed that the highest
MONDAY, DECEMBER 5, 2016 mortality rates occur in the states that comprise the categories with low and
very low marginalization. Moreover, decline in mortality was also observed in
those categories, unlike the categories of high and very high marginalization,
P1.01-051 PREDICTOR VARIABLES TO ECOG SCALE OF where a slightly increase was observed during the period of study. Conclusion:
PERFORMANCE STATUS IN LUNG CANCER AT A DEVELOPING Mortality from lung cancer has declined during the studied period, a situation
COUNTRY IN LATIN AMERICA that may be due to various situations such as diagnosis at earlier clinical
Silvia Josefina Ayala Leon1, Miguel Antonio Agüero Pino1, Cinthia Viviana stages or treatments more effectively, or under registry of mortality in the
Gauna Colás1, Miguel Ayala León2 states that make up the categories with high or very high marginalization.
1
Capiata, National Cancer Institute Prof.Manuel Riveros, Capiata/Paraguay, Such situations must be studied in greater depth to identify the causes for the
2
Mexico DF, National Institute of Cardiology Ignacio Chavez, Mexico DF/Mexico decline in mortality from lung cancer.
Background: We need to understand the living quality in our population, so Keywords: Degree of marginalization, Mexico, lung cancer, Mortality rate
we review performance status focus on ECOG 3,4,5 that includes a concept of
capable of limited self-care, because this increases expenses at families and
health system. We need to understand the variables that increases risk of

POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ Institution 1030 patients underwent anatomical lung resection for lung cancer
PREVENTION
DESCRIPTIVE EPIDEMIOLOGY –
between 1986 and 2015. 64.5% were males, average age 62.1 years, 40.6%
MONDAY, DECEMBER 5, 2016 squamous cell carcinoma and 44.5% adenocarcinoma, 23% advanced stage
IIIA. The female proportion increased from 26.6% on first period to 44.2% on
last period. Mean age at surgery treatment was 56.4 years for women and 58.9
P1.01-053 LUNG CANCER IN BRAZIL: MEN AND WOMEN for men on first period, and 62.2 for woman and 64.6 for men on the last period
DIFFERENCES (p<0.001). The proportion of squamous cell changed from initially 49.6%,
Maria Teresa Ruiz Tsukazan1, Álvaro Vigo2, Vinícius Duval Da Silva1, Arthur then 43% to 34.8% on the last period (p<0.001). In comparison in the same
Vieira1, Renata Rosenthal1, Flavio Cabral1, Gabriel Schwarcke1, João Schmitt1, sequence we have for adenocarcinoma prevalence starting on 38.1%, 41.2%
Maicon Cimarosti1, Jayme Rios1, José Antônio Figueiredo Pinto1 and most recently 49.5%. Stage IIIA was predominant on all periods with 23%,
1
Hospital São Lucas Da Pucrs, Porto Alegre/Brazil, 2Universidade Federal Do Rio however early stages IA and IB combined represent 47.1% in the last group.
Grande Do Sul - Ufrgs, Porto Alegre/Brazil Type of surgery was predominantly lobectomy and was verified decreasing in
pneumonectomy rate. Conclusion: Analyses including gender showed that lung
Background: The objective of this study was to describe the trends of cancer in women is raising over the years but didn’t surpassed men yet. Women
histology and age of patients with non-small cell lung cancer (NSCLC) treated adenocarcinoma has increased the participation on total cases. The significant
with lung resection according to gender. The histology of lung cancer is decrease of pneumonectomy reinforces the changes on surgical management
changing in developed countries and there is still little information available technics and also correlates with more early staging diagnosis. The mean
for developing countries. Methods: Retrospective analysis of all patients average age on surgery has increased for both men and women.
(N=1030) with resected NSCLC between 1986 and 2015 in a university hospital
of Southern Brazil. Differences in histology, stage and type of surgery were Keywords: histology, gender, lung cancer, epidemiology
analyzed by sex and period (1986-1995, 1996-2005 and 2006-2015). Results:
Most patients were males (64.5%), main histologic types were
adenocarcinoma (44.5%) and squamous cell carcinoma (40.6%). Mean age at
surgery was 56.5 years for women and 58.9 years for men in first period, and
62.2 for women and 64.6 for men in the last period (p<0.001), suggesting that PREVENTION
it was approximately 2.4 years higher for men (p<0.001), in spite of the period. DESCRIPTIVE EPIDEMIOLOGY –
The proportion of histologic types were different by gender (p<0.001), MONDAY, DECEMBER 5, 2016
showing that overall squamous cells carcinoma was more frequent in men
(46.9%) than in women (29%), and the opposite occurred for adenocarcinoma
P1.01-055 CLINICOEPIDEMIOLOGICAL TRENDS OF LUNG CANCER
(40.4% versus 51.8% for men and women, respectively). Analyses by period
FROM A PREMIER REGIONAL CANCER CENTRE IN SOUTH INDIA
showed squamous cells carcinoma declined from around 38.9% in the first
period to 23.2% in 2005-2015 for men, virtually equaling the proportion of Abhijit Das, Arvind Krishnamurthy
adenocarcinoma in the last period. The proportion of adenocarcinoma in Surgical Oncology, Cancer Institute (Wia), Chennai/India
women increased from 11.9% in the first period to 24% in the last. Considering
all NSCLC patients, females with adenocarcinoma represented 11.9% in the Background: Lung Cancer is one of the leading causes of morbidity and
first and 24% in the last period. mortality worldwide. It is most commonly attributed to smoking; a smaller
proportion is attributed to occupational exposure. However, an earlier
published study by Krishnamurthy et al 2012 from the authors institute
reported the increasing trends of “Nonsmoking associated lung cancers” in
the Indian subcontinent. A larger prospective study aimed at validating the
initial findings was planned and this formed the basis of the present study.
Methods: All consecutive histologically confirmed patients with lung cancer
who presented to the outpatient department over a year (November 2014 to
October 2015) were included in this current prospective study. A comprehensive
questionnaire administered by a trained social worker captured all the
demographic details including age, sex, occupation, smoking habits including
exposure to second hand smoke, type of cooking fuel, histopathology and
stage at presentation among others. (And later analyzed by SPSS Version 22.0)
Conclusion: As seen in developed countries, rates of lung cancer in females are Results: 713 patients presented with clinico-radiologicaly suspicious findings
rising over the last three decades, but have not surpassed men rates yet. of lung cancer in the said period. A pathological confirmation of lung cancer
Adenocarcinoma is consistently the most frequent histological type in could be ascertained in 495 patients and this cohort was further analyzed.
women. In men squamous cell rate has decreased. The median age of presentation was 58 years; the male to female ratio was
approximately 2.5:1. 52.12 % patients were nonsmokers. Adenocarcinoma
Keywords: lung cancer, epidemiology, histology, gender (63 %) was the predominant histology. Nonsmokers, both among men
(p=0.02) and women (0.001) presented more frequently with adenocarcinoma
histology. Interestingly, 84.9 % (45/53) rural and 76.1 % (19/25) urban women
who were nonsmoker reported exposure to indoor air pollution (second hand
smoke/fuel used for cooking purposes) which was significantly associated
POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/ with adenocarcinoma histology. (p=0.01) A majority of the patients (69.1 %)
PREVENTION
DESCRIPTIVE EPIDEMIOLOGY – presented with clinical stage IV. (7th edition TNM) Nearly 60% of patients
MONDAY, DECEMBER 5, 2016 presented in ECOG performance status 3-4, nonsmokers incidentally presented
in a better performance status than smokers (p = 0.017). 53% of the patients
unfortunately were deemed suitable only for best supportive care. Only 97
P1.01-054 LUNG CANCER: HISTOLOGY, GENDER AND AGE CHANGES patients (19.6 %) were offered potentially curative treatment and radical
OVER PAST 30 YEARS IN BRAZIL surgery accounted for < 3 % of the overall management. Conclusion: This
Maria Teresa Ruiz Tsukazan1, Álvaro Vigo2, Vinícius Duval Da Silva1, Flávio prospective study validated our initial observation of the increasing trends of
Cabral1, Renata Rosenthal1, Arthur Vieira1, Jayme Rios1, José Antônio lung cancers among nonsmokers. Further, this study also reflected the global
Figueiredo Pinto1 trend of rise in adenocarcinoma histology. These findings in a larger perspective
1
Hospital São Lucas Da Pucrs, Porto Alegre/Brazil, 2Universidade Federal Do Rio will help clinicians better understand the magnitude and the direction of the
Grande Do Sul - Ufrgs, Porto Alegre/Brazil lung cancer epidemic and also aid policymakers in better channelizing the
resources for effective public health interventions.
Background: Lung is the leading death cause cancer related worldwide when
considering both genders. The great effort to reduce smoking and introduce Keywords: smoking, lung cancer, epidemiology, Adenocarcinoma
of cigarette changed lung cancer epidemiology. In developed countries the
increase of adenocarcinoma and decrease of squamous cell carcinoma are well
known. Other characteristic reported is the rising number of with the disease.
Better understanding of current lung cancer epidemiology is necessary to
design public health strategies for prevention, diagnosis and treatment. POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
Methods: Retrospective analysis of all patients with non small cell lung DESCRIPTIVE EPIDEMIOLOGY –
cancer submitted to anatomical lung resection between 1986 and 2015 in an MONDAY, DECEMBER 5, 2016
University Hospital of South Brazil. Patients were divided in three periods
1986-1995, 1996-2005 and 2006-2015. The same pathologist group made
P1.01-056 LUNG CANCER EPIDEMIOLOGY IN CROATIA
histology diagnosis and all staging was updated according to the new IASLC
7th edition. All analyses were performed using the SAS program. Results: In our Robert Zorica, Vida Popović, Toni Božinović
University Hospital “split”, Split/Croatia POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
PREVENTION
Background: To analyze principal histological types of lung cancer, as well MONDAY, DECEMBER 5, 2016
as sex and the age of patients, staging, tumor location, smoking history,
Chronic obstructive pulmonary disease (COPD) history, and survival of lung
cancer patients in Croatia. Methods: This was a retrospective study based on P1.01-058 DEMOGRAPHIC PROFILE OF LUNG CANCER FROM
the analysis of medical charts of patients treated at the University Hospital EASTERN INDIA
„Split“, Split, Croatia, during 2015. and 2016. Results: From July 2015 to Prasanta Mohapatra1, Sourin Bhuniya2, Manoj Panigrahi2, Susama Patra2,
February 2016, 332 patients with lung cancer, most of whom (75,30%) were Pritinanda Mishra3, Gourahari Pradhan2, Saroj Das Majumdar2, Priyadarshini
male, were treated. Patients were between 36 and 85 years, with median age Behera2, Dillip Muduly2, Madhabananda Kar2
65,5 years. There were 273 (84,78%) patients with NSCLC (Non-Small Cell 1
Pulmonary Medicine, All India Institute of Medical Sciences, Bhubaneswar/India,
Lung Cancer) and 49 (15,22%) patients with SCLC (Small Cell Lung Cancer). The 2
All India Institute of Medical Sciences, Bhubaneswar/India, 3Pathology, All India
most common histological type in patients with NSCLC was adenocarcinoma Institute of Medical Sciences, Bhubaneswar/India
(58%), followed by squamos cell carcinoma (38%), NSCLC NOS (not otherwise
specified) (2%), adenosquamos carcinoma (1%) and large cell carcinoma (1%). Background: The clinico-pathological profile of primary lung cancer has
Among patients with NSCLC 13% are EGFR positive. Patients had mostly lung changed considerably over the last few decades in India. Available literature
cancer in right lung (59,35%), most of them were smokers (88,40%), 20,70% suggests that the features of lung cancer in India like prevalence, incidence,
patients had COPD and 21,05 % patients had pleural effusion. Concerning aetio-pathogenesis and presentation vary markedly from the west. We
staging, 73,80% patients had stage IIIB and IV at the time of diagnosis, and performed a prospective evaluation of the unique demographic features of
the remaining 26,20% were classified as stage I-IIIA. The principal sites of lung cancer with specific emphasis on smoking and histopathological trends.
metastases were lungs (24,45%), bones (23,6%), and liver (12,9%). One- Methods: We analysed all pathologically proven lung cancer cases registered
year survival was 23,21% and median overall survival was 8,82 months for over a period of initial 30 months in the department of Pulmonary Medicine of
patients presented with stage IIIB and IV. Median age at death was 67,5 years. this All India Institute of Medical Sciences, Bhubaneswar. The patients were
Conclusion: In accordance with the literature most of the lung cancer patients evaluated for their epidemiological, clinical and pathological profiles. The
in Croatia are men, older age (but younger compared to developed countries), data were recorded in MS Excel spreadsheets and subjected to appropriate
the most common histological type is adenocarcinoma. Most of the patients statistical analysis. Data was collected directly from patients’ paper and
have cancer in the right lung, most of them are smokers and minority had electronic medical records. All patients of histologically proven lung cancer
COPD or pleural effusion. Most cases are presented in advanced stages at the were included. Results: A total of 179 patients were included in the database
moment of diagnosis. This affects on survival rate, which is lower compared of which 6 patients were excluded for significant missing data. There were
to developed countries. To increase survival rate in Croatia smoking cessation 114 male and 59 women) average age 57.24 with a M:F ratio of 1.93 :1. Over half
should be encouraged, lung cancer screening, diagnosis and therapy should be (56%) of the patients were active or past smokers, while 48% patients had
improved, patients should be included in clinical trials and palliative care for not been exposed to active or passive smoking. Bidi (tobacco flake wrapped in
terminal patients should be improved. tendu leaf) smoking was more common (37%) than cigarettes (19%) while 9%
smoked both. Exclusive chewed tobacco use was seen in 12% while combined
Keywords: lung cancer, epidemiology, Croatia use of chewed and smoked tobacco was seen in 4% patients. The proportion
of women never-smokers with lung cancer was significantly higher (89%)
compared to men (28%). More than two-thirds patients (69.8%) presented
with metastatic disease. Amongst patients with a definitive cytohistological
diagnosis, the prevalence of adenocarcinomas was highest (56.3%) followed
PREVENTION by squamous (30.8%), small cell (8%) and NSCLC NOS (4.9%). Conclusion:
DESCRIPTIVE EPIDEMIOLOGY – Adenocarcinoma is the commonest histological subtype in this region.
Prevalence of lung cancer among non-smokers is also high in the eastern part
of India. The demographic profile of patients with lung cancer in eastern India
P1.01-057 METASTATIC LUNG CANCER AT A TERTIARY CANCER is unique with a much higher proportion of tobacco chewers and non-smoker
CENTRE IN SOUTH INDIA especially in women. There is significant epidemiological trends towards a
predominant adenocarcinoma histology. Most of the patients present at an
Govind Babu, Lakshmaiah Kc, Mangesh Kamath, Lokanath D
advanced stage, probably due to lack of awareness and limited diagnostic
Medical Oncology, Kidwai Memorial Institute of Oncology, Karnataka/India resources in this part of the country. Although there are direct association
with smoking, there has been an increase in the non-smoking lung cancers
Background: Nonsmall cell lung cancer (NSCLC) has varying epidemiological
worldwide.
patterns in different countries and also in different regions of each country.
In a country with a high prevalence of lung cancer such as India, regional Keywords: smoker, never-smoker, lung cancer, demography, India
variations in demography exist. Methods: We did a retrospective analysis
of histologically confirmed metastatic NSCLC patients who presented to
our Department of Medical Oncology between August 2012 and July 2014.
The patients were interviewed regarding their history of smoking (never
smokers, light smokers, and heavy smokers). Never smokers were defined as POSTER SESSION 1 - P1.01: EPIDEMIOLOGY, TOBACCO CONTROL AND CESSATION/
those who have smoked <100 bidi/cigarettes in their life until disease onset. PREVENTION
Light smokers were defined as those who smoke <10–100 bidi/cigarette pack MONDAY, DECEMBER 5, 2016
years. Heavy smokers were defined as those who smoke more than 100 bidi/
cigarette pack years until disease. All lung cancer biopsy specimens were
histologically characterized by morphology and immunohistochemistry (IHC). P1.01-059 LUNG CANCER EPIDEMIOLOGY AMONG THE BAHRAINI
A diagnosis of AC was made if IHC staining was positive for CK7, TTF1, and POPULATION, 2000-2011
napsin A; similarly, SCC was diagnosed if CK5/6 and p63 staining was positive. Najat Abulfateh1, Randah Hamadeh2, Majida Fikree1
After confirmation of the histology subtype, patients were confirmed 1
Ministry of Health, Manama/Bahrain, 2 Arabian Gulf University, Manama/Bahrain
to have metastatic disease after assessment with contrastenhanced
computerized tomography thorax, abdomen scan, and radiolabeled bone Background: Lung cancer is the fourth most common cancer in the Gulf
scan. Our study did not include the small cell lung cancer patients. The data Cooperation Council countries among males and the third among females.
were analyzed on SPSS version 22 (IBM) software. Results: A total of 304 It is the commonest cancer among Bahraini males accounting to 16.9% of all
patients were analyzed. About 55.6% of the patients were in the age group cancers and the third in Bahraini females contributing to 5.8 % of all female
of 41–60 years. About 79.6% of the patients were symptomatic for <6 months cancers. The aim of this study was to describe the epidemiology of lung cancer
before presentation. About 63.5% of the patients were smokers presenting among the Bahraini population during the period 1998-2011. Methods: All
with a median age of 59 years whereas nonsmokers formed 36.51% of the Bahraini registered lung cancer cases in the national cancer registry from
patients presenting with a median age of 47 (P < 0.001). About 82.6% of the 1 January 1998 to 31 December 2011 were included in the study. Incidence
male patients and 4.1% of female patients were smokers. Equal number of rates were calculated using the CANREG software, in which the annual
all patients had adenocarcinoma (AC) and squamous cell carcinoma (SCC) crude incidence rates, age specific incidence rates and the age standardized
histology. AC histology was more common in the nonsmoking group (62% incidence rate (ASR) were computed. Results: Six hundred sixty four lung
of patients). SCC histology was seen in 54.3% of smokers. Metastasis to the cancer cases (72.4%, males and 27.6% females) were diagnosed during the
contralateral lung and pleura was seen in 58.2% of patients. Conclusion: study period. The annual average number of cases was 47.5 per year. The mean
NSCLC presents at a young age. Smoking is a significant risk factor and it age at diagnosis during the study period was 70.1 years. The average annual
is common in the urban populations as in the rural areas. Both AC and SCC ASR was 26.1/ 100,000 among males and 10.0 / 100,000 among females. There
histologies presented in equal proportions was a tendency for a decreased trend of the ASR during 1998-2011 in both
sexes. Twenty six percent of lung cancer cases were squamous cell carcinoma
Keywords: non small cell lung cancer, south India and 17.9% adenocarcinoma. The grades of 70.3% were unknown and 13.4%

were poorly differentiated. The stage was unknown for 65.0% of the cases, in individual NSCLC patients. We hypothesize that T790M mutation may
while 18.5% had distant metastasis and 9.8% were localized. The majority be a “regulating” mechanism for EGFR signal transduction pathway and is
(88.9 %) of the lung cancer cases were dead by the end of the study period probably cleared quickly by DNA repair system in healthy persons. Methods:
with a five-year survival rate of 3.0%. Conclusion: A welcomed decline in the Peripheral blood samples were taken from 50 healthy volunteers, 12
incidence of lung cancer has been noted over the past 14 years. However, resectable lung adenocarcinoma (LADC), 100 advanced LADC (11/100 acquired
more efforts should be put to reduce the proportion of lung cancer cases resistance for gefitinib). A novel cSMART assay (circulating single-molecule
with unknown stage and grade. The incidence of histological types, which are amplification and resequencing technology, which counts single allelic
strongly dependent on tobacco smoking, notably small cell, squamous cell molecules in plasma base on next generation sequencing) was performed
and large cell carcinomas, accounted for over one third of lung cancer cases. for detection and quantitation of EGFR mutation in ctDNA from plasma.
Future research should be directed towards better understanding of the lung Matching tumor biopsy samples were obtained from 100 advanced LADC, the
cancer risk factors and the effectiveness of tobacco control measures in in the EGFR gene mutations were determined by amplification refractory mutation
country. system (ARMS) -PCR analysis. Results: The sensitivity and specificity of
cSMART plasma assay for EGFR L858R, 19del and T790M was showed in Table
Keywords: Trends, Cancer Registry, epidemiology, lung cancer 1. The sensitivity and specificity for T790M was obviously lower (50.0% and
72.9% respectively). No L858R and 19del but 14.0% T790M DNA copies were
found in plasma from 50 healthy volunteers, and only 1 copy T790M was
detected. The T790M positive rate of resectable and advanced LADC patients
were almost similar (33.3% and 28.0%) in plasma, 1 or 2 T790M copies were
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY found in the resectable patients and varied from 1 to 622 T790M copies
Driver Genes in NSCLC, Resistance, and Other – with an average of 34.0 in advanced LADC patients. Patients with acquired
MONDAY, DECEMBER 5, 2016 resistance to gefitinib, 45.4% harbored T790M with an average of 268.2 copies
in plasma. All but one advanced patients harboring T790M mutation were
accompanied with other EGFR mutations. Conclusion: T790M mutation may
be of a “regulator” and has physiological function.
P1.02-001 EXPRESSIONS OF RESISTANCE EGFR TKIS IN NON SMALL
CELL LUNG CANCERAT PHAM NGOC THACH HOSPITAL - VIET NAM
Table 1 EGFR mutations detection by plasma cSMART assay
Nguyen Lam1, Tran Thanh2, Nguyen Nhan3, Nguyen Vu2 and tumor samples ARMS-PCR in advanced LADC patients
1
Pathology Department, Pham Ngoc Thach Hospital, Ho Chi Minh City/Viet Nam,
2
Oncology Department, Pham Ngoc Thach Hospital, Ho Chi Minh City/Viet Nam, EGFR mutations Sensitivity Specificity
3
Oncology Department, The No. 115 People, Ho Chi Minh City/Viet Nam L858R 91.7%(22/24) 100.0%(76/76)
Background: In the patients with NSCLC were tested for diagnostic EGFR 19Del 79.2%(19/24) 100.0%(76/76)
mutation, in addition to activating mutations, such as Exon 19 Deletion & Exon
T790M 50.0%(2/4) 72.9%(70/96)
21 L858R that is occupies a large amount. The mutation is said to be resistant
to EGFR TKIs occupies smaller amount. However, this is also a challenge for Keywords: next generation sequencing, ctDNA, non-small cell lung cancer,
the care and treatment for patients with NSCLC. Methods: Retrospective, T790M
cross-sectional descriptive statistics, clinical case series. Results: PRIMARY
MUTATIONS WITH EGFR TKIs RESISTANCE §Activating EGFR Mutations:
Exon 19 Deletion: 356/597 cases = 59,63% and Exon 21 L858R: 176/597 cases
= 29,48%. §Primary Mutations with EGFR TKIs Resistance - Single mutations:
46/597 cases = 7,71% (Male: 27 cases + Female: 19 cases), including: Exon 20 POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
Insertion: 25 cases, Exon 18 G719X: 14 cases, Exon 20 S768i: 5 cases, Exon DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
20 T790M: 2 cases. §Primary Mutations with EGFR TKIs Resistance - Double
mutations: 19 / 597 cases = 3,18% (Male: 11 cases + Female: 8 cases), including:
Exon 21 L858R + Exon 20 T790M: 6 cases, Exon 19 Deletion + Exon 20 T790M: P1.02-003 ROS1 (D4D6) IS RELIABLE FOR IMMUNOHISOCHEMISTRY
5 cases, Exon 18 G719X + Exon 20 Insertion: 2 cases, Exon 21 L858R + Exon 20 DETECTING OF ROS1 FUSION LUNG ADENOCARCINOMA IN
G786i: 3 cases, Exon 18 G719X + Exon 20 S768i: 3 cases. ACQUIRED MUTATIONS MALIGNANT PLEURAL EFFUSION
WITH EGFR TKIs RESISTANCE §Total cases with the gene mutation diagnosis
Zheng Wang 1, Dongge Liu1, Yuankai Shi2, Xinlin Mu3, Xiaohong Han4, Li Yang1,
repeating again (Sampling with Histology or Cytology): 113/597 cases (18,93%).
Jing Di1
Detection rate for new resistance EGFR TKIs mutations: Number of Cases: 56 1
cases/113 cases (49,56%). §Distribution rate % of acquired resistance mutations Beijing Hospital, Beijing/China, 2Department of Medical Oncology, Cancer
Institute and Hospital Chinese Academy of Medical Sciences Peking Union Medical
in EGFR TKIs: · Exon 20 T790M (Single & Double Mutations): 28 cases (50 %) ·
College, Beijing/china, Beijing/China, 3Department of Respiratory and Critical Care
MET Amplification: 4 cases (7,14 %) · HER2 Amplification: 13 cases (23,21 %) · Medicine, Peking University People’s Hospital, Beijing/China, 4 Cancer Institute
Small Cell Carcinoma Transformation: 5 cases (8,93 %) · PIK3CA Mutation: 2 and Hospital Chinese Academy of Medical Sciences Peking Union Medical College,
cases (3,58 %) · The Other Mutations: 4 cases (7,14 %) §The expression of EGFR Beijing/china, Beijing/China
T790M mutation: T790M Single Mutation: 14 cases; T790M + Exon 20 Insertion:
3 cases; T790M + A763V: 4 cases; T790M + L777G: 1 case; T790M + Y801C: 3 Background: ROS1 fusion is of a low frequency genetic alteration in non-
cases; T790M + G719X: 2 cases; T790M + S768i: 1 case. Conclusion: § There are small cell lung cancer (NSCLC). The clinical trial showed that NSCLC patients
the expressed resistance mutations EGFR TKIs in NSCLC patients at Pham harboring ROS1 fusion could benefit from crizotinib treatment. Several
Ngoc Thach Hospital, including: Primary EGFR TKIs Resistance & Acquired studies reported that immunohistochemistry (IHC) could be employed as a
EGFR TKIs Resistance. § The rate of drug-resistant mutant EGFR TKIs are screening method for detecting ROS1 fusion in tumor tissue using Anti-
small but still important issues in the Care and Treatment of lung cancer. ROS1(D4D6) antibody. Malignant pleural effusion (MPE) is the common
sample type in advanced NSCLC, the reliability of ROS1(D4D6) for detecting
Keywords: EGFR TKIs Resistance Mutations, Primary Resistance Mutations, ROS1 fusion in MPE cell blocks (CBs) should be explored. Methods: Anti-
Acquired Resistance Mutations, EGFR TKIs ROS1(D4D6) monoclonal antibody (Cell Signaling Technology, Danvers, USA)
IHC testing was performed on 227 formalin fixed paraffin embedded (FFPE)
MPE CBs from lung adenocarcinoma patients. RT-PCR using ROS1 fusion gene
detection kit (AmoyDx) was performed to detected ROS1 gene fusion as a
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
comfirming test. Some other lung cancer driver genes were also detected in
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – both IHC/RT-PCR ROS1 positive samples, among which EGFR, KRAS, BRAF,
MONDAY, DECEMBER 5, 2016 PIK3CA and HER2 20 exon mutation was tested by amplification refractory
mutation system kits(AmoyDx), ALK and RET fusion was tested by RT-PCR
kits(AmoyDx). Results: 4 of 227 MPE samples(1.76%) of lung adenocarcinoma
P1.02-002 IS T790M MUTATION A “REGULATOR” FOR EGFR SIGNAL
were interpreted as ROS1 fusion-positive cases by IHC staining, and the
PATHWAY NOT AN ONCOGENE?
cytoplasmic and membranous granular positive signals were displayed.
Zheng Wang 1, Dongge Liu1, Yuankai Shi2, Xiaohong Han2, Hongfeng Tong 3, Comparison with RT-PCR testing results, 3 of 4 IHC positive cases were
Qingjun Wu3, Jianguang Zhang4, Tianyang Wang4, David Cram4 verified by RT-PCR, the sensitivity was 100% and specificity of was 99.6%.
1
Pathology, Beijing Hospital, Beijing/China, 2Cancer Institute and Hospital Chinese The clinicopathologic features and other genes status of 3 both IHC/RT-PCR
Academy of Medical Sciences Peking Union Medical College, Beijing/China, 3Beijing positive patients were showed Table 1. One ROS1 IHC/RT-PCR positive lung
Hospital, Beijing/China, 4Berry Genomics, Beijing/China adenocarcinoma patient received crizotinib therapy and obtained partial
response. Conclusion: ROS1 (D4D6) would be a reliable antibody for screening
Background: Threonine 790 is regarded as a “gatekeeper” to inhibit ATP from
ROS1 fusion-positive lung adenocarcinoma on FFPE MPE CBs by IHC assay and
binding to EGFR Tyrosine kinase domain. T790M mutation could increase
shows high specificity in the FFPE MPE CBs samples .
the affinity for ATP. About 30% de novo T790M mutation was detected in
NSCLC patients and showed spatiotemporal heterogeneity and variation
Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase

Table 1 Clinicopathologic features and genes status of ROS1 IHC/RT-PCR
positive patients inhibitors have improved the outcome of patients with EGFR-mutated lung
adenocarcinoma (ADC). However, EGFR mutation occurred in about only
E/k/ 10-15% of ADC, but other alterations are emerging as potential target of
PFS/
TTF1/ B/ Effi- drugs. We analyzed the frequency of potentially targetable driver alterations
Gender Age Smoking A/R Therapy Follow
P63 P/ cacy
-up in a series of advanced EGFR-wild type (wt) NSCLC patients. Methods: 724
H
advanced EGFR-wt NSCLC patients enrolled from the Wide Catchment Area
crizo- 10m+/ of Romagna (AVR) between January 2013 to December 2014 were included
p1 Male 55 Smoker +/- WT WT PR
tinib alive in the study. KRAS, BRAF, ERBB2, PIK3CA, NRAS, ALK, MAP2K1, RET and
DDR2 mutations were analyzed by Myriapod®Lung Status kit (Diatech
1m/
p2 Female 60 Never +/- WT WT No Pharmacogenetics) on MassARRAY® (SEQUENOM® Inc, California). ERBB4 was
Dead
evaluated by direct sequencing and EML4-ALK and ROS1 rearrangements were
PEM 9m+/ assessed by immunohistochemistry or fluorescence in situ hybridization.
P3 Male 62 Never +/- WT WT PR
+CIS alive Results: 331 (45.7%) patients showed at least one alteration. Of these, 72.2%,
6.3%, 3.6%, 1.8%, 2.1% and 1.2% patients had mutations in KRAS, BRAF,
E/K/B/P/H: EGFR/KRAS/BRAF/PIK3CA/HER-2 20 exon mutation, A/R: ALK/ PIK3CA, NRAS, ERBB2 and MAP2K1 genes, respectively. Only one patient
RET fusion, WT: wild type, PEM+CIS: Pemetrexed plus Cisplatin,PR: partial showed a mutation in ERBB4 gene. EML4-ALK and ROS1 rearrangements were
response, m: months observed in 4.3% and 1.4% of all patients, respectively. The distribution of
mutations in relation to gender and smoking habits is reported in the Table.
Keywords: non-small cell lung cancer, ros1, Immunohistochemistry, RT-PCR
Overlapping mutations were observed in 7 KRAS-mutated patients: 2 (28.6%)
patients were also mutated in PIK3CA, 4 (57.1%) showed also an EML4- ALK
translocation and one (14.3%) had a ROS1 rearrangement. One (0.3%) patient
showed both BRAF and PIK3CA alterations. Correlation analyses between the
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY different mutations and patient outcome are ongoing.
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
Gender Smoking Habits*
Mutated
GENE Patients Never
P1.02-004 A RETROSPECTIVE ANALYSIS OF FREQUENCY OF ALK Female Male Smoker
N (%) Smoker
GENE REARRANGEMENT IN SAUDI LUNG PATIENTS (%) (%) (%)
(%)
Fouad Al Dayel1, Shamayel Mohammed2, Asma Tulbah2, Hamad Al Husaini3
1 KRAS 239 (33) 93 (39) 146 (61) 115 (48.1) 9 (3.8)
Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research
Centre, Riyadh/Saudi Arabia, 2Pathology and Laboratory Medicine, King Faisal BRAF 21 (3) 11 (52.4) 10 (47.6) 11 (52.4) 1 (4.8)
Specialist Hospital and Research Center, Riyadh/Saudi Arabia, 3Oncology Center,
King Faisal Specialist Hospital and Research Center, Riyadh/Saudi Arabia NRAS 6 (0.8) 4 (66.7) 2 (33.3) 4 (66.7) -
PIK3CA 12 (1.6) 4 (33.3) 8 (66.7) 5 (41.7) -
Background: Lung carcinoma represents 2.9% of cancers seen at King Faisal
Specialist Hospital and Research Centre (KFSH&RC) as per KFSH&RC Tumor MAP2K1 4 (0.5) - 4 (100) 1 (25) -
Registry (2013), and 4% of cancers in Saudi Arabia as per National Cancer
ERBB2 7 (0.9) 5 (71.4) 2 (28.6) - 1 (14.3)
Registry (2010). EML4-ALK re-arrangement play an important oncogenic
driver role in lung adenocarcinoma tumorgenesis in 3-5% of cases. ALK gene 20
EML4-ALK 31 (4.3) 11 (35.5) 12 (38.7) 8 (25.8)
rearrangement (inversion in chromosome 2) testing can identify patients with (64.5)
adenocarcinoma who are sensitive to ALK tyrosine kinase inhibitors. No data
ROS1 10 (1.4) 7 (70) 3 (30) 3 (30) 5 (50)
is available on the prevalence of ALK rearrangement changes in Saudi lung
cancer patients. The aim of this study is to evaluate the prevalence of ALK *: some data are missing Conclusion: Driver mutations were detected in about
gene rearrangement in lung adenocarcinoma of Saudi patients. Methods: A 50% of EGFR wt lung ADC patients. Such alterations could represent potential
total of 172 cases of lung adenocarcinoma diagnosed at KFSH&RC between targets for therapy and could be evaluated in routine multiplexed testing to
January 2013 to May 2016 were identified. Formalin-fixed paraffin embedded obtain a wider tumor molecular characterization.
tissue samples of these patients were analyzed for ALK gene rearrangement
using fluorescence in situ hybridization (FISH), utilizing break-apart probes Keywords: driver alterations, EGFR wt, MassARRAY
from Vysis (Abott Molecular, II, USA). Results: Eleven (11) cases exhibited ALK
gene rearrangement (6.4%). Nine out of eleven cases were stage IV and two
cases were stage III. Median patients age was 47 years (21-71 year) with male
predominance (males 77%, female 25%). All cases were moderately to poorly
differentiated adenocarcinoma. None of our cases showed signet ring cells or POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
abundant intracellular mucin. Conclusion: Our findings showed the incidence MONDAY, DECEMBER 5, 2016
of ALK gene rearrangement in lung adenocarcinoma in Saudi patients is 6.4%.
This is slightly higher in comparison to the published data which may be
attributed to KFSH&RC being a tertiary referral Center. P1.02-006 INTERLABORATORY VARIATION IN MOLECULAR TESTING
(EGFR, KRAS AND ALK) IN STAGE IV NON-SQUAMOUS NON-SMALL
Keywords: lung adenocarcinoma, ALK rearrangement CELL LUNG CANCER IN THE NETHERLANDS IN 2013
Chantal Kuijpers 1, Lucy Overbeek2, Sandra Rotteveel3, René Van Ommen4,
Koos Koole1, Henk-Jan Van Slooten5, Michel Van Den Heuvel6, Ronald
Damhuis7, Stefan Willems1
1
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY Pathology, University Medical Center Utrecht, Utrecht/Netherlands, 2Foundation
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – Palga, Houten/Netherlands, 3Roche, Woerden/Netherlands, 4Pfizer, Capelle Aan
MONDAY, DECEMBER 5, 2016 Den Ijssel/Netherlands, 5Symbiant Pathology Expert Centre, Alkmaar/Netherlands,
6
Thoracic Oncology, Netherlands Cancer Institute - Antoni Van Leeuwenhoek
Hospital, Amsterdam/Netherlands, 7Netherlands Comprehensive Cancer
P1.02-005 FREQUENCY OF ACTIONABLE ALTERATIONS IN EGFR Organisation (Iknl), Utrecht/Netherlands
WT NSCLC: EXPERIENCE OF THE WIDE CATCHMENT AREA OF
ROMAGNA (AVR) Background: Adequate testing for molecular changes in non-small cell lung
cancer (NSCLC) is necessary to ensure the best possible treatment. However,
Elisa Chiadini1, Angelo Delmonte2, Laura Capelli1, Nicoletta De Luigi2,
it is unknown how well molecular testing is performed in daily practice.
Alessandro Gamboni3, Claudia Casanova4, Claudio Dazzi4, Maximilian Papi5,
Therefore we aimed to assess the performance of testing for EGFR, KRAS
Sara Bravaccini1, Maria Maddalena Tumedei1, Alessandra Dubini6, Maurizio
mutation and ALK translocation in metastatic NSCLC on a nationwide basis.
Puccetti7, Lucio Crinò8, Paola Ulivi1
1 Methods: Using the Netherlands Cancer Registry, all stage IV non-squamous
Biosciences Laboratory, Istituto Scientifico Romagnolo Per Lo Studio E La Cura
NSCLC from 2013 were identified and matched to the Dutch Pathology
Dei Tumori (IRST) IRCCS, Meldola/Italy, 2Medical Oncology, Istituto Scientifico
Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) IRCCS, Meldola/Italy, 3Medical Registry (PALGA). Data on molecular testing for EGFR, KRAS and ALK were
Oncology, Degli Infermi Hospital, Faenza/Italy, 4 Medical Oncology, S. Maria extracted from excerpts of pathology reports. Proportions of tested and
Delle Croci Hospital, Ravenna/Italy, 5Medical Oncology, Infermi Hospital, Rimini/ positive cases were determined and interlaboratory variation was assessed.
Italy, 6Pathology Unit, Morgagni-Pierantoni Hospital, Forli/Italy, 7Pathology, S. Finally, degree of concordance between ALK immunohistochemistry (IHC)
Maria Delle Croci Hospital, Ravenna/Italy, 8 Medical Oncology, Santa Maria Della and fluorescent in situ hybridization (FISH) results was evaluated. Results: In
Misericordia Hospital, Azienda Ospedaliera Di Perugia, Perugia/Italy total, 3393 stage IV non-squamous NSCLCs were identified, and 3183 (93.8%)
were matched to PALGA. Fifty-two tumors were excluded as pathology

reports described a lung tumor other than non-squamous NSCLC or a tumor the unselected nature of this population. Many Alk+ patients were too
with another origin, leaving 3131 tumors. All 48 laboratories had access to unwell to receive chemotherapy or tolerated it poorly and did not have the
molecular testing, either in house or via outsourcing. The table shows the opportunity to access an alk inhibitor. First line Alk inhibitors may improve
nationwide proportions of cases tested and positive for EGFR, KRAS and outcomes for this group of patients.
ALK, as well as the interlaboratory variation. EGFR and KRAS mutations
occurred together in 8 patients, ALK translocation occurred together with Keywords: ALK, crizotinib
EGFR mutation in 3 patients and with KRAS mutation in 2 patients. In 272
cases, ALK had been tested using both IHC and FISH, and the methods were
conclusive in 253 cases. IHC and FISH were concordant in 239 cases (94.5%;
Kappa 0.728, p=0.069), 5 discordant cases were IHC+/FISH- and 9 were IHC-/
FISH+. DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
Nationwide proportions of tested and positive cases and interlaboratory

variation. P1.02-008 2-YEAR SINGLE INSTITUTION EXPERIENCE WITH EGFR
Range in PLASMA TESTING IN ADVANCED NSCLC
Tested Range in tested Positive
positive cases Izidor Kern1, Mitja Rot2, Jerneja Oman2, Katja Mohorcic2, Tanja Cufer2, Partha
Total cases; cases between cases; n
between
n (%) Laboratories (%) Das3
laboratories 1
University Clinic of Respiratory and Allergic Diseases Golnik, Golnik/Slovenia,
2237 2
University Clinic of Respiratory and Allergic Diseases, Golnik/Slovenia, 3Roche
EGFR 3131 33.7% to 93.5% 243 (10.9) 6.1% to 21.6%
(71.4) Molecular Systems, Pleasanton/CA/United States of America
2292 845 27.0% to Background: Lung adenocarcinoma patients in advanced stage of disease that
KRAS 3131 20.9% to 93.6%
(73.2) (36.9) 48.1% harbor EGFR sensitizing mutations are eligible for treatment with tyrosine
905 kinase inhibitors (TKI) due to a high likelihood of response. Most patients will
ALK 3131 7.0% to 72.6% 51 (5.6) 0% to 13.6% ultimately develop resistance at disease progression. The T790M mutation
(28.9)
is a dominant resistance mechanism to TKI. EGFR plasma testing enables
ALK (in non-invasive monitoring and detection of T790M. We followed patients
case of with EGFR sensitizing mutations by measuring EGFR mutations in plasma
685
EGFR and 1227 19.4% to 100%
(55.8) during TKI treatment. Methods: We analyzed patients who were diagnosed
KRAS
wildtype) lung adenocarcinoma stage IV, detected EGFR sensitizing mutations in
tumor tissue samples and treated with TKI at University Clinic Golnik. We
Conclusion: These results suggest that in 2013 molecular testing was collected baseline plasma samples prior to TKI treatment and consecutive
suboptimal in the Netherlands, especially for ALK. To determine whether plasma samples at different time intervals after initiation of therapy. At the
molecular testing has improved, 2015 data will be analyzed in the near future beginning, two separate tests, cobas® EGFR Mutation Test for tissue (CE-IVD)
as well. and plasma (under development) were used, and since October 2015 one test
for tissue and plasma, cobas® EGFR Mutation Test v2 (Roche, Pleasanton, CA,
Keywords: non-small cell lung cancer, molecular testing, interlaboratory USA) is used. Detected EGFR mutations in plasma samples were expressed
variation, quality assessment as semi-quantitative index (SQI) which reflects a proportion of mutated
versus wild-type copies of the EGFR gene. Results: During 2-year period we
collected 414 peripheral blood samples from 63 patients and performed 619
EGFR plasma tests. There are 25 patients with baseline and serial follow-up
EGFR plasma tests, 16 patients with only serial follow-up EGFR tests since
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – they started with TKI treatment before EGFR plasma testing was available, 5
MONDAY, DECEMBER 5, 2016 patients are included in adjuvant setting, and 17 patients had no monitoring
due to various reasons. Maximum number of EGFR plasma tests done per
patient was 27 at 20 time-points. When introducing EGFR plasma testing,
P1.02-007 ALK TRANSLOCATED NSCLC IN THE WEST OF SCOTLAND: we prepared two aliquots of plasma out of 10 ml blood sample in EDTA-tubes
PATIENT DEMOGRAPHICS AND OUTCOMES and run test for both aliquots. Results of reproducibility study showed 95%
Nicola Steele 1, Paul Westwood2, Stacey Parker2, Nicola Williams2, Craig Dick 3, concordance rate between both aliquots and thus we modified protocol to run
Leena Mukherjee1 the second aliquot only if the first one was negative. At disease progression,
1
Beatson West of Scotland Cancer Centre, Glasgow/United Kingdom, 2West of reappearance of EGFR sensitizing mutations with increasing SQI levels was
Scotland Genetics Services, Glasgow/United Kingdom, 3Pathology, Qeuh, Glasgow/ detected. In 14 patients who progressed we detected T790M mutation, in 10
United Kingdom of them during monitoring TKI treatment. We also observed daily variation in
EGFR mutation levels in the plasma. Conclusion: These data support the value
Background: A translocation in the anaplastic lymphoma kinase gene is found of EGFR plasma testing to monitor the patient`s response to TKI and detect
in 3-5% of non-small cell lung cancer (NSCLC). Patients with this mutation T790M resistance mutation prior to clinical progression in a routine clinical
(ALK+) have shown marked responses to the tyrosine kinase inhibitor setting.
crizotinib. Second line Crizotinib has been available in Scotland since October
2013 for patients with ALK+ NSCLC. Since January 2014, reflex testing at Keywords: EGFR mutations, T790M, plasma testing
diagnosis of all non-squamous NSCLC has been carried out in the West of
Scotland (WoS) regardless of stage. Here we present the demographics
of an Alk +ve cohort from an unselected Scottish NSCLC population and
their clinical outcomes. Methods: Details of patients with Alk+ NSCLC were
obtained from the regional molecular genetics laboratory. 60 patients with POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
NSCLC from WoS tested ALK+ between 1st January 2014 and 30th June 2016. MONDAY, DECEMBER 5, 2016
Patient records were reviewed retrospectively. Results: Median laboratory
turnaround for alk testing was 21 days in 2014, 14 days in 2015 and 13 days in
2016. 3 (5%) patients were under 50 years, 8 (13%) 50-60 years, 23 (38%) 60-70 P1.02-009 HIGH CONCORDANCE OF ALK REARRANGEMENT
years, 17 (28%) 70-80 years and 9 (15%) patients were > 80 years old at time of TESTING BETWEEN ALK RNA-IN SITU HYBRIDIZATION AND IHC/
testing. Median age was 69. 55% were male and 45% female. 67% were current FISH IN PATIENTS WITH LUNG ADENOCARCINOMA
or ex smokers. Only 22% were never-smokers. The majority (82%) had stage Akihiko Yoshizawa
3 or 4 disease at diagnosis. Only 39% (17/38) of patients with stage 4 ALK+
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto/Japan
NSCLC were well enough to receive chemotherapy and 4 of these (24%) did
not complete all planned cycles. 10 patients have received crizotinib so far. Background: Patients with anaplastic lymphoma kinase (ALK) gene
Median number of cycles is 3 overall (range 1-9). Where documented, reasons rearrangements manifest good responses to ALK inhibitors and thus, accurate
for discontinuation were disease progression or death from NSCLC (4), sudden and rapid identification of ALK gene rearrangements is essential for the
death not related to NSCLC (2), intercurrent illness (2) and pneumonitis (1) . clinical application of ALK-targeted therapies. The aim of this study was to
3 patients continue on crizotinib as of June 2016. Of the 13 patients who have investigate the diagnostic accuracy of the recently developed ALK RNA-in
received crizotinib, 3 have had a PR, 4 SD 2 PD and 4 NE. Updated outcomes situ hybridization (RNA-ISH) assay, using formalin fixed paraffin embedded
will be presented. Conclusion: A high quality reflex ALK testing service is samples of lung adenocarcinoma tissue. Methods: We first tested whether
being delivered in WoS with clinically acceptable turnaround times. Our ALK+ ALK RNA-ISH could be performed in 11 resected lung adenocarcinomas in
patients do not entirely reflect the literature and are frequently elderly, which ALK gene rearrangements were confirmed by immunohistochemistry
current or ex-smokers with advanced and aggressive disease. This may reflect (IHC, D5F3), and/or fluorescence in situ hybridization (FISH), and also clarified
the intra-tumor heterogeneity of ALK RNA-ISH by counting 100 tumor ARCHIVAL TISSUE AND CIRCULATING TUMOR DNA: THE IMPACT OF
cells in 10 different loci (total, 1000 tumor cells) in each tumor. Secondly, TUMOR HETEROGENEITY
we analyzed the diagnostic accuracy of ALK RNA-ISH in tissue microarrays
Ying Wang 1, Cheryl Ho1, Kevin Bushell2, Solomon Vandt1, Ian Bosdet2, Lucas
(TMAs) containing 294 lung adenocarcinoma cores (by counting 100 tumor
Swanson2, Janessa Laskin1, Sophie Sun1, Barbara Melosky1, Nevin Murray1,
cells in each core) with no information about ALK gene rearrangements
Ryan Morin2, Aly Karsan2, Hagen Kennecke1
and compared these results with those of conventional IHC and FISH 1
Medical Oncology, BC Cancer Agency, Vancouver/BC/Canada, 2Genome Sciences
tests. Results: ALK mRNA expression was observed in all 11 resected lung
Centre, BC Cancer Agency, Vancouver/BC/Canada
adenocarcinomas by the ALK RNA-ISH assay and the median of positive tumor
cells was 67.7%, whereas ALK mRNA expression was not observed in normal Background: In non-small cell lung cancer (NSCLC), circulating tumour DNA
lung cells in the background. Next, 5 ALK positive cases were found by IHC (ctDNA) has gained acceptance as a potential alternative to tissue biopsies
and/or FISH in the 294 cases of lung adenocarcinoma. The median of positive to identify targetable mutations. Individual ctDNA platforms have varying
cells by ALK RNA-ISH in these 5 cases was 75.6% (range: 40-94%), whereas abilities to detect specific mutations. A prospective, multicenter study was
the median of positive cells by ALK RNA-ISH in the remaining 289 cases was conducted to determine concordance, sensitivity, and specificity of ctDNA
0.3% (range: 0-15%). When the cutoff value was set as 15% based on the genotyping, with archival tissue DNA (atDNA) as the reference standard.
first test, the ALK RNA-ISH–positive and ALK RNA-ISH–negative cases were Methods: Patients with incurable advanced NSCLC at the BC Cancer Agency
readily distinguishable with 100% sensitivity and specificity compared with were enrolled over 14 months. Next-Generation Sequencing (NGS) and high-
the results of IHC and/or FISH. Conclusion: Our findings suggest that the ALK throughput multiplex amplification of a 27-gene panel (Raindance) was used
RNA-ISH assay is useful for detecting ALK positive lung adenocarcinomas with for atDNA analysis. Four mL of plasma was collected in Streck (Cell Free DNA
high sensitivity and specificity compared with the conventional IHC and FISH BCT) tubes for ctDNA genotyping using the Boreal Genomic OnTarget. Analysis
test. Thus, this study provides important and timely insight into the clinical of concordance, sensitivity, and specificity was conducted with atDNA used
testing of ALK in lung cancer because the RNA-ISH assay detects the target as the standard. Results: Seventy-six patients were enrolled, median age 66,
mRNA easily and rapidly. 33 (44%) male, 69 (91%) metastatic disease, 47 (62%) with primary disease in-
situ. Twenty-six EGFR mutations in 22 atDNA samples, and 12 mutations in 11
Keywords: ALK, lung adenocarcinoma, RNA in situ hybridization
ctDNA samples were detected, with a concordance of 78%, sensitivity of 39%,
and specificity 98%. One EGFR T790M mutation was positive by ctDNA alone.
Twenty-one KRAS mutations in 21 atDNA samples were detected. Within
this subgroup, 10 ctDNA samples had KRAS mutations with a concordance of
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY 76%, sensitivity of 50%, and specificity of 80%. Fourteen KRAS mutations
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – were detected by ctDNA only. The interval between archival tissue and
MONDAY, DECEMBER 5, 2016 ctDNA collection, and time between treatment and ctDNA collection, did not
significantly impact the rate of concordance (p> 0.05). Conclusion: Although
P1.02-010 FREQUENCY OF UNCOMMON EGFR MUTATIONS IN NSCLC the sensitivity is limited, the Boreal Genomic OnTarget ctDNA analysis is
specific in identifying clinically relevant EGFR mutations and has acceptable
IN AN ARGENTINEAN UNIVERSITY INSTITUTION
concordance rates between ctDNA and atDNA testing. Targetable EGFR and
Carolina Gabay 1, Martin Krasnapolski2, Maria Nazareth Rusjan2, Liliana KRAS mutations were detected in ctDNA but not atDNA, which may reflect
Gimenez2, Erica Rojas Bilbao2, Luis Thompson1, Monica Castro1 site of biopsy, tumor heterogeneity, or technical limitations of assays used.
1
Thoracic Oncology and Translational Research Unit, Instituto de Oncología Angel Given the high specificity and non-invasive nature of this test, positive results
H.Roffo, University of Buenos Aires, Buenos Aires/Argentina, 2Molecular Pathology in EGFR mutations can be used to direct therapeutic decisions, especially
Department, Instituto de Oncología Angel H.Roffo, University of Buenos Aires,
accounting for clonal evolution overtime in detection of resistance mutations.
Caba/Argentina
Keywords: NSCLC, ctDNA, EGFR, KRAS
Background: EGFR mutations are present in approximately 15% of NSCLC
Caucasian patients, with a similar frequency described in Argentina.Exon
19 deletions and exon 21 L858R are consider common mutations (>90 %)
that predict better progression free survival with EGFR-TKIs than with
chemotherapy treatment. Most relevant uncommon mutations had a POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
frequency ranged from 1.9% to 7.9% between different populations and their DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
outcome, in general, is less favorable. Methods: We analyzed, retrospectively, MONDAY, DECEMBER 5, 2016
our dataset of EGFR mutational status in the last two years with the objective
to describe the frequency and characteristics of the patients with uncommon P1.02-012 FREQUENCIES OF ACTIONABLE MUTATIONS AND
EGFR mutations in our population of NSCLC patients. The mutational analysis
SURVIVAL IN VARIANTS OF INVASIVE ADENOCARCINOMA OF THE
was performed on formalin fixed paraffin-embedded tissue blocks. EGFR
LUNG
exons 18 through 21 were amplified by PCR- based technology. Results: A
total of 113 patients underwent EGFR testing since January 2014 until June Zhengbo Song 1, Xinmin Yu2, Yiping Zhang2
1
2016. Among them, 29 cases (25.7 %) harbored EGFR mutations. The exon Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer
19 deletions (n=9; 8%) and L858R point mutation (n=6; 5.3%) accounted for Hospital, Hangzhou/China
the 51.7 % of EGFR mutated cases (13.3% of the population explored) while
Background: 2015 new WHO classification lists four rare variants of invasive
48.3 % were uncommon mutations (12,4%). In the last group, mutations sites
adenocarcinoma of the lung (VIA): invasive mucinous adenocarcinoma,
were: G719X in exon 18 (n=9; 8%), L861Q in exon 21 (n=2; 1.8%), INS20 in exon
colloid adenocarcinoma, fetal adenocarcinoma and enteric adenocarcinoma.
20 (n=2; 1.8%) and S768I in exon 20 (n=1; 0.9%). All the 14 patients carrying
Very little information is known regarding the molecular alterations and
EGFR uncommon mutations had adenocarcinoma histology. In addition, they
prognostic values for rarity of VIA. The aim of present study was to investigate
were more frequently observed in men than in women (79% versus 21%) and
the common actionable mutations and survival in VIA. Methods: Patients who
in smokers than in nonsmokers (65% versus 45%). The mean age was 62.5
with pathologic confirmed as VIA with completely resected stage I-IIIA were
years. Most of the patients (n=11; 75.6%) had advanced disease (stage IIIB-IV)
enrolled from 2010 to 2013. For comparison, we evaluated the gene status and
at diagnosis. No one had Asian ethnicity. Seven patients (50%) received
survival from 380 non-VIA lung adenocarcinoma patients in 2012. RT-PCR was
EGFR-TKIs for first or second line treatment (4 erlotinib, 2 afatinib and 1
utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF,
gefitinib). None of them showed sustained clinical benefit. At present, 7 out
HER2 and the fusion of ALK, ROS1 and RET. Survival curves were plotted
of 12 patients had died. Conclusion: Although the clinical characteristics of
with Kaplan-Meier method. Results: Thirty one patients were recruited from
our cohort are similar to the data published, we noted a higher and unusual
1120 lung adenocarcinoma,including invasive mucinous adenocarcinoma
frequency of EGFR uncommon mutations especially exon 18 G719X.All cases
(n=15), enteric adenocarcinoma(n=9), colloid adenocarcinoma (n=4) and fetal
treated with EGFR-TKIs showed poor sensitivity to therapy. Time to treatment
adenocarcinoma(n=3) . The overall frequency of gene abnormality in VIA was
and accessibility to appropriate therapy in this subgroup are important issues
48.4% (15/31). The genes abnormality was as follows: KRAS mutation (n=5),
to explore in future reports from public institutions of our region.
ALK rearrangement (n=4),PIK3CA (n=2), EGFR mutation (n=2), HER2 mutation
Keywords: EGFR mutation, TKI, NSCLC (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS, BRAF or RET were
observed . The frequency of gene abnormality was lower in VIA than non-VIA
patients (48.4% vs.74.7%,P=0.0015). No recurrence free survival difference
existed in the VIA and non-VIA patients (38.0 vs.47.0 months,P=0.524) .
A trend of worse overall survival in VIA than those with non-VIA patients
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY was found(48.0vs.57.0 months, P=0.052). Conclusion: VIA is rare in lung
adenocarcinoma with lower frequency of common gene abnormality. Invasive
mucinous adenocarcinoma was the most frequent subtype and KRAS was a
predominant actionable mutation in VIA patients. A trend of worse survival
P1.02-011 COMPARISON OF EGFR AND KRAS MUTATIONS IN existed in VIA than non-VIA patients.

Keywords: non-small cell lung cancer, survival, variants of invasive POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
adenocarcinoma, gene abnormality MONDAY, DECEMBER 5, 2016
P1.02-015 A MULTICENTER STUDY OF EGFR AND EML4-ALK

DETECTION IN NON-SQUAMOUS, NON-SMALL-CELL LUNG CANCER
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – PATIENTS WITH MALIGNANT PLEURAL EFFUSION
MONDAY, DECEMBER 5, 2016 Xun Shi1, Zhengbo Song 2, Xinmin Yu1, Yiping Zhang1
1
P1.02-013 CLINICOPATHOLOGICAL CHARACTERISTICS AND Hospital, Hangzhou/China
SURVIVAL OF ALK, ROS1 AND RET ARRANGEMENTS IN NON- Background: Currently, multicenter studies involving a large number of
ADENOCARCINOMA NON-SMALL CELL LUNG CANCER PATIENTS patients have not been not undertaken to detect the frequencies of EGFR
Zhengbo Song 1, Xinmin Yu2, Yiping Zhang2 mutations and ALK rearrangement in malignant pleural effusion (MPE)
1
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer samples of patients with non-squamous, non-small-cell lung cancer (NSCLC),
Hospital, Hangzhou/China we undertook a multicenter, observational study of Asian patients with
untreated stage IV NSCLC. Methods: Eligible patients had untreated of EGFR
Background: ALK, ROS1 and RET rearrangements represent three and ALK inhibitor stage IV non-squamous NSCLC patients with MPE. The EGFR
most frequency of fusion genes in non-small cell lung cancer (NSCLC). and ALK status of MPE and partially paired tumor tissue was determined with
Rearrangements of the three genes are predominantly found in lung reverse transcription polymerase chain reaction (RT-PCR). Results: Among 210
adenocarcinoma, while,rare in non-adenocarcinoma. The aim of this study patients with pleural effusion samples confirmed as malignant, 16 had EML4-
was to investigate the frequency, clinicopathological characteristics and ALK fusion gene rearrangements and 89 had EGFR mutations. No ALK/EGFR
survival of ALK, ROS1 and RET arrangements in non-adenocarcinoma coaltered gene was found. Tumor tissue of 56 patients were collected. EGFR
NSCLC patients. Methods: We screened ALK,ROS1 and RET arrangements in and ALK concordance rates between MPE samples and matched tumor tissue
patients with completely resected non-adenocarcinoma NSCLC using reverse samples from 56 patients were 87.5% (49/56) and 96.1% (49/51), respectively.
transcriptase polymerase chain reaction (PCR). All positive samples were There was a tendency for a longer progression free survival in patients with
confirmed with fluorescence in situ hybridization (FISH). Survival analysis EGFR accordance in comparison with those with EGFR discordance between
was performed with Kaplan-Meier method and log-rank for comparison. tumor tissue and MPE samples (9.8 vs 6.2 months, respectively; p = 0.078).
Results: Totally, 385 patients, who underwent complete resection, including A same trend was found in patients with ALK accordance and discordance
245 with squamous cell carcinoma, 85 with adenosquamous carcinoma and (10.0 vs 3.2 months, respectively; p = 0.004) . Conclusion: These results
55 with large cell carcinoma were enrolled. Twelve patients were identified demonstrate that MPE can be substituted for tumor tissues for EGFR and ALK
as harboring fusion genes,including seven with ALK, three with ROS1 and gene detection. Patients with gene mutations or arrangement discordance
two with RET rearrangements. The frequencies of fusions in adenosquamous between tumor tissue and MPE samples showed a inferior efficacy of targeted
carcinoma, squamous cell carcinoma, and large cell carcinoma were 8.2%,1.6% therapy than those with accordance.
and 1.8%, respectively. The median age of 12 patients was 49.5 years and
three patients had smoking history. No survival difference existed between Keywords: Epidermal growth factor receptor, Anaplastic lymphoma kinase,
fusion genes positive and negative patients (36.7 vs.50.2 months,P=0.21). malignant pleural effusion, Non-small-cell lung cancer
Conclusion: The frequencies of ALK, ROS1 and RET rearrangements are low
in non-adenocarcinoma NSCLC patients, and the clinical characteristics are
similar with those in lung adenocarcinoma. Fusions of the three genes are not
prognostic marker for non-adnocarcinoma NSCLC patients.
Keywords: fusion gene, frequency, survival, non-small cell lung cancer MONDAY, DECEMBER 5, 2016
P1.02-016 HER4 EXPRESSION WAS RELATED TO THE SENSITIVITY

OF EGFR-TKI IN NON-SMALL CELL LUNG CANCER
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – Masaaki Inoue, Junichi Yoshida, Takashi Iwanami, Yusuke Nabe, Masatoshi
MONDAY, DECEMBER 5, 2016 Kanayama, Daisei Yasuda
Chest Surgery, Shimonoseki City Hospital, Shimonoseki/Japan
P1.02-014 HER2 MUTATIONS IN CHINESE PATIENTS WITH NON- Background: EGFR-TKIs show significant therapeutic effects against non-
SMALL CELL LUNG CANCER small cell lung cancer (NSCLC) with EGFR-activating mutations, however
Zhengbo Song, Yiping Zhang 20-30% of them have no response to EGFR-TKIs. HER-family receptors play
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China a critical role in tumor progression, differentiation and survival in lung
cancer. Recent studies suggest that the overexpression of HER-family
Background: ERBB2 (HER2) is a driver gene identified in non-small cell receptors have a potential risk of EGFR-TKIs resistance. The aims of this
lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability study were to investigate the association between EGFR-mutation and the
and treatment of HER2-positive NSCLC in Chinese population are unclear. expression of HER-family receptor in regard to clinical outcomes. Methods:
Methods: Eight hundred and fifty-nine patients with pathologically We invested EGFR mutation by direct PCR analysis and HER2-4 expression
confirmed NSCLC were screened for HER2 mutations using Sanger by immunohistochemistry (IHC) of 231 consecutive non-small cell lung
sequencing. Next-generation sequencing (NGS) was performed in positive cancers, who had undertaken an operation from January 2007 to July 2012.
cases. HER2 amplification was detected with FISH. Overall survival (OS) was The intensity of HER2-4 was graded (score: 0-3) from negative (score: 0-1) to
evaluated using Kaplan-Meier methods and compared with log-rank tests. positive (score: 2-3). The observed protein expression levels were analyzed
Results: Twenty-one cases carrying HER2 mutations were identified with for correlation to EGFR mutation status, clinicopathological parameters and
a prevalence of 2.4%. HER2 mutations were more frequently encountered the responses of EGFR-TKI treatment. Results: EGFR mutation was observed
in females, non-smokers and adenocarcinoma. NGS was performed in 19 in 40% of lung cancer, 61% of p.[Leu858Arg]and 31% of exon 19 deletion.
out of 21 patients, The results showed 16 cases with additional genetic Positive expression rates of HER2, HER3 and HER4 were 22.9%, 1.2%, 38.5%,
aberrations, most commonly associated with TP53 (n = 6), followed by EGFR respectively. HER4 positive rare of EGFR positive group was significantly
(n = 3), NF1 (n = 3), KRAS (n = 2) and other mutations. One patient harbored higher than that of EGFR negative group (52% vs 30%, P<0.01), however there
HER2 amplification(figure 1). Four patients with stage IV received afatinib was no difference in HER2 expression. In histological type, positive rates
treatment, and three showed stable disease with a median progression-free of HER2 and HER4 in adenocarcinoma were higher than that in squamous
survival of 4 months and one patient was diagnosed with progressive disease. cell carcinoma (HER2: 26% vs 13%, P=0.07, HER4: 49% vs 13%, P<0.01). HER4
No survival difference existed between HER2 positive and negative patients( positive rate of HER2 positive group was significantly lower that of HER2
(49.3 months vs.45.0 months, P = 0.150). Conclusion: HER2 mutations negative group (43% vs 26%, P=0.03). The response rate of EGFR-TKIs in HER2
represent a distinct subset of NSCLC. NGS showed that HER2 mutations positive group was low, but high in HER4 positive group. Conclusion: Our
commonly co-existed with other driver genes. Afatinib treatment displayed data showed that HER4 expression was independent form EGFR mutation
moderate efficacy in patients with HER2 mutations. and HER2 expression, but related to the sensitivity against EGFR-TKIs. HER4
positive patients may be candidate for pan-HER inhibitor augments.
Keywords: PREVALENCE, treatment, HER2 mutation, genetic variability
Keywords: HER family receptor, EGFR mutation, non-small cell lung cancer
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY pulmonary lesion confirmed T790M mutation and additional metastatic
lesions found in T2 and T5 vertebral bodies were removed by surgical
curettage. Rebiopsy of the metastatic bone lesions of these two patients
showed metastatic adenocarcinoma merging with poorly differentiated
P1.02-017 RELATIVE ABUNDANCE OF EGFR MUTATIONS PREDICT sarcomatous components. Remarkably, the spindle shaped sarcomatous
TUMOR METASTASIS AND EGFR-TKIS PROGNOSIS IN PATIENTS tumor cells produced ill-defined eosinophilic lace-like osteoid. These osteoid
WITH NON-SMALL CELL LUNG CANCER components were closely associated with the tumor cells and deposited as
disorganized features. The sarcomatous neoplastic cells intermingled with
Qiming Wang 1, Hongyan Wang2, Hong Tang2, Yufeng Wu2, Zhen He2, Lili
osteoid demonstrate unequivocal features of malignancy, which is different
Wang2, Zhe Zhang2, Dongdong Zhao2, Li Yang2, Bing Wei2, Jie Ma2, Yongjun
from reactive osteoid or callus formation. EGFR mutation status were same
Guo2
1
from that of primary lung specimen and IHC showed vimentin expression
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou
and decreased E-cadherin (EMT feature). Conclusion: To the best of our
University, Henan Cancer Hospital, Zhengzhou/China, 2 Affiliated Cancer Hospital
of Zhengzhou University, Henan Cancer Hospital, Zhengzhou/China knowledge, this is the first report to describe pulmonary adenocarcinoma
with osteosarcomatous differentiation in rebiopsy specimens of EGFR-TKI
Background: The most lethality in NSCLC is due to uncontrolled tumor resistant patients. As the evaluation of metastatic sites for rebiopsy were
metastasis. Epidermal growth factor receptor (EGFR) has been confirmed bone lesions in both patients, the role of the tumor microenvironment may
to be an effective biomarker in EGFR-TKIs treatment for advanced NSCLC. support the transformation from adenocarcinoma to osteosarcomatous
Previous studies have demonstrated EGFR mutation abundance could predict phenotype. A few previous studies suggested that a bone environment is
benefit from EGFR-TKIs treatment. However, there is no investigation on the essential for osteosarcoma development from transformed mesenchymal
correlation between EGFR mutation abundance and tumor metastasis. Here stem cells. Our findings suggest that the differences of the intrinsic nature
we aimed to explore potential effect of EGFR mutation abundance on tumor between epithelial and osteosarcomatous mesenchymal cancers may be the
metastasis and EGFR-TKIs prognosis. Methods: 3913 patients from Henan cause of the acquired resistance of EGFR-TKI.
Cancer Hospital diagnosed with NSCLC were enrolled. The EGFR mutation
abundance in tumor specimens was quantified by amplification refractory Keywords: pulmonary adenocarcinoma, osteosarcomatous differentiation,
mutation system (ARMS). Above 10% was defined as high abundance, and EGFR-TKI resistance, rebiopsy
below 10% was defined as low abundance. Results: The ratio of high mutation
abundance in age < 60 years group was significantly higher than that in
age ≥ 60 years group (55.4% vs. 42.5%, P=0.000), similar distribution was
also detected in 19 exon deletion and L858R subgroup (P=0.003 and 0.030, POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
respectively). Whereas the distribution of EGFR mutation abundance was no DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
difference between surgery and biopsy specimens (P=1.000). Additionally, MONDAY, DECEMBER 5, 2016
the ratio of high abundance in 19 exon deletion was obviously higher than
that in L858R and rare mutations (66.5% vs. 31.6% vs. 51.1%, P=0.000).
P1.02-019 COMPLEX MUTATION OF EPIDERMAL GROWTH FACTOR
Meanwhile, the ratio of high abundance in patients with hepar metastasis
RECEPTOR (EGFR) IN PATIENTS WITH NON-SMALL LUNG CANCER
was significantly higher than that in patients without hepar metastasis
(57.2% vs. 47.8%, P=0.036), but that in brain or bone metastasis was Hiromasa Arai1, Michihiko Tajiri1, Junya Morita1, Yohei Kameda1, Kimihisa
demonstrated no significant difference (P=0.897 and P=0.293, respectively). Shiino1, Koji Okudela2, Munetaka Masuda3
1
The subgroup analysis among above metastasis patients indicated the ratio General Thoracic Surgery, Kanagawa Cardiovascular and Respiratory Center,
of high abundance in 19 exon deletion was significantly higher that in L858R. Yokohama/Japan, 2Pathology, Yokohama City University Graduate School of
Furthmore, the difference in median PFS between 19 exon deletion and L858R Medicine, Yokohama/Japan, 3Surgery, Yokohama City University Graduate School of
Medicine, Yokohama/Japan
group was significant (17.5 months vs. 9.2 months, P=0.003). Conclusion:
EGFR mutation abundance was not associated with the methods of collecting Background: Analysis of the epidermal growth factor receptor (EGFR)
specimens. The younger patients more likely harbor high EGFR mutation gene is currently one of the most important tests in establishment of a
abundance. Hepar metastasis status was associated with EGFR mutation treatment strategy for primary lung cancer. Major mutations of exon 19
abundance. Median PFS in 19 exon deletion patients was notablely longer deletion and exon 20 point mutation (L858R) are particularly well known
than that in L858R group for EGFR-TKIs treatment, which may refer to high in adenocarcinomas, and tyrosine kinase inhibitors (TKIs) have provided
abundance in 19 exon deletion. significant benefits to patients with such mutations. Complex mutation
patterns of EGFR have also been reported, but their significance is unknown.
Keywords: metastasis, Abundance, Prognosis, EGFR mutution
Methods: Clinicopathological features and response to treatment of non-
small lung cancer (NSCLC) with complex mutation of the EGFR gene were
investigated in cases treated at Kanagawa Cardiovascular and Respiratory
Center from June 2014 to March 2016. Results: EGFR gene analysis was
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY performed in 334 cases, of which 108 had EGFR mutations. These cases
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – included 7 (6.5%) with complex mutations: two males (28.6%) and five
females (71.4%) with an age of 71.0±6.0 (mean±SD) years. Five of the 7 cases
underwent surgery and two were inoperable. The histological diagnoses
P1.02-018 OSTEOSARCOMATOUS DIFFERENTIATION IN THE were adenocarcinomas (n=6) and squamous cell carcinoma (n=1). The
REBIOPSY SPECIMENS OF PATIENTS HARBORING PULMONARY pathological stage in the surgical cases (all adenocarcinomas) were IB, IIA,
and IIIA in 2, 1 and 2 cases, respectively. Both inoperable cases were clinical
ADENOCARCINOMA WITH EGFR-TKI RESISTANCE
stage IV. The EGFR complex mutation patterns were 19 deletion and 20
Hyun Jung Kwon1, Hyein Ahn1, Eunhyang Park2, Hyojin Kim1, Jin-Haeng Chung1 T790M (n=2, with one case with acquired TKI resistance), 18 G719X and 21
1
Pathology, Seoul National University Bundang Hospital, Seongnam/Korea, L861Q (n=3), 19 deletion and 21 L858R (n=1), and 20 T790 and 21 L858R (n=1).
Republic of, 2Pathology, Seoul National University Hospital, Seoul/Korea, Republic In the five surgical cases, two (pStage IIA, 19 deletion and 20 T790M; pStage
of
IIIA, 18 G719X and 21 L861Q) received postoperative TKI therapy because
Background: Histological transformation including small cell carcinoma of recurrence. Both patients had a poor response to TKIs and both died.
and epithelial to mesenchymal transition (EMT) is one of the discovered The patients in another three surgical cases are alive without receiving TKI
mechanisms of the acquired resistance to EGFR-TKI. We report two cases therapy. Two inoperable cases (19 deletion and 20 T790M; 18 G719X and 21
of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor(EGFR- L861Q) were treated with standard chemotherapy and TKIs, and also died.
TKI) resistant pulmonary adenocarcinoma associated with EMT features The disease-free survival period in the surgical cases was 532±319 days and
that showed osteosarcomatous differentiation in rebiopsy specimens. the overall survival period in the case with postoperative recurrence and the
Methods: We identified two patients with primary lung adenocarcinoma inoperable cases was 810±563 days. The progression-free survival period in
that showed osteosarcomatous transformation on second biopsy (n = 60) patients treated with TKIs was 101.5±90.6 days. Conclusion: In patients with
between 2010 and 2016. Histomorphologic features and EGFR mutation EGFR mutation, 6.5% have complex mutations, of which 85.7% are minor-on-
results were compared between initial and second biopsy samples. Results: minor or minor-on-major mutations. Lung cancer with complex mutation of
Case 1 A 55-year-old female, non-smoker presenting chronic cough was EGFR tends to have a poorer response to TKIs compared to cases with a major
found to have pulmonary adenocarcinoma harboring EGFR exon 19 deletion single mutation.
mutation with disseminated intrapulmonary metastasis. After 1 year of
Keywords: Epidermal growth factor receptor, Complex mutation, single
gefinitib treatment, radiologic evaluation showed left iliac metastases with
mutation, non-small lung cancer
extraosseous ossification. Case 2 A 58-year-old man who had undergone
right upper lobectomy of the lung was diagnosed as adenocarcinoma
with pT1N0M0 harboring an EGFR exon 19 deletion mutation. Three years
after surgery, metastatic lesions developed in the right lower lobe and
pleura. After 15 months of conventional chemotherapy, 2nd biopsy for the

POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY mutation or fusion identified; EGFR (n=33), KRAS (n=76), BRAF (n=8), ERBB2
(n=2), ALK-fusion (n=5), RET fusion (n=1). Additionally, one off-target fusion
was detected during assay QC. Of the above results 31 EGFR and 5 ALK would
have been detected using the benchmark Roche Cobas EGFR and Abbott
P1.02-020 THE EFFECT OF EGF-PATHWAY TARGETED Vysis ALK FISH methodologies. The additional detections can be classified
IMMUNIZATION (EGF PTI) ON STAT3 AND CANCER STEM CELLS IN as nonactionable (KRAS, BRAF) or actionable (RET fusion, 2 EGFR mutations
EGFR MUTANT NSCLC CELLS not identified by Cobas, 2 ERBB2 mutations and one off-target fusion). Of the
6 actionable genetic lesions, 4 selected for targeted therapies in lung cancer
Jordi Codony Servat 1, Miguel Angel Molina Vila1, Jordi Bertrán-Alamillo1, Silvia
(EGFR, ERBB2). Two fusions detected by this assay (CCDC6-RET and TMPRSS2-
García2, Niki Karachaliou3, Erik D’Hondt4, Rafael Rosell5
1
ERG) suggested an alternative diagnosis to that of lung cancer when reviewed
Laboratory of Cellular and Molecular Biology, Pangaea Biotech Sl, Ior Quirón-
with morphology, immunohistochemistry and clinicopathological correlation.
Dexeus University Institute, Barcelona/Spain, 2Institut Químic de Sarrià- Iqs,
Barcelona/Spain, 3Instituto Oncológico Dr Rosell (IOR), Hospital Universitario Conclusion: When compared with standalone assay testing, panel testing
Quirón-Dexeus, Barcelona/Spain, 4R&d and Regulatory, Bioven (Europe), Aberdeen/ of lung cancer identified mutations in an additional 39% of patients and
United Kingdom, 5Laboratory of Cellular and Molecular Biology, Catalan Institute identified genetic lesions that altered targeted therapy selection (2%) or
of Oncology and Institut D’Investigació En Ciències Germans Trias I Pujol, Badalona/ diagnosis (1%). Broad mutation panel testing using NGS has shown itself to
Spain be superior at the level of clinical decision making by ascribing a molecular
subtype to 39% more cancers and identifying an additional 2% of cases where
Background: The vast majority of advanced non-small cell lung cancer (NSCLC) targeted therapies may be of benefit. Crucially, the addition of ‘off-target’
patients with EGFR mutant tumors will develop disease progression following mutations and fusions prompts re-examination and, where necessary,
successful treatment with an EGFR tyrosine kinase inhibitor (TKI). Resistance correction of primary diagnosis at a rate of 1% in our hands. This feature
to EGFR-TKIs is due to various mechanisms, such as the secondary mutation of panel testing has been overlooked and it is critical for the oncology and
(T790M) or the activation of alternative pathways (MET, AXL). What has pathology communities to be aware of its significance.
not been fully appreciated is that EGFR blockade induces an imbalance in
favor of survival, increases activity of STAT3 and enriches lung CSCs through Keywords: Molecular Pathology, EGFR, ALK
Notch3-dependent signaling. EGF-PTI was designed to elicit an antibody
response against EGF, in order to reduce EGF receptor signaling and limit
tumor growth. We have explored whether EGF-PTI alone or in combination
with EGFR TKIs may efficiently inhibit STAT3 and target CSCs. Methods: EGF
PTI was provided by Bioven (Europe) Ltd. Gefitinib, erlotinib and the recently POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
FDA-approved third-generation EGFR TKI, AZD9291 (osimertinib) were MONDAY, DECEMBER 5, 2016
purchased from Selleck chemicals. Western blotting was used to assess the
effect of the drugs on ERK, AKT and STAT3 phosphorylation and on Notch and
PARP cleavage in EGFR (del19) mutant NSCLC PC9 cells and gefitinib-resistant P1.02-022 ESTABLISHING REFLEX NGS TESTING IN NSCLC IN A
PC9-GR4 cells. PC9-GR4 cells have been established in our lab and harbor REGIONAL NETWORK OF COUNTY HOSPITALS IN CENTRAL SWEDEN
the resistant T790M mutation (T790M+). The protein expression of AXL and Johan Isaksson1, Linda Willén2, Linnea La Fleur3, Stephanié Mindus4, Magnus
CSCs markers such as HES1 (downstream effector of Notch) and Bmi1 was also Sundstrom3, Eva Brandén1, Hirsh Koyi1, Martin Sandelin4, Kristina Lamberg4,
examined. Results: Gefitinib, erlotinib or AZD9291 suppressed EGFR, ERK1/2 Patrick Micke3, Lotte Moens3, Gabriel Lundberg5, Johan Botling 3
and AKT phosphorylation in PC9 cells but increased STAT3 phosphorylation on 1
Dept. of Respiratory Medicine, Gävle Hospital, Gävle/Sweden, 2Dept. of Oncology,
the tyrosine residue 705 in both PC9 and PC9-GR4 cells. EGF-PTI suppressed Gävle Hospital, Gävle/Sweden, 3Department of Immunology, Genetics and
STAT3, EGFR and ERK1/2 and the combination of each of the three EGFR TKIs Pathology, Uppsala University, Uppsala/Sweden, 4Dept. of Medical Sciences,
with EGF-PTI lead to more potent inhibition of STAT3, EGFR and ERK1/2. Respiratory Medicine, Uppsala University, Uppsala/Sweden, 5Dept. of Respiratory
The EGF-PTI induced AKT phosphorylation was reversed when EGF PTI was Medicine, Falun County Hospital, Falun/Sweden
combined with EGFR TKIs. Interestingly, EGF-PTI blocked Notch cleavage and
decreased the expression of HES1. The expression of Bmi1 and AXL were also Background: Extended genetic testing of NSCLC tumor samples provides
attenuated with EGF PTI and apoptosis was enhanced through the induction a foundation for personalized cancer treatment and use of new targeted
of PARP cleavage. Conclusion: EGF PTI may reverse mechanisms of resistance medication. Testing with Next Generation Sequencing (NGS), mostly
to single EGFR inhibition and the combination of EGF PTI with EGFR TKIs performed at university hospitals, has not been available for all patients
efficiently inhibits downstream signaling pathways in T790M+ cells. Based due to geographic and economic reasons. Many lung cancer patients carry
on these results, the design of a proof-of-concept trial with the combination a heavy burden of disease and extensive travelling can negatively impact
of EGF PTI with gefitinib for the first line treatment of EGFR mutant NSCLC quality of life. The ability to perform a modern state-of the art work-up at
patients is in progress. local hospitals, without compromising on diagnostic quality, will enable
equal access to personalized treatment for lung cancer patients. Methods:
Keywords: non-small cell lung cancer, STAT3, Cancer Stem Cells, EGF pathway In Gävle County hospital routine diagnostic immunohistochemistry (IHC)
targeted immunization on biopsies is performed at the local pathology lab. In the case of NSCLC the
formalin-fixed, paraffin embedded (FFPE) tissue samples are sent to Uppsala
University hospital for further molecular pathology and NGS testing. A
targeted NGS test (18 gene panel) was established for mutation screening
of small biopsies and cytology specimens (Moens et al., J Mol Diagn, 2015).
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY Fusion genes - ALK, ROS1 and RET - are analysed by IHC, FISH and nanoString.
MONDAY, DECEMBER 5, 2016 Structured biobanking of surplus biopsies and blood samples during
treatment, for explorative biomarker testing and research, was set up as a
regional extension of the UCAN infrastructure, including detailed registration
P1.02-021 REVIEW OF CLINICAL OUTCOMES ATTRIBUTABLE TO of clinical baseline and real-time follow-up data in a dedicated database.
NEXT GENERATION SEQUENCING BASED BROAD MUTATION PANEL Results: Inclusion of patients in the biobanking cohort started gradually
TESTING IN LUNG ADENOCARCINOMA during 2015 in Uppsala, and in February 2016 in Gävle. The cumulative
Cathal O’Brien1, Kathleen Brosnan2, Sinead Cuffe3, Stephen Finn2 inclusion in the UCAN biobank is updated at www.u-can.uu.se (see Statistics).
1 To date (July 2016) 70 patients have been included at Gävle County hospital
Cancer Molecular Diagnostics, St James’ Hospital, Dublin/Ireland, 2Dept of
Histopathology, St James’ Hospital, Dublin/Ireland, 3Dept of Medical Oncology, St covering 95% of the newly diagnosed NSCLC patients. So, far 242 patients
James’ Hospital, Dublin/Ireland from the region were tested by NGS yielding 23 EGFR+ (9.5%), 75 KRAS+ (31%),
5 BRAF+ (2.1%, codon 600), 2 MET (0.8%, exon 14 skipping), 1 ERBB2 (0.4%,
Background: Molecular testing of lung cancer is currently performed on a exon 20 insertion), and 6 PIK3CA (2.5%, exon 9/20) cases. Fusion gene analysis
relatively restricted set of standard-of-care markers (normally EGFR and ALK). resulted in 5 ALK+ (2.1%), 1 ROS1 and 1 RET patients. Conclusion: Decentralised
The introduction of next generation sequencing (NGS) in clinical laboratories local patient care, tissue/blood sampling and biobanking in combination
has permitted the adoption of broader testing using mutation panels. This with centralised molecular testing allows advanced lung cancer diagnostics
study compared the number of mutations detected and outcomes generated and clinical research in networks of county hospitals. Survival benefits from
as a result of replacing standalone EGFR and ALK assays with a combined modern targeted drugs, for national lung cancer cohorts, can only be achieved
mutation and gene fusion assay based on NGS in routine clinical practice. and evaluated in population-based settings without bias related to selective
Methods: Panel testing was implemented using a bioinformatically selected referral to major cancer centers.
subset of targets from the Thermo-Fisher OncomineTM Focus assay. The
results of testing were compared against the incumbent assay platforms Keywords: FFPE, next generation sequencing, NSCLC
(Roche Cobas® EGFR, Abbott VysisTM ALK) to determine differences in
mutation detection and resultant alterations to patient treatment. Results:
Over a 5 month period of testing, 231 lung adenocarcinomas were analysed
using the extended mutation and fusion panel. In total 126 of 231 cases had a
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY in 129 ALK-positive cases for their molecular characterization. Additional
clinical analysis and drug viability assays between EML4-ALK long and short
forms were assessed as well. We also conducted multiplexed direct mRNA
expression profiling using a panel of 770 essential key driver genes that
P1.02-023 APPLICATION OF AN AMPLICON-BASED NGS STRATEGY take part in most cancer pathways. Target gene silencing, overexpression,
IN THE MOLECULAR DIAGNOSIS OF NSCLC: COMPARABLE migration assay, and immunoprecipitation were conducted for functional
PERFORMANCE WITH FISH AND ARMS-PCR analysis of identified molecules. Results: We found that most ALK genomic
breaks occurred at intron 19 (92.7%), which conjoined with partner genes
Dongmei Lin1, Lei Li2, Dongfeng Niu3, Yang Yu2, Lixin Zhou3, Lianju Gao2,
through non-homologous end joining repair system. ALK fusion profiling
Xuehong Meng2, Zhi Jiang2, Jiafu Ji3
1
exhibited that 82% of fusions were EML4-ALK (129/158), 2.4% were HIP1-
Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry
ALK (4/158), 1.8% KIF5B-ALK (3/158), 1 case was KLC1-ALK, and the rest
of Education), Peking University Cancer Hospital & Institute, Beijing/China,
2
Novogene Bioinformatics Institute, Beijing/China, 3Department of Pathology, Key were unrecognized ALK fusions (21/158). From the unknown partners, we
Laboratory of Carcinogenesis and Translational Research (Ministry of Education), identified 3 novel ALK fusion partners: GCC2, LMO7, and PHACTR1. We
Peking University Cancer Hospital & Institute, Beijing/China also identified 4 novel somatic mutations of ALK: T1151R, R1192P, A1280V,
and L1535Q. RNA expression profiling further revealed that NSCLC with
Background: Next generation sequencing (NGS) enables us to detect ALK rearrangement showed higher expression of ITGB3 with statistical
comprehensive genetic aberrations within a tumor sample, which provides significance. Combinatorial treatment of ALK (crizotinib) and ITGB3 (LM609
potential alternative to well adopted clinical diagnostic approaches such antibody) decreased cell migration and invasive properties of ALK-positive
as amplification refractory mutation system PCR (ARMS-PCR) and FISH. cell lines. Furthermore, from our new classification system of EML4-ALK
However, there is no enough data to illustrate the overall concordance variants, the cases with short EML4-ALK form showed more advanced stages
between NGS with traditional clinical diagnostic approaches. This study is and more frequent metastases than the cases with long form in NSCLCs.
aimed to fill in this blank. Methods: We have used 20 cell lines from ATCC and Conclusion: This is the primary mass-scale study of ALK-rearranged NSCLC to
19 FFPE samples to construct molecular standards and there are 50, 34 and our knowledge. Through this integrated analysis, we provide genomic details
48 samples for SNV and Indel, CNV and fusion, respectively. All the mutations and clinical insight of NSCLC with ALK rearrangement. Also, we suggest a
were verified by Sanger sequencing or QuantStudio 3D digital PCR. To assess novel therapeutic approach of treating ALK-rearranged NSCLC patients with
the performance of NGS, an amplicon-based NGS strategy was used to detect ALK and ITGB3 inhibitors.
gene mutations in molecular standards. In order to illustrate the overall
concordance between NGS with ARMS-PCR and FISH, we further verified NGS Keywords: Genomic landscape, ALK, ITGB3, NSCLC
in 2500 retrospective FFPE samples from non-small lung cancer (NSCLC) and
breast cancer patients. Results: So far, we have detected genetic aberrations
in 108 FFPE samples. For SNV and Indel, we focused on the mutation profile
of EGFR, KRAS, BARF and PIK3CA, which were the most common mutations
in NSCLC. In molecular standards, 34 of 50 (68%) were positive for Sanger and DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
33 of 50 were positive for NGS, thus the sensitivity, specificity and accuracy MONDAY, DECEMBER 5, 2016
was 97%, 100% and 98%, respectively. In FFPE samples from 31 lung cancer
patients, NGS results were consistent with ARMS-PCR. For CNV, in molecular
standards, the copy number of HER2, MET, EGFR and FGFR1 detected by NGS P1.02-025 EVALUATION OF NGS AND RT-PCR METHODS FOR ALK
was high consistent with digital PCR and R2 was 0.9673. In FFPE samples from ASSESSMENT IN EUROPEAN NSCLC PATIENTS: RESULTS FROM THE
45 breast cancer patients, 80% of cases (36/45) were HER2 amplification ETOP LUNGSCAPE PROJECT
positive and 20% (9/45) were negative for FISH, 34 HER2 positive and 9 HER2 Stephen Finn1, Igor Letovanec2, Panagiota Zygoura3, Paul Smyth1, Alex
negative for FISH were also classified by NGS. Thus, the overall concordance Soltermann4, Lukas Bubendorf5, Ernst-Jan Speel6, Antonio Marchetti7,
between NGS and FISH were 95.56%. For ALK and ROS1 gene fusion, the Daisuke Nonaka8, Kim Monkhorst9, Henrik Hager 10, Miguel Martorell11,
overall concordance were both 100% in 48 molecular standards (NGS versus Aleksandra Sejda12, Richard Cheney13, Javier Hernandez-Losa14, Eric
Sanger sequencing) and 32 FFPE samples (NGS versus FISH). Conclusion: Verbeken15, Walter Weder 16, Spasenija Savic5, Alessia Di Lorito7, Atilio
Our result reveal that the amplicon-based NGS strategy for detecting Navarro11, Enriqueta Felip17, Arne Warth18, Paul Baas19, Peter Meldgaard20,
genetic aberrations is of high accuracy and comparable with standard Fiona Blackhall21, Anne-Marie Dingemans22, Hendrik Dienemann18, Rafal
clinical diagnostic approaches, and therefore provides a promising diagnosis Dziadziuszko23, Johan Vansteenkiste24, Thomas Geiger25, Jon Sherlock26,
approach for clinical in the future. Jeoffrey Schageman27, Urania Dafni3, Roswitha Kammler28, Keith Kerr29,
Erik Thunnissen30, Solange Peters31, Rolf Stahel32, On Behalf Of The Etop
Keywords: amplicon-based next generation sequencing, gene aberrations, Lungscape Consortium28
clinical diagnosis 1
Dept of Histopathology, St James’ Hospital, Dublin/Ireland, 2Pathology, Centre
Hospitalier Universitaire Vaudois - Chuv, Lausanne/Switzerland, 3Etop Statistical
Center, Frontier Science Foundation- Hellas, Athens/Greece, 4Dept. of Clinical
Pathology, University Hospital Zurich, Zurich/Switzerland, 5Institute of Pathology,
University Hospital Basel, Basel/Switzerland, 6Department of Pathology,
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY Maastricht University Medical Center, Maastricht/Netherlands, 7Anatomia
MONDAY, DECEMBER 5, 2016 Patologica, Ospedale Clinicizzato, Chieti/Italy, 8Dept. of Histopathology, The
Christie NHS Foundation Trust, Manchester/United Kingdom, 9Thoracic Oncology,
The Netherlands Cancer Institute, Amsterdam/Netherlands, 10 Pathology, Aarhus
P1.02-024 THE MOLECULAR BREAKDOWN: A COMPREHENSIVE University Hospital, Aarhus/Denmark, 11Sevicio de Anatomía Patológica, Consorcio
Hospital General Universitario de Valencia, Valencia/Spain, 12Pathology, Medical
LOOK AT NON–SMALL-CELL LUNG CANCER WITH ALK University Gdansk, Gdansk/Poland, 13Pathology, Roswell Park Cancer Institute,
REARRANGEMENT Buffalo/AL/United States of America, 14Servicio de Anatomía Patológica, Vall
Ka-Won Noh1, Mi-Sook Lee2, Ji Young Song2, Joungho Han3, Jhingook Kim4, D’Hebron University Hospital, Barcelona/Spain, 15Pathology, University Hospital
Se-Hoon Lee5, Yoon-La Choi3 Leuve, Leuven/Belgium, 16Division of Thoracic Surgery, University Hospital
1 Zurich, Zurich/Switzerland, 17Vall D’Hebron University Hospital, Barcelona/Spain,
Department of Health Sciences and Technology (Saihst), Sungkyunkwan 18
Heidelberg University Hospital, Heidelberg/Germany, 19Thoracic Oncology, The
University, Seoul/Korea, Republic of, 2Laboratory of Cancer Genomics and
Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Amsterdam/
Molecular Pathology, Samsung Medical Center, Seoul/Korea, Republic of,
3 Netherlands, 20 Department of Oncology, Aarhus University Hospital, Aarhus/
Department of Pathology and Translational Genomics, Sungkyunkwan University
Denmark, 21Christie Hospital NHS Foundation Trust, Manchester/United Kingdom,
School of Medicine, Seoul/Korea, Republic of, 4Department of Thoracic Surgery, 22
Pulmonary Diseases, Maastricht University Medical Center, Maastricht/
Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of,
5 Netherlands, 23Oncology and Radiotherapy, Medical University of Gdansk, Gdansk/
Department of Medicine, Sungkyunkwan University School of Medicine, Seoul/
Poland, 24Respiratory Oncology Unit (Pneumology), University Hospital KU Leuven,
Korea, Republic of
Leuven/Belgium, 25European Thoracic Oncology Platform, Bern/Switzerland,
26
Clinical Sequencing Division, Thermo Fisher Scientific, Paisley/United Kingdom,
Background: Chromosomal rearrangements of anaplastic lymphoma kinase 27
Thermo Fisher Scientific, Austin/TX/United States of America, 28Translational
(ALK) compose approximately 4-6% of non–small-cell lung cancer (NSCLC) Research Coordination, European Thoracic Oncology Platform, Bern/Switzerland,
and the patients can be prescribed with targeted therapy. Nevertheless, 29
Pathology, Aberdeen University Medical School, Aberdeen/United Kingdom,
acquired resistance towards existing ALK-specific inhibitors is inevitable in 30
Department of Pathology, VU University Medical Center, Amsterdam/
most cases. This suggests that a detailed molecular characterization of NSCLC Netherlands, 31Department of Oncology, Centre Hospitalier Universitaire Vaudois
with ALK rearrangement and dissection of ALK-specific signaling pathway are (CHUV), Lausanne/Switzerland, 32Clinic for Oncology, University Hospital Zurich,
strongly needed. Methods: Approximately 3000 NSCLC cases with EGFR and Zurich/Switzerland
KRAS wild types were screened for ALK alterations by immunohistochemistry
Background: The reported prevalence of ALK rearrangement in NSCLC
(IHC). From the 158 ALK IHC-positive samples, we further validated ALK
ranges from 2%-7%, depending on population and detection method. The
rearrangement through fluorescence in situ hybridization and RNA color-
primary standard diagnostic method is fluorescence in situ hybridization
coded probes. We then performed targeted deep sequencing using a
(FISH). Recently, immunohistochemistry (IHC) has also proven to be a
customized panel embedded with 81 select set of cancer associated genes

reproducible and sensitive technique. Reverse transcriptase-polymerase POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
chain reaction (RT-PCR) has been advocated and most recently the advent of MONDAY, DECEMBER 5, 2016
targeted Next-Generation Sequencing (NGS) for ALK and other fusions has
become possible. This is one of the first studies comparing all 4 techniques in
resected NSCLC from the large ETOP Lungscape cohort. Methods: 96 cases P1.02-027 A COMPARATIVE ANALYSIS OF DIFFERENT CYTOLOGICAL
from the ETOP Lungscape iBiobank (N=2709) selected based on any degree SAMPLES FOR THE ASSESSMENT OF ALK GENE REARRANGEMENTS
of IHC staining (clone 5A4 antibody, Novocastra, UK) were examined by IN NSCLC PATIENTS
FISH (Abbott Molecular, Inc.; Blackhall, JCO 2014), central RT-PCR and NGS.
Maria Lozano Escario 1, Luis Mejias1, Marta Abengozar 1, Tania Labiano2, Jose
H-score 120 is used as cutoff for IHC+. For both RT-PCR and NGS, RNA was
Subtil3, Alfonso Gurpide4, Mercedes Aguirre1, Nerea Gomez1, Maria Eugenia
extracted from the same formalin-fixed, paraffin-embedded tissues. For
Echarri1, M Amada Maset1, Jorge Arabe1, Pablo Panadero1, Jose Paricio1, Miguel
RT-PCR, primers were used covering the most frequent ALK translocations.
Idoate1, Jose Echeveste1
For NGS, the Oncomine™ Solid Tumour Fusion Transcript Kit was used, 1
Pathology, University of Navarra, Pamplona/Spain, 2Pathology, Hospital de
allowing simultaneous sequencing of 70 ALK, RET and ROS1 specific fusion
Navarra, Pamplona/Spain, 3Gastroenterology, University of Navarra, Pamplona/
transcripts associated with NSCLC, as well as novel ALK translocations Spain, 4 Medical Oncology, University of Navarra, Pamplona/Spain
using 5’-3’ ALK gene expression ‘Imbalance Assay’. Results: NGS provided
results for 90 cases, while RT-PCR for 77. Overall, 70 cases have results for all Background: Determination of ALK gene rearrangements has been
4 methods, with fully concordant 60 (85.7%) cases (49 ALK-, 11 ALK+). Before traditionally performed in biopsies and/or surgical specimens. However,
employing the ‘Imbalance Assay’, in 5 of the remaining 10 cases, NGS differs advanced lung cancer is often diagnosed by FNA cytology obtained through
from the other methods (3 NGS-, 2 NGS+), while in the other 5, NGS agrees minimally invasive procedures, and frequently cytological specimens are
with RT-PCR in all, IHC in 2, and FISH in 1. Using the concordant result of at the only samples available, thus emphasizing the necessity to expand ALK
least two of the three methods as true negative/positive, the specificity and analysis to cytologic specimens. We assessed the feasibility of determining
sensitivity of the fourth is 96/94/100/96% and 94/94/89/72% for IHC/FISH/ ALK gene rearrangements in different types of cytological samples. Methods:
RT-PCR/NGS, respectively (incorporating imbalance: NGS sensitivity=83%). We studied prospectively 268 cytological samples from 268 NSCLC patients
Imbalance scores are presented here for 18 NGS- cases: 9 ‘NGS-/FISH+/IHC+’, for ALK gene rearrangements by FISH (Vysis LSI ALK Dual Color Break
9 ‘NGS-/FISH-/IHC-‘. Among the ‘NGS-/FISH+/IHC+’, there is strong evidence Apart and ZytoLight SPEC ALK Dual Color Break Apart). Tumour samples
of imbalance in 4 cases (score’s range: 0.0144-0.0555), uncertain in 5 (range: were obtained by bronchoscopy -FNA in 45 cases (19.79%), EBUS-FNA in 63
0.0030-0.0087), and no evidence (scores≤0.0004) in the 9 negative cases. (23.50%), EUS-FNA in 56 (20.89%), CT-FNA in 28 (10.44%), Ultrasonography
Conclusion: NGS is a useful screening tool for ALK rearrangement status, guided-FNA in 24 (8.95%), and direct FNA in 23 cases (8.58%). Two cavity
superior to RT-PCR when RNA yield is limited. When using NGS, it is critically fluids (0.74%), 4 imprints from surgical specimens (1.49%), and 22 cases
important to integrate the 5’-3’ imbalance assay and to confirm with one or received for consultation (8.20%) were also studied. ROSE was done in all FNA
more additional methods in the ‘imbalance’ cases. Data further highlight the procedures. FISH was performed on stained smears in 133 cases (49.62%) (114
possibility of missing actionable rearrangements when only one screening Papanicolau and 19 Diff-Quick), ThinPrep in 48 (17.91%), SurePath in 12 (4.47%),
methodology is available. and cell block in 75 cases (27.98%). All cases were tested for EGFR and KRAS
mutations. Results: Two hundred thirty five samples (87.68%) were adequate
Keywords: ALK, NGS, ETOP, Lungscape for FISH analysis. Fifteen cases (5.59%) had ALK gene rearrangements. One
case had a concurrent EGFR mutation in exon 21 plus the T789M mutation,
and two had also KRAS mutations (G12D and G12C respectively). FISH study
was unsuccessful in 33 cases (12.31%): 8 from stained smears (6.01%), 12 from
ThinPrep (25%), 8 from SurePath (66.66%), and 5 from cell blocks (6.66%).
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – Correlation cytological / paraffin embedded samples was performed in 10
MONDAY, DECEMBER 5, 2016 cases with a concordance rate of 100%. Conclusion: ALK gene rearrangements
may be definitely detected in cytological samples and particularly in direct
smears. Both, Papanicolau and Diff-Quick smears are suitable samples
P1.02-026 DETECTION OF LOW-ABUNDANT EGFR SOMATIC
for FISH analysis. The nuclei on cytology smears are not truncated, which
MUTATIONS BY PNA CLAMPING-ASSISTED FLUORESCENCE
allows for the detection of the true number of FISH signals in a nucleus. It is
MELTING CURVE ANALYSIS mandatory an exquisite management and care of the samples to preserve
Jihye Yoon, Hyunsun Kim, Jaejin Choi, Seung Kyo Park, Sung Kee Kim quality. Coexistence of ALK gene rearrangements and EGFR and KRAS
Panagene Inc., Daejoen/Korea, Republic of mutations were observed in one and two cases respectively, indicating that
such alterations are not necessarily mutually exclusive
Background: Detecting mutations is becoming important for both predicting
disease progression and drug responses to treatment of cancer patients. Keywords: ALK, cytology, FISH, Smears
Current mutation detection methods for cancer diagnosis are mainly based
on the invasive sampling technique such as a tissue biopsy, but some patients
may not available for this invasive procedure. Therefore, circulating tumor
DNA (ctDNA) would be a good alternative for those patients. However, testing
methods for tissue biopsy sample are not applicable to ctDNA samples due POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
to relatively lower sensitivity. A highly sensitive assay method is required for MONDAY, DECEMBER 5, 2016
detecting mutations in liquid biopsy samples. Methods: We have developed
a highly sensitive and simple method to detect somatic mutation from
ctDNA in patient’s plasma. This new real-time PCR-based testing method P1.02-028 DETECTION OF ONCOGENIC DRIVERS IN PLEURAL
(PANAMutyper™) has maximized unique properties of peptide nucleic EFFUSIONS AND ARCHIVED FNA SMEARS OF PULMONARY
acid (PNA). It contains a PNA clamp and PNA detection probes in the each ADENOCARCINOMA
reaction tubes. A optimized PNA clamp can tightly bind to only wild-type Deepali Jain1, Ramesh Kumar 1, Varsha Singh1, Prabhat Malik2, Karan Madan3,
DNA sequences, and then suppress amplification during the PCR reaction. Mohammad Farooq4
Meanwhile, a PNA detection probe that conjugated with a fluorescent dye 1
Pathology, All India Institute of Medical Sciences, New Delhi/India, 2Medical
and a quencher, can detect a specific target mutant-type DNA and each Oncology, All India Institute of Medical Sciences, New Delhi/India, 3Pulmonary
mutation can be genotyped by melting peak analysis. PANAMutyper™ is able Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi/
to detect 47 different mutations in exon 18, 19, 20 and 21 of EGFR gene with India, 4 Csir-Institute of Genomics & Integrative Biology, Delhi/India
detection limits as low as 0.01%. Results: In order to confirm the validity in
real condition, we conducted spiking test. Ten of mutant clones DNA were Background: Cytological materials are widely used in diagnosis and staging of
used as standard materials. (G719A, G719S, G719S, S768I, Exon19 deletion, lung cancer due to advanced stage of disease at the time of presentation.
two Exon20 insertion, T790M, L858R, L861Q). Mix the each mutant clone DNA Mutational oncogenic drivers in pulmonary adenocarcinoma (ADC) include
and human plasma to 1, 10, 100, 1000 copies per microliter concentration. And EGFR, Kras and Her-2/neu. We utilized archived FNA smears and pleural
then we extracted ctDNA from prepared sample. As a result, all of ten mutant effusion samples of ADC for detection of oncogenic molecular drivers.
clone DNA was detected 1 copy/μl. This result suggest that PANAMutyper™ Methods: Pleural fluids (36) and May Grunwald stained FNA smears (18) were
is applicable to ctDNA derived from patient’s plasma sample. Conclusion: The used for mutation anaysis. Sanger sequencing and ARMS and Scorpions PCR
high concordance, specificity, and sensitivity of this test have demonstrated performed. Each tumor sample was evaluated for all classes of genomic
that EGFR mutation status can be accurately assessed by PANAMutyper™ alterations, including base-pair substitutions, insertions/deletions, as well as
using ctDNA. Therefore, PANAMutyper TM can be used in various clinical areas intronic/CDS polymorphisms. Results: There were 31 males and 23 females,
including companion diagnostics and monitoring acquired mutations. aged 18 to 82 years with mean age 65.5 years. A total of 9 patients (16.6%)
were found positive for EGFR mutations (Table 1, Figure 1). EGFR exon 18
Keywords: EGFR, Circulating Tumor DNA, PNA, Melting curve analysis intronic poylmorphism was seen in 4 cases and EGFR exon 20 showed intronic
and CDS polymorphism in most cases. However, none of the cases were found
to be positive for EGFR, exon 18, 20, Kras and Her-2/neu mutation.
to an acid decalcified specimen and was not evaluated by FISH. Focal intense
stain was observed in 5 samples, 3 corresponded to surgical specimens and the
rest to small needle biopsies, one of the surgical specimens was FISH positive
and the rest, negative. Conclusion: Since FDA approval of Ventana ALK (D5F3)
IHC CDx Assay, IHC has become a widely used tool for assessing ALK status.
Guidelines suggest that weak granular stain should be interpreted as negative
and focal intense granular stain in any number of cells, as positive. Even though
our sample is small, moderate granular stain was consistently negative by FISH
analysis, however, focal intense stain shows more discordant results between
tests. To date, no suggestions are made on what should be the minimum
amount of tumor in a sample to report an IHC assay. Even though some of
these patients with IHC positive/FISH negative results have been reported
as responders to Crizotinib, further studies are needed. One specimen with
moderate cytoplasmic IHC stain was uninformative due to lack of signals. This
raises the issue of the need to standardize preanalytical variables, which can be
difficult in some areas of Latin America.
Keywords: ALK, Non Small Cell Lung Carcinoma, Immunohistochemistry

P1.02-030 PERFORMANCE EVALUATION OF ALK/ROS1 DUAL BREAK

APART FISH PROBE KIT (RUO) IN NON-SMALL-CELL LUNG CANCER
Hyun Chang 1, Sun Min Lim2, Hye Ryun Kim2, Yoon Jin Cha3, Liang Shel4, Gu Li4,
Yan Chin Tai5, Ekaterina Pestova4, Frank Polichit4, Thomas Perez4, Ross Soo6,
Won Young Park7, Hyo Sup Shim7, Byoung Chul Cho2
1
Hematology and Medical Oncology, Catholic Kwandong University International
St. Mary’s Hospital, Incheon/Korea, Republic of, 2Division of Medical Oncology,
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/Korea, Republic
of, 3Department of Pathology, Gangnam Severance Hospital, Seoul/Korea, Republic
of, 4 Abbott Molecular Inc, Des Plaines/IL/United States of America, 5 Abbott
Laboratories (Singapore), Singapore/Singapore, 6Haematology-Oncology, National
University Health System, Singapore/Singapore, 7Department of Pathology,
Severance Hospital, Yonsei University College of Medicine, Seoul/Korea, Republic of
Background: ALK and ROS1 gene rearrangements are distinct molecular

subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive
biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib. Thus,
it is clinically important to detect patients who will benefit from such
treatment and develop an effective screening strategy. In this study, we
aim to evaluate the diagnostic performance of ALK/ROS1 RUO FISH probes
Conclusion: These findings verify the feasibility of analysis of oncogenic drivers which can concurrently detect ALK and ROS1 rearrangements. Methods:
in cytological specimens in advanced ADC. Stained aspiration smears can be The study populations were composed of three patient cohorts with
used after establishing diagnosis and checking adequacy of the specimen. histologically confirmed lung adenocarcinoma (ALK rearrangement, ROS1
rearrangement and both wild type). Patient specimens consisted of 12
Keywords: oncogenic Drivers, pulmonary adenocarcinoma, pleural effusions, ALK-positive, 9 ROS1-positive and 21 ALK/ROS1-wild type formalin-fixed
FNA smear paraffin-embedded samples obtained from surgical resection or excisional
biopsy. ALK rearrangement status was determined by Vysis LSI Dual Color
Break Apart Rearrangement Probe (Abbott Molecular, Abbott Park, IL, USA)
and ROS1 rearrangement status was assessed by ZytoLight SPEC ROS1 dual
color break apart probe (Zytovision. Bremerhaven, Germany). All specimens
were re-evaluated by ALK/ROS1 Break Apart FISH RUO 4-color kit. FISH
MONDAY, DECEMBER 5, 2016 images were scanned via the BioView Duet and interpreted remotely via
BioView SoloWeb. Results: A total of 42 patient samples were evaluated.
The concordance of results obtained from ALK/ROS1 Break Apart FISH RUO
P1.02-029 INFREQUENT STAINING PATTERNS IN ALK 4-color kit was evaluated relative to the ALK and ROS1 rearrangement status
IMMUNOHISTOCHEMISTRY: CORRELATION WITH FISH ANALYSIS of the specimen, as previously determined. One ROS1-positive and 2 wild-type
Paola De La Iglesia1, Mercedes Dalurzo2 samples were excluded from analysis due to high background. Regarding 12
1
Pathology, Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 2Pathology, ALK-positive samples, 12 were ALK-positive by ALK/ROS1 RUO FISH, showing
Hospital Italiano de Buenos Aires, Ciudad Autonoma de Buenos Aires/Argentina 100% (n=12/12) sensitivity to predict ALK rearrangement. Regarding 8 ROS1-
positive samples, 6 cases were ROS1-positive by ALK/ROS1 RUO FISH, showing
Background: AKL gene rearrangements are predictive alterations in non small 75% (n=6/8) sensitivity to predict ROS1 rearrangement. Two cases showed
cell lung carcinomas (NSCLC). Immunohistochemistry (IHC) has become a weak ROS1 signals that could not be enumerated. Regarding 19 wild type
valuable tool in assessing ALK status, however unusual staining patterns, such cases, 18 cases were negative by ALK/ROS1 RUO FISH, showing 95% (n=18/19)
as heterogeneous diffuse moderate and focal intense stains, may occur and specificity, while one case showed poor ROS1 signals which could not be
can make evaluation difficult. Methods: We correlated immunohistochemistry properly enumerated. Conclusion: ALK/ROS1 RUO FISH can detect ALK and
unusual staining patterns with ALK status by fluorescence in situ hybridization ROS1 rearrangements simultaneously in NSCLC. The fluorescence of ROS1
(FISH). Of 851 cases tested, we found 14 (1.6%) cases with inconclusive staining signal may be weakened by slide shipment and remote scoring.
patterns that can be summarized in: a) diffuse granular cytoplasmic moderate
stain, with or without background mucin stain (10 cases) b) focal intense Keywords: ALK, ROS1, fluorescent in situ hybridization, non-small-cell lung cancer
granular cytoplasmic stain in overall negative or weakly positive tumors (4
cases). IHC was performed on an automatized Benchmark staining module
using Ventana ALK (D5F3) CDx assay with Optiview amplification kit. FISH was
performed using ALK break-apart probe set (Vysis LSI ALK Dual Color, Abbott DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
Molecular). Cases were considered ALK-FISH positive if ≥15% tumor cells showed MONDAY, DECEMBER 5, 2016
split red and green signals (separation of 2 diameters or more) and/or single red
signals Results: Of 10 moderate granular cytoplasmic stain cases, 4 had also
abundant mucin backround stain 6 where markedly heterogeneous with areas P1.02-031 MUTATIONS IN TP53, PIK3CA, PTEN AND OTHER GENES
of weak and moderate cytoplasmic granular stain. Nine were FISH negative, IN EGFR MUTATED LUNG CANCERS: CORRELATION WITH CLINICAL
one yielded no signals (uninformative result) and one specimen corresponded OUTCOMES

Paul Vanderlaan1, Deepa Rangachari2, Susan Mockus3, Vanessa Spotlow3, LUNG CANCER PATIENTS WITH EGFR-TKI RESISTANCE
Honey Reddi3, Joan Malcom3, Mark Huberman2, Loren Joseph4, Susumu Hyein Ahn, Hyun Jung Kwon, Eunhyang Park, Soo Young Park, Hyojin Kim, Se
Kobayashi2, Daniel Costa2 Hyun Kim, Jin-Haeng Chung
1
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical Pathology, Seoul National University Bundang Hostpital, Bundang-Gu, Seongnam-
School, Boston/MA/United States of America, 2Division of Hematology/Oncology, Si/Korea, Republic of
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston/MA/United
States of America, 3Jackson Laboratory for Genomic Medicine, Farmington/United Background: Histomorphologic changes are known to be associated the
States of America, 4Pathology, Beth Israel Deaconess Medical Center, Harvard acquired resistance of the epidermal growth factor receptor tyrosine kinase
Medical School, Boston/MA/United States of America
inhibitors (EGFR-TKI) treatment. Rebiopsy is usually used to detect the
Background: The degree and duration of response to epidermal growth factor underlying molecular mechanism of resistance, however meticulous histologic
receptor (EGFR) inhibitors in EGFR mutated lung cancer are heterogeneous. examination is very important to identify the change of cancer phenotype.
We hypothesized that the concurrent genomic landscape of these tumors, Here we tried to investigate histomorphologic changes between the initial
which is currently largely unknown in view of the prevailing single gene assay and rebiopsy specimens. Methods: We retrospectively evaluated the initial
diagnostic paradigm in clinical practice, could play a role in clinical outcomes biopsy and rebiopsy specimens of 60 patients with acquired resistance to
and/or mechanisms of resistance. Methods: We retrospectively probed EGFR-TKI between 2010 and 2016 in Seoul National University Bundang
our institutional lung cancer patient database for tumors harboring EGFR Hospital, Republic of Korea. EGFR mutation tests were performed in all
kinase domain mutations that were also evaluated by more comprehensive specimens. Various histologic parameters including spindle cell components,
molecular profiling, and assessed tumor response to EGFR tyrosine kinase discohesive growth pattern and stromal change, subtype of the tumor and
inhibitors (TKIs). Results: Out of 171 EGFR mutated tumor-patient cases, 20 nuclear grade were evaluated. In addition, immunohistochemistry (IHC) for
were sequenced using at least a limited comprehensive genomic profiling epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin)
platform. 50% of these harbored concurrent TP53 mutation, 10% PIK3CA and neuroendocrine markers (CD56 and synaptophysin) was perfomed. Results:
mutation, and 5% PTEN mutation, among others. The response rate to EGFR In rebiopsy specimens, 18 cases (30%) showed changes of cellular morphology
TKIs, the median progression-free survival (PFS) to TKIs, the percentage of including spindle cell components and discohesive growth pattern representing
EGFR-T790M TKI resistance and survival were higher in EGFR mutant/TP53 EMT features. On IHC, acquisition of vimentin expression in spindle cell
wild-type cases when compared to EGFR mutant/TP53 mutant tumors; with a components and decreased expression of E-cadherin in adenocarcinoma of
significantly longer median PFS in EGFR-exon 19 deletion mutant/TP53 wild- rebiopsy specimens were identified. Furthermore, histologic transformation to
type cancers treated with 1st generation EGFR TKIs. Conclusion: Concurrent small cell carcinoma (2 cases, 3.3%) with expression of neuroendocrine markers
mutations, specifically TP53, are common in EGFR mutated lung cancer and and squamous differentiation (2 cases, 3.3%) were observed. Conclusion: In
may alter clinical outcomes. Additional cohorts will be needed to determine this study, histologic transformation to EMT is the most frequent finding in
if comprehensive molecular profiling adds clinically relevant information to rebiopsy samples of the patients with EGFR-TKI resistance while small cell
single gene assay identification in oncogene-driven lung cancers. carcinoma has been known to be the most common in the literaturesAlthough
EMT has been reported to be about 5% of EGFR-TKI resistance, we observed it
Keywords: tyrosine kinase inhibitor, EGFR mutation, p53 mutation, NSCLC in approximately 30% of our rebipsy cases. These findings suggest that detailed
and meticulous pathologic evaluation plays an important role to find delicate
histomorphologic changes associated with EGFR-TKI resistance.
Keywords: lung cancer, EGFR TKI, Resistance, epithelial-mesenchymal

POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY transition
P1.02-032 DIAGNOSIS AND TREATMENT OF EGFR MUTATED NSCLC

AMONG ARABIC PATIENTS DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
1 1 1
Mor Moskovitz , Mira Wollner , Mahmoud Abu-Amna , Abed Agbaria 2 MONDAY, DECEMBER 5, 2016
1
Medical Oncology, Rambam Medical Center, Haifa/Israel, 2Omcology, Bnay Zion
Medical Center, Haifa/Israel P1.02-034 EGFR MUTATIONS AND ALK TRANSLOCATIONS IN LUNG
Background: About 15% of western patient population with advanced NSCLC CANCER - A NATIONAL STUDY
harbor the epidermal growth factor receptor (EGFR) mutation compared to Erik Jakobsen1, Karen Ege Olsen2, Maria Iachina3, Anders Green4
about 50% in the Asian population. These mutations are more frequently 1
Cardiothoracic Surgery, Odense University Hospital, Odense/Denmark,
2
found in NSCLC with an adenocarcinoma histology, in women, East Asians Department of Pathology, Odense University Hospital, Odense/Denmark, 3Center
and never smokers. EGFR tyrosine kinase inhibitors (TKIs) are the first-line for Clinical Epidemiology, Odense University Hospital, Odense/Denmark, 4 Open,
treatment of choice for NSCLC patients harboring EGFR mutation. Nowadays Odense University Hospital, Odense C/Denmark
there is only a scares information regarding EGFR epidemiology and response
Background: The Danish Lung Cancer Registry (DLCR) has since 2003 reported
to EGFR TKI among other ethnicities, although there has been limited reports
all cases of lung cancer in Denmark. Since 2012 data on EGFR mutations and ALK
regarding increased rate of EGFR mutation among arabic patients. Methods:
translocations have been included. Little is known on the distribution of EGFR
Single institution retrospective analysis of serial advanced NSCLC patients
mutations and ALK translocations on a national level in a primarily Caucasian
tested for EGFR mutation in 2011-2015. Information was obtained using the
population like the Danish lung cancer population. Methods: All Danish lung
medical records. Results: Of 616 patients with advanced NSCLC tested for
cancer patients are ascertained based on coded information in the National
EGFR in our institutions in 2011-2015, there were a total of 134 Arabic patients,
Patient Register. Supplementary information for each patient is obtained from
38 of them harboring EGFR mutation (28%), as opposed to 64 (13%) among
the clinical units as well as from the National Pathology Register (NPR). Based
the non-arabic population. Twenty patients had exon 19 deletion, 9 patients
on SNOMED coding by all departments performing lung cancer pathology
had L858R and 1 patient had exon 21 mutation. The median age at diagnosis
evaluation and registered in the NPR the subgroups of lung cancer are
was 58 (39-80), 22 patients were males and 16 females, of them- 13 were
identified. The patients are tested for EGFR mutations and ALK translocations
never smokers, 5 are previous smokers, and 20 are active smokers. Thirty-six
according to national guidelines and the results are registered in the NPR. It is
patients had adenocarcinoma histology while 2 patients had carcinosarcoma
estimated that 95 % of all Danish lung cancer patients are present or former
and squamous cell carcinoma. The median survival was longer than 9 months.
smokers and that the sex distribution is equal between the sexes. Results: 4667
Thirty patients were treated with EGFR TKI, 27 of them as 1ST line treatment,
patients diagnosed in 2015 are included. Table 1. Distribution of EGFR mutations
and 3 as 2ND line treatment. Of the 30 patients treated with EGFR TKI, 69%
and ALK translocation in the 2015 lung cancer population:
had partial response, 16% had stable disease. Conclusion: Among Arabic
patients with NSCLC, the frequency of EGFR mutation is higher than in
western population, and is more frequent among males and smokers. The
response to EGFR TKI matches the reported literature.
Keywords: EGFR, Metastatic NSCLC, epidemiology

P1.02-033 MESENCHYMAL TRANSFORMATION IS THE MOST

COMMON HISTOMORPHOLOGIC CHANGES IN THE REBIOPSY OF
83.3 % of all patients with lung cancer and adenocarcinoma in Denmark are CLASSICAL SENSITIZING MUTATIONS
tested for EGFR mutations and 9.4 % are positive. 73.1 % of adenocarcinomas Hirotsugu Notsuda1, Ming Li2, Christine Ng1, Ni Liu1, Vibha Raghavan1, Chang-
are tested for ALK translocations and 1.4 % is found to be positive. In total Qi Zhu3, Nhu-An Pham4, Geoffrey Liu5, Frances Shepherd2, Ming Tsao6
only 8.8 % of all tested lung cancer patients are found to be EGFR mutated 1
Ontario Cancer Institute, Toronto/ON/Canada, 2Princess Margaret Cancer Centre,
and 1.3 % has an ALK translocation. Conclusion: Data from primarily Asian Toronto/ON/Canada, 3Department of Laboratory Medicine and Pathobiology,
lung cancer populations have shown significant higher rates of EGFR University Health Network, Toronto/Canada, 4Departments of Laboratory Medicine
mutations and ALK translocations that the findings in this Danish population. and Pathobiology, University of Toronto, University Health Network, Toronto/
Based on these data the cost-effectiveness of the chosen strategy for reflex ON/Canada, 5Princess Margaret Cancer Centre, Toronto/Canada, 6Departments of
testing lung cancer patients up front should be reconsidered. Pathology, Princess Margaret Cancer Centre and University of Toronto, Toronto/
Canada
Keywords: ALK translocations, lung cancer, EGFR mutations
Background: Mutations in the tyrosine kinase (TK) domain of EGFR
are oncogenic driver in 10-20% of lung adenocarcinoma (AdC) patients
in Western countries. Approximately 90% of EGFR-TK inhibitor (TKI)
sensitizing mutations occur as small in-frame deletions in exon 19 or L858R
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY point mutations in exon 21. Recently, novel driver mutations in EGFR with
oncogenic and TKI sensitizing activity have been reported. We present
here an AdC patient-derived xenograft (PDX) model (PDX12) that is highly
sensitive to EGFR-TKI, yet failed to demonstrate classical TKI sensitizing
P1.02-035 CONCOMITANT DRIVER MUTATION DETERMINES TUMOR mechanisms. Methods: Comprehensive genomics profiling was used to
GROWTH IN EGFR MUTATION-POSITIVE LUNG ADENOCARCINOMA characterize the genotype of PDX12, which was established from a resected
Kazuhiro Nagayama1, Takahiro Karasaki1, Hideki Kuwano1, Jun-Ichi Nitadori1, stage IIIA AdC patient grafted in NGS mouse. The primary human lung cancer
Masaaki Sato1, Masaki Anraku1, Hirokazu Matsushita2, Kazuhiro Kakimi2, Jun cell line (PHLC12) was extracted from its PDX model (PDX12). Aberrant
Nakajima1 EGFR cell lines used were H3255 (L858R), H2935 (exon 19 deletion), H1975
1 (L858R and T790M), and H1944 (wild type). Cell viability was assessed after
Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo/Japan,
2
Immunotherapeutics, The University of Tokyo Hospital, Tokyo/Japan erlotinib treatment at 1nM - 2μM for 72 hours using MTS assay. Levels of
EGFR activation in both pre- and post-treatment by Western blot analysis.
Background: In the practice of precision medicine, understanding tumor Results: PDX12 model had no known oncogenic mutations (EGFR wild type)
characteristics in the individual patient is crucial. The aim of this study was to on exons 18-21 by next-generation sequencing, RT-qPCR, and SISH, but was
analyze tumor aggressiveness from two perspectives: actual growth rate highly sensitive to EGFR-TKI. The IC50 to erlotinib treatment at 72 hr was
calculated from the tumor; and molecular profiles obtained by next- 67.13 ± 7.63 nM for PHLC12, compared to 9.70 ± 2.64 nM for H3255, 64.88 ±
generation sequencing. Methods: Participants comprised patients who 8.49 nM for HCC2935, > 2 μM for H1975, and > 2 μM for H1944 EGFR mutant or
underwent preoperative CT two or more times. DNA and RNA of 10 lung wild type cells, respectively. Western blot analysis demonstrated a relatively
adenocarcinoma tumor samples were extracted. Whole-exome and higher molecular weight band for EGFR protein with high expression level in
-transcriptome data were obtained, and somatic mutations were detected. PHLC12 when compared to other lung cancer cell lines. Using RT-qPCR, relative
Preoperative CT scans were retrospectively reviewed and volume doubling expression level of each EGFR domain (extracellular, tyrosine kinase, and
time (VDT) of each tumor was calculated using a modified Schwarz equation. c-terminal domain) in PHLC12 showed no difference compared to EGFR wild
Results: Median VDT was 104 days (range, 42-653 days). Median number of type. Phosphorylation status of EGFR in PHLC12 was similar in activity as
somatic missense mutations was 20 (range, 7-306). EGFR mutations were compared to erlotinib sensitive cell lines. Conclusion: PHLC12 represents an
present in 6 patients. Patients were divided into two groups by VDT for enigmatic EGFR TKI sensitive lung PDX model without classical TKI sensitizing
further analyses: Slow group with VDT ≥104 days (n=5); and Rapid Group with aberrations. Additional potential mechanisms of EGFR dependency including
VDT <104 days (n=5). All patients with EGFR mutation without concomitant exon duplication, or post-translational modification of EGFR protein are being
KRAS mutation were in the Slow Group. In contrast, a patient with investigated.
concomitant mutations of EGFR and KRAS showed a considerably rapid
growing tumor with a VDT of 45 days. A patient with concomitant mutations Keywords: no oncogenic mutations, EGFR mutations, patient-derived
in EGFR and PIK3CA had a relatively slow-growing tumor, although VDT was xenograft model, EGFR-TKI sensitive model
the shortest in the Slow Group (120 days).

P1.02-037 MUTATIONS OF EGFR AND KRAS GENES IN BELORUSSIAN

PATIENTS WICH NON-SMALL CELL LUNG CANCER
Alena Mikhalenka1, Anna Shchayuk1, Evelina Krupnova1, Michael Shapetska2,
Natalia Chebotaryova1, Svetlana Pissarchik 3
1
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus,
Minsk/Belarus, 2Belarusian State Medical University, Minsk/Belarus, 3City Clinical
Pathologoanatomic Bureau, Minsk/Belarus
Background: Mutations of the epidermal growth factor receptor (EGFR) cause

increased activation of EGFR and sensitivity of patients with non-small cell
lung cancer (NSCLC) to tyrosine kinase inhibitors (TKIs). The effectiveness of
TKIs also depends on mutations of the KRAS gene that encodes small GTPase
Conclusion: EGFR mutation was associated with slow growth of the tumor,
that is activated in response to a signal from EGFR and transmits it to the
although the growth rate may be influenced by concomitant mutation of
cascade of tyrosine kinases. Treatment of patients with KRAS mutations
other driver genes. This may be one of the reasons that the clinical response of
by TKIs is inefficient. Therefore, the research of these alterations plays an
tyrosine kinase inhibitors are poor in some patients with EGFR mutation.
important role in determining the possibility of additional factors prognosis
Assessment of tumor aggressiveness by molecular profiling and by sequential
of NSCLC and adjusting individual tumor therapy. The aim of this study is to
CT are both important for the practice of precision medicine.
identify mutations in the exons 19 and 21 EGFR gene and in the exon 2 KRAS
Keywords: EGFR mutation, Volume doubling time, next generation gene in patients with NSCLC. Methods: Analysis of mutations in the EGFR and
sequencing, Concomitant driver mutation KRAS genes was performed by PCR followed by sequencing DNA, which was
extracted from the tumor and non-tumor lung tissues and blood samples of 97
patients with NSCLC (71 men, 26 women). 51 people have an adenocarcinoma
(AC) and 46 people - squamous cell carcinoma (SCC). Results: Analysis of
mutations in the EGFR gene showed that the frequency of classical mutations
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY is 5,2% of deletions in exon 19 (p.E746_A750del and p.L747_P753>S) and
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – 1,1% of p.L858R mutation in exon 21. All mutations were detected only in the
tumor tissue of non-smoking women with AC. Thus, 27,3% of women with
AK are carriers of mutations in EGFR gene. These types of mutations were
P1.02-036 AN EGFR TYROSINE KINASE INHIBITOR SENSITIVE not detected among men. Also in the researched group was identified silent
PATIENT-DERIVED LUNG CANCER XENOGRAFT MODEL WITHOUT mutation c.2508C>T in exon 21 in the tumor, non-tumor tissue and blood

among 3,3% of patients. multiple biomarker analyses and tumor heterogeneity. Mutation detection in
circulating cell-free tumor DNA (ctDNA) can overcome these caveats and also
Analysis of mutations in exon 2 KRAS gene detected 3 types of mutations: be used for tracking tumor dynamics. The aim of this study was to evaluate
p.G12D (1,03%), p.G12C (2,06%) и p.G13C (1,03%). The frequency of all KRAS mutation detection in plasma samples from LA. Methods: Plasma
mutations was 4,1% in the total group of patients. The mutations were found samples from 35 patients with histologically confirmed KRAS mutant LA were
only in tumor tissues of men. 75% of mutations carriers are smokers. Analysis collected at initiation of chemotherapy. KRAS mutations were assessed using
of KRAS gene mutations in association with the development of a specific digital PCR technology (QuantStudio3D Digital PCR System, Thermofisher
histological type of lung cancer showed that mutations are more common in Scientific). Correlation between ctDNA and tumor biopsies in terms of
patients with AC (5,9%) than in patients with SCC (2,2%). Conclusion: Thus, mutation detection was analysed. In 5 cases plasma samples were obtained
in the researched group of patients mutations in the EGFR gene were found during the course of the disease to monitor clonal dynamics. Results: Most
only among non-smoking women with AC, mutations in the EGFR gene were cases were male (71%), with stage IV disease (83%), and showed KRAS
detected only among men independently of histological type of NSCLC. mutation on codon12 (94%). KRAS mutation was found in plasma samples in
28/35 cases, showing a concordance with the tumor of 80%. In patients whose
Keywords: Epidermal growth factor receptor, mutations, non-small cell lung
disease was limited to thorax (stages II, III, and IVa) KRAS mutation was
cancer
detected in 7/10 (70%) plasma samples. Plasma/tumor biopsy concordance in
cases with extra-thoracic metastases was 84% (21/25). The 4 false negative
cases had low burden of extra-thoracic disease, with bone (2 cases), brain (1
case), and abdominal lymph node (1 case) as the only metastatic location
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY outside the thorax. KRAS clonal dynamics in plasma showed a good
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – correlation with treatment responses in some cases (figure 1).
P1.02-038 OVER- EXPRESSION OF EPIDERMAL GROWTH FACTOR

RECEPTOR 1 (EGFR1) GENE IN SERUM OF ADENOCARCINOMA LUNG
AT A TERTIARY LEVEL CENTRE IN NORTH INDIA
Ashraf Ansari1, Anant Mohan1, Mirza Masroor2, Alpana Saxena2, Kalpana
Luthra3, Karan Madan4, Vijay Hadda4, G. Khilnani5, Randeep Guleria4
1
Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences,
Delhi/India, 2Biochemistry, Maulana Azad Medical College, New Delhi/India,
3
Biochemistry, All India Institute of Medical Sciences, New Delhi/India, 4Pulmonary
Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi/
India, 5Dept of Pulmonary Medicine and Sleep Disorders, All India Institute of
Medical Sciences, New Delhi/India
Background: Epidermal growth factor receptor (EGFR) is a cell surface protein

that binds to epidermal growth factor. Over expression of EGFR1 in tumor
tissue has been observed in upto 65% of advanced non small cell lung cancer,
and has shown promising prognostic potential. In this study, we compared the
EGFR1 gene expression in serum adenocarcinoma lung with healthy controls.
Methods: We analyzed 61 newly diagnosed patients of adenocarcinoma lung
and 50 healthy controls. RNA was isolated from blood serum of all subjects
and real time PCR (RT- PCR) was performed after complementary DNA (cDNA)
synthesis. The level of EGFR1 expression in serum was calculated by relative Conclusion: High concordance in the detection of KRAS mutations was found
quantification method and expressed as fold-increase compared to compared between plasma and tumor tissue using digital PCR technology, particularly in
with controls. Expression levels were also correlated with various clinico- cases with extra-thoracic disease. Digital PCR allows for tracking clonal
pathological parameters. Results: Out of 61 patients, 42 were males. The dynamics in KRAS mutant LA.
mean (SD) age of the entire group was 54.5 (11.5) years. Most of the patients
(79%) had stage IV disease. 23 (38%) patients were current/ ex- smokers, with Keywords: liquid biopsy, KRAS, Clonal dynamics, lung adenocarcinoma
median pack years of 10 (range, 0.5- 100). Majority of patients had KPS of
90 (51%) and ECOG 1 (74%) respectively. Activating mutations in EGFR were
observed in the tissue of 14 (21.3%) of 61 patients; of these, 9 were exon- 19
deletions and 4 were exon- 21 point mutations. In the patients, a 19.66
mean- fold increase in serum EGFR gene expression was observed compared DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
to healthy controls. No significant association was found between EGFR MONDAY, DECEMBER 5, 2016
expression and other variables i.e., sex, age, smoking habit, performance
status, stage of disease and EGFR mutation status. Conclusion: Serum
P1.02-040 HETEROGENEITY OF THE EGFR / KRAS GENE MUTATION
EGFR1 gene was over expressed by >16 fold in advanced adenocarcinoma lung
compared to healthy controls. The association of EGFR expression with other
IN MULTIFOCAL LUNG ADENOCARCINOMA AND THE CLINICAL
clinical disease characteristics needs further exploration. SIGNIFICANCE
Lin Li1, Susu Zhang2, Hongshuang Dai2, Jianming Ying1, Yanning Gao2
Keywords: EGFR expression, RT-PCR, adenocarcinoma lung 1
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences,
Beijing/China, 2 State Key Laboratory of Molecular Oncology, Cancer Hospital,
Chinese Academy of Medical Sciences, Beijing/China
Background: Significant advances on EGFR-targeted therapy have allowed

POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY increasing availability of therapeutic options for non small cell lung
MONDAY, DECEMBER 5, 2016 cancers. For multifocal lung adenocarcinoma patients in clinic, the EGFR
gene mutation is generally examined only on the largest tumor or the one
containing the most tumor cells, which could omit the tumors harboring the
P1.02-039 ASSESSMENT OF KRASMUTATIONS (BY DIGITAL PCR) EGFR mutation and thus loss of opportunity for the tyrosine kinase inhibitors
IN CIRCULATING TUMORAL DNA FROM LUNG ADENOCARCINOMA therapy. Methods: A total of 58 cases of multifocal lung adenocarcinoma,
PATIENTS including 129 intrapulmonary tumors resected surgically, was recruited for
Álvaro Taus 1, Laura Camacho2, Ainhoa Hernández1, Gabriel Piquer2, Eva this study. The genome DNA samples were prepared from formalin-fixed and
López1, Alba Dalmases3, David Casadevall1, Lara Pijuan3, Max Hardy1, Raquel paraffin-embedded tumor tissues. The EGFR / KRAS mutational status of
Longarón3, Pedro Rocha1, Arnau Zafra2, Joan Albanell1, Beatriz Bellosillo3, each tumor was examined by Sanger’s DNA sequencing. The targeted hotspot
Edurne Arriola1 mutations in EGFR gene included p.G719S/C/A (exon 18), p.T790M (exon 20),
1 p.S768I (exon 20), p.L858R (exon 21), p.L861Q (exon 21) and deletions in exon
Medical Oncology Department, Hospital Del Mar, Barcelona/Spain, 2Imim (Institut
Hospital Del Mar D’Investigacions Mèdiques), Barcelona/Spain, 3Pathology
19. The hotspot mutations in KRAS gene were within codon 12 including
Department, Hospital Del Mar, Barcelona/Spain p.G12C/V/S/R/D/A. Results: In this group of 58 patients with multifocal
lung adenocarcinoma, 38 patients were found EGFR or KRAS mutations
Background: KRAS mutations are detected in approximately 25% of lung in their tumors. Among them, the EGFR mutations were detected in 59
adenocarcinomas (LA). Targeted therapies against KRAS are under tumors derived from 34 cases; while the KRAS mutations were detected in
investigation. The use of tumor biopsy for molecular testing may be 7 tumors from 5 cases. One patient (Case 30) was identified EGFR (exon 18,
challenging due to the invasiveness of the procedure, the limited material for p.G719A) or KRAS (p.G12A or p.G12C) mutation in her 3 tumors, respectively.
It is noteworthy that there were 21 (36.2%) in the 58 cases showing the Cronenberger3, Fabio Tavora1, Ana Claudia Oliveira1
mutational heterogeneity among the multiple intrapulmonary tumors 1
Pathology, Argos Patologia / Hospital de Messejana Do Coração E Do Pulmão,
derived from one individual, and that 6 tumors harbored 2 different types Fortaleza/Brazil, 2Thoracic Surgery, Hospital de Messejana Do Coração E Do
of EGFR mutation. However, none of the specimens investigated contained Pulmão, Fortaleza/Brazil, 3Oncology, Hospital de Messejana Do Coração E Do
both EGFR and KRAS mutations within a same tumor. Comparing data from Pulmão, Fortaleza/Brazil
the present study along with the molecular pathological diagnosis records
from the Department of Pathology, among the 58 cases enrolled, 30 cases Background: There have been very few studies on ALK status in lung
accepted routine molecular pathological examination to check the EGFR / adenocarcinomas in Latin American population. No prior reports in
KRAS mutation, and 28 cases did not. However, 37 out of 66 tumors from Northeastern Brazil have been published. Methods: We analyzed ALK protein
the 30 cases were tested -- only 5 patients had all their tumors examined; expression with a specific antibody (D5F3 clone) with the Ventana system
whereas in the rest total 92 tumors unchecked, 42 EGFR sensitive mutations in a series of consecutive cases from Northeastern Brazil, a previously
were identified in this study. Conclusion: Current finding suggests that the untested population, and correlated with histologic subtypes according to
EGFR and KRAS mutational heterogeneity is widely existed in multifocal lung the 2015 WHO Classification. Results: A total of 94 patients (55% female,
adenocarcinomas. Therefore, reliable and exhaustive examination for EGFR mean age 62 years) were tested, including 51 solid, 29 acinar, 6 lepidic, 6
/ KRAS mutation should be executed in the every tumor, to provide more papillary predominant and 2 sarcomatoid carcinomas with adenocarcinoma
individualized therapy choices for the patients. components. There were 9 positive cases (9.5%), 5 solid predominant, 3
acinar predominant and 1 lepidic. One of the 3 acinar cases had a mucinous
Keywords: Heterogeneity, multifocal lung adenocarcinoma, EGFR gene component. The positive cases were more often male (p<0.05) with no
mutation significant differences in relation to age, smoking history or histologic
subtype. The negative cases showed a 32% EGFR mutation rate. Follow-
up will be presented. Conclusion: We will describe a series of consecutive
adenocarciomas from a population with unknown ALK status with a higher
than expected rates, and correlate with the 2015 WHO Classification of
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY Tumors.
Keywords: Adenocarcinoma, ALK, biomarker, Latin America
P1.02-041 CHARACTERIZATION OF MET-N375S AS AN ACTIVATING

MUTATION IN SQUAMOUS CELL CARCINOMA OF THE LUNG
Li Ren Kong 1, Nur Afiqah Binte Mohamed Salleh1, Tuan Zea Tan1, Dennis POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
Kappei1, Boon Cher Goh2 DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
1 2 MONDAY, DECEMBER 5, 2016
Cancer Science Institute Singapore, Singapore/Singapore, Pharmacology, Cancer
Science Institute Singapore, Singapore/Singapore
P1.02-043 MULTIPLEXED FISH (ALK/ROS1, RET, NTRK1) IN LUNG
Background: Over the years, significant progress has been made in the
treatment of lung carcinoma. While targeting EGFR mutations in the tyrosine ADENOCARCINOMAS: NOVEL DUAL ALK/ROS1 PROBE AND
kinase domain and EML4-ALK rearrangements have yielded impressive AUTOMATED SCANNING SYSTEM
therapeutic gains in lung adenocarcinoma; the rarity of genetic aberration in Susana Hernandez 1, Esther Conde1, Mario Prieto1, Rebeca Martinez1,
squamous cell carcinoma (SCC) has restricted the use of molecular-targeting Margarita Rodriguez1, Raquel Martin2, Luis Jimenez3, Luis Madrigal3, Barbara
agents. Next-Generation sequencing analysis has identified a high frequency Angulo1, Fernando Lopez-Rios1
of c-MET mutation in Asian lung SCC specimens, in particular the MET-N375S 1
Pathology-Laboratorio de Dianas Terapeuticas, Hospital Universitario Hm
mutant. This study aims to characterize the functional significance and Sanchinarro, Madrid/Spain, 2Laboratorio de Dianas Terapeuticas, Hospital
therapeutic implications of MET-N375S in lung SCC cells. Methods: MET Universitario Hm Sanchinarro, Madrid/Spain, 3Thoracic Surgery, Hospital
(N375S) mutation in tumour tissues was verified with droplet digital PCR. Universitario Hm Sanchinarro, Madrid/Spain
c-MET mutant expressing clones were generated through site-directed
Background: Although the use of NGS (next-generation sequencing) is
mutagenesis and single cell clonal selection. The impact of MET-N375S in lung
indeed feasible for the study of druggable rearrangements, the sensitivity
SCC cells was characterized by defining the downstream effectors (Proteome
and specificity of targeted NGS has been challenged on several grounds: use
profiling), biological functions (anchorage-independent growth, invasion and
of fixed tissue, poor quality/insufficient sample, RNA-contamination risk
migration assays), transciptomic regulation (RNAseq) and protein-protein
or long turn-around time. Our relatively high rate of failures (7.6%) with the
interaction (SILAC). Novel binding partners of MET-N375S was verified
RNA workflow of targeted NGS (data not shown), prompted us to investigate
using co-immunoprecipitation (co-IP) and proximity ligation assay (PLA).
possible alternatives. The objective of this study is to demonstrate an
Sensitivity of c-MET mutant to various kinase inhibitors was determined
efficient solution based on multiplexed fluorescence in situ hybridization
with CellTiter-Glo assay. Results: MET (N375S) mutation was confirmed in
(FISH) for the comprehensive characterization of fusions (ALK, ROS1, RET
9/45 lung SCC specimens (20%). Ectopic expression of MET-N375S in lung SCC
and NTRK1) in lung adenocarcinomas (ACs). We have implemented for the
cells significantly elevated the activation of downstream Src, p38 and ERK1/2
first time in the literature a novel four-colour ALK/ROS1 probe and used an
kinases, increased hsp27 expression, while enhanced migratory, invasive
automated scanning system for scoring these four translocations. Methods:
and anchorage-independent colony forming ability in vitro. Despite so,
A total of 64 patients with early stage lung ACs who underwent surgery at
comparative transcriptomic analysis revealed that epithelial-mesenchymal
HM Sanchinarro University Hospital were considered. All slides were carefully
signature genes were not induced in cells expressing mutant c-MET. On
reviewed to identify the different histological patterns. Afterwards we
the contrary, SILAC and co-IP analyses on the MET-N375S interactome
performed FISH to study ALK, ROS1, RET and NTRK1 in each pattern. We used
demonstrated an increase in binding affinity towards receptor tyrosine
both commercially (RET and NTRK1) and non-commercially (ALK/ROS1 dual)
kinases (RTKs) as compared to wild type c-MET, which was confirmed with in
available Vysis break-apart probes (Abbott Molecular, USA). Slides were
situ PLA. Moreover, MET-N375S augmented in vitro sensitivity to selective
captured and scored with the BioView (Rehovot, Israel) automated imaging
MET inhibitors. Conclusion: These findings suggest the role of MET-N375S
and analysis system, using dedicated applications for each probe. Positive
as an activating mutation that strongly enhance malignant transformation
cases were all confirmed with targeted NGS (Oncomine Focus AssayTM, Life
and metastatic potential in lung SCC cells. Mechanistically, the dysregulation
Technologies, USA). Results: Seven out of 420 slides did not hybridize (1.6%).
of various oncogenic events could be associated with the formation of
We found two ALK (2.8%) and two ROS1 (2.8%) positive tumors, while no
heterodimers with RTKs. Clinically, MET-N375S could be utilized as a potential
translocations were identified in RET or NTRK1. The rearrangements were
predictive biomarker for patients with advanced SCC of the lung to be treated
present in all the different histological patterns within a given tumour, with a
with selective MET inhibitors.
similar proportion of positive cells. The two major patterns of positivity were
Keywords: Lung Squamous cell carcinoma, c-MET mutation represented. The mean percentage of positive cells was 65% (range 46 to 84%).
The NGS results confirmed the FISH findings. Conclusion: Simultaneous FISH
testing for ALK and ROS1 is feasible on a single slide. The strategy reported
herein provided reduced overall scoring time and ensured sensitive counting.
This model might be easier to reconcile (lower cost, shorter turn-around time,
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY and less failure rate) with subsequent comprehensive genotyping. Therefore,
it could be used prospectively in advanced lung ACs to align the use of several
technologies. Acknowledgements This study was partially funded by Abbott
Molecular and Instituto de Salud Carlos III (ISCIII), Fondo de Investigaciones
P1.02-042 DETECTION OF ALK PROTEIN EXPRESSION IN LUNG Sanitarias (FIS), Fondos FEDER-Plan Estatal de I+D+I 2013-2016 (PI14-01176).
ADENOCARCINOMAS, A CONSECUTIVE SERIES OF CASES FROM
Keywords: ALK, NTRK1, ros1, FISH
NORTHEASTERN BRAZIL
1 2 3 1
Ana Mendes , Francisco Neto , Marclesson Alves , Igor Costa , Eduardo

POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY crizotinib inhibits the ALK protein and not specifically ALK rearrangements,
it could be speculated that NSCLCs without IHC ALK expression could be not
sensitive to crizotinib. The ALK FISH+/IHC negative discordant group showed
a loweer percentage of nuclei positive for ALK rearrangement (19.1% in split
P1.02-044 EGFR STATUS IN A PREVIOUSLY UNTESTED POPULATION signals and 21.7% in 5’ deletions) as compared with 64% of gene amplification
FROM NORTHEASTERN BRAZIL in one case and with polysomy (45.7%) observed in all cases. These preliminary
Ana Mendes1, Cleto Nogueira1, Eduardo Cronenberger2, Marclesson Alves2, data highlight the role of IHC analysis and of the percentage of the genetic
Francisco Neto3, Alba Torres4, Fabio Tavora1, Ana Claudia Oliveira1 pattern of ALK rearranged cells in FISH analysis to select patients for anti
1 ALK treatment. Further investigation is suggested about the correlation of
Pathology, Argos Patologia / Hospital de Messejana Do Coração E Do Pulmão,
Fortaleza/Brazil, 2Oncology, Hospital de Messejana Do Coração E Do Pulmão, complex mutational findings and clinical outcome.
Fortaleza/Brazil, 3Thoracic Surgery, Hospital de Messejana Do Coração E Do
Pulmão, Fortaleza/Brazil, 4Pathology, Johns Hopkins University, Baltimore/MD/
Keywords: ALK rearrangements, advanced NSCLC, IHC/FISH discordance
Background: There is limited Brazilian data on epidermal growth

factor receptor (EGFR) gene activating mutations prevalence and their
clinicopathologic associations especially in the Northeast, with no previous POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
epidemiological reports. The current study aimed to assess the relationship MONDAY, DECEMBER 5, 2016
between EGFR mutations and histologic subtypes according to the 2015 WHO
Classification. Methods: We assessed the frequencies of EGFR mutations
in consecutive pulmonary adenocarcinomas among a population-based P1.02-046 ALK IHC IS HIGHLY SENSITIVE TO FIXATION
sample in Northeastern Brazil. A sample of 351 patients diagnosed from PARAMETERS
2014-2016 was analyzed by direct sequencing (45.5%), real time PCR (34.1%) Isabell Loftin1, Rachel Miller 1, Patricia Thorne-Nuzzo1, Abigail Mcelhinny2,
or next generation sequencing (20.4%). Results: The overall mutation rate Penny Towne1, Shalini Singh1, June Clements1
was was 30.5%. The ratio of exon 19 deletions to exon 21 L858R mutations 1
Ventana Medical Systems Inc., A Member of the Roche Group, Tucson/AZ/United
was 1.2:1. Three patients had T790M mutations detected after progression States of America, 2Personal Genome Diagnostics, Baltimore/MD/United States of
in use of targeted therapy. Female sex (P = 0.002), never smoking status America
(P = 0.002), and nonsolid subtype of ADC (P = 0.001) were associated with
EGFR mutations on univariate analyses. Acinar predominant and lepidic Background: An ALK genetic translocation event occurs in ~2-7% of non-small
predominant tumors had a higher rate of mutation but with no statistical cell lung carcinoma patients (NSCLC), resulting in the constitutive expression
significance when evaluated solely. Papillary component did not show of an active chimeric ALK protein, which leads to tumor proliferation. Ventana
correlation with mutations. Tumor differentiation correlated significantly has developed a fully automated immunohistochemistry (IHC) assay using
with their incidence of EGFR mutations, lower in poorly differentiated tumors the VENTANA anti-ALK (D5F3) Rabbit Monoclonal Primary Antibody (ALK
(p=0.005). Follow-up will be presented. Conclusion: We will describe a series (D5F3)) to detect the ALK protein in formalin fixed paraffin embedded tissue.
of consecutive adenocarciomas from a population with unknown status with ALK IHC testing is becoming more widespread in NSCLC; however, information
a higher than expected rates (higher than Southern Brazil and similar to other concerning the impact of pre-analytical conditions on the ALK antigen is
Latin American countries), and correlate with the 2015 WHO classification of limited. We used human cell lines expressing ALK, generated as xenografts to
tumors. evaluate the effect of Fixation Type, Time, and Delay to Fixation (Ischemia) on
the ALK antigen as measured by the ALK (D5F3) antibody staining intensity.
Keywords: EGFR, lung adenocarcinoma, Latin America Methods: NCI-H2228 human NSCLC cell lines were used to generate xenograft
tumors in SCID mice. In order to assess ischemia (delay to fixation) H2228
xenografts were used to model ischemia in 10% NBF. The impact of fixation
on staining performance of the ALK (D5F3) primary antibody was assessed
using the H2228 xenografts to model fixation type and fixation time for
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY 10% NBF, Zinc Formalin, 95% Alcohol, Alcoholic Formalin Acid, B5, and Prefer
MONDAY, DECEMBER 5, 2016 for 1, 6, 12, 24 and 72 hours. Each of the stained slides were evaluated by a
pathologist using a qualitative assessment and scored on a 0-3+ intensity
scale (0 = no staining detected, 1+= weak staining detected, 2+= moderate
P1.02-045 DISCORDANCE (FISH+, IHC-) BETWEEN FISH AND IHC staining detected, 3+ = strong staining detected). Results: Fixation in all
ANALYSIS OF ALK STATUS IN ADVANCED NON SMALL CELL LUNG time points in B5, Prefer, and AFA, as well as ethanol, severely compromised
CANCER (NSCLC): A UNEXPECTED ISSUE IN 7 CASES staining intensity of ALK (by decreasing staining intensity greater than 0.5
Anna Scattone1, Stella Petroni1, Anita Mangia1, Annamaria Catino2, Domenico points). Ischemia greater than 6 hours also decreased staining intensity. In
Galetta3, Laura Schirosi4, Lucia Caldarola1, Elisabetta Sara Montagna3, Dario contrast, EGFR (5B7) and TTF1 (SP141) antigens were robust across a wide
De Ceglia5, Pia Perrotti5, Giovanni Simone1 range of fixation times and types, as well as ischemia times. Conclusion: The
1
Pathology, National Cancer Research Centre, Istituto Tumori “Giovanni Paolo Ii” ALK antigen is highly sensitive to fixative time, type and ischemia. The data
Bari, Italy, Bari/Italy, 2National Cancer Research Centre, Istituto Tumori “Giovanni indicate that the detection of ALK by IHC is impacted by fixation conditions.
Paolo Ii” Bari, Italy, Bari/Italy, 3Medical Oncology, National Cancer Research Strikingly, antigens detected by other lung antibodies (EGFR, TTF1) are
Centre, Istituto Tumori “Giovanni Paolo Ii” Bari, Italy, Bari/Italy, 4Biomorphology more robust in comparison across a range of conditions. Standardized pre-
Laboratory, National Cancer Research Centre, Istituto Tumori “Giovanni Paolo Ii” analytical conditions are critical to achieve appropriate staining for ALK IHC
Bari, Italy, Bari/Italy, 5Radiology, National Cancer Research Centre, Istituto Tumori and to mitigate the risk of false negative results. The recommendations for
“Giovanni Paolo Ii” Bari, Italy, Bari/Italy pre-analytical conditions for ALK are to fix at least 6 hours in 10% neutral
buffered formalin.
Background: Anaplastic lymphoma kinase (ALK ) rearrangement represents
a landmark in the targeted therapy of NSCLC. Several reports showed that Keywords: ALK, IHC, Fixation
IHC is sensitive and specific to detect ALK protein expression, possibly
alternative to ALK FISH assay. In this study the concordance between the ALK
status by FISH and IHC assay has been determined in a series of 95 advanced
NSCLCs; discordant cases were evaluated on the basis of the percentage and
the rearrangement pattern of ALK. Methods: 95 lung NSCLC specimens were POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
tested for ALK rearrangements by IHC assay (ALK D5F3 antibody Ventana,CE- DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
IVD system) and by fluorescence in situ hybridization (FISH). Clinical
characteristic and response to crizotinib were reviewed. Results: Seven cases
(7.3%) showed discordant results with ALK FISH-positive and IHC negative. P1.02-047 EFFECT OF DASATINIB ON EMT-MEDIATED-MECHANISM
Among these cases the mean number of FISH positive rearranged nuclei OF RESISTANCE AGAINST EGFR INHIBITORS IN LUNG CANCER
was 40.2% (range 20-54%). All cases showed coexistent split signals pattern CELLS
positivity with mean percentage 19.1% (range 10-32%.), 5’ deletions pattern
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Masaya
positivity with mean percentage 21.7% (range 12-34%) and one case also had
Nishino, Masato Chiba, Masaki Shimoji, Katsuaki Sato, Kenji Tomizawa,
gene amplifications pattern positivity with percentage of 64%. The polysomy
Toshiki Takemoto, Tetsuya Mitsudomi
was observed in all cases with mean percentage of 45.7% (range of 16-72%).
Five patients with discordant ALK FISH and IHC results received crizotinib; Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama/Japan
of them, four progressed and one has stable disease. Conclusion: In most of
Background: The epithelial to mesenchymal transition (EMT) is associated
discordant cases, a coexistent complex pattern of rearrangements (deleted,
with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine
invertited and amplified/polysomic patterns) of ALK positive cells in FISH
kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor
analysis was observed; these complex rearranged cases were not detectable
EGFR mutations. Because no currently available drugs specifically kill cancer
by IHC, probably due to the lack of protein expression. Considering that
cells via EMT, novel treatment strategies that overcome or prevent EMT are POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) MONDAY, DECEMBER 5, 2016
inhibits EMT induced by transforming growth factor (TGF)-beta in lung
cancer cells. In this study, we analyzed effects of dasatinib on the resistance
mechanism in HCC4006 cells harboring EGFR exon 19 deletion, which tend P1.02-049 EGFR, KRAS AND ALK GENE ALTERATIONS IN LUNG
to acquire resistance to EGFR-TKIs via EMT in previous reports.The epithelial CANCER PATIENTS IN CROATIA
to mesenchymal transition (EMT) is associated with acquired resistance to Marko Jakopovic 1, Luka Brcic2, Marija Misic 3, Gordana Bubanovic1, Fran
epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Seiwerth4, Gordana Drpa4, Branka Cucevic4, Mihovil Roglic4, Sanja Plestina4,
certain non-small cell lung cancers that harbor EGFR mutations. Because no Suazana Kukulj4, Silvana Smojver-Jezek4, Sven Seiwerth3, Miroslav Samarzija1
currently available drugs specifically kill cancer cells via EMT, novel treatment 1
Department for Respiratory Diseases “Jordanovac”, University Hospital Centre
strategies that overcome or prevent EMT are needed. A recent report Zagreb, Zagreb/Croatia, 2Department of Pathology, University of Graz, Graz/
suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced Austria, 3 Zagreb Medical School, Zagreb/Croatia, 4University Hospital Centre
by transforming growth factor (TGF)-beta in lung cancer cells. In this study, Zagreb, Zagreb/Croatia
we analyzed effects of dasatinib on the resistance mechanism in HCC4006
cells harboring EGFR exon 19 deletion, which tend to acquire resistance to Background: Rates in targetable gene changes varies between different
EGFR-TKIs via EMT in previous reports. Methods: HCC4006ER cells with an populations of lung cancer patients. Targetable gene changes include changes
EMT phenotype were previously established by chronic exposure to increasing in EGFR and ALK gene, as well as KRAS gene. Primary aim of this study was
concentrations of erlotinib. Sensitivity to dasatinib in parental HCC4006 to determine mutation status in purely Caucasian Croatian population.
and HCC4006ER cells was analyzed. Subsequently, HCC4006EDR cells were Methods: Rates in targetable gene changes varies between different
established by chronic treatment with combination of erlotinib and dasatinib. populations of lung cancer patients. Targetable gene changes include changes
The expression of EMT markers of these cells and the mechanism of acquired in EGFR and ALK gene, as well as KRAS gene. Primary aim of this study was to
resistance to this combination therapy were analyzed. Results: Short-term or determine mutation status in purely Caucasian Croatian population. Results:
long-term, ranging OOhours to XXXmonth, treatment with dasatinib did not During 6 months period 324 newely diagnosed primary lung adenocarcinoma
reverse EMT in HCC4006ER. In contrast, HCC4006EDR cells maintained an were tested. Out of 324 tested patients, 194 were males (60%) and 130 females
epithelial phenotype, and the mechanism underlying resistance to erlotinib (40%) mean age 64 years (range 35 to 88 years). Vast majority of patients were
plus dasatinib combination therapy was attributable to a T790M secondary in stages 3 and 4 (more than 80%). Among males, 87% of patients were ever
mutation. HCC4006EDR cells, but not HCC4006ER cells, were highly smokers, and among females 61% of patients were ever smokers. Significantly
sensitive to a third-generation EGFR-TKI, osimertinib. Conclusion: Although higher rates of evers smokers were recorded among males. EGFR mutations
dasatinib monotherapy did not reverse EMT in HCC4006ER cells, preemptive were present in 15.7% of patients (51 patients). There was a difference in
combination treatment with erlotinib and dasatinib prevented the emergence EGFR mutation rates between males and females (5.6 vs 30.8%, p<0.0001).
of acquired resistance via EMT, and led to the emergence of T790M. Our KRAS mutations (codones 12/12 and 61) were present in 35.8% (116) patients,
results indicate that preemptive combination therapy may be a promising and ALK translocation detected by IHC in 3.7% (12) patients. Conclusion:
strategy to prevent the emergence of EMT-mediated resistance. Molecular testing in primary lung adenocarcinoma patients was done in
purely Caucasian Croatian population. EGFR mutation and ALK translocation
Keywords: dasatinib, epithelial-mesenchymal transition, third-generation rates were similar to previously published data. However, KRAS mutation
EGFR-TKI, Acquired resistance rates were higher than previously published. This can be associated with high
smoking rates in Croatian population.

MONDAY, DECEMBER 5, 2016 POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
P1.02-048 MET EXON 14 SKIPPING MUTATIONS AND GENE

AMPLIFICATIONS ARE NOT SIMULTANEOUS EVENTS IN NSCLC P1.02-050 ACQUIRED RESISTANCE TO EGFR TYROSINE KINASE
Sergi Clavé 1, Alba Dalmases1, Raquel Longarón1, Lara Pijuan1, David INHIBITORS (TKIS) IN EGFR-MUTANT LUNG ADENOCARCINOMA
Casadevall2, Álvaro Taus2, Joan Albanell2, Blanca Espinet1, Edurne Arriola2, AMONG HISPANICS (RBIOP-CLICAP)
Beatriz Bellosillo1, Marta Salido1 Andrés Cardona1, Oscar Arrieta2, Leonardo Rojas3, Beatriz Wills4, Noemi
1
Pathology Department, Hospital Del Mar, Barcelona/Spain, 2Medical Oncology Reguart5, Hernan Carranza1, Carlos Vargas1, Jorge Otero1, Pilar Archila6,
Department, Hospital Del Mar, Barcelona/Spain Claudio Martin7, Luis Corrales8, Mauricio Cuello9, Carlos Ortiz1, Sandra
Franco1, Rafael Rosell10
Background: Mutations in the MET exon 14 RNA splice acceptor and donor 1
Medical Oncology, Clinical and Traslational Oncology Group, Institute of Oncology,
sites, which lead to exon skipping, have been described with responsiveness
Clínica Del Country, Bogota/Colombia, 2Laboratory of Experimental Oncology and
to crizotinib. Until now, patient selection has been made in view of MET Thoracic Oncology Unit, National Cancer Institute, Mexico City/Mexico, 3Centro
amplification/high polysomy and protein overexpression, with discrepancies Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá/Colombia,
in positivity criteria. We investigated the prevalence of abnormal MET 4
Internal Medicine Department, Johns Hopkins Hospital, Rochester/United States
mutational status and the subsequent gene copy number alterations (CNAs) of America, 5Medical Oncology, Hospital Clinic, Translational Genomics and
in NSCLC. Methods: We routinely tested 190 lung adenocarcinomas and Targeted Therapeutics in Solid Tumors, Institut D’Investigacions Biomèdiques
adenosquamous carcinomas for MET exon 14 and flanking introns mutations August Pi I Sunyer (Idibaps), Barcelona/Spain, 6Pathology, Foundation for Clinical
by PCR-direct sequencing, and for MET gene CNAs by FISH (Abbott Molecular). and Applied Cancer Research – Ficmac, Bogota/Colombia, 7Department of Clinical
Oncology, Instituto Alexander Fleming, Buenos Aires/Argentina, 8 Clinical Oncology
Amplifications were defined as mean gene by mean centromere ratio
Department, Hospital San Juan de Dios (San José, Costa Rica), San Jose/Costa Rica,
≥2.2, and high gains as mean gene ≥5.0. RT-PCR was performed to validate 9
Medical Oncology Department, Udelar (Montevideo, Uruguay), Montevideo/
mutations leading to exon 14 skipping. We collected clinical-pathological Uruguay, 10 Hospital Germans Trias I Pujol, Catalan Institute of Oncology, Barcelona/
data together with EGFR and KRAS mutational status and ALK, ROS1 and RET Spain
rearrangements. Results: MET alterations were found in 34 patients (17.9%):
11 mutated cases (5.8%), eight gene amplifications (4.2%), and 15 high gains Background: Patients with epidermal growth factor receptor (EGFR)-mutant
(9.1%). Six out of 11 mutations were confirmed to lead to exon 14 skipping lung carcinoma eventually develop acquired resistance to EGFR tyrosine
(3.2%). Remarkably, none of these exon 14 skipped cases had concurrent kinase inhibitors (TKI). In 50% of these cases, a secondary EGFR mutation,
MET amplification nor high gains. Although, KRAS p.G12C and EGFR 19 exon T790M, underlies the acquired resistance. Other alterations include
mutations were found concomitant with MET mutation in two of these amplification of MET, PI3K mutations, changes in MAPK1, Her2, AXL and even
cases. Among the 14 confirmed MET altered cases (6 exon 14 skipped and transformation to small cell lung carcinoma (SCLC). We assessed histological,
8 amplified): 13 patients were male (93%), with a median age of 65.7 years clinical characteristics and survival outcomes in Hispanic patients with EGFR
(range: 40-91), nine current smokers (64%) (40 pack-years, range: 20-60), and mutation after disease progression. Methods: 34 EGFR-mutant lung cancer
eight diagnosed in an advanced stage disease (III and IV) (57%). Correlation patients with acquired resistance to EGFR TKIs were identified as part of a
with c-MET protein expression by IHC is ongoing, and data will be presented prospective registry (active between January 2011 and January 2015) in which
at the meeting. Conclusion: As no concurrent MET mutated and amplified post-progression tumor specimens were collected for molecular analysis using
cases were found, our data support prospective identification of both, MET SNaPshot tumor genotyping assay to detect mutations in EGFR, KRAS, BRAF,
exon 14 skipping mutations and gene amplifications. These mutations define PI3KCA, TP53, MET and Her2, and FISH for MET, ALK and EGFR. Samples also
a new subset of NSCLC patients that should be analyzed independently of the underwent immunohistochemistry analysis for E-cadherin, synaptophysin,
status of MET gene copy number. CD56 and PDL1. Post-progression interventions, response and survival were
assessed and compared to those with and without T790M. Results: Mean
Keywords: MET amplification, FISH, MET exon 14 skipping, MET alterations age was 59.4±13.9 years; 62% were female, 65% were never-smokers and 53%
had a performance status ≥80%; main metastatic sites were lung (16/47%),

bone (20/58%), brain (18/52%) and liver (13/38%). All patients received POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
erlotinib as first- line treatment and documented mutations were: 60% DelE19 MONDAY, DECEMBER 5, 2016
(Del746–750) and 40% L858R. Overall response rate (ORR) with first line
TKI was 61.8% and progression free survival (PFS) was 16.8 months (range,
13.7–19.9 m). After progressing to TKI, all patients were re-biopsied, of whom P1.02-052 SIGNAL REGULATORY PROTEIN A (SIRPA): A KEY
16 had the T790M mutation (47.1%); 5 had PI3K mutations (14.7), 5 had EGFR REGULATOR OF THE EGFR PATHWAY DEMONSTRATES BOTH
amplification (14.7%), 2 had a KRAS mutation (5.9%), 3 had MET amplification TUMOR SUPPRESSIVE AND ONCOGENIC PROPERTIES
(8.8%), 2 had Her2 alterations (5.8%, deletions/insertions in e20), and one
Erin Marshall1, Larissa Pikor 1, Raj Chari2, Jennifer Kennett1, Stephen Lam1,
had SCLC transformation (2.9%). 79.4% received treatment after progression.
Wan Lam1
ORR for post-TKI treatments was 47.1% (CR 2/PR 14) and median PFS was 1
Integrative Oncology, BC Cancer Research Centre, Vancouver/BC/Canada, 2Harvard
8.3 months (CI95% 2.2–36.6). There were no differences in PFS according to
Medical School, Boston/MA/United States of America
gender (p=0.10) or type of acquired alteration (p=0.63). Median survival was
32.9 months (CI95% 30.4–35.3), and only the use of post-progression therapy Background: The epidermal growth factor receptor (EGFR) signaling pathway
affected OS in multivariate analysis (p=0.05). Conclusion: Hispanic patients is one of the most frequently deregulated pathways in non-small cell lung
with acquired resistance to EGFR TKIs continued to be sensitive to other cancer. While targeted therapy prolongs survival in patients harbouring
treatments after progression. Proportion of T790M+ patients appears to be EGFR mutations, resistance to treatment eventually develops in all cases. As
similar to previously reported results in Caucasians. multiple genetic and epigenetic alterations are known to disrupt signaling
pathways, the objective of this study is to perform a multidimensional
Keywords: Acquired resistance, EGFR-mutant lung adenocarcinoma, EGFR
analysis of signaling pathways to identify alterations essential to
Tyrosine Kinase Inhibitors, Hispanics
tumorigenesis that are overlooked when assessing a single genomic
dimension. Methods: Multidimensional integrative analysis of copy number,
DNA methylation, and gene expression profiles of 77 lung adenocarcinomas
and matched non-malignant tissues identified Signal Regulatory Protein A
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY (SIRPA) as a novel candidate tumor suppressor gene. Following validation
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – of genomic findings in multiple external data sets, the tumor suppressive
MONDAY, DECEMBER 5, 2016 effects of SIRPA were assessed in vitro and in vivo with a panel of lung cancer
cell lines. Results: SIRPA negatively regulates receptor tyrosine kinase
P1.02-051 CONCOMITANT DRIVER MUTATIONS IN ADVANCED signaling through activation of the protein phosphatases SHP1 and SHP2 and
was found to be underexpressed in 70% of lung tumours, ranking it in the 95th
STAGE NON-SMALL-CELL LUNG CANCER OF ADENOCARCINOMA
percentile of altered genes within the EGFR pathway. Immunohistochemistry
SUBTYPE WITH ACTIVATING EGFR-MUTATION
(IHC) confirmed reduced protein expression in tumors, which was found to
Jens Benn Sørensen1, Morten Grauslund2, Linea Melchior2, Jan Jakobsen1, Eric correlate with EGFR mutation and adenocarcinoma histology. In vitro, SIRPA
Santoni-Rugiu2 knockdown promoted migration while simultaneously inducing a dramatic
1
Dept. Oncology, Finsen Centre/national University Hospital, Copenhagen/ senescent phenotype, suggesting SIRPA may act as a barrier to tumorigenesis.
Denmark, 2Dept. Pathology, National University Hospital, Copenhagen/Denmark This phenotype is dependent upon upregulation of the CDK inhibitor p27,
which hypophosphorylates RB leading to cell cycle blockade and reduced
Background: Patients having non-small-cell lung cancer (NSCLC) with
tumor growth in vivo. Importantly, increased expression of p27 resulted in
activating EGFR-mutations benefit from EGFR-Tyrosine Kinase Inhibitor
mis-localization into the cytoplasm where it is known to promote an invasive
(TKI) treatment. However, other driver mutations may occur simultaneously
phenotype. Inhibition of p27 confirmed previous findings and emphasized
and other pathways may be amplified/overexpressed, potentially hampering
the importance of this pathway in lung tumorigenesis. Surprisingly,
efficacy of EGFR-TKI treatment. The frequency of such alterations at time of
overexpression of SIRPA increased cell growth and migration, suggesting
diagnosis was examined. Methods: All patients referred to Rigshospitalet,
SIRPA may also possess oncogenic properties due to its regulation of multiple
Copenhagen University Hospital for pulmonary adenocarcinoma (ADC)
signaling pathways. Overexpression of SHP2 following ectopic expression
from July 2013 to August 2015 were routinely tested for EGFR-mutations
of SIRPA promotes migration through the inhibition of focal adhesions.
by EGFR Cobas RT-PCR technique (Roche Diagnostics) on DNA extracted
This phenotype is abrogated upon siRNA knockdown of SHP2. Conclusion:
from diagnostic tumor biopsies or cytological samples. If positive for
SIRPA is an important player in lung tumor biology, capable of acting as both
EGFR-mutations these patients were, prior to any treatment, also tested by
an oncogene and tumor suppressor due to its ability to regulate multiple
targeted Next Generation Sequencing (NGS; Ion Torrent Ampliseq Colon-Lung
signaling pathways. Due to the complex nature in its signaling, future work
v.2 panel and PGM NGS-sequenator) for other simultaneous cancer-relevant
should focus on elucidating how the timing of alterations to SIRPA affects
mutations, by fluorescence in-situ hybridization (FISH) for MET-amplification,
tumorigenesis to design treatment strategy.
and by immunohistochemistry (IHC) for expression of MET receptor as well
as ALK fusion-protein. Results: Totally 512 ADC patients were tested, among Keywords: non-small cell lung cancer, SIRPA, oncogene, tumour supressor
whom 22 out of 282 advanced stage patients (7.8%) had activating EGFR-
mutations, distributed as follows: 1 G719C-mutation, 13 exon 19-deletions,
1 T790M-mutation, 1 S768I-mutation and 8 L858R-mutations with 2 of the
patients harboring EGFR-double-mutations G719C + S768I and L858R + T790M
(i.e., activating and resistance mutation), respectively. Complete concordance POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
between EGFR-mutation-status by EGFR Cobas and NGS was observed for MONDAY, DECEMBER 5, 2016
all NGS tested patients. For one of the patients NGS analysis could not be
carried out, due to lacking DNA-extract and remaining tumor tissue. NGS-
analysis identified several concomitant driver mutations in the 21 analyzed P1.02-053 COMPARISON OF TWO DIFFERENT COMMERCIALLY
patients, including one 1 with KRAS-mutation (G12V), 12 with TP53-mutations AVAILABLE PROBES FOR THE DETECTION OF ALK
(7 in TP53-exon 5), 1 with FGFR-mutation (S125_E126insS), 2 with CTNNB1- REARRANGEMENTS IN CYTOLOGICAL SMEARS
mutations (S33C and S37F), 1 with MET-mutation (T1010I), 1 with SMAD4-
Maria Lozano Escario 1, Mercedes Aguirre1, Maria Eugenia Echarri1, Jose
mutation (R135stop), and 1 with PIK3CA-mutation (E545K). FISH and IHC for
Echeveste1, Nerea Gomez1, Maria Amada Maset1, Marta Abengozar 1, Luis
MET were successful in tumor samples from 16 and 19 patients, respectively.
Mejias1, Alfonso Gurpide2, Salvador Martin-Algarra2
Three patients had concomitant MET-amplification (1 with and 1 without 1
Pathology, University of Navarra, Pamplona/Spain, 2Medical Oncology, University
corresponding MET-overexpression, 1 with unsuccessful IHC), whereas 2 other
of Navarra, Pamplona/Spain
patients had increased copy number (ICN; both with corresponding MET-
overexpression). Interestingly, 4 of these 5 patients with MET-amplification Background: Many patients with NSCLC are diagnosed at advanced stages.
or -ICN also carried TP53-mutations. Expression of ALK fusion-protein was A high percentage of those patients have only cytological samples for
not detected in any of the 22 patients with activating EGFR mutations. morphological and molecular analysis. Furthermore ALK analysis by FISH has
Conclusion: At time of diagnosis, concomitant mutations in other cancer to be performed using a specific commercially available probe. The aim of this
driver genes can be detected in advanced EGFR-mutation-positive NSCLC of study is to compare two different commercially available probes for analysis
ADC subtype. These concomitant mutations may impact the response to first- of ALK gene rearrangements by FISH using cytological stained smears.
line EGFR-TKI treatment and represent additional therapeutic targets. Methods: We analyzed 37 cytological stained smears from 37 consecutive
cases of FNA (14 Diff-Quick and 23 Papanicolau). ROSE was performed in all
Keywords: EGFR mutation, next generation sequencing, MET amplification,
procedures. The status of EGFR, KRAS and BRAF was kwon in 28 patients.
MET expression
Two probes were used: LSI ALK BREAK APART (Vysis, Ref: 53206N38020,
Izasa) was apply in all 37 cases. Additionally, in 25 of these cases we used
the ZytoLight SPEC ALK Dual Color Break Apart (ZYTOVISION, Ref: Z-2124-
200, Menarini Diagnostics) probe. Protocols were modified from Basel
and Zytolight manufacture guidelines. In order to optimize the amount of
probe and to evaluate individual nuclei, we delimited an area on each smear
with no nuclear overlap. Results: All cases were adenocarcinomas. Two ~30% of lung adenocarcinomas (LACs). Yet, as several observers have noted,
cases showed ALK rearrangement (5.4%). Of the 34 negative cases, 27 were no individual LAC appears to carry mutations in both, even in the setting of
negative-polysomic (77.14%). One case was no assessable (2.7%) due to the resistance to EGFR kinase inhibitors. The typical explanation given is that
impossibility of getting hybridization. Concordance between two probes was the two genes are entirely functionally redundant, thereby eliminating
100%. No differences were found between Papanicolau and DiffQuick stained any selective advantage to mutation of both. In this study we tested an
smears . Conclusion: FISH-ALK in cytological stained smears gives excellent alternative hypothesis for this mutual exclusivity: that co-occurrence of
results. Both commercially avialable probes showed identical performance, mutations in both KRAS and EGFR is deleterious to the evolving cancer
both are equally valid. No differences between Papanicolau and Diff-Quick cell. Furthermore, we aimed to characterize the specific cellular effects and
stained smears were observed. In our experience, stained cytological smears signalling pathways induced by mutant KRAS and EGFR co-induction and
are the best choice for the analysis of ALK rearrangements in NSCLC patients, determine whether this information could be used to design new strategies
keeping paraffin for cases in which adequate cytological smears are not to inhibit LACs. Methods: Next-generation sequence data for over 600 human
available. LACs were acquired from public sources and analyzed for co-incidence of
KRAS and EGFR mutation and the relationship to smoking status. Transgenic
Keywords: Zytolight, Vysis, ALK, cytological smears. mice that express both mutant oncogenes specifically in the lung epithelium
were generated to test the effects on LAC development. LAC cell lines with
endogenous mutations in either KRAS or EGFR were engineered with lentiviral
vectors to conditionally express the second oncogene and assessed for cell
viability, gene expression and protein phosphorylation changes. Temporal
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – phosphoproteome assessment of cells co-expressing both oncogenes is
MONDAY, DECEMBER 5, 2016 currently ongoing to determine the specific signalling pathways affected.
Results: We confirmed the mutual exclusivity of KRAS and EGFR mutations
and demonstrated that this relationship is not due to limited power to detect
P1.02-054 GENOMIC COMPLEXITY IN KRAS MUTANT NON-
concurrent mutations in either smokers or non-smokers. While no effect on
SMALL CELL LUNG CANCER (NSCLC) BY SMOKING STATUS WITH tumor latency was observed in transgenic mice that express both mutant
COMPARISON TO EGFR MUTANT NSCLC oncogenes, the resulting tumors preferentially expressed only one of the two
Amanda Redig 1, Emily Chambers1, Christine Lydon2, Ryan Alden2, Pasi Jänne1 transgenic oncogenes, indicating negative selection against co-expression.
1
Dana-Farber Cancer Institute, Boston/MA/United States of America, 2Lowe Center Introduction of the second oncogene into LAC cells expressing either mutant
for Thoracic Oncology, Dana-Farber Cancer Institute, Boston/MA/United States of KRAS or EGFR stimulated the loss of cell viability. The most prominent
America features accompanying loss of cell viability were vacuolization, other changes
in cell morphology, and increased macropinocytosis. Activation of ERK, p38
Background: KRAS is the most frequently mutated oncogene in NSCLC
and JNK was observed in cells expressing both mutants suggesting that an
and lacks an effective targeted therapy. Notably, KRAS mutations occur in
overly active MAPK signaling pathway may mediate this synthetic lethal
both never/light-smokers and smokers. However, the relationship between
phenotype. Lastly, this effect is dependent on functionally active EGFR,
smoking status and a KRAS+ tumor’s genomic complexity (mutation burden,
since inhibition of the EGFR tyrosine kinase with erlotinib rescued cells
copy number changes, concurrent mutations in key oncogenic pathways) is
from the detrimental effects of co-expression. Conclusion: Together, our
unclear. Similarly, the relationship between genomic complexity in tumors
findings indicate that mutual exclusivity of oncogenic mutations may reveal
from never/light smokers but with a KRAS v EGFR activating mutation is also
unexpected vulnerabilities and therapeutic possibilities.
unknown. Methods: Targeted next-generation sequencing (NGS) data at our
institution from 7/13-1/16 was reviewed to identify KRAS+ NSCLC tumors. All Keywords: Synthetic lethality, Oncogenes, Therapy, cell signaling
patients with a <10 pack-year (py) smoking history (NS) and a subset of heavy
smokers (HS) (>40 py) were identified, with clinical and genomic analysis.
A comparison cohort of 48 patients with EGFR+ NSCLC was also identified.
Fisher’s exact test was used to compare frequency of gene mutations.
Results: 41 NS and 104 HS KRAS patients were evaluated. NS patients were POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
more likely to be female (34/41 v 66/104, p<.01) and diagnosed with Stage I MONDAY, DECEMBER 5, 2016
disease (14/41 v 13/104, p<.01). Compared to KRAS NS patients, tumors from
KRAS HS patients were also genomically more complex, with increased total
nucleotide variants (median=10 v 7, p<.001) and total copy number variations P1.02-056 TUMOR HETEROGENEITY IN LESION SPECIFIC RESPONSE
(median=22.5 v 5, p<.01). Intriguingly, in the cohort of EGFR tumors, total CREATES ROS1 FUSION MEDIATING RESISTANCE TO GEFITINIB IN
nucleotide variants resembled the KRAS NS cohort (median=6.5) but the total EGFR 19 DELETION LUNG ADENOCARCINOMA
copy number variants were more similar to the KRAS HS cohort (median=25). Xiaomin Niu1, Xinghao Ai1, Zhiwei Chen1, Shaochuan Chuai2, Yi Yang1, Shun Lu1
Compared to KRAS NS tumors, KRAS HS tumors were also more likely to 1
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai
have: a) concurrent mutation in TP53 (43/104 v 8/41, p=.012) and b) concurrent Jiao Tong University, Shanghai/China, 2Burning Rock Diagnostics, Shanghai/China
mutations/2-copy deletions in >1 tumor suppressor (TS)/tumor (panel of
TP53, STK11, APC, CDKN2A/B, RB) (26/104 v 4/41, p=.042). Although the total Background: Non-small cell lung cancer (NSCLC) is one of the leading causes
number of nucleotide variants in the EGFR cohort was most similar to the of cancer related death worldwide. In recent years molecular characterisation
KRAS NS cohort, TS distribution in these EGFR tumors was closer to the KRAS of NSCLC has led to the identification of several driver events including EGFR
HS cohort (TP53 variants in 31/48 and multiple TS variants in 14/48). Finally, constitutive activation, ALK-rearrangement and ROS1 fusion. Whilst there are
median OS for KRAS HS patients with Stage IV disease was 9.7m v 28.7m in several mechanisms of EGFR-mutation stated in the literature, how genomic
KRAS NS patients (HR=0.56). Conclusion: The genomic landscape of KRAS+ heterogeneity related with acquired EGFR resistance to second targeted
NSCLC from HS patients is distinct from NS patients and includes increased agent affects response to subsequent therapy has not been noted. Methods:
total mutations and frequency of TS loss. EGFR mutant tumors share some We studied EGFR-TKI, gefitinib, in an EGFR 19 deleted lung adenocarcinoma
similarities with KRAS tumors from both NS and HS patients. Overall, NS patient to assess whether tissue and liquid biopsy could be integrated with
KRAS+ tumors may be a genetically distinct cohort within the broader context radiologic imagings to demonstrate the impact of individual actionable
of KRAS+ NSCLC. driver mutation on lesion specific response. Results: A 60-year old female,
with no previous or family history of malignancy initially presented with
Keywords: KRAS, Genomics, NSCLC EGFR 19 deletion mutation, ROS1 fusion negative and ALK rearrangement
negative stage IV, T2aN3M1a lung adenocarcinoma detected in primary lung
cancer tissue at the first diagnosis. Biopsy of this patient’s metastatic right
cervical lymph node following prolonged response to gefitinb led to the
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY loss of detection of EGFR mutation, and the novel mechanism of acquired
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – resistance with EZR-ROS1 fusion where crizotinib was demonstrated to have
MONDAY, DECEMBER 5, 2016 good efficacy in all lesions, especially the enlarged lymphadenopathy, and
also including diminishing efficacy on metastatic brain lesions. In circulating
P1.02-055 SYNTHETIC LETHALITY DICTATES THE MUTUAL tumor DNA (ctDNA), mutant EGFR levels disappeared followed by gefitinib
treatment, and a recognized EZR-ROS1 fusion was meanwhile identified
EXCLUSIVITY OF ONCOGENIC MUTATIONS IN LUNG
before crizotinib therapy. Conclusion: This case displays tumor heterogeneity
ADENOCARCINOMA in action, where targeted therapy selects against primary drivers, allowing
William Lockwood1, Arun Unni2, Harold Varmus2 for the establishment of sub-colonies with new drivers within the specific
1
Integrative Oncology, British Columbia Cancer Research Centre, Vancouver/BC/ lesion. Parallel analysis of tumor biopsies when disease progressed and ctDNA
Canada, 2Meyer Cancer Center, Weil Cornell Medical College, New York/NY/United monitoring showed that lesion specific radiographic responses to subsequent
States of America targeted therapies could be driven by district resistant mechanism in the
separate tumor lesions within the same patient. This demonstrates that the
Background: EGFR mutations are present in ~15% and KRAS mutations in
importance of molecular heterogeneity surveillance ensuing from acquired

resistance in managing NSCLC, and the usage of liquid biopsies to allow for a Background: Tumor heterogeneity, which causes different EGFR mutation
holistic viewpoint of the molecular landscape of this heterogeneous disease. abundance, is believed to be responsible for varied progression-free survival
(PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment.
Keywords: EGFR, ros1, lung adenocarcinoma, drug resistance Frequent EGFR amplification and its common affection inEGFR mutant
allele promote the hypothesis that EGFR mutant abundance might be
determined by EGFR copy number variation and therefore examination of
EGFR amplification status in EGFR mutant patients could predict the efficacy
of EGFR-TKI treatment. Methods: 72 lung ADC patients who harbored EGFR
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – activating mutations and received erlotinib as first line treatment, were
MONDAY, DECEMBER 5, 2016 examined for EGFR amplification by FISH. EGFR mutational and copy number
status were compared with response, overall-survival (OS), and progression-
free-survival (PFS). Results: Median age was 62-yo (r, 20-87 years), 53
P1.02-057 CLINICAL UTILITY OF CTDNA FOR DETECTING ALK
patients were females (73%), and 89% have common mutations. Twenty-two
FUSIONS AND RESISTANCE EVENTS IN NSCLC: ANALYSIS OF A (30.6%) samples with EGFR activating mutations were identified with EGFR
LABORATORY COHORT amplification. EGFR amplification was more frequent in patients with exon
Robert Doebele 1, Kimberly Banks2, Nnamdi Ihuegbu2, Joseph Diaz2, Richard 19 deletion (p=0.05) and in those with better performance status (p=0.01).
Lanman2, Collin Blakely3 Patients with EGFR gene amplification had a significantly longer PFS than
1
Division of Medical Oncology, University of Colorado, Aurora/CO/United States those without [(25.2 months, 95%CI 22.0-38.5) vs. (12.4 months, 95%CI 5.3-
of America, 2Guardant Health, Inc, Redwood City/CA/United States of America, 19.5); p=0.002] as well as better OS [(EGFR amplified 37.8 months, 95%CI 30.9-
3
Hematology and Oncology, University of California, San Francisco, San Francisco/ 44.7) vs. (EGFR non-amplified 27.1 months, 95%CI 12.8-41.3); p=0.009]. EGFR
CA/United States of America amplification significantly influenced the response to erlotinib (p=0.0001).
Conclusion: EGFR amplification occurs in one third of patients with lung ADC
Background: Advanced NSCLC patients whose tumors harbor ALK fusions
harboring EGFR activating mutations, and could serve as an indicator for
benefit from first line treatment with ALK inhibitors (ALKi). However,
better response and survival from EGFR-TKI treatment.
insufficient tissue for testing (QNS) occurs ~25% of the time. Patients treated
with ALKi ultimately progress. Historically, identification of the resistance Keywords: EGFR, mutation, amplification, outcome
mechanism/s required repeat tumor biopsy. Circulating tumor DNA (ctDNA)
may provide a non-invasive way to identify ALK fusions and actionable
resistance mechanisms without a repeat biopsy. Methods: The Guardant360
(G360) de-identified database of NSCLC cases was queried to identify 57
patients (2/2015-6/2016) with 58 ctDNA-detected ALK fusions. G360 is a POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
CLIA-laboratory ctDNA test that detects point mutations in 70 genes and DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
select amplifications, fusions and indels. Available records were reviewed
to characterize patients at baseline and at progression. Results: Identified
fusion partners included EML4 (n=51, 88%), STRN (7%), KLC1 (3%), KIF5B (2%). P1.02-059 EVALUATION OF PLASMA DNA EXTRACTION, DROPLET
Thirty patients had no history of targeted therapy (new diagnosis or no prior PCR AND DROPLET NEXT GENERATION SEQUENCING METHODS
genotyping, “cohort 1”); 23 patients were drawn at ALKi progression (“cohort FOR LIQUID BIOPSY ANALYSIS
2”). In 6 samples, the patients’ clinical status was unknown. Three additional
Lina Salleh1, Michelle Rozario1, Xue Qing Koh2, Ross Soo3, Richie Soong1
cases had ALK resistance mutations (F1174C, F1269A/I1171T, D1203N) 1
Cancer Science Institute of Singapore, National University of Singapore,
detected in ctDNA but no fusion detected; historical tissue testing was ALK+.
Singapore/Singapore, 2National University of Singapore, Singapore/Singapore,
Conversely, in cohort 1, 10 (33%) were tissue QNS (7) or tissue ALK negative 3
Haematology-Oncology, National University Cancer Institute, Singapore/
(3) while 4 (13%) were tissue ALK+ and 16 (54%) had unknown tissue status. As Singapore
expected, no documented or putative resistance mechanisms were identified
in cohort 1, although TP53 mutations were identified in 43%. Among 18 Background: The ability to detect tumour mutations from blood and other
patients progressing on an ALKi, 7 (39%) contained 1 (4 patients), 2 (1 patient) bodily fluids promises many sample access, convenience, and monitoring
or 3 (2 patients) ALK resistance point mutations (F1174C/V: 3 occurrences; benefits. However, the extremely rare levels at which mutations are present
G1202R: 3; L1196M: 3; G1128A: 1; L1189F: 1; I1171T: 1). Additional events coin these fluids obliges the use of optimal extraction and detection methods.
occurring in the resistance cohort included 1 each of: BRAFV600E, METE14skip, Here, the performance of two extraction, two droplet PCR (dPCR) and a
KRASG12, KRASG13, HRASQ61, EGFRE330K , KITamp, BRAFamp. 5 EGFR-mutant NSCLC droplet next generation sequencing (dNGS) method for blood plasma analysis
cases at progression harbored ALK fusions (4 STRN, 2 EML4; 1 patient had both) was systematically evaluated. Methods: Limits of detection were assessed
representing 1% of all EGFR-mutant progressing NSCLC cases in the G360 using 15 blinded healthy donor blood samples spiked with equivolume
database. Four of these patients also harbored EGFRT790M, but the presence mixtures of H1975 (containing EGFR L858R and T790M mutations) and H1650
of an ALK fusion may represent further subclonal evolution following the (EGFR exon 19 deletion, e19del) cells at 10%, 1%, 0.1%, 0.01%, 0.001% H1650
selective pressure of an EGFR inhibitor. Conclusion: These results add to the cells in triplicate. A series of 32 blinded blood plasma samples from non-small
growing body of literature demonstrating that comprehensive ctDNA assays cell lung cancer (NSCLC) patients with known tumour EGFR mutation status
provide a non-invasive means of detecting targetable alterations in the first was also tested. Samples were processed for plasma, and 1ml plasma each
line when tissue is QNS as well as detecting known and novel resistance underwent Qiagen Circulating Nucleic Acid and Promega Maxwell Circulation
mechanisms that may inform treatment decisions at progression. Cell Free DNA extraction processing. The plasma DNA samples were analysed
using the Biorad dPCR and Raindance Raindrop dPCR method for L858R
Keywords: ALK fusion, resistance mechanisms, NSCLC, Circulating Tumor DNA and exon 19 deletion mutations, and the 50-gene Raindance Thunderbolts
dNGS protocol. Results: No significant difference in DNA yield and detection
patterns was observed between the two extraction methods. L858R
mutations were detected by both dPCR methods at 0.001% in 1/3 replicates
and 0.01% in 3/3 replicates. Of 4 cases with L858R tumour mutations,
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER – mutations were detected in the same 3 plasma samples by both Biorad and
MONDAY, DECEMBER 5, 2016 Raindance dPCR (sensitivity 75%). “False positive” L858R mutations were
identified in 2 (specificity 92%) and 7 (75%) cases respectively. For 8 tumour
e19del mutations, the sensitivities were 38% and 25%, and specificities were
P1.02-058 EGFR AMPLIFICATION AND SENSITIZING MUTATIONS
96% and 75% respectively. Of 16 clinical samples analysed by dNGS, an average
CORRELATES WITH SURVIVAL FROM ERLOTINIB IN LUNG of 20 mutations per sample were identified after filtering for quality, non-
ADENOCARCINOMA PATIENTS (MUTP-CLICAP) synomyous, and non-germline variant status. The sensitivity and specificity
Andrés Cardona1, Oscar Arrieta2, Luis Corrales3, Leonardo Rojas4, Mauricio for detecting 2 L858R tumour mutation was 100% and 50%, and 1 e19del
Cuello5, Claudio Martin6, Hernan Carranza1, Carlos Vargas1, Rafael Rosell7 tumour mutation was 100% and 55% respectively. The allele frequencies
1
Medical Oncology, Clinical and Traslational Oncology Group, Institute of Oncology, for the majority of “false positives” for dPCR and dNGS were less than 5%,
Clínica Del Country, Bogota/Colombia, 2Thoracic Oncology Unit and Laboratory of although some “true positives” were also detected at that level. Conclusion:
Personalized Medicine, Instituto Nacional de Cancerologia, Mexico City/Mexico, dPCR and dNGS methods can enable detection of tumour mutations in blood,
3
Clinical Oncology Department, Hospital San Juan de Dios (San José, Costa Rica), albeit imperfectly. Future work to determine optimal detection thresholds
San Jose/Costa Rica, 4 Centro Javeriano de Oncología, Hospital Universitario San
will help to maximize sensitivity and specificity.
Ignacio, Bogotá/Colombia, 5Medical Oncology Department, Udelar (Montevideo,
Uruguay), Montevideo/Uruguay, 6Department of Clinical Oncology, Instituto Keywords: droplet PCR, circulating free DNA, liquid biopsy, next generation
Alexander Fleming, Buenos Aires/Argentina, 7Molecular Biology Laboratory of
sequencing
Cancer Dr. Rosell., Can Ruti Campus: Institute for Predictive and Personalized
Medicine of Cancer ( Imppc)- Institut of Health Germans Trias I Pujol (IGTP). Catalan
Institute of Oncology (ICO), Badalona, Barcelona/Spain
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY 17/20 (85%) were adenocarcinomas, all stage IV. Median patient age was
61 years (range 41-81), and 59% were female. 13 (4.5%) cases harbored ALK
fusions with partners as follows: nine EML4 (one each of novel partners
PPFIBP1 and CACNB4), and two with unidentified partners. All but one case
P1.02-060 EGFR MEDIATES ACTIVATION OF RET IN LUNG had breakpoints in ALK intron 19, the remaining harboring a novel intron
ADENOCARCINOMA WITH NEUROENDOCRINE DIFFERENTIATION 17 breakpoint. Three cases (1%) harbored KIF5B-RET (canonical breakpoint
CHARACTERIZED BY ASCL1 EXPRESSION intron 12), three (1%) had CD74-ROS1 (breakpoints: ROS1 intron 33(2) and
intron 32(1)), and one had FGFR3-TACC3. ALK, RET, and ROS1 fusions were
Farhad Kosari, Kaustubh Bhinge, Lin Yang, Simone Terra, Aqsa Nasir, Prasuna
observed by tissue testing of NSCLC in the FoundationCore database with
Muppa, Marie Christine Aubry, Joanne Yi, Nafiseh Janaki, Irina Kovtun,
similar frequencies. Five patients had a biopsy with insufficient tissue for
Stephen Murphy, Hamed Rahi, Aaron Mansfield, Mariza De Andrade, Ping
CGP; three had both sufficient tissue and ctDNA available. The remainder
Yang, George Vasmatzis, Tobias Peikert
had no tissue available. For one patient, EML4-ALK fusion was detected in
Mayo Clinic, Rochester/United States of America
both ctDNA and tissue, collected six days apart. For another, CGP identified
Background: Achaete-scute homolog 1 (ASCL1) is a neuroendocrine EGFR L858R + EGFR L709K and the patient had a durable response to afatinib/
transcription factor expressed in 10-20 % of lung adenocarcinomas (AD) with cetuximab. After progression, ctDNA assay identified FGFR-TACC3 as well as
neuroendocrine (NE) differentiation. Previously, we demonstrated that EGFR L858R. For a pre-menopausal, therapy naïve never smoker, female of
ASCL1 functions as an upstream regulator of the RET oncogene in AD with east Asian heritage, both assays detected a CD74-ROS1 fusion, whereas ROS1
high ASCL1 expression (A+ AD). In this study, we examined the potential role rearrangement was not identified by the prior use of another commercially
of wild type RET in influencing the oncogenic properties of A+ AD. We also available ctDNA test. The patient had a major radiographic response by
screened for drugs that could selectively target RET signaling and examined the second cycle of crizotinib treatment. Conclusion: Hybrid capture based
the role of the two RET isoform separately. Methods: The association of ctDNA assay can identify kinase fusions in NSCLC when CGP of biopsied tissue
the mRNA expression for the long (RET51) and short (RET9) RET isoforms cannot be performed and can direct rational use of first line TKIs. This series
with overall survival (OS) were assessed in a case-control study of stage-1 identified a novel mechanism of acquired resistance to EGFR inhibitors, novel
A+ AD patients surgically resected at the Mayo Clinic (1994-2007). Cases and fusion partners and intronic breakpoints for ALK, and a case of false negative
controls were defined as patients who survived < 3.5 years after surgery testing by another ctDNA assay.
(n= 29) and > 5 years after surgery (n=38), respectively. mRNA was isolated
Keywords: fusions, ctDNA, NSCLC, kinase
from FFPE tissue and analyzed by a nanostring assay. Associations of each
isoform mRNA with the OS was determined by the area under the receiver
operative characteristics (AUC). For drug screening, HCC1833 lung AD cells
with endogenously high expression of ASCL1 were stably transfected with
either empty vector or an ASCL1-shRNA. Differential sensitivities of tyrosine
kinase inhibitors (TKIs) in the pair of syngeneic cell lines were measured by POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
Cell-Titer Glo (Promega). Interactions between EGFR and RET was examined Other Mutations in Thoracic Malignancies –
by co-immunoprecipitation. Results: Expression of RET51 mRNA was MONDAY, DECEMBER 5, 2016
associated with poor OS (p=0.005, AUC 0.71). We detected modestly increased
sensitivity to sunitinib and vandetanib in A+ AD compared with A - AD cells.
However, the EGFR inhibitors gefitinib and the dual EGFR and HER2 inhibitor P1.02-062 CONSENSUS OF GENE EXPRESSION PHENOTYPES
lapatinib resulted in ≥ 10 fold higher cytotoxicity in A+ AD cells than in A - AD
AND PROGNOSTIC RISK PREDICTORS IN PRIMARY LUNG
cells. Subsequent experiments demonstrated that EGF stimulation of EGFR
ADENOCARCINOMA
mediates the phosphorylation of RET in multiple A+ AD cells. RET and EGFR
were found to interact only in presence of EGF and predominantly through Markus Ringner 1, Johan Staaf 2
1
the long RET isoform (RET51). Conclusion: Herein we demonstrate that wild Lund University, Lund/Sweden, 2Department of Oncology and Pathology, Lund
type EGFR predominantly interacts with the long isoform of RET (RET51) in University, Lund/Sweden
A+ AD cells. In the presence of EGF this results in activation of RET. High RET51
Background: Transcriptional profiling of lung adenocarcinomas has
is associated with worse OS. Furthermore, compared to A - AD cells, A+ AD cells
identified numerous gene expression phenotype (GEP) and risk prediction
appear to be more sensitivity to EGFR inhibitors. In summary, our results
(RP) signatures associated with patient outcome. However, classification
suggest that A+ AD patients may benefit from treatment with EGFR inhibitors
agreement between signatures, underlying transcriptional programs,
even in the absence of an EGFR mutation.
and independent signature validation are less studied. Methods:
Keywords: ASCL1, neuroendocrine, RET, EGFR Published transcriptional profiles from 17 cohorts comprising 2395 lung
adenocarcinomas with available patient outcome data were collected from
authors’ websites or public repositories as described in the original studies.
Tumors were classified according to 18 different GEPs or RPs derived from
microarray analysis of lung adenocarcinoma or NSCLC cohorts, using reported
original classification schemes or consensus clustering of gene signatures
on a per cohort basis. To independently assess the connection between
classifications by the lung cancer derived signatures and classification by
MONDAY, DECEMBER 5, 2016 expression of proliferation-related genes only, a 155-gene breast cancer
proliferation signature was used to classify all tumors as low-proliferative
(average expression of the 155-genes < median) or high-proliferative. Tumors
P1.02-061 KINASE FUSIONS IN NON-SMALL CELL LUNG CARCINOMA were also scored according to five reported expression metagenes in lung
IDENTIFIED BY HYBRID CAPTURE BASED CTDNA ASSAY cancer representing different biological processes; proliferation, immune
Lauren Young 1, Siraj Ali1, Alexa Schrock1, Mark Kennedy1, Laurie Gay1, Justin response, basal / squamous, stroma / extra cellular matrix (ECM), and
Allen1, James Suh1, Victoria Wang2, Eric Bernicker3, Sai-Hong Ignatius Ou4, expression of Napsin A / surfactants on a per cohort basis to contrast subtype
Davood Vafai5, Jeffrey Ross1, Phil Stevens1, Vincent Miller 1 classifications with biological functions. Results: 16 out of 18 signatures
1
Foundation Medicine, Cambridge/United States of America, 2Hematology- were associated with patient survival in the total cohort and in multiple
Oncology, University of California San Francisco Medical Center, San Francisco/CA/ individual cohorts. For significant signatures, total cohort hazard ratios were
United States of America, 3Houston Methodist Hospital, Houston/TX/United States ~2 in univariate analyses (mean=1.95, range=1.4-2.6). Signatures derived in
of America, 4University of California, Irvine School of Medicine, Orange County/ adenocarcinoma generally displayed better classification agreement than
CA/United States of America, 5Eisenhower Medical Associates, Rancho Mirage/CA/ signatures derived in mixed NSCLC cohorts. Strong classification agreement
between signatures was observed, especially for predicted low-risk patients
Background: For the detection of genomic driver alterations in NSCLC, by adenocarcinoma-derived signatures, despite a generally low gene overlap.
comprehensive genomic profiling(CGP) or focused molecular testing of Expression of proliferation-related genes correlated strongly with GEP
biopsied tissue is a well-accepted approach for matching targeted therapies subtype classifications and RP scores, driving the gene signature association
in first line treatment. For NSCLC patients where invasive biopsy represents with prognosis. A three-group consensus definition of samples across 10
a serious risk, assessment of circulating tumor DNA(ctDNA) is an emerging GEP classifiers demonstrated aggregation of samples with specific smoking
alternative. Methods: In patients with clinically advanced NSCLC, two 10 mL patterns, gender, and EGFR/KRAS mutations, while survival differences were
aliquots of peripheral, whole blood were collected and plasma was isolated. only significant when patients were divided into low- or high-risk resembling a
ctDNA was extracted to create adapted sequencing libraries prior to hybrid terminal respiratory (TRU) like and non-TRU division, respectively. Conclusion:
capture and sample-multiplexed sequencing on an Illumina HSQ2500 to By providing this consensus of current GEPs and RPs in lung adenocarcinoma
>5000x unique coverage. Results were analyzed with a proprietary pipeline to we have connected molecular phenotypes, risk predictions, patient outcome
call substitutions, indels, rearrangements and copy number amplifications. and underlying transcriptional programs of the different classifier types. Our
Results: In 288 NSCLC patients evaluated, 20 (6.9%) harbored kinase fusions. results provide a general insight into the nature and agreement of GEP and RP
signatures in the disease, and their prognostic value.

Keywords: Prognostic, Gene Expression, risk predictor, lung adenocarcinoma 1

Divisione Di Oncologica Toracica, Istituto Europeo Di Oncologia - Ieo, Milano/
Italy, 2Instituto Oncológico Dr Rosell (IOR), Hospital Universitario Quirón-Dexeus,
Barcelona/Spain, 3Oncology, Ospedale Santa Maria Delle Croci, Ravenna/
Italy, 4Laboratory of Cellular and Molecular Biology, Pangaea Biotech Sl, Ior
Quirón-Dexeus University Institute, Barcelona/Spain, 5Laboratory of Cellular
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY and Molecular Biology, Institut D’Investigació En Ciències Germans Trias I Pujol,
OTHER MUTATIONS IN THORACIC MALIGNANCIES – Badalona/Spain, 6Laboratory of Cellular and Molecular Biology, Catalan Institute of
MONDAY, DECEMBER 5, 2016 Oncology and Institut D’Investigació En Ciències Germans Trias I Pujol, Badalona/
Spain, 7Laboratory of Cellular and Molecular Biology, Hospital of Integrated
Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,
P1.02-063 MUTATION PROFILING BY TARGETED NEXT-GENERATION Nanjing, Jiangsu/China, 8Division of Thoracic Oncology, European Institute of
SEQUENCING OF AN UNSELECTED NSCLC COHORT Oncology, Milano/Italy, 9Medical Oncology, Istituto Di Ricovero E Cura A Carattere
Linnea La Fleur 1, Elin Falk-Sorqvist1, Patrik Smeds1, Magnus Sundstrom1, Scientifico, Ospedale San Raffaele, Milano/Italy
Johanna Mattsson1, Eva Brandén2, Hirsh Koyi2, Johan Isaksson2, Hans Background: Targeting the MAPK pathway by MEK inhibition results in limited
Brunnström3, Martin Sandelin4, Kristina Lamberg4, Per Landelius5, Mats activity in patients with KRAS-mutant non-small cell lung cancer (NSCLC).
Nilsson6, Patrick Micke7, Lotte Moens1, Johan Botling7 The lack of effectiveness may be associated with activation of other effectors
1
Department of Immunology, Genetics and Pathology, Uppsala University, including STAT3, as well as MEK inhibition relief from negative feedback
Uppsala/Sweden, 2Dept. of Respiratory Medicine, Gävle Hospital, Gävle/Sweden,
3 loops. Indeed, in KRAS-mutant colorectal cancer, MEK inhibition decreases
Pathology, Regional Laboratories Region Skåne, Lund/Sweden, 4Dept. of Medical
the activity of the metalloprotease ADAM17, which normally inhibits MET
Sciences, Respiratory Medicine, Uppsala University, Uppsala/Sweden, 5Dept.
of Thoracic and Cardiovascular Surgery, Uppsala University Hospital, Uppsala, signaling and STAT3 activation by promoting shedding of MET endogenous
Sweden, Uppsala University, Uppsala/Sweden, 6Dept. of Biochemistry and antagonist, soluble “decoy” MET. Herein, we explore the MET-dependent
Biophysics, Stockholm University, Stockholm/Sweden, 7Dept. of Immunology, activation of STAT3 as a mediator of resistance to MEK inhibitors, and
Genetics and Pathology, Uppsala University, Uppsala/Sweden whether MET or STAT3 inhibitors can synergistically increase MEK-inhibitor-
induced growth inhibition in KRAS-mutant NSCLC cells in vitro. Methods:
Background: Non-small cell lung cancer (NSCLC) is a heterogeneous disease, Cell viability was assessed by MTT (thiazolyl blue) assay after treatment with
with a wide diversity when it comes to molecular variations. In the non- the allosteric MEK inhibitor, selumetinib, the small-molecule dual inhibitor
squamous subset a large variety of altered driver genes have been identified. of the MET and ALK receptor tyrosine kinases, crizotinib, and evodiamine, an
Methods: The mutational status was evaluated in a consecutive Swedish alkaloid isolated from the dried, unripe Evodia rutaecarpa (Juss.) Benth fruit,
NSCLC cohort consisting of 354 patients, who underwent surgical resection that exerts an anticancer effect by inhibiting STAT3. RNA was isolated from
between 2006 and 2010. DNA was prepared from either fresh frozen or four KRAS cell lines and the STAT3 and MET mRNA expression analysis was
formalin fixed paraffin embedded tissue (FFPE) and used for library performed by TaqMan based qRT-PCR. Western blotting was used to assess
preparation using a Haloplex gene panel and subsequently sequenced on an the effect of selumetinb on ERK, AKT and STAT3 phosphorylation. Results: We
Illumina Hiseq instrument. The gene panel covers all exons of 82 genes, first evaluated the efficacy of the MEK inhibitor selumetinib in our KRAS-
previously identified in NSCLC. The panel design utilizes two strand capture mutant NSCLC cell line panel using an MTT cell proliferation assay. H460 cells
and reduced target fragment length compatible with degraded FFPE samples were relatively insensitive to selumetinib. Following 48-hour treatment with
(Moens et al., J Mol Diagn, 2015). Results: All previously known hotspot selumetinib, ERK1/2 and AKT phosphorylation were suppressed but a rebound
alterations in the driver genes KRAS, EGFR, HER2 (exon 20 insertions), NRAS, activation of STAT3 occurred in H460 cells. We next investigated whether
BRAF, MET (exon 14-skipping) and PIK3CA (exon 9 and 20) were analyzed in the MET expression was related to the feedback activation of STAT3 signaling
252 non-squamous cases, see figure. KRAS mutations were found in 98 following MEK inhibitor treatment. We compared gene expression profiles of
patients (39%) whereas EGFR alterations were present in 33 (13%). The the H460 cell line before and after treatment with selumetinib. Interestingly,
prevalence of KRAS mutations is higher than normally reported and could be we found significant upregulation of MET and STAT3 mRNA expression
due to the large fraction of smokers included in this cohort. The EGFR after seven days of selumetinib treatment. To further interrogate the
prevalence is a bit higher than previously demonstrated (Sandelin et al. relationship between MEK inhibition and MET-mediated STAT3 reactivation,
Anitcancer Res, 2015). Mutations in the other driver genes were detected at H460 cells were treated with the combination of selumetinib and crizotinib
low frequencies (HER2(3%), BRAF(2%), NRAS(1%), MET(1%) and PIK3CA(1%)). or selumetinib and evodiamine. A 72-hour exposure to both combinations
resulted in a clear cell synergism, as measured by the combination index (CI)
analysis, with a CI of 0.79 and 0.78 respectively. Conclusion: Collectively our
results showed that the feedback STAT3 activation induced by MET, mitigates
the effect of MEK inhibition, and provides rationale for further assessment of
combined MEK and MET or STAT3 inhibition in KRAS-mutant NSCLC.
Keywords: lung cancer, KRAS, STAT3, MEK inhibitors

OTHER MUTATIONS IN THORACIC MALIGNANCIES –
P1.02-065 ELUCIDATING THE ROLE OF PIM KINASE AND ITS

Conclusion: The preliminary analysis of mutational status in this large THERAPEUTIC POTENTIAL IN NSCLC
unselected Swedish NSCLC cohort reveals mutation frequencies in the Gillian Moore 1, Susan Heavey1, Clara Lightner2, Lauren Brady2, Kenneth
common driver genes resembling previous reports on western populations O’Byrne3, Stephen Finn2, Sinead Cuffe4, Michael O’Neill5, Kathy Gately1
with a high smoking rate. Ongoing analysis of the remaining genes will be used 1
Clinical Medicine, Trinity College Dublin/st. James’ Hospital, Dublin/Ireland,
for pathway analysis and could provide a more complete picture of the lung 2
Dept of Histopathology, St James’ Hospital, Dublin/Ireland, 3Institute of Health
cancer pathogenesis. and Biomedical Innovation, Queensland University of Technology, Brisbane/
Australia, 4Dept of Medical Oncology, St James’ Hospital, Dublin/Ireland, 5Inflection
Keywords: Targeted resequencing, Consecutive cohort, NSCLC Bioscience Ltd., London/United Kingdom
Background: PIM kinases are a family of three serine/threonine kinases: PIM1,

PIM2 and PIM3 that have been shown to play a role in tumorigenesis. PIM1
is a downstream effector of oncoproteins ABL and JAK/STAT and regulator
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY of BCL2/BAD and CXCR4. PIM activity is synergistic with the PI3K/Akt/
MONDAY, DECEMBER 5, 2016 mTOR pro-survival pathway and PIM2 has been shown to phosphorylate
translational repressor 4E-BP1 and p70S6 independently of the PI3K pathway.
Furthermore a synergism between PIM kinases and c-Myc has been reported.
P1.02-064 MET-DEPENDENT ACTIVATION OF STAT3 AS MEDIATOR Here we investigate the expression of PIM1/PIM2/PIM3 in NSCLC cell lines
OF RESISTANCE TO MEK INHIBITORS IN KRAS-MUTANT LUNG and patient matched normal/tissue samples. The effect of a novel combined
CANCER inhibitor of PI3K/mTOR/PIM kinases (IBL-301) on cell signalling, cell death
and proliferation is also examined. Methods: PIM1/PIM2/PIM3 expression
Chiara Lazzari1, Niki Karachaliou2, Alberto Verlicchi3, Carles Codony Servat4,
were examined by Western blot analyses in NSCLC cells (H1975 and H1838).
Ana Gimenez Capitan4, Jordi Codony Servat4, Jordi Bertrán-Alamillo4, Miguel
Additionally, the frequencies of PIM1/PIM2/PIM3 expression in NSCLC patient
Angel Molina Vila4, Imane Chaib5, José Luis Ramírez Serrano6, Peng Cao7,
tumour and matched normal adjacent samples (n=31) were investigated. The
Filippo De Marinis8, Vanesa Gregorc9, Rafael Rosell6
effectiveness of IBL-301 on cell signalling, cell viability and proliferation were
examined by Western blot analysis, cell titre blue and BrdU assay respectively. cancer during the last 4 years. The technical success rates for the repeated
Results: All three PIM isoforms were detected in the lung cancer cell lines biopsy and the adequacy rates of specimens were evaluated. Biopsy-related
tested. Similarly, all three PIM isoforms were expressed across the 31 NSCLC complications were recorded. Clinical details were collected, specially focusing
patient tumour and match normal adjacent tissue samples. To investigate in EGFR mutation data. Results: 110 repeated biopsies were performed in
this further PIM1 staining of FFPE tumour and match normal tissue from this 74 patients (34 women, 40 men, mean age 63 [36-84]), the histology was:
cohort is currently underway. In two lung cancer cell lines, H1975 and H1838, 74% adenocarcinoma, 12% squamous cell carcinoma, 11% NOS, 3% other. The
IBL-301 was found to have a dose dependent effect on proliferation/viability mean number of repeated biopsies per patient was 1 (1-4). The main reasons
with IC50 values in the nanomolar range. Additionally, western blot analyses for repeated biopsy were immunohistochemical +/- mutational analysis
have indicated that these novel drugs can suppress the phosphorylation of (34/110, 31%), mutational analysis (16/110, 14.6%) and EGFR at progression
key players in cell signalling pathways linked to tumorigenesis including pAkt, (28/110, 24.4%). The technical success rate for biopsy was 98/110 (89.1%),
p4E-BP1 and peIF4B. Conclusion: This is the first study to investigate the and postprocedural complications occurred in 3/110 cases: 2 pneumothorax
expression of all 3 isoforms of PIM in lung cancer specifically. All 3 isoforms and 1 wound infection. Biopsy specimens came mostly from primary tumor
were abundantly expressed across cells lines and patient tumour samples. (56/110, 51%), lymph nodes (26/110, 23.6%) and pleura (9/110, 8.2%), the
Observed PIM expression in the immune cells of normal adjacent tissue may most used technique was bronchoscopy +/- EBUS (45/110, 40%), followed
indicate a role in inflammation. This finding coupled with the promising in by percutaneous transthoracic lung biopsy (28/110, 26%) and thoracoscopy
vitro data demonstrate the therapeutic potential of targeting PIM in NSCLC. and/or mediastinoscopy: (19/110, 17%). Results from repeated biopsy were
used to select the next line of treatment in 86/110 procedures (78%), and
Keywords: Pim kinase, biomarker, therapeutic target, NSCLC 40/86 of them (46.5%) allowed to include the patient in a clinical trial. 28
repeated biopsies were performed in 21 EGFR mutant lung cancer patients
with acquired resistance at disease progression, T790M was detected in 13/28
(46%) of samples, corresponding to 10/21 (47.6%) EGFR mutant lung cancer
patients. Conclusion: Our data demonstrate that repeated biopsy in non small
OTHER MUTATIONS IN THORACIC MALIGNANCIES – cell lung cancer is safe and clinically feasible. Findings from repeated biopsy
MONDAY, DECEMBER 5, 2016 were used to direct subsequent treatment in 78% of patients.
Keywords: repeated biopsy, Acquired resistance in EGFR mutant lung cancer

P1.02-066 GENOMIC PROFILING IN THE DIFFERENTIAL
DIAGNOSTICS OF PULMONARY TUMOURS: A CASE SERIES
Kajsa Ericson Lindquist1, Anna Johansson1, Per Levéen1, Göran Elmberger2,
Göran Jönsson3, Johan Staaf3, Hans Brunnström 4
1 POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
Pathology, Regional Laboratories Region Skåne, Lund/Sweden, 2Department of OTHER MUTATIONS IN THORACIC MALIGNANCIES –
Pathology, Örebro University Hospital, Örebro/Sweden, 3Department of Oncology MONDAY, DECEMBER 5, 2016
and Pathology, Lund University, Lund/Sweden, 4Department of Clinical Sciences
Lund, Division of Oncology and Pathology, Lund University, Lund/Sweden
P1.02-068 THE IMPACT OF TP53 OVEREXPRESSION ON EMT AND
Background: Histopathological diagnosis is important for prognostication THE PROGNOSIS IN LUNG ADENOCARCINOMA HARBORING DRIVER
and choice of treatment in patients with cancer in the lung. Lung metastases MUTATIONS
are common and need to be distinguished from primary lung cancer.
Shigeto Nishikawa, Toshi Menju, Terumasa Soawa, Koji Takahashi, Ryo
Furthermore, cases with synchronous or metachronous primary lung cancers
Miyata, Hiroyuki Cho, Shinya Neri, Takao Nakanishi, Masatsugu Hamaji,
(although infrequent) are often handled differently than cases with lung
Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Fengshi
cancer with intrapulmonary metastasis or relapse, respectively. In some cases,
Chen, Makoto Sonobe, Hiroshi Date
morphology and immunohistochemical (IHC) staining is not sufficient for
certain diagnosis. Methods: Five cases were selected where molecular genetic Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto/Japan
analysis in form of pyrosequencing or targeted next-generation sequencing
Background: Epithelial-mesenchymal transition (EMT) and p53 mutations
(NGS) was of value, not only for treatment prediction, but for certain
are known to be pivotal for driving metastasis and recurrence in lung cancer,
diagnosis of tumours in the lung. Results: Two of the included cases were
but the nature of these factors is not completely understood. Some papers
rare metastases to the lung – rectal cancer with IHC profile consistent with
have previously described the relationship between EMT and TP53 in other
primary lung cancer and malignant myoepithelioma of the breast, respectively
carcinomas, however there have been few reports about the impact of TP53
– where molecular genetic analysis was of aid for proving the relationship with
on EMT and prognosis in lung adenocarcinoma harboring driver mutations
the primary tumour. The other three cases had multiple lung adenocarcinomas
such as EGFR or K-ras. Methods: The aim of the present study is to clarify
with similar morphology where molecular genetic analysis was of aid to
the impact of TP53 overexpression in lung adenocarcinoma with driver
distinguish between an intrapulmonary metastasis and a synchronous
mutations. A total of 282 lung adenocarcinoma specimens were collected
primary tumour. Conclusion: Comparison of molecular genetic profile may
from patients who had undergone surgery in our institute from January 2001
be an important tool for determination of relationship between tumours, at
to December 2007. Both EMT markers (E-cadherin, vimentin) and TP53 were
least in some situations, and should always be considered in unclear cases.
analyzed through immunostaining of tumor specimens. The association
Further studies on concordance and discordance of molecular genetic profiles
between EMT and TP53 as well as the patients’ clinical information was
between spatially or temporally different tumours with common origin may
integrated and statistically analyzed. EGFR and K-ras mutation were
be helpful for improved diagnostics of pulmonary tumours.
determined by single stranded conformational polymorphism and direct
Keywords: next-generation sequencing, pyrosequencing, histopathology, sequencing. Correlations were compared using Pearson’s chi-square test
metastasis and overall survival were compared using the log-rank test. Results: Both
mesenchymal type (E-cadherin negative, vimentin positive) and TP53
overexpression were significantly correlated with poor prognosis (P=0.0001,
P=0.0019). A positive correlation was found between EMT activation level
and TP53 overexpression (P=0.017). TP53 overexpression was significantly
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY correlated with poor prognosis in the subgroup of lung adenocarcinoma
OTHER MUTATIONS IN THORACIC MALIGNANCIES – with driver mutation (EGFR or K-ras) (P=0.011, P=0.026), whereas there was
no significant correlation between TP53 overexpression and the prognosis
in adenocarcinoma without driver mutations (P=0.359). Conclusion: TP53
P1.02-067 REPEATED BIOPSY FOR IMMUNOHISTOCHEMICAL overexpression is supposed to be the key factor that affects EMT and the
AND MUTATIONAL ANALYSIS OF NON SMALL CELL LUNG CANCER: prognosis, and also might be an additional therapeutic target for lung
FEASIBILITY AND SAFETY adenocarcinoma with driver mutations.
Mariona Riudavets, Georgia Anguera, Alfons Torrego, Virginia Pajares, Ana Keywords: Driver mutation, TP53, epithelial-mesenchymal transition, lung
Gimenez, Laura López Vilaró, Elisabeth Martínez Tellez, Joan Carles Trujillo, adenocarcinoma
Núria Farré, Enrique Lerma, Josep Belda, Valle Camacho, Alejandro Fernandez,
Ana Muñoz, Margarita Majem
Hospital de La Santa Creu I Sant Pau, Barcelona/Spain
Background: Repeated biopsy in lung cancer may be necessary at diagnosis POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
or after cancer progression on initial therapy to properly target treatments. OTHER MUTATIONS IN THORACIC MALIGNANCIES –
The objective of this study is to evaluate the feasibility and safety of repeated
biopsy for immunohistochemical and/or mutational analysis in patients
with non small cell lung cancer. Methods: We have retrospectively analyzed P1.02-069 GENOMIC ALTERATIONS AND SURVIVAL IN YOUNG
repeated biopsies performed in patients with advanced non small cell lung PATIENTS UNDER 40 YEARS WITH COMPLETELY RESECTED NON-

SMALL CELL LUNG CANCER Hiromasa Yamamoto1, Junichi Soh1, Kazunori Tsukuda1, Shinichiro Miyoshi1,
Xinmin Yu1, Zhengbo Song 2, Yiping Zhang1 Shinichi Toyooka1
1
1
Zhejiang Cancer Hospital, Hangzhou/China, 2Medical Oncology, Zhejiang Cancer Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate
Hospital, Hangzhou/China School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan,
2
Bioinformatics, Okayama University Graduate School of Medicine, Dentistry and
Background: Young patients diagnosed as non-small cell lung cancer (NSCLC) Pharmaceutical Sciences, Okayama/Japan
is rare. Little is known for its genomic alterations and survival. This study
Background: Recent advantage of next-generation sequencing (NGS) in
retrospectively evaluated the genomic alterations,treatment and prognosis
the field of cancer genome research has revealed extreme levels of genetic
with NSCLC in our institution between January 2009 and July 2014 . Methods:
heterogeneity, suggesting the major roles of subclonal mutations in cancer
All patients were examined for EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2
relapse and in rapid emergence of acquired resistance. Unlike inherited
mutations and ALK, ROS1, RET fusion genes based on reverse transcription
mutations, somatic variants often occur at low allele frequencies that require
PCR. The Kaplan-Meier method was used to estimate survival and comparison
sensitive methods for detection. Based on the results using another highly
using the log-rank test. Results: Totally, 54 were with age under 40 years
sensitive method, such as digital PCR, the study of cancer subclones requires
old among 640 patients. Among the 640 patients, three hundred and fifty
to detect mutations that are present in <1% frequency, however, such a level
eight patients were with identified genomic alterations with frequency of
of resolution cannot be obtained by conventional NGS approaches. In the
55.9 %. The frequencies of genomic alterations in younger and older were
current study, we performed molecular-barcode sequencing for primary lung
68.5% and 54.8%,respectively (P=0.05). The frequencies difference between
adenocarcinoma cases in order to analyze mutations with <1% low frequency.
younger and older existed in fusions genes ( 22.2% vs.4.1%,P<0.001), but
Methods: Fresh frozen tumor samples from 58 primary lung adenocarcinoma
not mutations genes (46.3% vs.45.6%,P=0.92). There was a trend of shorter
patients whose tumors previously tested positive for EGFR by conventional
recurrence free survival in younger than older (35.2 vs.43.8 months,P=0.050),
method (the PNA-LNA PCR clamp method) were collected. All samples
while no survival difference was found between younger and older (50.2 vs
were obtained from surgically resected specimen. We used HaloPlex HS
51.4 months,P=0.112). Conclusion: We concluded that younger age of NSCLC is
method, which is a high sensitivity amplicon-based targeted sequencing
associated with a trend of increased of harboring targeted genes and mainly
method incorporating molecular barcodes in the DNA library, allowing for
with difference of fusion genes . An inferior overall survival existed in younger
the identification of duplicate reads to significantly improve the base calling
than older.
accuracy even at low allelic frequencies compared to conventional NGS
Keywords: non-small cell lung cancer, age, survival, genomic alterations methods. We used a panel designed for 47 cancer-related genes including
EGFR, and sequenced data was obtained by using Illumina Miseq Reagent
v3 (600 Cycle). Normal tissue samples were also sequenced for threshold
adjustment. Results: Out of 58 samples, EGFR ‘major’ mutation (L858R,
Exon19 deletion, G719A/S, T790M) profiles of 57 samples by molecular-
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY barcode sequencing corresponded to those by clinical method (98.3%).
The mean coverage of EGFR major mutation was 3078 (243-8285), and the
minimal detectable frequency was 0.45%. Of note, we could detect the minor
frequency of T790M mutation in addition to the major frequency of L858R
P1.02-070 GENE SPECTRUM AND SURVIVAL ANALYSES OF mutation, at the allele frequency of 1.92% (20/1042) for T790M and 10.62%
PATHOLOGIC SUBTYPES IN RESECTED LUNG SQUAMOUS CELL (155/1459) for L858R mutation, respectively. Minor genetic alterations,
CARCINOMA except major mutation, in EGFR were detected in 82.8% (48/58) cases, and
the mean number was 2.3 (0-11). These results suggest the clinical applicability
Zhengbo Song 1, Yiping Zhang2, Xinmin Yu2
1 of this method. Conclusion: We could demonstrate good concordance rate
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer
between clinical examination and molecular barcode sequencing. Minor
Hospital, Hangzhou/China
genetic alterations in EGFR were detected in 82.8% (48/58) cases. Further
Background: Based upon the 2015 Lung Cancer Pathologic Classification, investigations are warranted to establish the confident detection of
squamous cell carcinoma of lung (SQCC) has been classified as three types of subclonal mutations with low frequency.
keratinized, non-keratinized and basaloid squamous cell carcinoma (BSCC).
Keywords: next generation sequencing, molecular-barcode, low-frequency
The spectrum of common driver genes and clinical prognosis were examined
mutation, EGFR
for different subtypes in SQCC in present study. Methods: From 2009 to
2013, a total of 201 patients with completely resected stages I-IIIA SQCC were
recruited. Reverse transcription-polymerase chain reaction (RT-PCR) was
utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF,
DDR2, HER2 and the fusion genes of ALK, ROS1 and RET. Survival curves POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
were plotted with Kaplan-Meier method. Cox’s proportional hazard model OTHER MUTATIONS IN THORACIC MALIGNANCIES –
was used for multivariate analysis. Results: The pathological types were MONDAY, DECEMBER 5, 2016
BSCC (n=16), non-keratinizing (n=83) and keratinizing (n=102). The overall
frequency of gene abnormality was 18.4%. The most common driver genes in P1.02-072 COMPREHENSIVE GENOMIC ALTERATIONS IDENTIFIED
a decreasing frequency were PIK3CA mutation (n=14), EGFR mutation (n=8),
BY NEXT-GENERATION SEQUENCING OF LUNG ADENOCARCINOMA
DDR2 mutation (n=8), KRAS mutation (n=3), HER2 mutation (n=2), ALK
IN JAPANESE POPULATION
rearrangement (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS,
BRAF or RET were observed . The frequency of gene abnormality was greater Seijiro Sato 1, Masayuki Nagahashi2, Tatsuya Goto1, Akihiko Kitahara1,
in keratinized (19.6%) ,followed with non-keratinized (19.2%) and BSCC types Terumoto Koike1, Kazuki Takada3, Tatsuro Okamoto3, Keisuke Kodama4,
(6.3%). Targeted therapy was offered for 35 patients, including 32 on EGFR- Hiroshi Izutsu4, Mitsutaka Nakada4, Yoshihiko Maehara3, Toshifumi Wakai2,
TKIs (EGFR mutation, n=5; EGFR wild-type, n=27), ALK-positive on crizotinib Masanori Tsuchida1
1
(n=1) and HER2 mutation on afatinib (n=1). The median progression-free Thoracic and Cardiovascular Surgery, Niigata University Graduate School of
survival (PFS) of EGFR-TKIs were 6.0 and 1.87 months in EGFR mutant and wild Medical and Dental Sciences, Niigata/Japan, 2Division of Digestive and General
types respectively (P=0.004). And the PFS for those two with crizotinib and Surgery, Niigata University Graduate School of Medical and Dental Sciences,
Niigata/Japan, 3Department of Surgery and Science, Kyushu University, Graduate
aftatinib treatment were 8.0 and 3.5 months respectively. . The SQCC patients
School of Medical Sciences, Fukuoka/Japan, 4Diagnostics Research Department,
of BSCC subtype had significantly worse overall survival than those with non- Life Innovation Research Institute, Denka Innovation Center, Denka Co., Ltd,
BSCC subtypes (29.0 vs.47.0 months, P<0.001). Conclusion: The subtypes of Machida/Japan
SQCC were associated with varying frequency of gene abnormality. BSCC had
a lower frequency of common driver gene abnormality and worse survival. Background: Therapeutic approaches to lung cancer have shifted toward an
emphasis on molecularly targeted therapy in genotypic subsets of patients
Keywords: Pulmonary squamous cell carcinoma, Basaloid squamous cell (pts). Recent advances in next-generation sequencing (NGS) technologies
carcinoma, gene abnormality, survival have improved the ability to detect potentially targetable mutations. In this
study, we aimed to analysis the genomic alterations of lung adenocarcinoma.
Methods: A retrospective analysis of genomic data obtained from 99 archived
formalin-fixed, paraffin-embedded samples from Japanese pts with lung
adenocarcinoma were analyzed by NGS panel of 415 genes. Mutations and
OTHER MUTATIONS IN THORACIC MALIGNANCIES – frequency of variants present in key oncogenic drivers for each pts were
MONDAY, DECEMBER 5, 2016 quantified. Fisher’s exact and t-tests were used to identify associations
between genomic alterations and clinical characteristics. Results: Sex: male
66 pts, female 33 pts. Smoking status: pack-year (PY) <30 (light smoker) 61
P1.02-071 DETECTION OF MULTIPLE LOW-FREQUENCY MUTATIONS
pts, PY≥30 (heavy smoker) 38 pts. Of all, the median number of mutation
BY MOLECULAR-BARCODE SEQUENCING burden and actionable mutation were 13.5 (range 5-33) and 4 (range 1-19),
Kei Namba1, Shuta Tomida2, Hidejiro Torigoe1, Hiroki Sato1, Kazuhiko Shien1, respectively. The most frequent genomic alterations were EGFR (48%),
TP53 (40%), CDKN2B (32%), RB1 (21%), and CDKN1B (19%). Representative POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
genomic alterations with a FDA approved targeted therapy such as EGFR MONDAY, DECEMBER 5, 2016
mutation (exon 19 deletion and exon 21 L858R), ALK fusion, ROS1 fusion,
RET fusion, BRAF (V600E) mutation and, MET amplification were detected
in 56 pts (R-GAs group) and the others were 43 pts (O-GAs group). In the P1.02-074 THE GENE EXPRESSION SIGNATURES OF PULMONARY
O-GAs group, 39 pts had genomic alteration with targeted agent available ADENOCARCINOMA WITH MICROPAPILLARY FEATURES
on or off a clinical trial. As for smoking habit, R-GAs group were significantly Yuki Sata1, Takahiro Nakajima1, Keisuke Matsusaka2, Masaki Fukuyo2, Junichi
associated with light smoker than O-GAs group (p<0.01). In R-GAs group, the Morimoto1, Yuichi Sakairi1, Taiki Fujiwara1, Hironobu Wada1, Hidemi Suzuki1,
median number of mutation burden and actionable mutation were 13 (range Takekazu Iwata1, Masako Chiyo1, Atsushi Kaneda2, Ichiro Yoshino1
5-20) and 4 (range 1-10), respectively. O-GAs group were significantly greater 1
General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba/Japan,
mutation burden and actionable mutation than R-GAs group (16.2 ± 6.8 vs. 2
Molecular Oncology, Chiba University Graduate School of Medicine, Chiba/Japan
12.3 ± 4.3, p<0.01; 6.5 ± 5.0 vs. 4.5 ± 2.2, p = 0.02, respectively). Of the 43 EGFR
pts, there were no concurrent genomic alterations of ALK, ROS1, RET, BRAF Background: Invasive lung adenocarcinomas have been classified into
and, MET. The most frequent concurrent mutations in EGFR were CDKN2B 5 subtypes by the new WHO classification, of which the micropapillary-
(37%), TP53 (28%), CDKN2A (23%), CDKN1B (21%), ARID1A (19%), RB1 (16%), predominant subtype is known to have a poor prognosis. However, we
and STK11 (16%). Among the EGFR cases, 38 (88%) pts had further genomic previously reported that lung adenocarcinomas harboring a micropapillary
alteration with targeted agent available on or off a clinical trial excluding component (MPC) of more than 5% showed poorer disease-free survival
EGFR-TKI. Conclusion: With help of NGS, we found most pts might be treated and overall survival in comparison to the other subtypes (JTCVS 152: 64-72;
by targeted therapies. Further study may emerge whether concurrent 2016), despite the MPC not being predominant. Specific biomarkers for the
mutations, mutation burden and the number of actionable mutation are MPC are yet to be developed for the initial diagnosis of adenocarcinoma with
associated with survival outcome in lung adenocarcinoma. an MPC. Methods: Total RNA was extracted from snap frozen archived lung
adenocarcinoma samples that had been obtained by radical thoracotomy.
Keywords: next-generation sequencer, lung adenocarcinoma, genomic The diagnosis of each subtype was made by independent pathologists using
alteration formalin-fixed paraffin-embedded samples. Frozen sections were made
using the archived frozen sample; RNA was isolated after the confirmation
of the diagnosis of each sample. RNA-sequencing was conducted using 22
adenocarcinomas and 3 normal lung tissue samples. The 22 adenocarcinomas
included micropapillary (n=6), papillary (n=5), lepidic (n=5), acinar (n=3) and
OTHER MUTATIONS IN THORACIC MALIGNANCIES – solid (n=3) subtypes. The reads per kilo base of exon per million mapped
MONDAY, DECEMBER 5, 2016 reads data derived from RNA-sequencing were calculated to analyze the
gene expression profiles of the MPCs. The expression levels of the genes
were validated by a real-time PCR. Results: A hierarchical clustering analysis
P1.02-073 CHARACTERIZING THE GENOMES OF LUNG
revealed a cluster of tumor samples with MPCs. Two hundred four genes
ADENOCARCINOMAS FROM NEVER SMOKERS REVEALS SHPRH AS
were differentially expressed in adenocarcinomas that contain an MPC. A
A NOVEL CANDIDATE TUMOUR SUPPRESSOR GENE gene-ontology analysis showed the enrichment of signal-related genes, with
Tanya De Silva1, Victor Martinez1, Kelsie Thu1, Daniel Lu1, Min Oh1, Stephen 50 significantly upregulated genes, including BAMBI, CXCL14 and VSIG1.
Lam2, Wan Lam1, Harold Varmus3, William Lockwood1 Conclusion: The results of a gene expression analysis using next generation
1
Integrative Oncology, British Columbia Cancer Research Centre, Vancouver/BC/ sequencing revealed the specific gene expression profile of adenocarcinomas
Canada, 2Department of Integrative Oncology, British Columbia Cancer Research that contain an MPC, and several genes might be candidate diagnostic
Centre, Vancouver/BC/Canada, 3Sandra and Edward Meyer Cancer Center, Weil biomarkers for the subtype. In addition, these genes may play an important
Cornell Medical College, New York/NY/United States of America role in the unique characteristics of adenocarcinomas that contain an MPC.
Background: Approximately 15 to 25% of lung adenocarcinomas (LAC) arise in Keywords: RNA-sequencing, Micorpapillary component, Biomaker, Gene
never smokers. They develop through mechanisms distinct from those that Expression
affect smokers and are associated with unique histological and molecular
characteristics. A significant fraction of LACs in never smokers do not
have mutations in known oncogenic driver genes such as EGFR/ALK/KRAS.
Furthermore, mutations in oncogenic driver genes appear to be insufficient
for tumorigenesis, suggesting that additional alterations are required. POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
Methods: To address these issues, we used whole-exome sequencing to OTHER MUTATIONS IN THORACIC MALIGNANCIES –
comprehensively study 15 LACs from never smokers - seven “triple negative”
tumors (with normal EGFR/ALK/KRAS) and eight EGFR-mutant tumors - with
the goal of identifying novel mutant genes in these subsets. To identify P1.02-075 ANALYSIS OF DRIVER GENES ALTERATION AND
mutated genes that confer a selective advantage a multistep approach was CLINICOPATHOLOGICAL FEATURES IN PULMONARY MARKER-NULL
used to filter variants based on gene expression level, background mutation LARGE CELL CARCINOMA
rate and gene size. Targeted sequencing of 180 genes in the original 15 and
Likun Hou1, Chunyan Wu2
an extended panel of 85 tumor/normal pairs validated these alterations 1
and indicated their prevalence in LAC. Sequence data was integrated with Department of Pathology Shanghai Pulmonary Hospital, Tongji University School
of Medicine, Shanghai/China, 2 Shanghai Pulmonary Hospital Affiliated To Tongji
copy number and gene expression levels to determine mechanisms, and
University, Shanghai/China
consequences, of gene disruption. Animal and cell models were used to
functionally validate identified genes of interest and explore their role in Background: Pulmonary large cell carcinoma (LCC) was an undifferentiated
LAC biology. Results: 32 unique genes demonstrated significant evidence of and marker-null non-small cell lung cancer (NSCLC) according to 2015 WHO
conferring a selective advantage including known oncogenes (EGFR/ERBB2/ classification criteria. However, there are few studies presented molecular
MET) and tumor suppressor genes (p53/RB1/ATM). In addition, RNA-seq analysis and clinical features of this subtype. The aim of this study is to
revealed fusions involving RET or ROS1 in one tumour each. The variations in investigate profile of driver mutations and clinicopathological features of
MET consisted of truncating and splice-site mutations that we are currently marker-null LCC. Methods: From January 2008 to February 2015, 327 cases of
investigating in transgenic mouse models. Pathway analysis indicated surgically resected primary large cell carcinoma diagnosed by H&E staining
frequent mutation in genes implicated in PI3-kinase signaling, RNA splicing were enrolled from Shanghai pulmonary hospital affiliated to Tongji university
and histone modification. Importantly, we identified the hemizygous and (Lymphoepithelioma-like carcinoma and large cell neuroendocrine carcinoma
homozygous loss of multiple genes from chromosome arm 6q - a genetic were excluded with typical morphologic features). Large cell carcinoma was
locus associated with familial lung cancer susceptibility - including a novel reclassificated with a panel of immunophenotypic markers (adenocarcinoma
candidate tumor suppressor gene, SHPRH, based on its high frequency of [ADC]-specific, thyroid transcription factor-1, napsin A and anti-diastase PAS
biallelic disruption. SHPRH is an evolutionarily conserved E3-ligase that staining; squamous cell carcinoma [SQCC]-specific, cytokeratin5/6, and p40;
mediates crucial processes related to DNA repair. We found that SHPRH epithelial mesenchymal transition [EMT], cytokeratin, vimentin and ZEB1;
silencing increased transformation of normal lung cells, increased DNA neuroendocrine differentiation, synaptophysin and CD56). Molecular analysis
damage and induced cell cycle changes while SHPRH inhibition sensitized LAC (EGFR, KRAS, BRAF, ROS1, ALK and PIK3CA) and immunomarker PD-L1 of
cells to topoisomerase II and PARP inhibitors. Conclusion: SHPRH inactivation marker-null LCC were detected by ARMS method and immunohistochemistry,
may induce genetic alterations that cooperate with mutations in driver respectively. Results: 113 cases (113/327, 34.6%) were rediagnosed as ADC
oncogenes to promote LAC development. Together, this work will expand our with solid growth pattern, which showed TTF-1 positive rate 59.3% (67/113,
understanding of LAC initiation and progression in never smokers and may 59.3%), Napsin A positive rate 82.3% (93/113, 82.3%)( P<0.001)) and positive
offer new biomarkers for response to therapy. PAS staining (5/113, 4.4%) . 47 (47/327, 14.4%) cases were reclassificated as
SQCC, which positively expressed p40 (44 cases, 44/47, 93.6% ) and CK5/6 (31
Keywords: Genomics, NSCLC, mouse models, oncogene signaling
cases, 31/47, 66%)( P<0.01). 5 (5/327, 1.5%) cases of large cell neuroendcrine
carcinoma showed both neuroendocrine morphological feature and CD56,

Syn expression. 26 (26/327, 8.0%) were redefined as sarcomatoid carcinoma subtypes: subtype-1 includes pleomorphic, spindle-cell, and giant-cell
expressed cytokeratin, vimentin and ZEB1. 136 (136/327, 41.6%) cases of marker- carcinomas (PSCGC), subtype-2 carcinosarcoma and subtype-3 blastoma.
null LCC were diagnosed for lack of specific markers expression. 30 (30/136, The value of different subtypes for clinical management and their molecular
22.1%) cases of marker-null LCC showed PD-L1 positive. Driver genes alteration characteristics are unclear. The aim of this study is to get new insights into
were found in 3 cases from 30 cases marker-null LCC, including KRAS (n=1), BRAF PSCs carcinogenesis by a high-throughput sequencing of RNA (RNA-seq).
(n=1) and PIK3CA (n=1). Clinicopathological characteristics indicated that LCC Methods: A whole-transcriptome targeted-gene quantification analysis was
patients were older and more likely to be male nonsmokers. Conclusion: Large retrospectively performed on RNA from formalin-fixed paraffin-embedded
cell carcinoma was differentially diagnosed by combining with undifferentiated tissues of 13 PSCs (5 pleomorphic, 2 spindle-cell, 2 giant-cell carcinomas, 4
NSCLC morphology and marker-null features. Driver genes mutation testing carcinosarcomas). RNA-seq reads were mapped to the amplicon sequences
may significantly impact on the choice of targeted therapy. of the panel and quantified by tools based on alignment algorithms.
Differentially expressed genes between subtype-1and -2 were determined
Keywords: large cell carcinoma, molecular analysis, differential diagnosis, using a non-parametric Mann-Whitney U-test (p-value < 0.01) with linearity
clinical features correction. Moreover, within subtype-1 we compared gene expression levels
between monophasic (spindle- and giant-cell) and biphasic (pleomorphic)
carcinomas. Results: 216 genes resulted down-regulated and 15 up-regulated
in PSCGC compared to carcinosarcomas (Table 1). There were not significant
differences between monophasic and biphasic PSCGC.
P1.02-076 DNA METHYLATION PROFILING UNRAVELS A TGF-Β

HYPERRESPONSE IN TUMOR ASSOCIATED FIBROBLASTS FROM
LUNG CANCER PATIENTS
Rafael Ikemori1, Miguel Vizoso2, Marta Puig1, Anna Labernardie3, Marta
Gabasa1, Xavier Trepat3, Noemi Reguart4, Manel Esteller2, Jordi Alcaraz 1
1
Dept of Biomedicine, Facultat de Medicina, Universitat de Barcelona, Barcelona/
Spain, 2Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research
Institute, L’Hospitalet de Llobregat/Spain, 3Institute for Bioengineering of
Catalonia, Barcelona/Spain, 4 Medical Oncology, Hospital Clinic, Barcelona
University, Barcelona/Spain
Background: Tumor associated fibroblasts (TAFs) are drawing increasing

attention as potential therapeutic targets owing to its direct implication
in major steps of tumor progression in solid tumors including non-small cell
lung cancer. Accordingly, there is growing interest in defining the aberrant
molecular differences between normal and TAFs that support tumor
progression. For this purpose, we recently conducted a genome-wide DNA
methylation profiling of TAFs and paired control fibroblasts (CFs) from non-
small cell lung cancer patients, and reported a widespread hypomethylation
concomitantly with a focal gain of DNA methylation indicative of a marked
epigenetic reprogramming. Of note, the aberrant epigenome of lung TAFs
had a global impact in gene expression and a selective impact on the TGF-β
pathway, including the hypermethylation of SMAD3, which is an important
transcription factor of the TGF-β pathway. However, the functional
implications of the aberrant TGF-β pathway in lung TAFs remains undefined.
Methods: Patient-derived TAFs and paired control fibroblasts from either
adenocarcinoma (ADC) or squamous cell carcinoma (SCC) patients were
stimulated with TGF-β1 and their responses were examined in terms of
activation and contractility. Activation markers included expression of alpha-
smooth muscle actin (α-SMA) and collagen-I, which were assessed by western-
blotting and qRT-PCR, respectively. The contractility of single fibroblasts was
assessed by traction force microscopy. Results: We found a larger expression
of activation markers including α-SMA and collagen-I in TAFs compared to
control fibroblasts. Likewise, TGF-β1 elicited a larger contractility in TAFs Conclusion: PSCs are heterogeneous tumours, barely characterized
than in control fibroblasts as assessed by traction force microscopy. Of note, from a molecular point of view. WHO has recently classified PSCGC and
these results were consistent with previous observations reported on skin carcinosarcoma as two distinct entities, and our results demonstrated
fibroblasts from Smad3 knock-out mice. Conclusion: Our findings reveal that that they effectively have different gene expression profiles. Deregulated
lung TAFs are hyperresponsive to TGF-β1, even though their expression of genes mostly belong to pathways crucial for cancer, like p53-, MAPK- and
SMAD3 is epigenetically down-regulated. This aberrant response to TGF-β1 Wnt-signaling, and future investigation should clarify their specific role in
may underlie the expansion and/or maintenance of the tumor-promoting PSCs. Interestingly, we did not find statistically deregulated genes among
desmoplastic stroma in lung cancer. monophasic and biphasic carcinomas of subtype-1, thus indicating their
molecular similarity. Although this is a preliminary and explorative study,
Keywords: SMAD3, DNA methylation, TGF-β, cancer associated fibroblasts needing further validation, it constitutes a starting point to increase our
knowledge of these rare tumours.
Keywords: Pulmonary Sarcomatoid Carcinomas, Whole Transcriptome,

Histopathologic subtypes
P1.02-077 WHOLE-TRANSCRIPTOME GENE EXPRESSION ANALYSIS POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY

OF PULMONARY SARCOMATOID CARCINOMAS MONDAY, DECEMBER 5, 2016
Rossella Bruno1, Greta Alì2, Riccardo Giannini1, Agnese Proietti2, Alfredo
Mussi3, Gabriella Fontanini1
1
Department of Surgical, Medical, Molecular Pathology and Critical Area, University
P1.02-078 EXPRESSION PROFILING OF LKB1 PATHWAY IN YOUNG
of Pisa, Pisa/Italy, 2Unit of Pathological Anatomy, University Hospital of Pisa, Pisa/ AND OLD LUNG ADENOCARCINOMA PATIENTS
Italy, 3Department of Surgical Medical Molecular Pathology and Critical Care, Laura Boldrini1, Mirella Giordano 1, Adele Servadio1, Cristina Niccoli1, Marco
University Hospital of Pisa, Pisa/Italy Lucchi2, Franca Melfi3, Alfredo Mussi2, Gabriella Fontanini1
1
Background: Pulmonary sarcomatoid carcinomas (PSCs) are rare, poorly Department of Surgical, Medical, Molecular Pathology and Critical Area, University
of Pisa, Pisa/Italy, 2Department of Surgical Medical Molecular Pathology and
differentiated non-small cell lung cancers (NSCLCs) containing sarcoma
Critical Care, University Hospital of Pisa, Pisa/Italy, 3Unit of Thoracic Surgery,
or sarcoma-like features, with a worse prognosis than other NSCLCs. University Hospital of Pisa, Pisa/Italy
The World Health Organization (WHO) classifies three histopathologic
Background: The youthful lung cancer may constitute an entity with distinct Laura Tafe 1, Francine De Abreu1, Jason Peterson1, David Finley2, Candice Black1
clinicopathologic characteristics. The serine/threonine kinase LKB1, also 1
Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical
known as Serine/Threonine Kinase 11-STK11, is a known tumor suppressor Center, Lebanon/NH/United States of America, 2Department of Thoracic Surgery,
gene involved in cellular responses such as energy metabolism, cell polarity Dartmouth-Hitchcock Medical Center, Lebanon/NH/United States of America
and cell growth, but the role of LKB1 pathway in lung adenocarcinoma (ADC) is
barely studied, especially in young patients. Methods: Fifty lung ADC patients Background: Atypical adenomatous hyperplasia (AAH) is considered the
were retrospectively analysed. After RNA purification from formalin fixed precursor lesion of adenocarcinoma (ADC), and adenocarcinoma in-situ (AIS)
and paraffin embedded tumor tissues, we analysed the mRNA expression the pre-invasive phase of invasive ADC. Finding incidental synchronous AIS/
levels of LKB1 and of genes involved in its pathway, such as cyclin D1 (CCND1), AAH within lung resection specimens of ADC is an opportunity to evaluate
beta catenin (CCNNB1), lysyl oxidase (LOX), yes-associated protein-1 (YAP-1), and compare the genomic profiles of the lesions. Different mutation profiles
and survivin, with NanoString technology, a new tool for a more accurate would suggest a field effect with the formation of an early second primary.
expression profiling. KRAS mutations were investigated by pyrosequencing Identical mutations might suggest a closer relationship with the primary
analysis. Clinicopathologic characteristics and survival analysis were tumor such as an early intrapulmonary metastasis from spread through
available for all patients. Results: Patients under 50 years old (including 50) air spaces. In this study we evaluate the genomic profiles of synchronous
were defined as the younger group and patients above 50 years old were AIS/AAH lesions and separate primary ADC in the same lobe of resection
defined as the older group. Among all the clinicopathologic characteristics, specimens. Methods: We tested the 13 lesions from six patients identified
in the younger group there were more women, less solid and more acinar between August 2015 and June 2016 by targeted next generation sequencing
adenocarcinoma prevalent pattern in comparison to the older group. Younger (NGS) using the 50 gene AmpliSeq Cancer Hotspot Panel v2 and FISH for ALK
and older groups showed similar survival rates, as well as KRAS mutations rearrangements. All of our patients had a single radiographically evident
frequencies. Also, in the comparison between the gene expression level of the ADC and one patient had a second smaller lesion which was proven ADC at
analyzed genes and the two different age subgroups,no statistical difference resection. All six patients had at least one additional incidental focus of AIS/
was found. We then focused on the LKB1 pathway in all series, independently AAH, not detected radiographically. Our patients ranged in age from 51-67.
from the age stratification, founding LKB1 low expression associated with Five patients were female (83%) and all were current or former smokers.
low cyclin D1 (CCND1) (p<0.0001), beta catenin (CCNNB1) (p<0.0001), and YAP1 Results: All cases were successfully tested and somatic alterations were
(p=0.0024) levels, suggesting a target regulation by LKB1. We next tested found in all ADC and three AAH/AIS lesions. None of the samples had an ALK
the expression level of LOX, one of its downstream target, and we found that rearrangement. Patient 3, with two ADC, had different profiles between all
lung ADC with a high LOX mRNA expression showed a significantly worse three lesions tested. In Patient 6, the ADC had an activating EGFR p.L858R
prognosis, either in terms of disease-free interval or overall post-operative mutation and the synchronous AAH lesion showed a KRAS p.G12D mutation.
survival. Conclusion: Based on our preliminary results young patients seem
to show similar LKB1 pathway expression levels to older group, even if further Results
investigations will be necessary. Moreover, our data suggest LKB1 as a key
AIS/AAH
pathway in lung ADC regardless of age, with a relevant sfavorable role of LOX. Patient ADC site ADC molecular AIS/AAH site
molecular
A robust assessment of LKB1 and of its downstream gene, LOX in particular,
may elucidate the role of this pathway deregulation in lung adenocarcinoma 1 RUL, ADC STK11 p.E342Q RUL, AAH WT
in order to identify potential target for lung cancer therapy.
2 LUL, ADC TP53 p.R158L LUL, AIS WT
Keywords: lung adenocarcinoma, LKB1 pathway, expression analysis KRAS p.G12V
LLL, ADC1
KRAS G12V; TP53 p.H168Q;
3 LLL, LLL, AIS
PIK3CA TP53 p.S94fs
ADC2
p.H1047L
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY 4 LUL, ADC TP53 p.V157F LUL, AIS ATM p.F858L
MONDAY, DECEMBER 5, 2016 KRAS p.G12A;
5 RUL, ADC RUL, AIS WT
FLT3 p.Y599H
P1.02-079 DNA PLOIDY, CPA4 AND REL B EXPRESSION IN 6 LLL, ADC EGFR p.L858R LLL, AAH KRAS p.G12D
NON SMALL CELL LUNG CANCER: CORRELATION WITH
RUL – right upper lobe; LUL/LLL – left upper/lower lobe; WT – wild-type
CLINICOPATHOLOGIC PARAMETER Conclusion: All of the synchronous lesions, including the AAH/AIS lesions,
1 1 2 1
Kyriakos Hainis , Eleftheria Haini , Angelos Tsipis , Maria Gonidi , Pauline showed different genomic profiles supporting the concept of field
Athanassiadou2, Anna Maria Athanassiadou2 cancerization, suggesting that these incidental AAH/AIS foci likely represent
1
Corfu General Hospital, Corfu/Greece, 2University of Athens, Athens/Greece de novo secondary tumors.
Background: The aim of this study was to evaluate the expression of CPA4 Keywords: synchronous tumors, adenocarcinoma in situ, Genomics,
a member of carboxypeptidase family and Rel B a member of nuclear Adenocarcinoma
transcription factor Kappa B family in imprints of resected NSCLC and
correlate these expressions with DNA ploidy and classical prognostic factors.
Methods: A total of 45 smears of patients who underwent surgical treatment
for NSCLC were examined immunocytochemicaly for the expression of CPA4
and Rel B. Imprint smears also were stained using the Feulgen procedure in POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
order to evaluate DNA ploidy in the same cases. Results: Thirty two (71,1%) MONDAY, DECEMBER 5, 2016
of the tumors were classified as aneuploid. CPA4 positive expression was
observed in 18 (40%) and Rel B in 21 (46,7%) of the tumors. We found a
significant relationship between DNA ploidy and grade (p=0,005). CPA4 and P1.02-081 THE RELATIONSHIP OF CDH3 EXPRESSION AND DNA
Rel B expression correlated with grade (p<0,0001 for both) and also with METHYLATION IN THYMIC EPITHERIAL TUMORS
nodal status (p=0,004 and p=0,017, respectively). Cox regression multivariable Koichiro Kajiura1, Kazuya Kondo2, Toru Sawada1, Naoya Kawakita1, Mitsuhiro
analysis demonstrated that CPA4 and Rel B expression were independent Tsuboi3, Hiromitsu Takizawa4, Akira Tangoku5
prognostic factors. The mean DNA index was higher for tumors with negative 1
Department of Thoraci,endocrine Surgery and Oncology, Institute of Biomedical
expression of CPA4 and Rel B (P=0,045 and p=0,025 respectively) Conclusion: Sciences, Tokushima University Graduate School, Tokushima City/Japan,
DNA aneuploidy correlates with poor and moderately differentiated tumors. 2
Department of Oncological Medical Services, Tokushima University, Tokushima/
CPA4 and Rel B positive expression is in relation to well differentiated Japan, 3Department of Thoracic, Endocrine Surgery and Oncology, Institute of
carcinomas and nodal status Biomedical Sciences, Tokushima University Graduate School, Tokushima City/
Japan, 4University Tokushima, Tokushima/Japan, 5Department of Thoracic and
Keywords: NSCLC, DNA ploidy, CPA4, Rel B Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of
Tokushima Graduate School, Tokushima/Japan
Background: The genome wide sequence and microarray has performed

flourishingly for major cancer specimen in recent day. However, thymic
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY epithelial tumor(TET) was rare tumor comparatively, there are few reports
OTHER MUTATIONS IN THORACIC MALIGNANCIES – about epigenetic alternation in TET. Cadherin-3, also known as P-cadherin,
is a protein encoded by the CDH3 gene. This study was aimed at identifying
the relationship DNA methylation and gene expression of CDH3 gene in TET,
P1.02-080 GENOMIC RELATIONSHIP BETWEEN LUNG especially B3 thymoma and thymic cancer. Methods: A)DNA methylation 1)
ADENOCARCINOMA AND SYNCHRONOUS AIS/AAH LESIONS IN THE DNA were extracted fresh frozen samples of B3 thymoma and thymic cancer,
diagnosed as squamous cell carcinoma. These samples collected from the
SAME LOBE

patients, diagnosed as TET, underwent surgery at Tokushima university from POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
1990 to 2016. 2) DNA was treated by bisulfite conversion. 3) DNA methylation MONDAY, DECEMBER 5, 2016
level was measured by infinium methylation assay(Human Methylation 450K
DNA Analysis Kit ; Illumina) exhaustively. 7 cases of thymic cancer and 8 cases
of B3 thymoma applied this assay. 4) The methylation levels of CpG sites were P1.02-083 GENE FUSION PROFILE IN LUNG ADENOCARCINOMA
calculated as β-values (β = Intensity (methylated)/intensity (methylated + PATIENTS IN BRAZIL
unmethylated) by applying default settings of the GenomeStudio Software’s Tatiane Montella1, Giovana Torrezan2, Mariano Zalis2, Marcelo Reis3, Carlos
DNA methylation module (Illumina). Analysis of this methylation assay used Gil Ferreira1
by R package. B) Immunostaining Immunostaining was performed Envision 1
Thoracic Oncology, Neotorax, Rio de Janeiro/Brazil, 2Biologia Molecular,
method. It was used Anti-pan-Cadherin (antibody (ab16505), dilution 1300 Progenética, Rio de Janeiro/Brazil, 3Clinical Oncology, Instituto Dor de Pesquisa, Rio
times as first antibody. DAKO Chemomate EnVsion kit was used as second de Janeiro/Brazil
antibody. Results: CDH3 had 2 CpG islands. 450K methylation assay set 5 CpG
sites on first CpG island as promoter region. (CpG sites:B3 thymoma averageβ- Background: The detection of driver mutations and targeted therapy have
values : thymic cancer averageβ-values : p-value by t-test)=(cg0900242 transformed the landscape of treatment of non-small cell lung cancer
: 0.07±0.08 : 0.45±0.05 : 2.7×10-7), (cg07061260 : 0.21±0.21 : 0.55±0.09 : (NSCLC). In addition to EGFR mutation oncogene fusions such as ALK, RET,
3.3×10-3), (cg00748373 : 0.19±0.20 : 0.45±0.07 : 0.01), (cg06575065 : 0.28±0.18 : ROS and others have been identified as targetable genetic aberrations in
0.50±0.07 : 0.02), (cg27417609 : 0.35±0.21 : 0.59±0.09 : 0.02). Immunostaining NSCLC. Access to personalized therapy could be increased with the help of
specimen were classified by scoring system measured by stain intensity multiplex diagnosis platforms able to detect multiple druggable gene fusions
and stain expanding. It was classified 2points;strong, 1point;weak, simultaneously. In this study, using Next Generation Sequencing (NGS), we
0point;none, in stain intensity. It was classified 3points;diffuse(>80%), describe the prevalence of oncogene fusions in a Brazilian cohort. Methods:
2point;moderate(50-80%), 1point;focal(20-50%), 0point;none(<20%) in stain We included consecutive adenocarcinoma patients referred to a private
stain expanding. Expression rate(stain intensity point and stain expanding reference center in Brazil from November-2015 to June-2016. DNA and RNA
point) defined more than 4point as expression promotion. Expression were extracted from paraffin-embedded tissue from core biopsy or fine
promotion rate is 0% in B3 thymoma and 75% in thymic cancer. Conclusion: needle aspiration specimens. Next generation sequencing was performed for
DNA methylation of CDH3 was increasing and P-cadherin protein expression target regions using the Oncomine® Focus Assay on an Ion PGM platform. This
was increasing in thymic cancer compared to B3 thymoma. panel evaluates 132 hotspot sites of driver mutations in 35 genes, gene copy
number variations in 19 genes and 23 gene fusions. Results: So far 115-lung
Keywords: DNA methylation, thymic epithelial tumor, CDH3 adenocarcinoma have been included. Genetic alterations were detected in 72
% (82 of 115) of all patients. The most common genetic alteration detected in
this study were KRAS (22%) and EGFR mutations (20%). Oncogene fusions
were detected in 13% (15 of 115) of patients. ALK were the most common
fusion (7%) followed by RET (3%) and ROS (3%). Of note a FGFR2 fusion
OTHER MUTATIONS IN THORACIC MALIGNANCIES – detected in a adenocarcinoma patient at odds with previous reports limiting
MONDAY, DECEMBER 5, 2016 this type of fusion to squamous histology. In contrast no other protein
kinase fusions, such as NTRK1, AXL-MBIP and SCAF-PDGFRA were detected
in this initial cohort.d. Conclusion: In a representative Brazilian cohort, the
P1.02-082 THE FEASIBILITY OF CELL-FREE DNA SEQUENCING FOR
percentage of ALK, RET and ROS fusions detected matches data published
MUTATION DETECTION IN NON–SMALL CELL LUNG CANCER WAS elsewhere. An extended cohort will be presented during the meeting and will
DETEMINED BY TUMOR VOLUME allow a better description of rarer fusions.
Tatsuo Ohira1, Kazuko Sakai2, Sachio Maehara1, Junichi Maeda1, Koichi
Yoshida1, Masaru Hagiwara1, Masatoshi Kakihana1, Tetsuya Okano1, Naohiro Keywords: oncogene fusion, RET fusion, ROS fusion, multiplex diagnosis
Kajiwara1, Kazuto Nishio2, Norihiko Ikeda1 plataform
1
Thoracic Surgery, Tokyo Medical University, Tokyo/Japan, 2Department of Genome
Biology, Kinki University Faculty of Medicine, Osakasayama/Japan
Background: Targeted therapeutics such as tyrosine kinase inhibitors of the

epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
(ALK) have recently been introduced into clinical practice for individuals with MONDAY, DECEMBER 5, 2016
NSCLC positive for actionable mutations of EGFR or ALK fusions, respectively.
Molecular profiling that is able to predict the response to such drugs has thus
become an important therapeutic strategy, allowing selection of the most P1.02-084 POLO-LIKE KINASE 1 (PLK1) INHIBITION DECREASES
appropriate treatment for individual patients. Methods: Matched lung cancer MUTATIONAL ACTIVITY IN BRONCHIAL EPITHELIAL CELLS
tissue and serum specimens were collected from 150 patients who underwent EXPOSED TO TOBACCO CARCINOGENS
surgery at Tokyo Medical University Hospital from January 2013 to July Daniel Merrick 1, Elizabeth Donald2, Jessica Malloy3, David Astling4, Wilbur
2014. All tissue samples were stored at –80°C until analysis. Tumor DNA and Franklin5, Dara Aisner6, Kristy Crooks4, Michael Seager3, Jerry Haney4, Robert
cfDNA samples were subjected to analysis with next-generation sequencing Keith7, Lori Dwyer-Nield4, Meredith Tennis8, Kenneth Jones9
(NGS) panels for mutation detection. Results: All tumor DNA samples were 1
Pathology, Mail Stop 8104, University of Colorado, Anschutz Medical Campus,
successfully sequenced with the Ion Proton platform. The median read Aurora/CO/United States of America, 2Pathology, University of Colorado, Denver/
number per amplicon was 15,632. We identified TP53 mutations in 58 cases CO/United States of America, 3Pathology, University of Colorado, Aurora/CO/United
(38.7%); EGFR mutations in 56 (37.3%); KRAS mutations in 15 (10.0%); CTNNB1 States of America, 4University of Colorado, Aurora/CO/United States of America,
5
mutations in 7 (4.7%); ERBB2, PIK3CA, BRAF, and PTEN mutations in 3 each Pathology, University of Colorado Anschutz Medical Campus, Aurora/CO/United
(2.0%); and ERBB4, MET, ALK, FGFR2, NRAS, AKT1, and FBXW7 mutations in States of America, 6University of Colorado School of Medicine, Aurora/CO/United
1 each (0.7%). No mutation was detected in 22.0% (33/150) of the samples. States of America, 7Pulmonary Medicine, Denver Veteran Affairs Medical Center,
Denver/CO/United States of America, 8University of Colorado Denver Anschutz,
Serum cfDNA was extracted for all 150 patients, with a median yield (copy
Aurora/CO/United States of America, 9Pathology, University of Colorado, Denver/
number) of 4936 (range, 572 to 373,658). A total of 149 of the 150 (99.3%) United States of America
cfDNA samples were successfully sequenced with the Ion Proton platform,
with sequencing failure being due to an insufficient read number per amplicon Background: Persistence of bronchial dysplasia (BD) is associated with
in the one unsuccessful case. The median read number per amplicon for the increased risk for the development of squamous cell carcinoma (SCC) of
149 successfully sequenced cfDNA samples was 33,982. Conclusion: These the lung. A comparison of persistent and regressive BD demonstrated that
results suggested that detection of mutations in cfDNA of patients with alterations in gene expression can distinguish these types of lesions. Using
disease at stage IA or IB or at T2a or lower is difficult, and that the feasibility the genes that differentiate persistent and regressive BD we have identified
of mutation detection with cfDNA may depend on the T factor rather than PLK1 as a key mediator of persistence and have hypothesized that the role
the N factor. Tumor volume in the cfDNA mutation–positive group was it plays in abrogating G2-M cell cycle arrest in the presence of mutational
significantly greater than that in the cfDNA mutation–negative group (159.1 ± alterations may be central to progression of premalignant airway lesions to
58.0 versus 52.5 ± 9.9 cm3, p = 0.014). The maximum tumor diameter calculated invasive SCC. Methods: Cultures of the bronchial epithelium derived BEAS-2B
at diagnosis was also larger in the cfDNA mutation–positive group than in the (B2B) cell line were exposed to airway mutagens (cigarette smoke condensate
cfDNA mutation–negative group (5.3 ± 0.7 versus 4.1 ± 0.3 cm, p = 0.050). These [CSC, Kentucky Reference Cigarette 3R4F] or Benzo[A]pyrene, [BaP]) alone
results suggested that tumor volume is a determining factor for the feasibility or in the presence of 100 nM PLK1 inhibitor Volasertib. Following treatment,
of mutation detection with cfDNA. clones were selected by ring isolation and DNA was collected to assess
mutational events as compared to untreated controls using the TruSightOne
Keywords: lung cancer, cell-free DNA sequencing, EGFR, T790M targeted next generation sequencing panel (12 megabase coverage, >4800
genes, Illumina, San Diego, CA). Modal distribution of mutation frequencies
indicated that ring clones were composed of between 1 - 3 distinct clones.
Mutation rates were calculated using these adjusted clone counts for
standardization. Results: Using the untreated B2B cultures as reference Background: Ataxia telangiectasia-mutated (ATM) is a critical first responder
sequence, CSC or BaP alone induced mean incidences of mutations of 15.7 and to DNA damage in the cell, but despite being one of the most mutated
60.9 per clone, respectively, although the induction of fewer mutations by genes in lung cancer, no specific mutation hotspots have been linked with
CSC made accurate estimates of clonal numbers more difficult. B2B cultures disease development. Our own quantitative analysis of ATM protein levels
treated with the same concentration and duration of mutagen in the presence in patient samples suggests that ATM is lost in 20-25% of cases and that
of Volasertib showed mean mutational incidences of 13 and 17 per clone, this loss correlates with poor overall survival and increased response to
respectively. The ratio of mutation rate for the CSC and BaP treated groups adjuvant chemotherapy treatments. We believe that this may be the result
with versus without Volasertib were 0.83 and 0.28, respectively. All mutations of increased genomic instability within the cancer cells caused by a lack of
detected were single nucleotide variants and characteristic patterns of base adequate DNA repair. Given that ATM-deficient cancers may have higher
changes were noted between mutagen groups with C>A and G>T transversions genetic instability, and that ATM is so highly mutated in lung cancer, we
being more prominent in BaP treated cultures. Ongoing analyses using sought to quantify the relationship between ATM mutations and genomic
whole genome sequencing will allow for more accurate enumeration of instability, as measured by total somatic mutations. Methods: Using genomic
clones represented and a richer assessment of mutation rates including and sequencing data available from the Broad Institute Cancer Cell Line
rearrangements and copy number variants in mutagen treated cells in the Encyclopedia (CCLE) and the NIH Cancer Genome Atlas (TCGA), we correlated
presence and absence of PLK1 inhibition. Conclusion: Preliminary analyses of mutations in ATM and other genes involved with the DNA damage response
bronchial epithelial cell cultures treated with mutagens show reduction of with the total number of mutations annotated in ~900 cancer cell lines
BaP induced mutations in the presence of PLK1 inhibition. The results suggest and ~500 lung adenocarcinomas. Results: We show that in cell lines across
PLK1 overexpression in BD may promote genomic instability. all cancer types, and particularly in lung, breast, and esophageal cancers,
mutations in ATM correlate with a significantly higher number of total
Keywords: Genomic instability, bronchial dysplasia, Polo-like kinase 1 mutations. Only mutations in the direct damage response genes appeared to
associate with total mutations, whereas p53 – while more commonly mutated
– did not correlate with higher mutations in cell lines or patients. In lung
cancer patients, ATM mutations were similarly correlated with high somatic
mutations. Conclusion: We have identified a potential relationship between
OTHER MUTATIONS IN THORACIC MALIGNANCIES – ATM mutation and total somatic mutations in cancer cell line and patient
MONDAY, DECEMBER 5, 2016 tumour genomes, which may be indicative of overall genetic instability.
Analysis of the ATM mutations in cell lines and patient samples clearly shows
that there are no specific hotspots for mutation in ATM that correlate with
P1.02-085 MOLECULAR PROFILE IN NSCLC BIOPSY SAMPLES:
increased total mutations. Thus screening for ATM mutations alone may not
A MULTICENTER LOCAL STUDY be sufficient to indicate loss of function or instability. However, this data may
Norma Pilnik 1, Veronica Bengio2, Maximiliano Canigiani3, Maria Ibero3, Pilar prove useful in developing panels of targets to screen as mutation hotspots
Diaz4 of instability, and ultimately to help identify patients that may benefit from
1
Internal Medicine Oncology Department, School of Medicine Cordoba University, targeted or modified therapy options based on ATM-deficiency or higher
Cordoba/Argentina, 2Pathology, Cordoba Hospital, Cordoba/Argentina, 3Medical genetic instability.
Oncology, Transito Hospital, Cordoba/Argentina, 4 Molecular Biology, Cordoba
University, Cordoba/Argentina Keywords: mutation, Genomic instability, ATM
Background: During the last time substantial progress have been made in
the characterization of the molecular abnormalities of NSCLC tumors such as
activations of oncogenes by mutations, translocations and amplifications,
which are being used as molecular targets and predictive biomarkers.
Currently these molecular analysis is mandatory for therapy selection.
Methods: 92 small biopsies and resection specimens of patients with NSCLC Miscellaneous –
(AC) in different institutions of Cordoba were studied during a period (2014 MONDAY, DECEMBER 5, 2016
2016). We determined the frequency of molecular alterations in EGFR and
gene fusion ALK in our Caucasian and Hispanic populations to decide the
adequate treatment . Histopathology Type,immunohistochemistry (IHC) P1.02-087 SENSITIVE DETECTION OF RARE CANCER CELLS BY
characteristics as well as molecular profile and several clinical variables were PREPROGRP-SPECIFIC RT-PCR AND ITS CORRELATION WITH
studied. To detect alterations of EGFR and fusion gene EML4-ALK expression,
CLINICOPATHOLOGICAL DATA AND SURVIVAL
different tests were used with the aim to identify our own profile and
decide the adequate therapeutical option. EGFR mutation was studied by Fatma Abou Elkasem1, Neviene Shafik2, Amal Shafik2, Mohamed Rahoma3,
therascreen kit, PCR, in order to detect genetic alterations in exons 18, 19, 20 Mohamed Arafa4
1
and 21. ALK translocations were analyzed by FISH (Vysis- Break Apart, Abbott) Medical Oncology, National Cancer Insititute, Cairo/Egypt, 2Clinical Pathology,
and IHC (clon D5F3, ventana, Roche). The molecular profiles were correlated National Cancer Insititute, Cairo/Egypt, 3Surgical Oncology, National Cancer
Insititute, Cairo/Egypt, 4 Orthopedic Surgery, Fayoum University, Cairo/Egypt
with different clinical variables (age, gender, and tobacco habits). The
statistical method used was the multiple regression logistic model. Results: Background: Reverse transcription polymerase chain reaction (RT-PCR)
58 men and 34 women out of 92 samples were tested for EGFR expression. based amplification of transcripts expressed in cancer but not in normal
Eight men and ten women expressed EGFR positive. Sixteen men and two non-neoplastic cells is increasingly used for the sensitive detection of rare
women were smokers. Activating kinase-domain mutations in EGFR were disseminated or exfoliated cancer cells to improve cancer staging and early
identified in 21 pts (22,82 %): exon 19 deletion = 11, L858R = 7, exon 20 insertion detection protocols. This study aimed to detection of Prepro–Gastrin-
= 1, other = 2. EGFR alterations were related with gender, women showed Releasing Peptide in peripheral blood in lung cancer patients referred
more alterations of the genes. Age and smoking habit of patients did not to National Cancer Institute, Cairo University, Egypt. And to identify its
show significant association . We used the multiple regression logistic model relationship with clinicopathological features, prognosis and survival.
to correlate EGFR expression to age, gender, tobacco habits. We identified Methods: Our study group consisted of 62 newly diagnosed lung cancer
4 pts (5%) with fusion gene EML4-ALK. ALK alterations were not related to cases and 30 healthy volunteers, RNA was isolated from peripheral blood
gender, age and smoking habit . Conclusion: Our results showed a comparable and then the samples were assayed by nested RT- PCR. Pearson’s chi (X2)
frequency in EGFR mutations and gene fusion ALK in relation to the data test was used to compare categorical variables. Kaplan Meier curves for
published in western population and our data presented in LALCA meeting survival analysis and Median and range for continuous variables were used
2016. These results permit an adequate diagnosis to provide these pts with for statistical analysis. Results: Our study included 62 cases of lung cancer (60
the most benefitial therapy. males, median age was 57(34-81) years. For clinicodemographic data( Fig.1).
Eleven (17%) cases had pleural effusion (stage IV). Seventeen (27%) cases had
Keywords: molecular profile, EGFR, ALK,
extensive SCLC, 7 cases had limited SCLC. Fourty-four (70%) cases received
chemotherapy, 20 (32%) cases received palliative radiotherapy to bone, brain
or mediastinum. Seventeen (27%) had elevated alkaline phosphatase level.
Seven (63%) out of the 11 cases with bone metastasis underwent splintage,
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY internal fixation ± bone cement injection to reinforce a bone defect prior
OTHER MUTATIONS IN THORACIC MALIGNANCIES – to palliative radiotherapy (pRTH). As regard SCLC, 10 (16%) cases received
platinum based chemotherapy. One case developed GIII mucositis and one
case developed jaundice and PS became III and shifted to best supportive
P1.02-086 ATM MUTATIONS IN LUNG CANCER CORRELATE TO treatment. One case received gamma knife to cerebellar metastasis, one case
HIGHER MUTATION RATES received palliative RTH to mediastinum and another pRTH to brain before
chemotherapy. Twenty-six (41.9%) cases were preprogastrin +ve(53.8% SCLC,
Lars Petersen, D. Gwyn Bebb
15.4% Squamous cell ca, 15.4%large cell ca, 11.5% adenocarcinoma and 3.8%
Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary/AB/Canada
undifferentiated carcinoma) . Median PFS=3.9 months (2.87-4.96). Median

PFS among preprogastrin –ve vs. +ve cases was 4 vs. 3 months. There was a Michal Ciborowski1, Kaolina Pietrowska1, Joanna Kisluk2, Paulina Samczuk1,
statistical significant relationship between preprogastrin and SCLC with Miroslaw Kozlowski3, Jacek Niklinski2, Adam Kretowski1
higher number of SCLC among +ve preprogastrin cases (P=0.038). Also, there 1
Clinical Research Centre, Medical University of Bialystok, Bialystok/Poland,
was a statistical significant relationship between preprogastrin and smoking 2
Department of Clinical Molecular Biology, Medical University of Bialystok,
with many smokers among +ve preprogastrin cases (P=0.010). Conclusion: Białystok/Poland, 3Department of Thoracic Surgery, Medical University of
SCLC and smoking are significantly correlated with preprogastrin. Median PFS Bialystok, Bialystok/Poland
was longer in preprogastrin -ve cases. So detection of circulating tumor cells
might be a suitable parameter to identify patients who might benefit from Background: Progress in understanding the pathogenesis of non-small cell
adjuvant therapy. Smoking cessation is mandatory. lung cancer (NSCLC) led to the development of molecularly targeted agents,
including those targeting selected growth factors: vascular endothelial
Keywords: preprogastrin, survival, peripheral blood sample, (VEGF), platelet-derived (PDGF), epidermal (EGF), insulin-like I (IGF-I), and
anaplastic lymphoma kinase (ALK) signaling. Interestingly, clinical trials
of targeted agents and newer chemotherapy agents yielded differences
in outcomes according to histologic subgroups providing a rationale for
histology-based treatment approaches. Consequently, a correct histologic
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/ diagnosis is becoming increasingly important. However, even the most careful
examination of biopsies by expert pulmonary pathologists leave about 10-
SCREENING 30% of NSCLC as not specified. Metabolomics is widely used for biomarkers
Biology – discovery and patients stratification. This novel tool may provide additional
MONDAY, DECEMBER 5, 2016 diagnostic markers, which could support proper NSCLC subtyping. In the
present study plasma samples obtained from patients with the major NSCLC
histologic subtypes and controls were fingerprinted by liquid chromatography
P1.03-001 THE UTILITY OF LIQUID-BIOPSY FOR DETECTING - mass spectrometry (LC-MS) method. Methods: The study was performed
EGFR MUTATION IN CLINICAL PRACTICE: 169 CASES IN A SINGLE on the group of 63 NSCLC patients and 32 controls. Based on the histology
evidence the patients were classified as ADC (n=20), LCC (n=13), and SCC
INSTITUTION RESEARCH STUDY
(n=30). Individuals in all studied groups were matched in age (62±10 years), sex
Kentaro Ito 1, Osamu Hataji2, Yuta Suzuki1, Haruko Saiki1, Tadashi Sakaguchi1, (15-38%F) and BMI (26±3). Metabolites extracted from plasma were analyzed
Kosuke Hayashi1, Yoichi Nishii2, Fumiaki Watanabe1, Tetsu Kobayashi3, by use of LC-QTOF-MS in positive and negative ion modes. Metabolic features
Esteban Gabazza4, Osamu Taguchi3 repetitively measured in QC samples (RSD<20%) and present in at least 90%
1
Respiratory Center, Matsusaka Municipal Hospital, Matsusaka,mie/Japan, of the samples were forwarded to statistical analysis. Depending on data
2
Respirtory Center, Matusaka Municipal Hospital, Matusaka/Japan, 3Respiratory distribution t-test or U-test were used to select metabolites significantly
Division, Mie University Graduate School of Medicine, Tsu,mie/Japan, 4Department
different between controls and NSCLC patients. ANOVA was used to
of Immunology, Mie University Graduate School of Medicine, Tsu,mie/Japan
select metabolites discriminating between NSCLC subtypes. Multivariate
Background: EGFR-TKIs have promising anti-tumor activities for EGFR-mutant analysis was used to show subtype-related patients’ classification. Results:
NSCLC, however, almost all patients invariably experience progression on Identification of plasma metabolites significantly different between controls
EGFR-TKI therapy. The T790M mutation is known as a major mechanism of and NSCLC showed differences in phospholipids (e.g. PC 34:3, +53% in NSCLC,
resistance to EGFR-TKIs, and re-biopsy is essential for detecting the T790M p=0.01; PC 36:4, +50% in NSCLC, p=0.001; Lyso PC 18:3, +37% in NSCLC, p=0.02;
mutation in EGFR-TKI failure patients. We conducted both tissue-biopsy PE 34:2, +36% in NSCLC, p=0.0002) and docosahexaenoic fatty acid (-34%
and liquid-biopsy for all patients who were diagnosed with NSCLC in our in NSCLC, p=0.02). Based on metabolites significant after ANOVA analysis
institution, and we retrospectively evaluated the utility of liquid-biopsy in it was possible to build good quality (R 2=0.652, Q2=0.408) partial least
clinical practice. Methods: We reviewed all patients who were diagnosed with square discriminant analysis (PLS-DA) model separating NSCLC subtypes.
or suspected of having NSCLC and received a liquid-biopsy between April 2015 Among metabolites responsible for this separation sphinganine (p=0.009),
and June 2016 in Matsusaka Municipal Hospital. The aim of this study was to anandamide (p=0.009), malonyl carnitine (p=0.001), and Lyso PE 20:5
evaluate the clinical benefit of liquid-biopsy by comparing of the results of (p=0.02) can be mentioned. Conclusion: Metabolic fingerprinting of plasma
the liquid-biopsies against the results of the tissue-biopsies. The proportions samples allowed for selection a panel of metabolites able to discriminate
were compared using Chi-square statistics, or the Fisher’s exact test where between NSCLC subtypes. Although promising, obtained results require
appropriate. Results: A total of 169 patients who received liquid-biopsy for further validation with target methods and on larger cohort of patients.
the purpose of detecting an EGFR mutation were enrolled in this assessment. Acknowledgements: The study was funded by National Science Centre, Poland
The median patient age was 74 (range 37-95); 104 patients were male, 66 (2014/13/B/NZ5/01256).
patients were never-smokers, 102 patients(58.3%) had been pathologically
Keywords: NSCLC subtypes, plasma metabolic fingerprinting, LC-MS-based
diagnosed with adenocarcinoma; 14 patients(8.3%) were both liquid-positive
metabolomics
and tissue-positive for an EGFR mutation, 32 patients(18.9%) displayed a
discrepancy, having a liquid-negative and a tissue-positive result, although
no patients were liquid-positive and tissue-negative.(sensitivity, 33.3%;
specificity, 100%) There were 20 patients who had an EGFR mutation detected
by liquid-biopsy, and all patients with a liquid-positive result were either POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
clinical stage 3B, 4, or in recurrence. There was a significant difference in the BIOLOGY –
proportion of stage 3B, 4, and recurrent patients between liquid-positive and MONDAY, DECEMBER 5, 2016
liquid-negative patients among EGFR mutated patients. (p<0.0001) Of all
patients, 19 patients with a liquid-positive result, and 4 patients with a tissue- P1.03-003 THE WARBURG EFFECT: PERSISTENCE OF STEM CELL
positive result alone, experienced EGFR-TKI therapy. There was no significant
METABOLISM IN LUNG CANCER AS FAILURE OF DIFFERENTIATION
difference in the response rate to EGFR-TKIs between the liquid-positive and
liquid-negative patients among EGFR mutated patients. (61.1% vs. 66.6%, Robert Downey 1, Markus Riester2, Hua-Jun Wu3, Junting Zheng4, Franziska
p=0.684) Conclusion: This study demonstrated that liquid-biopsy indicates Michor2
1
high specificity, and is available for detecting EGFR mutation in clinical Surgery, Memorial Sloan Kettering Cancer Center, New York/United States of
practice. In addition, our institutional experience indicated that liquid-biopsy America, 2Biostatistics and Computational Biology, Dana-Farber Cancer Institute,
Boston/MA/United States of America, 3Biostatistics and Computational Biology,
could be beneficial especially for patients who are unable to receive a tissue
Dana-Farber Cancer Institute, Boston/United States of America, 4Biostatistics,
biopsy procedure for any reason. Although some patients had a discrepancy Memorial Sloan Kettering Cancer Center, New York/United States of America
between the results of the liquid biopsy and the tissue-biopsy, advanced EGFR
mutated NSCLC was highly detectable by liquid-biopsy. Further investigation Background: Two recent observations are relevant to explaining Warburg’s
is warranted to confirm the clinical benefit of liquid-biopsy. observation the cancers constitutively utilize glycolysis in the presence of
oxygen sufficient for oxidative phosphorylation. First, the metabolism of
Keywords: liquid biopsy, EGFR mutation stem cells has been shown to be constitutive (‘aerobic’) glycolysis, with
differentiation involving a transition to oxidative phosphorylation. Second,
the degree of glucose uptake by a cancer has been associated with histologic
differentiation. We hypothesized that the high levels of glucose uptake
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
observed in poorly differentiated lung cancers may reflect persistence in
BIOLOGY – cancers of the glycolytic metabolism of stem cells that fail to fully
MONDAY, DECEMBER 5, 2016 differentiate. Methods: Tumor glucose uptake was measured by FDG-PET in
859 patients with histologically diverse cancers including NSCLC. We used
normal mixture modeling to explore SUV distributions and tested for
P1.03-002 CAN WE DISCRIMINATE BETWEEN DIFFERENT
association between glucose uptake and histological differentiation, risk of
SUBTYPES OF NON-SMALL CELL CANCER PATIENTS BASED ON
lymph node metastasis, and survival. Using microarray data, we performed
PLASMA METABOLIC FINGERPRINT? pathway and transcription factor analyses to compare tumors with high/low
glucose uptake. Results: Well-differentiated NSCLC had low FDG uptake, and Keywords: Percutaneous lung biopsy, next generation sequencing, lung
moderately/poorly differentiated tumors higher uptake. The distribution of cancer
FDG-PET uptake was modal with a low peak at SUV 2-4 and a high peak at SUV
8-11.
BIOLOGY –
P1.03-005 HIGH RESOLUTION METABOLOMICS IN DISCOVERING

PLASMA BIOMARKERS OF LUNG CANCER PATIENTS WITH EGFR
COMMON MUTATIONS (EXON 19 OR 21)
Sung Yong Lee 1, Kyung Ho Kang2, Aryo D Pamungkas3, Youngja Park 3
1
Division of Respiratory and Critical Care Medicine, Department of Internal
Medicine, College of Medicine, Korea University, Seoul/Korea, Republic of,
2
Department of Internal Medicine, Korea University Medical Center, Seoul/Korea,
Republic of, 3Metabolomics Laboratory, College of Pharmacy, Korea University,
Sejong/Korea, Republic of
Background: The epidermal growth factor receptor (EGFR) is a key target in

the treatment of advanced non-small cell lung cancer (NSCLC). The presence
of EGFR mutations predicts the sensitivity to EGFR tyrosine kinase inhibitors
(TKIs) of NSCLC patients. For this reason, EGFR mutation test is required to
provide personalized treatment options. Currently available DNA sources
are mainly small biopsies and cytological samples, providing limited and low-
quality material. So, there is the need of new biomarker discovery. Recently,
metabolomics, which is the comprehensive study of low molecular weight
The cancers in the two peaks were clinically distinct in terms of the risk metabolites, has also been developed. Integration of transcriptomic and
of nodal metastases and of death. Carbohydrate metabolism-related and metabolomic data has enabled deeper analysis of chemosensitive pathways.
pentose/nucleotide synthesis-related genes were elevated in the high SUV In this regard, this study aims to apply high resolution metabolomics (HRM)
clusters, Krebs cycle/glutamine metabolism-related genes were elevated in to detect significant compounds that might contribute in inducing EGFR
the low SUV mode samples. Expression of Myc target genes was associated mutations. Methods: Plasma samples from 2 healthy volunteers and 15 lung
with SUV mode, but Nanog, Sox2, Oct4 and PRC2 where not. Conclusion: cancer patients were analyzed to detect biomarkers which can predict EGFR
The biological basis for the Warburg effect is persistence of stem cell mutations. The comparison was made between healthy control and lung
metabolism in lung cancers as a failure to transition from glycolysis-utilizing cancer groups for metabolic differences. Ten patients had EGFR mutations
undifferentiated cells to oxidative phosphorylation-utilizing differentiated and five patients had wild type EGFR (n=5) in tumor tissue. The EGFR
cells. Lung cancers cluster along the differentiation pathway into two groups. mutation group was divided into exon 21 deletion group (n=6), and exon 19
Our results have implications for determining prognosis, cancer screening and deletion group (n=4). Differences in metabolic profiles of EGFR mutation
surveillance after resection. lung cancer populations and EGFR wild type lung cancer patients were
examined. Metabolites were separated using Agilent 1200 High Performance
Keywords: Lung cancer, PET, stem cells, Warburg effect
Liquid Chromatography and Agilent 6530 quadrupole time-of-flight LC/MS.
Results: From 216 metabolites, 112 metabolites were found to be significantly
different. Relative concentration of L-valine, linoleate, tetradecanoyl
carnitine, 5-MTHF, and N-succinyl-L-Glutamate-5 semialdehyde showed
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING significant difference (p<0.05). Linoleic acid was elevated in mutation
BIOLOGY – group while tetradecanoyl carnitine was found to be lowered in mutation
MONDAY, DECEMBER 5, 2016 group. These two compounds are related to the alteration of mitochondrial
energy metabolism (carnitine shuttle). Compounds related to amino acid
P1.03-004 PERCUTANEOUS LUNG BIOPSY FOR GENOMIC metabolism, L-valine and N-succinyl-L-Glutamate-5 semi aldehyde were
increased in mutation group. Conclusion: Our results show that HRM with
ASSESSMENT: COMPARISON BETWEEN TWO DIFFERENT NEXT
the combination of pathway analysis from significant metabolites was able
GENERATION SEQUENCING PLATFORMS
to discriminate an EGFR mutation positive patients (exon 19 or exon 21) from
Livia Maria Frota Lima, Sharjeel Sabir wild type advanced NSCLC patients. Therefore, high resolution metabolomics
MD Anderson Cancer Center, Houston/TX/United States of America can be the potential non-invasive tool to utilize clinically to detect the EGFR
mutations in NSCLC patients.
Background: Purpose: Compare the successful use of percutaneous lung
biopsy for two different next generation sequencing (NGS) platforms. Keywords: EGFR mutation, NSCLC, metabolomics, High resolution
Methods: Retrospective review of 232 consecutive lung cancer patients who metabolomics
underwent a histologically diagnostic image guided lung biopsy for NGS
between 4/2013 and 12/2014 with samples sent for NGS. Procedures were
performed using 19 gauge coaxial guide needles, 20 gauge side-cutting core
needles and 22 gauge Chiba FNA needles. If a request for analysis of 2 or more
gene mutations was received, samples were evaluated for NGS. A minimum POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
BIOLOGY –
sample tumor cellularity of 20% on pathology review was required to send MONDAY, DECEMBER 5, 2016
for NGS. Next DNA was extracted from the samples and amount of DNA was
assessed. Sequencing was performed with a 46-gene or 50-gene multiplex
platform (Iron Torrent Personal Genome Machine). Patient demographics, P1.03-006 QUANTIFICATION OF PD-L1 EXPRESSION ON TUMOR
lesion imaging, procedural technique and NGS success were collected. CELLS IN NON-SMALL CELL LUNG CANCER USING NON-ENZYMATIC
Descriptive statistics were tabulated. Two tailed Fisher’s exact test was TISSUE DISSOCIATION AND FLOW CYTOMETRY
calculated to compare success rate of the two NGS platforms. Results: The Amanda Chargin1, Rian Morgan1, Uma Sundram1, Navneet Ratti2, Ryan
average age of the patients was 66 years (34 – 91). 59.05% were female, Rodriguez1, Keith Shults1, Bruce Patterson1
65.52% had history of smoking, 89.22% of the tumors biopsied were primary 1
Incelldx, Menlo Park/CA/United States of America, 2Tissue Diagnostics, Hayward/
lung cancer and 10.78% were lung metastasis from lung cancer. Average lesion CA/United States of America
size was 4.07 cm (0.8 – 15.6). 84.91% of the lesions were spiculated, 78% were
solid and 4.74% had calcification. 20.69% of the patients had pleural effusion, Background: Tumors use many mechanisms to evade the immune system,
65.08% had known metastasis and 20.25% had systemic treatment within often manipulating pathways to evade cell death. The PD-L1/PD-1 pathway in
three months prior to the procedure. Average lesion distance from the pleura particular, has become a promising target for immuno-oncology drug
was 1.87 cm (0 to 8.5 cm). 48.70% of the biopsies had local hemorrhage during development. PD-L1/PD-1 therapy has been shown to be effective in patients
the procedure, 18.10% developed pneumothorax and 5.17% needed a chest with NSCLC, regardless of their PD-L1 expression profile by
tube. 44 biopsies were collected for NGS with 46-gene multiplex platform immunohistochemistry. This creates a challenge in determining potential
(CMS-46) and 188 for 50-gene (CMS-50) assessment. The success rate was responders from non-responders prior to treatment. The objective of this
59.09% for CMS-46 and 80.85% for CMS-50 (p=0.0048). Conclusion: There is a study was to develop a trulyquantitative technology for PD-L1 expression in
significant difference in the successful use of percutaneous lung biopsy with NSCLC. In addition, we also present a non-enzymatic technology that creates
two different NGS platforms. a tumor cell suspension from fresh tumor tissue so that either FNA or fresh
tissue can be used. Methods: 4 mm punches were taken from each tumor.

Non-enzymatic tissue homogenization (IncellPREP; IncellDx, CA) was

Cohort Biomarker Test Sesitivity Specificity PPV
performed. Cells were labeled with antibodies directed against CD45 and
PD-L1, fixed and permeabilized then stained with DAPI to identify intact, EDB1 35.0% 92.6% 14.3%
single cells, and to analyze cell cycle. Results: We compared PD-L1 expression
by flow cytometry using a 1% cut-off for positivity in the tumor cell population Autoantibody
56.4% 79.8% 8.9%
and a 1% cut-off of cells with at least 1+ intensity in immunohistochemically test + EDB1
stained tissue sections as positive (Table 1). As demonstrated in the table, 10 Cleveland Autoantibody
of 12 lung tumor samples were concordant while 2 were discordant, one 37.1% 87.4% 9.4%
clinic test
positive by flow and negative by IHC and one negative by flow and positive by
IHC. PD-L1 expression by flow cytometry varied widely (1.2% to 89.4%) even in EDB1 19.3% 83.7% 12.0%
the positive concordant cases. In addition, PD-L1 expression in the aneuploid
tumor population did not necessarily agree with the expression in the diploid Autoantibody
46.7% 83.7% 9.2%
tumor population. test + EDB1
Conclusion: Running a single biomarker (EDB1) in combination with the

autoantibody test improves the sensitivity for detection of lung cancer by
between 10 and 25% with minimal adverse effect on specificity so maintaining
the PPV of the test.
Keywords: biomarker, autoantibody panel, lung cancer
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/

SCREENING
Pneumonology –
P1.03-008 CLINICAL IMPORTANCE OF INDOLENT LUNG CANCERS

Conclusion: Fine, unequivocal, quantification of PD-L1 on tumor and immune
Gunnar Hillerdal1, Hirsh Koyi2
cells in NSCLC may allow for better prediction of response to therapies. The 1
present study also offers a technology that can create a universal sample type Pulmonary, Gavle Hospital, Gavle/Sweden, 2Dept. of Respiratory Medicine, Gävle
Hospital, Gavle/Sweden
from either FNA or fresh tissue.
Background: The occurrence and importance of “indolent” lung cancers is
Keywords: PD-L1, Immunotherapy, NSCLC, diagnostic
intensely discussed. In the National Lung Cancer Study Trial (NLST) (1) it
was estimated that 18% of all cancers were indolent (2). This was based on
comparison with the controls being “the golden standard”, i.e. assuming
that there were no indolent cancers among those. However, studies in the
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING 20th century with X-ray screening for lung cancers showed the incidence
BIOLOGY – of indolent tumors to be around 25% in such materials. Methods: We have
made some calculations of the NLST material based on the difference in
numbers of lung cancers found at the first screening and the subsequent
P1.03-007 IMPROVEMENT IN PERFORMANCE OF AN yearly ones. Results: Simple estimation: the 5-year “normal” survival of all
AUTOANTIBODY PANEL TEST FOR DETECTION OF LUNG CANCER BY lung cancers is 16%; in the NLST X-ray arm only (the controls) it was 53%. If
25% is due to indolence, 12% (53 minus 16 minus 25) must be due to selection.
ADDITION OF A SINGLE NOVEL BIOMARKER (EDB1)
In the screened arm (low CT), 66% cent were alive, and thus, 38% (66 minus 16
Caroline Chapman1, Jane Mcelveen2, Jared Allen2, Stacy Gilbert2, James Jett3, minus 12) must be due to indolent cancers. A sophisticated calculation: The
Peter Mazzone4, Andrea Murray2 difference in numbers of discovered cancers at first and following screenings
1
Bowel Cancer Screening Programme, Queen’s Medical Centre, Nottingham/ in the screened arm only (thus disregarding the controls) can be used to give
United Kingdom, 2Clinical Sciences Building, Oncimmune Ltd, Nottingham/United an indication of the proportion of indolent cancers. This will also result in a
Kingdom, 3Oncimmune Llc, Kansas/United States of America, 4Department of
percentage of indolent cancers of around 40. Conclusion: Screening for lung
Pulmonary Medicine, Cleveland Clinic, Cleveland/OH/United States of America
cancer with low-dose CT has been proven to save lives. However, this comes
Background: In order to provide optimal cost-benefit, the US national lung with the risk of doing more harm than good to those who actually have an
cancer screening program is restricted to a relatively narrow group of high indolent cancer. Of all confirmed and staged patients in the CT arm of the
risk individuals, with 70% of patients with lung cancer falling outside the NLST, 70 per cent were stage I and II, and almost all of them had surgery. The
CT screening inclusion criteria. Additional tests that can identify those at indolent cancers would be included among these, and if 30% of all cases they
increased risk who do not qualify for CT screening may be useful. A biomarker will amount to two thirds of the operated patients. Hopefully, new studies
assay that measures a panel of autoantibodies and is intended to be used as might make it possible to discriminate between indolent and life-threatening
an aid to early detection of lung cancer is commercially available. It has high tumors. In the meantime, we should choose therapies with as little side
specificity but moderate sensitivity. The aim of this study was to investigate effects as possible, even if these methods do not maximize the possibility of
the performance of an additional biomarker that may increase the sensitivity cure. 1. National Lung Cancer Screening Trial Research Team. Reduced lung
of the autoantibody test in order to improve its clinical utility. Methods: cancer mortality with low-dose computed tomography screening. New Engl
All lung cancer cases were individually matched to controls by age, gender J Med 2011; 365:395-409. 2. Patz EF, Pinsky P, Gatsonis et al. Over-diagnosis
and smoking history. Discovery screening of a panel of 39 potential protein in low-dose computed tomography screening for lung cancer. JAMA Int Med
biomarkers was performed on a multiplex Luminex system using a cohort 2014; 174:269-274.
of 44 lung cancers and 44 controls. Validation studies were performed on
Keywords: survival, Indolence, indolent lung cancers, Screening
334 lung cancers and 326 controls plus 140 samples from patients with
autoimmune disease obtained from Oncimmune biobanks as well as 197
cases and 301 controls obtained from the Cleveland Clinic using a singleplex
microtiter plate ELISA (Biotechne). The autoantibody test was performed
by Oncimmune Ltd. Results: The discovery screen identified one protein POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
biomarker (EDB1) that demonstrated clear cancer/normal differentiation PNEUMONOLOGY –
and high specificity in both control groups (risk matched and inflammatory/ MONDAY, DECEMBER 5, 2016
autoimmune disease). The validation studies provided the performance data
in the table. The specificity of EDB1 in patients with benign autoimmune P1.03-009 VENOUS THROMBOEMBOLISM (VTE) IN LUNG
disease was 97.8%.
CANCER - ASSOCIATIONS AND PROGNOSTIC ROLE: RESULTS OF A
PROSPECTIVE COHORT STUDY FROM NORTH INDIA
Cohort Biomarker Test Sesitivity Specificity PPV
R Lakshmi Narasimhan1, Navneet Singh1, Mandeep Garg2, Jasmina Ahluwalia3,
Oncimmune Autoantibody Digambar Behera1
31.0% 86.2% 7.3%
biobank test 1
Pulmonary Medicine, Postgraduate Institute of Medical Education and Research
(Pgimer), Chandigarh/India, 2Radiodiagnosis & Imaging, Postgraduate Institute

of Medical Education and Research (Pgimer), Chandigarh/India, 3Hematology,
Postgraduate Institute of Medical Education and Research (Pgimer), Chandigarh/
India
Background: Venous thromboembolism (VTE) in cancer remains an under-

evaluated and under-diagnosed entity. This prospective study aimed to
assess VTE incidence, risk factors for its occurrence and its effect on overall
survival (OS) in a cohort of lung cancer (LC) patients at diagnosis and during
first-line chemotherapy. Methods: Over a 1-year period (July 2014-June
2015), 301 patients with histology-proven LC were screened for deep venous
thrombosis (DVT) with compression ultrasonography and for pulmonary
thromboembolism (PTE) with CT pulmonary angiography at diagnosis and
after four cycles of chemotherapy. Patient demographics, comorbidities,
presenting symptoms of VTE events, treatment details and outcomes were
noted. Logistic regression and Cox proportional hazard analyses were done
to determine factors associated with VTE occurrence and OS respectively.
Results: Most patients had advanced disease (51.2% Stage IV; 31.9% stage
IIIB). Overall, 16/301 patients (5.3%) had VTE [DVT alone (n=5), PTE alone
(n=2) and DVT with PTE (n=9)] with incidence rate of 90 per 1000 person-
years. Median duration from LC diagnosis to VTE event was 96.5 days. All
DVT episodes were symptomatic. PTE events were symptomatic in 72.7%
and massive (attributable hypotension) in 36.4% for which thrombolysis
was done. VTE treatment was associated with minor bleeding in 3 patients
but no major bleeding occured. Age, COPD [odds ratio (OR) = 5.2], ECOG PS
≥2 (OR=3.1), and number of extrathoracic metastatic sites (OR=1.9) were
independent risk factors for VTE on multivariate logistic regression analysis.
No association was observed with histology, EGFR mutation status, other
comorbidities or baseline biochemical tests. Chemotherapy regimens, number
of chemotherapy cycles and radiological responses were similar amongst
patients with and without VTE. Median OS was significantly less in VTE
patients [161 (95% CI = 79-243) vs. 311 (95% CI = 270-352) days; p=0.007] with
death attributable to VTE in 50%. On multivariate Cox proportional hazard From the NLCA, there were an estimated 964 lung cancers recorded within the
analysis, VTE [hazard ratio (HR) = 2.1 (95% CI = 1.1-3.8)] was independently London cancer region during the study period. Of these, 310 (32%) lung
associated with poor OS as were smoking [HR = 1.7 (95% CI = 1.1-2.7)], ECOG cancers were recorded in the London Cancer registry as having presented via
PS ≥ 2 [HR = 1.6 (95% CI = 1.1-2.3)] and serum albumin [continuous variable the emergency route. The median age of these patients was 73. The majority
HR = 0.6 (95% CI = 0.4-0.8)]. Conclusion: VTE occurs in approximately 5% of of patients were white and from areas of increased social deprivation. The
newly diagnosed LC patients, is associated with inherently poor prognostic proportion of patients presenting with stage IV disease was 67%, while 58%
factors (COPD, ECOG PS≥2, hypoalbuminemia and extent of metastasis) and had a performance status of 0-2. The most common presenting symptoms
with worse OS independent of other variables. Since all DVT episodes are were respiratory. 95% of patients were treated with palliative rather than
symptomatic, compression ultrasonography remains the preferred mode for curative intent. Conclusion: Approximately one third of new lung cancers
cost-effective initial evaluation of suspected VTE in developing countries. within London Cancer are diagnosed following emergency admission. The
next phase of work includes incorporating results from the London Cancer
Keywords: venous thromboembolism, risk factors, overall survival, Incidence Alliance to provide pan-London data and to develop tools in primary care to
identify these patients prior to emergency admission.
Keywords: emergency presentation, routes to diagnosis, socioeconomic

deprivation
PNEUMONOLOGY –
P1.03-010 CHARACTERISTICS OF LUNG CANCER PATIENTS POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING

PNEUMONOLOGY –
DIAGNOSED FOLLOWING EMERGENCY ADMISSION MONDAY, DECEMBER 5, 2016
Mamta Ruparel1, Ayesha Ejaz2, Neil Chauhan3, Melanie Ridge4, Donna Chung4,
Martin Forster2, Sam Janes1, Thomas Newsom-Davis5, Tanya Ahmad2, Neal
Navani1 P1.03-011 CLINICAL CHARACTERS OF 19 BRONCHIAL ASTHMATIC
1
Lungs for Living Research Centre, UCL Respiratory, University College London, PATIENTS WITH LUNG CANCER
Wce Jf/United Kingdom, 2Cancer Division, University College Hospital London, Nw Jie Zhang, Yue Bai, Peng Gao, Zhen Su, Guang Meng, Qi Wang, Lin Zhang, Yue
Bu/United Kingdom, 3Haematology, Homerton University Hospital, E Sr/United Yao, Chun Li
Kingdom, 4London Cancer, Wt Ha/United Kingdom, 5Chelsea and Westminster NHS
Respiratory Medicine, Second Affiliated Hospital of Jilin University, Changchun/
Foundation Trust, Sw Nh/United Kingdom
China
Background: The proportion of patients with cancers diagnosed via the Background: To investigate the clinical features of lung cancer among
emergency route and their demographic characteristics vary according to asthmatic patients. Methods: Retrospectively analyzed the clinical
tumour type[1]. Patients with lung cancers diagnosed as emergency characteristics of 19 patients with bronchial asthmatic and lung cancer that
presentations suffer worse outcomes[2]. The aim of this observational study were treated by the second hospital of Jilin university from 2009 to 2015.
was to determine the characteristics of a sample of patients with new lung Results: The morbidity of lung cancer in bronchial asthma patients accounted
cancers presenting through the emergency route. Methods: Clinical and for 1.4% of the patients in our hospital. All patients were older than 40 years
demographic patient data were extracted from the London Cancer Registry. old, among which 11 (58%) were over 60. Cough and expectoration were the
Data relating to emergency presentations of lung cancer were collected major clinical symptoms which occurred in 14 cases(74%). According to the
prospectively between January and August 2013 from nine acute trusts across pathological results, 4 cases were squamous cell carcinoma(21%), 7 were
northeast and central London and west Essex. Clinical and demographic small cell carcinoma (37%), 7 wereadenocarcinoma(37%), and only 1 case
characteristics were collated. The total number of emergency presentations were poorly differentiated non-small cell carcinoma (5%). In the small cell
were compared to the total numbers of lung cancers diagnosed within the lung cancers, the primary cancer in 5 cases were still at limited stage, in 2
same region over the corresponding time frame from the National Lung cases had developed into a extensive tumor. In non small cell lung cancers,
Cancer Audit data (NLCA). Results: there were 2 cases at stage II, 2 cases at stage IIIa, 7 cases at stage IIIb and 1
cases at stage IV. From the chest CT performance, the patchy and mass like
nodules were recognized as the main manifestations. In all the 19 patients,
manifestations of asthma were not effectively managed. In 10 of the patients,
the PS score was poor and did not receive any anti tumor treatment,while
other 9 cases received anti tumor therapy. Conclusion: Bronchial asthma,
especially those being not well controlled, is a potential risk factor for lung
cancer., Lung cancer should be awared in the acute episode of asthma. For

asthma exacerbation in patients over 60 years old, the chest CT scan is a used for lung cancer. However, one of the major harms of these imaging tests
recommended choice, or regularly reviewed by low dose CT screening to is the potential for radiation-induced carcinogenesis. Whether radiographic
discover lung cancer at early stage and improve prognosis. But the anti tumor screening, diagnosing, staging, and assessing procedures increase cancer
therapy of severe asthma combined with lung cancer patients is still a difficult incidence and death in patients exposed to radiation of medical sources
problem. is ignored in the context of indefinite answer. We aimed to evaluate the
ability of radiation-free diffusion-weighted magnetic resonance imaging
Keywords: clinical characters, asthma, lung cancer (DW-MRI) to diagnose, assess and detect early response to chemotherapy in
lung cancer patients. Methods: This study was approved by the institutional
review board, and written informed consent was obtained from all subjects.
Ninety patients with lung cancer as confirmed by pathologic examination
(25 women, 65 men; mean age, 57 years) who underwent chemotherapy were
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/ enrolled between November 2014 and October 2015. All patients underwent
SCREENING MRI and computed tomography (CT), as the reference test, at baseline and
Radiology – after the second course of chemotherapy. The apparent diffusion coefficient
(ADC) of each lung carcinoma was calculated from images. Ki-67 scores and
MONDAY, DECEMBER 5, 2016 tumor markers in the serum, carcinoembryonic antigen (CEA), neuron-specific
enolase (NSE) and squamous cell carcinoma antigen (SCC), were determined.
ADC values were compared among different histopathologic types and
P1.03-012 EXPERIENCE WITH BIOSENTRYTM TRACT SEALANT between pretreatment and posttreatment. Receiver operating characteristic
SYSTEM FOR PERCUTANEOUS CT-GUIDED LUNG NODULE BIOPSIES (ROC) analysis was performed to evaluate the diagnostic performance of
IN AN ONCOLOGY POPULATION ADC and its combination with tumor markers. The relationship between the
Patricia De Groot 1, Girish Shroff2, Judy Ahrar2, Garrett Gladish1, Bradley baseline ADC values with Ki-67 scores and final tumor size reduction were
Sabloff 1, Cesar Moran3, Sanjay Gupta2, Joe Chang4, Gregory Gladish1, Jeremy analyzed by using the Pearson correlation coefficient. This study is registered
Erasmus1 with Clinical Trials.gov (NCT02320617). Results: Before treatment, there were
1 significant differences between NSCLC and SCLC (P=0.000), adenocarcinoma
Unit 1478, UT MD Anderson Cancer Center, Houston/TX/United States of America,
2
UT MD Anderson Cancer Center, Houston/TX/United States of America, 3U.T.- and SCLC (P=0.000), and squamous cell carcinoma and SCLC (P=0.002). ADC
M.D. Anderson Cancer Center, Surgical Pathology, Houston/TX/United States of values and Ki-67 score showed negative correlation (r=−0.408, P=0.000). In
America, 4Radiation Oncology, MD Anderson Cancer Center, Houston/United States ROC analysis, area under curve (AUC) of ADC in combination with CEA, SCC and
of America NSE was 0.772, 0.821 and 0.761, respectively. ADC values were significantly
different between pretreatment and posttreatment (P=0.001), and partial
Background: Tract sealants are being used more frequently to reduce response (PR) and stable disease (SD) groups. ADC at baseline was negatively
pneumothoraces and chest tube placement in patients undergoing lung correlated with tumor size reduction (r=−0.434, P=0.017). As well, AUC of ADC
biopsy. Use of a sealant plug can produce visible biopsy tracts on follow- after treatment to discriminate PR and SD groups was 0.804. Conclusion: Our
up imaging and can mimic the appearance of malignant tract seeding. The findings extended the previous findings by that ADC in DW-MRI could: (1)
purpose of our study was to characterize these tracts and determine the discriminate different histopathologic types; (2) evaluate the malignancy; (3)
likelihood of malignant seeding to inform further management including predict and monitor the early response to chemotherapy. Radiation-free DW-
localized radiation therapy and/or surgical planning. Methods: Over a 15 MRI seems to be a promising tool for management of lung cancer.
month period 407 lung biopsies were performed in patients with known or
suspected thoracic and extrathoracic malignancies using a BioSentry Tract Keywords: lung cancer, diffusion-weighted magnetic resonace imaging,
Sealant System; 321 cases had follow up CT studies. 4 chest radiologists diagnosis, chemotherapy
retrospectively analyzed subsequent imaging to determine the incidence,
appearance, temporal relationship and evolution of biopsy tracts. Tracts
that decreased or did not change on follow-up were considered benign. 10
surgically resected cases were retrospectively examined by a pathologist
for malignant tract seeding. Results: 321 cases were analyzed. 237 (74%) had POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
RADIOLOGY –
a visible biopsy tract on CT (95%CI 0.69, 0.78) (primary lung cancer n=90, MONDAY, DECEMBER 5, 2016
metastases n=81, benign nodule n=66). All tracts were identified on 1st follow-
up imaging at 1-3 months post-biopsy. Tracts were typically serpiginous and
smooth or lobulated with a thickness of 2-5 mm. 218/237 (92%) tracts were P1.03-014 VALUE OF PERFORMING FINE NEEDLE ASPIRATION
unchanged over time (mean follow up, 12 months). 15/237 (6.3%) decreased WITH CORE BIOPSY FOR GENOMIC MUTATION ASSESSMENT IN
in thickness. Unchanged or decreasing tracts were considered negative for PERCUTANEOUS LUNG BIOPSIES
malignant seeding. Increase in tract thickness or nodularity occurred in Sharjeel Sabir, Livia Maria Frota Lima
4/237 (1.8%), suspicious for malignant tract seeding. 0/90 (0%) biopsy tracts MD Anderson Cancer Center, Houston/TX/United States of America
in primary lung cancer showed progressive increase. 4/81 (4.9%) tracts in
patients with metastases showed increase (mean, 99 days post-biopsy). 10 Background: Personalized care of lung cancer patients requires determination
resected nodules (5 primary NSCLCs, 5 metastases) had no malignant tract of targetable genetic mutations. This study was performed to investigate the
seeding at histology. Conclusion: An observable biopsy tract on CT is common added value of performing fine needle aspiration (FNA) with core biopsy in
after lung biopsy using the BioSentryTM device. Tracts from biopsy of primary percutaneous lung biopsy to assess clinically relevant genomic mutations in
lung cancers using the BioSentry device had no malignant seeding and they EGFR, KRAS and BRAF. ALK mutation was assessed separately through FISH,
should have no impact on surgical resection or localized radiation therapy. which was not assessed in this study. Methods: Retrospective analysis of all
In the study population, patients who underwent lung biopsy for metastasis CT-guided lung biopsies in lung cancer patients with samples sent for next
had a higher than expected rate of malignant seeding manifested by increased generation sequencing (NGS) with a 50-gene multiplex panel during 2013 and
track thickness over time, requiring further investigation. 2014. Procedures were performed using 19 gauge coaxial guides, 20 gauge side-
cutting core needles and 22 gauge Chiba needles. Samples were processed for
Keywords: Biopsy tract, Lung biopsy, Malignant tract seeding, Biopsy tract histological evaluation. The remaining material was reviewed for adequate
sealant tumor cellularity (>20%) by pathology. If the specimen collected through
core biopsy did not present adequate tumor cellularity, the FNA material was
reviewed and sent for mutation analysis. DNA was extracted and sequenced
with a 50-gene multiplex platform (Ion Torrent Personal Genome Machine).
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING If the samples were not adequate for NGS, single gene sequencing was
RADIOLOGY – performed for the requested genetic mutations. Patient demographic, lesion
MONDAY, DECEMBER 5, 2016 imaging features, procedure technique and molecular results were collected.
Descriptive statistics were tabulated. Results: A total of 188 patient met the
P1.03-013 DIAGNOSIS, ASSESSMENT AND PREDICTION OF EARLY criteria for this study. 184 patients had FNA and core biopsy together and 4
had only FNA. 19 out of 184 (10.32%) core biopsy specimen had <20% tumor
RESPONSE TO CHEMOTHERAPY BY USING DIFFUSION-WEIGHTED
cellularity and had FNA material sent for NGS. The average age was 66 years
MRI IN LUNG CANCER old, 57.44% of the patients were female and 65.42% had history of smoking.
Long-Biao Cui1, Hong Yin1, Jian Zhang 2 29.78% had systemic treatment before the biopsy, 78.72% of the tumor were
1
Department of Radiology, Xijing Hospital, Fourth Military Medical University, solid and the average lesion size was 3.9 cm (range 0.8 to 15.6 cm). The overall
Xi’An/China, 2Department of Pulmonary Medicine, Xijing Hospital, Fourth Military adequacy of core biopsy specimen for assessing requested genetic mutations
Medical University, Xi’An/China was 78.80% (135 out of 184) and the adequacy of combined core biopsy and/
or FNA specimen for assessing requested genetic mutations was 87.76% (152
Background: Radiographic screening, diagnosing, staging, and assessing
out of 188). Conclusion: The addition of FNA to core during percutaneous lung
procedures with ironizing radiation-based tests are currently most widely
biopsies done in lung cancer patients for assessment of actionable genetic
mutations significantly increased the success rate from 78.89% to 87.76%. curves of visual assessment on growth of small pulmonary nodules were
0.975 for observer 1, 0.986 for observer 2, 0.989 for observer 3, and 0.913 for
Keywords: Percutaneous lung biopsy, fine needle aspiration, next generation observer 4, respectively. Sensitivities were 96.0% (120/125), 98.4% (123/125),
sequencing, Genomic mutation 98.4% (123/125), and 88.0% (110/125), respectively. Specificities were 99.2%
(124/125), 99.2% (123/125), 98.4% (124/125), and 96.8% (121/125), respectively.
Conclusion: Visual assessment showed high diagnostic performance for
determining growth of non-measurable target pulmonary nodules with 20%
increase in diameter.
RADIOLOGY –
MONDAY, DECEMBER 5, 2016 Keywords: pulmonary nodule, visual assessment, CT
P1.03-015 ASSESSMENT OF RESPONSE OF FDG-PET USING TOTAL

LESION GLYCOLYSIS (TLG) IN NSCLC PATIENTS TREATED WITH
NIVOLUMAB: RESULTS OF A PILOT STUDY POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
RADIOLOGY –
1 1 1 1
Giulia Fichera , Marco Aiello , Laura Noto , Nunzio Restuccia , Massimo MONDAY, DECEMBER 5, 2016
Ippolito2, Hector Soto Parra1
1
Medical Oncology, A.O.U. Policlinico Vittorio Emanuele, Catania/Italy, 2 Azienda
P1.03-017 DOES PET/CT SUVMAX VALUE CORRELATE WITH LONG-
Ospedaliera Cannizzaro, Catania/Italy
TERM SURVIVAL IN PATIENTS WITH SURGICALLY TREATED STAGE I
Background: Recent studies using FDG-PET measure the total volumes NON-SMALL CELL LUNG CANCER
of the FDG-avid lesions to represent whole-body total metabolic tumor Huseyin Melek1, Hasan Kara2, Adalet Demir3, Gamze Cetinkaya1, Akif Turna2,
volume (MTV) demonstrating prognostic significance in NSCLC. Total lesion Ahmet Sami Bayram1, Mehmet Erol1, Alper Toker3, Kamil Kaynak2, Cengiz
glycolysis (TLG) is the product of mean SUV and MTV and studies have Gebitekin1
shown the usefulness of TLG for evaluating treatment response. We decide 1
Thoracic Surgery, Uludag University, Bursa/Turkey, 2Department of Thoracic
to preliminarily explore the role of TLG, which combines the volumetric and Surgery, Istanbul University Cerrahpasa Medical School, Istanbul/Turkey, 3Thoracic
metabolic information of the FDG-PET, as an early predictor of response to Surgery, Istanbul University, Istanbul/Turkey
nivolumab in NSCLC patients and to determine whether in these patients
TLG could provide a better evaluation of response when compared to RECIST. Background: Positron emission tomography (PET/CT), which detects the
Methods: Between September 2015 and April 2016, we enrolled 15 previously biologic activity of tumor cells is routinely used in staging of non-small cell
treated advanced NSCLC patients to receive nivolumab 3 mg/kg q2w. The lung cancer (NSCLC). However, the role of PET/CT in predicting disease free
CT-scan and FDG-PET evaluation were performed before starting therapy long-term survival of surgically treated stage I NSCLC is not clear. In this study,
and after 8 weeks (early evaluation). We compared responses assessed by we aimed to investigate prognostic value of metabolic uptake (SUVmax) of
CT-scan and FDG-PET at 8 weeks according to RECIST 1.1 and TLG parameter the tumor in patients with surgically treated stage I NSCLC Methods: Two-
respectively. We also performed a CT-scan at 12 weeks to confirm or refute hundred and sixty patients who had preoperative PET/CT and pulmonary
the results of the assessement at 8 weeks. Results: There are no standard resection for stage I NSCLC between 2005 and 2015 were included into study.
cut-offs for the TLG parameter. A ROC curve was used to obtain thresholds The patients were devided into four groups according to the SUVmax value,
for the TLG criteria. The ROC study suggested a TLG value between -76% and 0-5, group 1, 5-10 group 2, 10-15 group 3 and over 15 group 4. Lung resection,
+76% to define an SD. We considered a TLG value above +76% to define a PD, segmentectomy/lobectomy, was performed within 30 days of PET/CT in
while a TLG inferior to -76% was necessary to define a PR. In one patient the all patients. Tumor SUVmax and other potential prognostic variables were
evaluation at 8 weeks according to TLG criteria showed PD. The same patient chosen for analysis in this study. Patients univariate and multivariate
presented SD according to RECIST assessed by CT-scan at 8 weeks. For this analyses were conducted to identify prognostic factors associated with
patient CT-scan at 12 weeks confirmed PD. In this case the TLG of the FDG-PET long-term survival. Results: There were 53 females and 207 males with a
early identified the patient’s progression better than CT-scan. In other two mean age of 61,5 (range 20-84). The mean SUVmax value of the tumors in
patients, TLG criteria assessed at 8 weeks identified a PR in contrast with PET/CT was 10,1 (1-48). The type of the lung resection was segmentectomy
SD according to RECIST assessed by CT-scan at 8 weeks. CT-scan at 12 weeks in 33(12,7%) and lobectomy in 227(87,3%). Pathologic staging of the tumor
confirmed PRs for both these patients. Even in this two cases the evaluation was stage 1A in 156(60%), and stage 1B in 104(40%). Median follow-up time
of TLG by FDG-PET early recognized patient’s responses better than CT-scan. was 44 months, and overall 5-year survival rate was 81,7% and there was
For the remaining 12 patients no differences in terms of responses were no statistically significant difference between the groups (p=0,3). SUVmax
observed between RECIST and TLG criteria at 8 weeks when compared to value of the tumor was not effected by age, gender, tumor type and location
RECIST assessed by CT-scan at 12 weeks. Conclusion: These preliminary (peripheral or central)(p>0,05). However, it was found that the SUVmax value
results from this small study suggest that TLG criteria could provide an early significantly increased along with tumor size (p<0,05. ). Logistic regression
identification of response to nivolumab in NSCLC patients. analysis revealed that, there is an association between perineural invasion
and SUVmax value of the tumor (p=0.049). Conclusion: Although the previous
Keywords: FDG-PET, RECIST, Nivolumab, total lesion glycolysis studies revealed correlation between higher SUVmax values and impaired
long term survival, this study revealed no correlation between SUVmax values
and long term survival in patients with surgically treated stage I NSCLC.
However, tumors with higher SUVmax values have higher chance of perineural
invasion. Further studies for possible relationship between metabolic activity
RADIOLOGY – and histopathologic characteristics of the tumors are warranted.
Keywords: lung carcinoma, PET CT, Prognosis
P1.03-016 DIAGNOSTIC ACCURACY OF VISUAL ASSESSMENT ON

GROWTH OF NON-MEASURABLE TARGET PULMONARY NODULES
ACCORDING TO RECIST CRITERIA
Jeong Min Ko 1, Hyun Jin Park1, Kyongmin Beck2, Dae Hee Han2, Hoon-Kyo Kim1 RADIOLOGY –
1
College of Medicine, St. Vincent’S Hospital, the Catholic University of Korea, MONDAY, DECEMBER 5, 2016
Suwon-Si/Korea, Republic of, 2College of Medicine, Seoul St. Mary’s Hospital, the
Catholic University of Korea, Seoul/Korea, Republic of
P1.03-018 FDG-PET/CT IN PATIENTS WITH EGFR-MUTATED NSCLC
Background: Two-dimensional CT measurement considered unreliable in the TREATED WITH TKI. CAN WE IDENTIFY EARLY LESIONS AT HIGHER
evaluation of small pulmonary nodule less than 2 cm, and a nodule less than 1 RISK OF PROGRESSION?
cm in diameter considered non-measurable according to RECIST criteria. The Gegory Petyt1, Dimitri Bellevre1, Amaury Adens1, Hélèné Lahousse1, Guillaume
aim of this study was to determine the accuracy of visual assessment on the Collet1, Claude Hossein-Foucher 1, Simon Baldacci2, Xavier Dhalluin2, Marie-
growth of immeasurable small pulmonary nodules less than 1 cm in diameter Capucine Willemin2, Anne Baranzelli2, Arnaud Scherpereel2, Alexis Cortot 2
on CT. Methods: We selected 125 CT images (1-mm slice thickness axial images, 1
Nuclear Medicine Department, Lille University Hospital, Lille/France, 2Thoracic
lung window setting, lung algorithm) which have a small pulmonary nodule Oncology, Lille University Hospital, Lille/France
less than 1cm. Then, we magnified the pulmonary nodules to 120% in diameter
using the Photoshop. We coupled these images to 125 sets of ingrowth and Background: EGFR TKIs in EGFR-mutated NSCLC patients yield heterogeneous
growth groups, respectively. Four radiologists with varying experience read progression-free survivals ranging from <3 months to >3 years. Early
these sets to five-point scale using visual assessment (definitely ingrowth, identification of lesions that are more likely to progress may provide rationale
probably ingrowth, possibly growth, probably growth, and definitely for aggressive treatment of these lesions. We questioned whether FDG-PET/
growth). Results: The areas under the receiver-operator characteristic CT could identify early lesions with higher risk of progression. Methods:

Eighty-nine lesions from 13 caucasian EGFR-mutated NSCLC patients treated cancer viability and that FDG accumulation is the result of altered tumor
with TKI were analyzed. Date of progression for each lesion was collected. glycolysis. The objective of this investigation is to use metabolic flux analysis
SUVmax, Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) were to determine if the SUVmax is predictive of tumor metabolism. Methods: In this
measured on baseline and early follow-up PET/CT performed 2-3 months prospective human subjects-approved clinical trial, 22 untreated potentially-
later. Variations between the 2 PET/CT (ΔSUVmax, ΔMTV, ΔTLG) were resectable patients with confirmed NSCLC underwent FDG-PET computed
calculated. Medians were used as cut-off values for statistical analysis. Risk tomography and dynamic contrast enhanced (DCE) magnetic resonance
of progression was analyzed according to PET/CT parameters and Odds Ratios imaging. On the day of surgery, the patients received an intravenous bolus
(OR) were calculated. Results: The best metabolic predictors of progression and then continuous infusion of 13C-glucose for 3 hours prior to resection.
were high SUVmax (>0, i.e. incomplete visual response, OR =9.6, p<0.001), high Blood samples were routinely taken and after the lung cancer was removed,
MTV (>0, OR=8.3, p<0.001) and high TLG (>0, OR=9.6, p<0.001) on the early biopsies from tumor (T) and normal lung (NL). Blood and tissue metabolite
follow-up PET/CT. ΔSUVmax<97.6% (OR=3.9, p=0.02) was also associated mass spectrometry analysis was performed and compared with clinical
with early progression, whereas ΔMTV (p=0.23) and ΔTLG (p=0.17) were not. parameters including SUVmax, DCE tissue perfusion, oncogenotype, tumor
Conclusion: Lesions with incomplete visual response on early follow-up FDG- volume (TV), stage, and grade. Results: There were 7 males, 8 never-smokers,
PET/CT upon EGFR TKIs in EGFR-mutated NSCLC show significantly higher risk mean age 67 (43-84), mean TV 18.7 cm3 (1.3-171.9), and mean SUVm 11.8
of progression. Aggressive treatment of these lesions with residual metabolic (0.7-32.0; 3 were < 2.5). The most relevant metabolite and clinical data can be
activity may be further evaluated. found in Spearman Correlation Analysis in Figure 1. T relative to NL revealed
increased glycolysis and glucose oxidation. SUVmax did not correlate with any
Keywords: TKI, FDG-TEP/CT, EGFR glucose-dependent metabolites. TV correlated with metabolic markers
related to fuel choice, larger tumors trending to use an alternative nutrient,
including lactate.

RADIOLOGY –
P1.03-019 IMAGING OF ANTI-PD1 THERAPY RESPONSE IN

ADVANCED NON-SMALL LUNG CANCER
Sharyn Katz 1, Mark Hammer 1, Stephen Bagley2, Charu Aggarwal2, Joshua
Bauml3, Corey Langer4
1
Radiology, Hospital of the University of Pennsylvania, Philadelphia/PA/
United States of America, 2Hematology/Oncology, University of Pennsylvania,
Philadelphia/PA/United States of America, 3 Abramson Cancer Center at
the University of Pennsylvania, Philadelphia/PA/United States of America,
4
Hematology/Oncology, University of Pennsylvania Health System, Philadelphia/
PA/United States of America
Background: Therapy with immune checkpoint inhibitors can lead to

unconventional tumor responses and autoimmune-mediated adverse effects
resulting from immune activation. Here we sought to determine pseudo-
progression and radiologically-evident anti-PD1 therapy mediated adverse
events in routine clinical management in the advanced non-small cell lung
cancer (NSCLC) population. Methods: A retrospective study was conducted
of all adult NSCLC patients treated with anti-PD1 agents at our institution.
Electronic medical records were reviewed to determine clinical assessment
of anti-PD1 therapy response and imaging reports at restaging. Patients that
did not have available follow-up imaging or clinical data while on anti-PD1-
therapy were excluded from the study. Patient imaging exams with clinically
suspected tumor pseudo-progression at 1st re-staging were analyzed to
determine if subsequent imaging demonstrated pseudo-progression or
true progression. The incidence of radiographically-evident adverse events
Conclusion: Although all FDG-PET-positive tumors metabolized glucose, the
attributed to anti-PD1 therapy by the oncologist were noted. Results: A total
SUVmax did not predict the overall extent or any specific pathway of glucose
of 228 patients were started on anti-PD1 therapy at our institution, of which a
metabolism. TV predicts a propensity to consume alternative fuels, such as
total of 166 were evaluable. Of the evaluable patients, 80% of those received
lactate, in addition to glucose.
nivolumab and the remaining 20% received pembrolizumab. The overall
response rate (complete response + partial response) was 23% at 1st restaging. Keywords: Response to Treatment, Tumor Metabolism, Staging, PET scan
Of these patients, 22 patients were suspected of pseudo-progression due
to tumor enlargement and/or development of new lesions during the 1st
4-6 weeks of therapy and were maintained on anti-PD1 therapy. Of these
patients, there were 5 confirmed cases of pseudo-progression at subsequent
restaging. Radiologically-evident adverse events occurred in less than 5% of POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
the population, primarily manifesting as pneumonitis. Conclusion: Pseudo- RADIOLOGY –
progression and radiographically-evident adverse events are important
but uncommon occurrences in the setting of anti-PD1 therapy for advanced
NSCLC. P1.03-021 INITIAL RESULTS FROM A NOVEL AND LOW COST
METHOD FOR MEASURING CT IMAGE QUALITY
Keywords: anti-PD1, Immunotherapy, response, non-small cell lung cancer
Ricardo Avila1, David Yankelevitz2, Rowena Yip2, Claudia Henschke2
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING 1
RADIOLOGY – Accumetra, Llc, Clifton Park/NY/United States of America, 2Radiology, ICAHN
MONDAY, DECEMBER 5, 2016 School of Medicine, New York City/NY/United States of America
Background: Accurate measurement of change in tumor size in Computed

P1.03-020 FDG-PET SUVMAX DOES NOT CORRELATE WITH Tomography images is critical for lung nodule differential diagnosis. Standard
GLUCOSE METABOLISM IN NON-SMALL CELL LUNG CANCER CT scanner calibration phantoms and methods are routinely relied upon to
Kemp Kernstine 1, Brandon Faubert2, Christopher Hensley2, Ling Cai3, ensure that image quality is generally sufficient for a wide range of imaging
Jose Torrealba2, Dwight Oliver2, Robert Lenkinski2, Craig Malloy2, Ralph tasks. However, high precision medical imaging applications, such as RECIST
Deberardinis2 and volumetric tumor change measurement, require much greater attention
1
Cardiovascular and Thoracic Surgery, University of Texas Southwestern, Dallas/TX/ to maintaining consistently high image quality characteristics. A new ultra-
United States of America, 2University of Texas Southwestern, Dallas/United States low cost, and cloud based method has been developed to quickly assess
of America, 3University of Texas Southwestern, Dallas/TX/United States of America the image quality of CT scanners and imaging protocols that provides both
estimates of clinical task performance, such as lung tumor size measurement
Background: In non-small cell lung cancer (NSCLC), 18fluoro-2-deoxyglucose error rates, and fundamental image quality performance metrics. In addition,
positron emission tomography (FDG-PET) assists in diagnosing, staging, and multiple large imaging organizations have made available lung cancer
evaluating treatment response. One parameter of the FDG-PET, the maximum screening guidance documents indicating that CT slice thicknesses of <=
standard uptake value (SUVmax), has been used as an objective measure of 1.25 mm are either required or preferred. Methods: To demonstrate the
image quality site measurement capability a global challenge was launched Background: There has been a great advancement in understanding natural
during May and June of 2016 that allowed lung cancer screening sites to scan history of ground-glass opacity (GGO), which represents histological
three rolls of 3M ¾ x 1000 inch Scotch Magic ™ Tape placed at increasing lepidic growth in early stage pulmonary adenocarcinoma. Among them,
distances from iso-center on the CT table and using their standard low dose some GGO lesions reveal increased density of GGOs without obvious
lung cancer screening protocol. Fully automated software detected the rolls consolidation on thin-section computed tomography (TSCT), i.e., GGO with
of tape and estimated fundamental image quality parameters including CT semi-consolidation. However, little is known regarding clinicopathological
linearity, 3D resolution, noise, and level of edge enhancement. In addition, and radiological relationship of this new entity. Methods: During 2004 and
metrics indicating the expected detection and volume change measurement 2016, we underwent AAA (2327) surgical resections for clinical-stage IA
performance for different diameter lung nodules were calculated. Results: A lung cadenocarcinoma. Among them, 286 (12.3%) GGO lesions without any
total of 27 clinical sites participated in the challenge and provided CT imaging consolidations were identified based on the findings on TSCT. They were
data on over 54 CT scanners representing 18 scanner models made by Siemens, categorized into two groups; pure-GGO (PG) and GGO with semi-consolidation
GE, Philips, and Toshiba. 17 out of 27 (63%) clinical sites provided data with (SC) according to the radiological findings. Semi-consolidation is defined as
<= 1.25mm DICOM specified slice thickness. However, only 19% of sites used GGO with increased homogenous density without consolidation on TSCT.
<= 1.25mm slice thickness and a reconstruction kernel that avoided excessive Clinicopathological factors were analyzed between these two groups.
smoothing and avoided high levels of edge enhancement. Conclusion: A new Survivals were calculated by Kaplan-Meier estimation methods. Results: Of
rapid, ultra-low cost, and cloud based method for assessing the quality of CT the cases, 172 (60.1%) showed PG and 114 (39.8%) showed SC. Significant or
imaging studies has revealed poor adherence to recommended protocols and marginal differences were clinically observed between PG and SG groups
large levels of variation in fundamental image quality properties. Utilization regarding age (59.4y vs. 63.0y, p=0.02), pack-year smoking status (10.2 vs. 11.6,
of these new tools has the potential to help correct image quality issues in p=0.084), tumor size (12.2cm vs. 13.9cm, p=0.06), respectively. Noninvasive
clinical studies. lesions including atypical adenomatous hyperplasia, adenocarcinoma in
situ or minimally invasive adenocarcinoma were observed in 144 patients
Keywords: volumetrics, calibration, RECIST, Image Quality (83.7%) of PG and 74 (64.9%) of SC, however, the frequency of invasive
adenocarcinoma or lymph-vascular invasions were significantly higher in SC
group compared to PG group (15.7% vs 33.9%, p=0.001: 4.3% vs 0.5%, p=0.040)
despite their GGO appearances. There was no lymph node metastasis in
both PG and SC groups. Overall lung-cancer specific survival is 100% to date
RADIOLOGY – in both PG/SC groups with mean follow-up period of 97months. Conclusion:
MONDAY, DECEMBER 5, 2016 Despite the conventionally same category as a native GGO appearance on
TSCT, invasive adenocarcinoma was frequently observed in radiologically
dense GGO lesions, indicating that PG might progress to SC over time. Surgical
P1.03-022 POSSIBILITY OF FDG-PET PREDICTING THE
outcome for both groups are excellent. Therefore, more studies regarding
CLINICOPATHOLOGICAL CHARACTERISTICS AND PROGNOSIS OF optimal surgical procedures and long-term outcome of these two groups
LUNG ADENOCARCINOMA: MULTICENTER STUDY should be warranted.
Kumi Matsuura1, Ken Taro Imai1, Naohiro Kajiwara1, Tatsuo Ohira1, Norihiko
Ikeda1, Haruhiko Nakayama2, Hiroyuki Ito2, Morihito Okada3, Yoshihiro Keywords: Adenocarcinoma, ground grass opacity, lung cancer imaging
Miyata3
1
General Thoracic Surgery, Tokyo Medical University, Tokyo/Japan, 2Department
of Thoracic Oncology, Kanagawa Cancer Center, Yokohama/Japan, 3Department of
Thoracic Surgery, Hiroshima University Hospital, Hiroshima/Japan
RADIOLOGY –
Background: This multicenter study aimed to investigate the relationship of MONDAY, DECEMBER 5, 2016
standardized uptake value (SUV) on [18F]-fluoro-2-deoxy-d-glucose positron
emission tomography (FDG-PET) and the clinicopathological characteristics
of lung adenocarcinomas, and if it can be a predictor of prognosis of those P1.03-024 ACCURACY OF COMBINED SEMANTIC AND
patients. Methods: A total of 870 patients of adenocarcinoma patients COMPUTATIONAL CT FEATURES IN PREDICTING NON-SMALL CELL
received FDG-PET preoperatively and underwent curative resection with LUNG CANCER SUBTYPE
systematic lymph node dissection. The relationship among histological Usman Bashir 1, Andrea Bille 2, Levon Toufektzian2, Emma Mclean2,
characteristics, pathological staging, prognosis, and SUV on FDG-PETmax was Muhammad Siddique1, Vicky Goh2, Gary Cook2
retrospectively examined. Results: The pathological stages of the cases were 1
King’s College London, London/United Kingdom, 2Guys’ & St. Thomas’ Hospitals,
IA 526, IB 182, IIA 62, IIB 27, IIIA 67, IIIB 1, and IV 5, respectively. Pathological London/United Kingdom
N1 (n = 60) and N2 (n = 58) cases showed a significantly higher SUVmax than
N0 (n = 752) (9.15 ± 7.13 and 8.58 ± 6.14 vs 3.23 ± 4.16). Cases with pathological Background: With improvements in molecular treatment, it is increasingly
tumor invasiveness such as lymphatic, vascular or pleural infiltration showed important to differentiate non-small cell lung cancer (NSCLC) subtypes, i.e.,
a significantly higher SUVmax than cases with no invasiveness. (Ly negative; adenocarcinoma(ADCA) from squamous cell cancer(SCCA). Many patients
n=687, 2.76±3.59 vs Ly positive; n=183, 7.67±6.23, and v0; n=641, 2.18±2.58 vs cannot undergo invasive biopsy procedures and so non-invasive classification
v1 or 2; n=229, 8.30±6.23. p<0.001, respectively) The areas under the receiver methods would be helpful in their management. Most studies using CT scans
operating characteristic curve for SUVmax used to predict the relapse-free for this purpose have used either semantic (visual assessment of CT images by
survival was 2.9 (p < 0.001) in adenocarcinoma. The 3-year relapse-free survival a radiologist) or computational texture features, yielding modest accuracy.
was 97%/66% (SUVmax lower/ higher than 2.9) in adenocarcinoma. SUVmax We hypothesized that combined semantic and computational assessment of
was parallel to the aggressive nature based on histological subtypes (AIS CT scans would improve the accuracy of CT in NSCLC classification. Methods:
+MIA; n=76, 0.51±0.58, Lepidic + Papillary + Acinar; n=686, 3.52±4.12, and 67 patients (38 ADC, 29 SCCA) underwent contrast-enhanced chest CT for lung
Solid + Micropapillary; n=84, 8.52±6.67), which was statistically significant. cancer staging. Tumor volumes of interests (VOI) were drawn semi-
(p<0.001 respectively) Conclusion: SUVmax of the primary tumor reflected automatically. 10 qualitative semantic and 361 computational texture
the biological malignancy of lung adenocarcinomas. SUVmax is also useful for features were derived from the VOIs. Univariate and multivariate logistic
predicting pathological stage and prognosis. Multimodality treatment might regression models(MLRM) were developed for combinations of semantic and
be recommended in cases of high UVmax. texture features. Sensitivity, specificity, and area under the receiver
operating characteristic (AUROC) curve were computed. 10-fold cross-
Keywords: Adenocarcinoma, FDG-PET validation was used to prevent overfitting. Results: Univariate models found
two semantic (air-bronchogram, shape) and five texture parameters
(wavelet-transform based: GLCM_Correlation, GLRL_LGRE, GLRL_LGRE,
GLRL_LGRE, and original VOI-based GLSZM_ZSN[1]) to be most predictive of
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING tumor class (p-value <0.01). Sensitivity, specificity, and AUROC for MLRM
RADIOLOGY – utilizing semantic features alone was 64.2%, 73.3%, and 0.76, and that of
MONDAY, DECEMBER 5, 2016 MLRM for texture features alone was 74.6%, 72.3%, and 0.79, respectively.
For combined model involving semantic and texture features (i.e., air-
P1.03-023 GROUND-GLASS OPACITY (GGO) WITH SEMI- bronchogram and GLCM_Correlation), respective values were 81.2%, 90%, and
0.9. [1] GLCM: gray-level cooccurence matrix, GLRL_LGRE: gray-level
CONSOLIDATION: CLINICOPATHOLOGICAL AND RADIOLOGICAL
run-length matrix-derived low gray run emphasis, GLSZM_ZSN: Gray-level
CORRELATIONS COMPARED TO PURE-GGOS OF THE LUNG size-zone matrix-derived zone-size nonuniformity
Jun Suzuki1, Aritoshi Hattori2, Takeshi Matsunaga1, Kazuya Takamochi1, Shiaki
Oh1, Kenji Suzuki1
1
General Thoracic Surgery, Juntendo University School of Medicine, Tokyo/Japan,
2
Juntendo University School of Medicine, Tokyo/Japan


RADIOLOGY –
P1.03-026 MEASUREMENT OF PULMONARY ARTERY ON CT TO

PREDICT ACUTE EXACERBATION OF INTERSTITIAL PNEUMONIA
AFTER PULMONARY RESECTION FOR LUNG CANCER
Akiko Ui, Masashi Kobayashi, Yu Kawada, Yasuyuki Kurihara, Yusuke Sugita,
Sachiko Kumazawa, Chihiro Takasaki, Hironori Ishibashi, Kenichi Okubo
Thoracic Surgery, Tokyo Medical and Dental University, Bunkyo-Ku/Japan
Background: Interstitial pneumonia (IP) is often accompanied by pulmonary

hypertension (PH) that is considered to be fatal and has relation to acute
exacerbation. To diagnose PH, right heart catheterization is generally
required, but it is invasive. Nowadays pulmonary artery diameter (dPA)
and the ratio of dPA to ascending aorta diameter (rPA) measured by CT are
reported to be indicators of PH. We examined whether dPA and rPA could
be predictors of acute exacerbation of IP after pulmonary resection for lung
cancer. Methods: We retrospectively analyzes 97 patients with IP who had
undergone pulmonary resection for lung cancer at Tokyo Medical and Dental
University between July 2010 and December 2015. We examined sex, surgical
Figure 1. ROC curves comparing performance of multivariate models procedures, KL-6, surfactant protein D, post-operative prolonged airleakage,
comprising semantic (blue line), texture (red line), and combined (semantic combined pulmonary fibrosis and emphysema (CPFE), percent diffusing
and texture - green line) predictors. Conclusion: Combined semantic and capacity of lung for carbon monoxide (%DLCO), dPA and rPA. Results: The
computational texture assessment of lung cancer CT images is highly accurate mean age was 71 years (range, 43-86 years), and 79 patients were males and
in differentiation of SCCA and ADCA. 18 were females. 47 patients was diagnosed with CPFE before surgery. Acute
exacerbation occurred in 8 patients. Univariate analysis revealed that CPFE,
Keywords: non-small cell lung cancer, CT, Texture analysis, Diagnostic accuracy
%DLCO and rPA were predictors of acute exacerbation after surgery. In
multivariate analysis, CPFE and rPA were identified as independent predictors
of acute exacerbation after surgery (p=0.046 and 0.036, respectively).
Conclusion: In interstitial pneumonia, rPA measured by CT is effective to
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING predict acute exacerbation after pulmonary resection for lung cancer.
RADIOLOGY –
MONDAY, DECEMBER 5, 2016 Keywords: Interstitial pneumonia, pulmonary hypertension, pulmonary
artery diameter
P1.03-025 SERUM KL-6 LEVELS IN PATIENTS WITH LUNG CANCER
Tatsuya Yoshimasu, Mitsumasa Kawago, Yoshimitsu Hirai, Shoji Oura, Yozo
Kokawa, Miwako Miyasaka, Mariko Honda, Yuka Aoishi, Aya Oku, Yoshiharu
Nishimura POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
RADIOLOGY –
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, MONDAY, DECEMBER 5, 2016
Wakayama/Japan
Background: Serum levels of KL-6 are widely used as an indicator of activity P1.03-027 CLINICAL AND HISTOLOGICAL FEATURES ASSOCIATED
of interstitial lung disease. Although KL-6 was initially developed as a serum
WITH SUV IN FDG-PET-CT IN PATIENTS WITH ADENOCARCINOMA
marker for malignancies, it is still unknown if KL-6 can be used as a biological
OF THE LUNG
marker of lung cancer. This study aimed to determine the properties of
serum KL-6 levels in patients with lung cancer. Methods: First, serum KL-6 Amanda Tufman1, Fiona Siokou2, Ullrich Mueller-Lisse3, Frank Berger3,
elimination kinetics after resection of lung cancer was investigated in 7 Kathrin Kahnert1, Thomas Pfluger3, Simone Reu4, Julia Stump1, Hauke
patients. Postoperative time course of serum KL-6 levels was analyzed using Winter5, Rudolf Huber 1
1
non-linear least square analysis with the fitting equation; C(t)=C0exp(-kt)+Cp, Respirology and Thoracic Oncology, Comprehensive Pneumology Center, Member
where k is the rate constant of elimination. The biological half-life was of the German Center for Lung Research Dzl, Ludwig Maximilian University
calculated as loge2/k. Next, serum KL-6, CEA, and CYFRA levels of patients of Munich, Munich/Germany, 2Respirology and Thoracic Oncology, Ludwig-
Maximilians University, Munich/Germany, 3Radiology, Ludwig-Maximilians
with lung cancer and benign chest disease were retrospectively reviewed.
University, Munich/Germany, 4Institute of Pathology, Ludwig-Maximilians
A total of 226 patients with lung cancer and 103 patients with benign chest University, Munich/Germany, 5Department of Thoracic Surgery, Comprehensive
disease were included in this study. Serum KL-6 levels were measured using Pneumology Center, Member of the German Center for Lung Research Dzl, Ludwig
the electrochemiluminescence immunoassay method. The cut-off level of Maximilian University of Munich, Munich/Germany
KL-6 was 500 U/ ml. Results: Rate constant of elimination and biological
half-life of KL-6 in initial 7 patients were 0.827±0.275 day-1 and 0.93±0.35 day, Background: FDG-PET-CT is increasingly used for staging and treatment
respectively. These data implies that lung cancer cells produce KL-6 molecule monitoring in NSCLC. The prognostic and possibly predictive value of the
and release it into the serum. Among 329 patients, serum KL-6 levels were standardized-uptake-value (SUV), and the clinical, molecular and pathological
above the cut-off level in 44 patients (19.5%) with lung cancer and 4 patients features contributing to SUV levels have not been well described. Methods:
(3.9%) with benign chest disease. The mean serum KL-6 level in patients with We retrospectively reviewed the records of patients staged with FDG-PET-
lung cancer was significantly (p=0.0027) higher (375 ± 232 U/ ml) than that CT and correlated SUV values before and during treatment with clinical and
in patients with benign chest disease (296 ± 177 U/ml). Serum KL-6 levels pathological features of the tumour including CRP as a marker of systemic
in patients with lung cancer were significantly correlated with tumor size inflammation, adenocarcinoma subtype (solid, lepidic etc.), and Ki67, as a
(p<0.0001), stage (p<0.0001), and individual TNM descriptors (T; p<0.0001, N; marker of tumour proliferation. Results: 190 patients with adenocarcinoma
p=0.0047, M; p=0.0003). ROC analysis revealed that AUC of KL-6 was 0.6348 of the lung were identified. 110 had FDG-PET-CT staging and were included in
(p=0.0015), and that was inferior to CEA (AUC=0.8127, p<0.0001) and CYFRA this analysis. Tumour subtypes were as follows: 50.0% solid, 16.4% acinar, 9.1%
(AUC=0.7103, p<0.0001). The sensitivity, specificity, true positive rate, true papillary, 7.3% lepidic, 1.8% micropapillary, 15.4% other. 70 patients received
negative rate, and accuracy of KL-6 were 19.5%, 95.0%, 91.7%, 35.2%, and systemic treatment and 40 were treated surgically. The mean primary-tumour-
43.5%, respectively. Conclusion: Serum KL-6 levels are well correlated with the SUV for all patients was 11.1 (for patients treated medically, 13.5, and for
progressiveness of lung cancer. KL-6 might be useful as a biological marker to those treated surgically, 8.6). Ki67 expression in the tumour was lowest in the
monitor the recurrence and the effect of therapy in lung cancer. group with SUV < 10 (38.6%) and highest in the group with SUV > 20 (56.0). The
group with SUV 11-19 had a moderate Ki67 expression (47.9%). In patients with
Keywords: tumor marker, KL-6 surgical tumour samples there was a trend towards higher SUV in patients
with tumours showing 30% or more solid growth pattern (mean SUV 11.4)
and lower SUV in patients with any lepidic growth (mean SUV 4.0) (p=0.002).
Systemic markers of inflammation were significantly higher in patients
whose tumours had SUV>10 (mean CRP, 2.3 mg/dl; mean leukocytes, 9.7 G/L)
than in patients with low-SUV tumours (<5) (mean CRP, 0.4 mg/dl, p=0.0186;
mean leukocytes, 7.2 G/L, p=0.014). Conclusion: Multiple factors appear to
be associated with higher or lower SUV values, including adenocarcinoma
subtype, proliferation index of the tumour and systemic inflammation. These
factors should be taken into account when interpreting FDG-PET-CT SUV to June 2016, 666 patients with a clear pathological diagnosis of SPN by
values in clinical practice. The correlation of FDG-PET-CT SUV values with surgical resection in Fujian Provicial Cancer Hospital were involved. Their
inflamed tumour phenotypes, and the possible predictive value of SUV for clinicopathologic data were collected and retrospectively analyzed. All
response to immune therapies, should be further investigated. patients were divided into testing and validating cohorts, testing cohort
consisted of patients from January 2011 to June 2015, whose data were used
Keywords: PET-CT, Adenocarcinoma, proliferation, inflammation to create a mathematical model via multivariate logistic regression analysis.
Patients from July 2015 to June 2016 were included in validating cohort,
whose data were used to verify the accuracy of the prediction model. The
positive rate of malignancy between cases discussed at MDT meeting and
evaluated by surgeon were compared. Results: The number of testing and
RADIOLOGY – validating cohorts was 446 and 220, respectively. In testing cohort, there
MONDAY, DECEMBER 5, 2016 were 8 case (1.8%) diagnosed as atypical adenohyperplasia (AAH) and 313
cases (70.2%) as malignant SPNs, mainly invasive adenocarcinoma (IA, 234
cases/ 52.5%), small cell lung cancer (SCLC, 28 cases/6.3%), minimally invasive
P1.03-028 WOLF IN SHEEP’S CLOTHING - PRIMARY LUNG CANCER
adenocarcinoma (MIA, 22 cases/4.9%) and adenocarcinoma in situ(AIS,10
MIMICKING BENIGN DISEASES cases/2.2%). Other were benign SPNs (125 cases, 28%), mainly including
Annemie Snoeckx 1, Damien Desbuquoit1, Amélie Dendooven2, Maarten inflammation or fibrosis(95 cases, 21.3%), hamartoma (17 cases, 3.8%) and
Spinhoven1, Birgitta Hiddinga3, Laurens Carp4, Paul Van Schil5, Paul Parizel1, inflammatory pseudotumor (11 cases, 2.4%).Univariate analysis showed
Jan Van Meerbeeck1 that there were significant differences between benign and malignant SPNs
1
Department of Radiology, Antwerp University Hospital and University of Antwerp, regarding age, sex, nodule type, maximum nodule diameter, CT value, nodule
Edegem/Belgium, 2Department of Pathology, Antwerp University Hospital and shape, spiculation, lobulation, pleural retraction sign, cavitation, bronchiole
University of Antwerp, Edegem/Belgium, 3Department of Thoracic Oncology, truncation and vascular convergence (P<0.05). Sex, age, nodule type,
Antwerp University Hospital and University of Antwerp, Edegem/Belgium, spiculation, vascular convergence, bronchiole truncation and nodule shape
4
Department of Nuclear Medicine, Antwerp University Hospital and University
were identified as independent predictors of malignancy in multivariate
of Antwerp, Edegem/Belgium, 5Department of Thoracic and Vascular Surgery,
Antwerp University Hospital and University of Antwerp, Edegem/Belgium logistic regression analysis.The area under curve (AUC) was 0.883 (95% CI,
0.885-0.915) in the model. An appropriate cut-off point was determined
Background: Lung cancer is the biggest cancer killer and typically presents as P=0.77, sensitivity and specificity of the model was 77.6% and 80.0%,
as mass or nodule, round or oval in shape. Recognition and diagnosis of these respectively. The positive rate of malignancy was 81.3%(104/128) in cases
typical cases is often straightforward, whereas diagnosis of uncommon discussed at MDT meeting, comparing with 72.0% in all patients(P<0.05).
manifestations of primary lung cancer certainly is far more challenging. The The positive rate of malignancy reach to 90.4% in 97 patients with model
aim of this pictorial essay is to illustrate the Computed Tomography (CT) and predicting positive and discussed by MDT. The validation data set is on-going.
histopathology findings of uncommon manifestations of primary lung cancer Conclusion: The prediction model established in this study could be useful
with focus on these entities that mimic benign diseases. Methods: Cases in assessing the likelihood of lung cancer in SPNs. And MDT consultation can
presented were collected during the Multidisciplinary Thoracic Oncology improve the accuracy of prediction.
Tumor Board between January 2014 and May 2016 and have histopathologic
proof. Results: Lung cancer can mimic a variety of benign diseases, Keywords: solitary pulmonary nodules, diagnosis, Multi-disciplinary team,
including infection, granulomatous disease, lung abscess, postinfectious logistic model
scarring, mediastinal mass, emphysema, atelectasis and pleural disease.
Previous history, clinical and biochemical parameters are certainly helpful
and necessary in the assessment of these cases, but often aspecific and
inconclusive. Whereas 18FDG-PET is the cornerstone in diagnosis and POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
staging of lung cancer, it’s role in these uncommon manifestations is less RADIOLOGY –
straightforward since benign diseases, such as granulomatous and infectious MONDAY, DECEMBER 5, 2016
diseases may also present with increased FDG-uptake. Chest CT is the
imaging modality of choice and plays a central role in these cases. ‘Irregular
P1.03-030 FDG-PET/CT MIGHT BE A PREDICTOR FOR RESIDUAL
air bronchogram sign’ in pneumonia-like lung cancer, ‘drowned lung sign’ in
DISEASE IN ADVANCED NSCLC AFTER CHEMORADIOTHERAPY
obstructive atelectasis and cortical bone erosion in lung cancer mimicking
pleural disease are important signs that point to a malignant etiology. The Toru Sawada1, Kazuya Kondo2, Mitsuhiro Tsuboi1, Naoya Kawakita1, Koichiro
stippled and eccentric morphology of calcifications in apical lesions aids Kajiura1, Hiroaki Toba1, Yukikiyo Kawakami1, Mitsuteru Yoshida1, Hiromitsu
in differentiating these lesions from postinfectious scarring. Mucinous Takizawa3, Akira Tangoku1
1
tumours can mimic a pulmonary abscess and small cell lung cancer can Department of Thoraci,endocrine Surgery and Oncology, Institute of Biomedical
typically present as mediastinal mass without parenchymal abnormalities. Sciences, Tokushima University Graduate School, Tokushima City/Japan,
2
Lung cancer presenting with a miliary pattern or cavitating nodules can Department of Oncological Medical Services, Tokushima University, Tokushima/
Japan, 3Department of Thoracic, Endocrine Surgery and Oncology, Institute of
mimic granulomatous disease. Lung cancer presenting with cystic airspaces
Biomedical Sciences, Tokushima University Graduate School, Tokushima City/Japan
and ‘emphysema-like’ morphology is an uncommon entity in which early
recognition is crucial since these tumors have an aggressive nature. Key Background: The standard treatment for locally advanced non-small-
imaging findings and tips and tricks for recognizing these uncommon faces cell lung cancer (NSCLC) is chemoradiotherapy (CRT), some patients are
of primary lung cancer will be discussed and illustrated. Conclusion: Primary considered for trimodality therapy represented by concurrent CRT followed
lung cancer can mimic a wide variety of benign entities. Knowledge of these by surgical resection. However, there is no validated clinical predictor for
uncommon and atypical manifestations is crucial to avoid delay in diagnosis surgical resection after CRT. In the present study, we analyzed that the
and treatment. A multidisciplinary approach in these cases is mandatory. correlation between SUVmax of FDG-PET/CT in pre/post CRT and treatment
effect. Methods: 22 patients with advanced NSCLC underwent CRT in
Keywords: lung cancer, computed tomography, Mimickers, nonnenplastic
Tokushima University Hospital between February 2006 to March 2016. we
pulmonary disease
reviewed the medical records of 22 patients to obtain information on age,
gender, histological type, clinical stage, adverse events, reduction ratio of
tumor, SUVmax of FDG-PET/CT in pre/post CRT. Radiographic response was
assessed by Modified Response Evaluation Criteria in Solid Tumors (RECIST)
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING criteria. Toxicities were assessed according to the National Cancer Institute
RADIOLOGY – Common Toxicity Criteria (NCI-CTCAE). Results: Patient characteristics
were as follows: average age of 65; male/female: 21/1, histologic type
adenocarcinoma/squamous cell carcinoma/other: 14/5/3; clinical stage IB/
P1.03-029 A USEFUL ALGORITHMATIC MODEL IN PREDICTING IIB/IIIA: 1/3/18. Chemotherapy were platinum doublets regimen in almost
THE LIKELIHOOD OF LUNG CANCER IN SOLITARY PULMONARY cases. The average amounts of radiotherapy were 42Gy. The response rate
was 29%. The number of PR/SD were 10/22 in RECIST. The adverse events
NODULES
were following: G2;11(50%), G3;8(36%), G4;5(23%). 2cases stopped treatment
Lin Gen, Zhuang Wu, Rao Ying, Zhu Shou, Zheng Feng, Chen Hui, Li Cheng, because of adverse events. Operative procedure were followings: lobectomy/
Chen Ping, Xu Wei, Wu Biao, Xu Wu, Huang Jian, Zhang Jin, Huang Cheng bilobectomy/pneumonectomy: 17/2/3. The complication rate of operation was
Fujian Provicial Cancer Hospital, the Affiliated Hospital of Fujian Medical 27.2%, however, there was no hospital death. Overall survival was 69.7±10.3
University, Fuzhou/China months. Relapse free survival was 64.5±12.3 months. Pathological Complete
Response(pCR) was recognized in 10cases(45.5%). The 4cases in 10cases
Background: The aim of this study was to establish a mathematic model to
of pCR got recurrence as distant metastasis, without local recurrence. The
predict the likelihood of lung cancer in surgically resected solitary pulmonary
SUVmax decreasing rate was 69.8% in CRT. The SUVmax decreasing rate was
nodules (SPNs) and investigate the value of multidisciplinary treatment
79% in the patients of pCR(n=5), however, this decreasing rate was 65% in not
(MDT) consultation in diagnosis of SPNs. Methods: From January 2011

pCR(n=7, p=0.059). All cases of pCR indicated the SUVmax decreasing rate was establish more effective treatment for controlling brain metastasis. Methods:
more than 70%. Conclusion: The pCR were recognized in 10/22(45/5%) cases, Methods: We established in vivo imaging brain tumor models by intracranial
underwent CRT. The treatment response in localregion was good in all cases. inoculation of human cancer cell lines, such as lung adenocarcinoma H1975
The SUVmax decreasing rate was more than 70% in all pCR cases. cells with EGFR-L858R and T790M mutations, HGF-dependent gastric
cancer NUGC4 cells, and TPM3-NTRK1-fusion gene positive colorectal cancer
Keywords: Chemoradiotherapy, SUVmax KM12SM cells, in SCID mice. We investigated the activity of several molecular
targeted drugs on cell proliferation of these cell lines in vitro. In addition,
we evaluated the efficacy of these drugs on brain tumor models, comparing
with extracranial tumor models. Results: Results: In vitro conditions, H1975
cells were sensitive to the 3rd generation EGFR inhibitor, osimertinib. HGF
RADIOLOGY – stimulated proliferation of gastric cancer NUGC4 cells, and the HGF-induced
MONDAY, DECEMBER 5, 2016 proliferation was inhibited by crizotinib, which has anti-MET activity, in a
dose-dependent manner. KM12SM cells, which are the highly liver metastatic
variant derived from TPM3-NTRK1 fusion gene positive colon cancer KM12C
P1.03-031 GYNECOLOGICAL MALIGNANCIES AND IMAGING
cells. KM12SM were sensitive to TRK-A inhibitors, crizotinib and entrectinib.
PATTERNS. AN INTERESTING CASE REPORT AND LITERATURE In H1975-cell in vivo models, osimertinib (25mg/kg) inhibited the progression
SURVEILLANCE of both brain tumors and subcutaneous tumors. In NUGC4-cell in vivo models,
Nektarios Alevizopoulos 1, Vasiliki Ntalapera1, Areti Dimitriadou1, Anna crizotinib (50mg/kg) delayed the progression of brain tumors as well as
Skoula2, Theodoros Vagdatlis2, Kiriaki Pissaki1, Nickie Loukas1, Michael peritoneal carcinomatosis, and prolonged the survival of the tumor bearing
Vaslamatzis1 mice. In KM12SM-cell in vivo models, we evaluated the effect of crizotinib
1
Oncology, Evaggelismos General Hospital, Athens/Greece, 2Imaging, Evaggelismos (50mg/kg) or entrectinib (15mg/kg) in the brain tumor model and liver
General Hospital, Athens/Greece metastasis model. Crizotinib treatment slightly delayed the progression
of brain tumors but failed to prolong the survival of the recipient mice.
Background: Gynecologic malignancies are a heterogeneous group of common Entrectinib treatment more discernibly delayed the progression of brain
neoplasms in women. Thoracic abnormal findings exhibit various imaging tumors and did prolong the survival. These results indicate that the effect
patterns and are usually associated with locally invasive primary neoplasms of targeted drugs against brain tumors can be different from that against
with intra-abdominal spread. It is not rare, thoracic involvement occurring extracranial tumors. Conclusion: Conclusion: Our in vivo imaging brain tumor
years post first diagnosis or as an isolated finding in patients without models may be useful for preclinical drug screening against brain metastasis.
evidence of intra-abdominal neoplastic involvement. Thoracic metastases
from gynecologic carcinomas typically manifest as pulmonary nodules and Keywords: in vivo imaging models, Brain metastasis, drug screening
lymphadenopathy. Ovarian cancer often presents small pleural effusions
and subtle pleural nodules whereas metastatic lung lesions, lymph nodes,
and pleura are thought to present calcification or mimicking granulomatous
disease. Metastases from fallopian tube carcinomas have imaging features
identical to ovarian cancers. Most cervical cancers are of squamous histology, POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/
and while solid pulmonary metastases are more common, the cavitary
SCREENING
metastatic lesions occur more often. Metastatic choriocarcinoma to lung
characteristically exhibits solid pulmonary nodules. There are also reported Screening –
pulmonary metastases from gynecologic malignancies with characteristic MONDAY, DECEMBER 5, 2016
features such as cavitation (as awaited in squamous cell cervical cancer)
and the “halo” sign (in hemorrhagic metastatic choriocarcinoma lesions)
at computed tomography. Methods: We report a case with a mass in left P1.03-033 ANALYSIS OF T0 LUNG-RADS SCORES IN UI HEALTH’S
paratracheal area invading the lung hinting primary lung cancer. Results: MINORITY-BASED LUNG CANCER SCREENING PROGRAM AND
The patient ,female ,36 years old with previous medical history of resected COMPARISON TO THE NLST
cervical cancer, underwent endoscopy with aim to have trasnsbronchial
Mary Pasquinelli, Kevin Kovitz, Juan Alban, Li Liu, Arkadiusz Dudek, Robert
aspiration but unfortunately the samples taken were consistent of
Winn, Karriem Watson, Martha Menchaca, Matthew Koshy, Arden Plumb,
inflammation infiltration. Thus she underwent thoracotomy due to high SUV
Lawrence Feldman
(12) uptake points at PET CT with intention to exclude lung cancer. She had the
mass removed with all the surrounding lung parenchyma but unfortunately The University of Illinois Hospital and Health Sciences System, Ui Cancer Center,
Chicago/IL/United States of America
the final histologic report documented metastatic infiltration from cervical
cancer in competence with her previous medical history 6 years ago(Ib stage Background: Lung Cancer (LC) is the leading cause of cancer death in the
with radiotherapy only treated in adjuvant basis).She recovered well and was U.S. The incidence and mortality rate differs depending on smoking status,
initiated chemotherapy for the gynecological malignancy stated She is now race, ethnicity, gender, and socioeconomic status (SES). African Americans
2 years later alive, with no residual disease The basic is that malignancies are (AA) have significantly higher incidence/mortality rates of LC. The National
always suspected to be primary originated but the medical previous history Lung Screening Trial (NLST) which showed a 20% reduction in LC mortality
should not be ignored ,even the imaging tests tend to resemble to other with low-dose CT (LDCT) screening only included 4.5% AA’s. LDCT screening
entities Conclusion: Therefore, radiologists should consider the presence of amongst high risk minority individuals has not been sufficiently investigated.
locoregional disease in combination with elevated tumor marker levels when The goals of this study are: (1) to compare UI Health’s Screened Population
interpreting imaging studies and all previous medical history of the patient’s (UIHSP) to the NLST and determine if NLST results are generalizable to an
malignancy to exclude metastatic disease. urban minority population; (2) to determine trends in UIHSP Lung-RADS based
on age, gender, race/ethnicity, smoking-history, and comorbidities. Methods:
Keywords: mass, gynecologic, imaging characteristics, cervical cancer
Patients were referred to LDCT based on U.S. Preventative Services Task
Force guidelines. Summary statistics, such as means, standard deviations,
and ranges for continuous variables, and frequencies for categorical variables
are provided. Spearman correlation coefficients are estimated between
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING continuous variables (i.e., age, smoking pack-years) and Lung-RADS scores
RADIOLOGY – are estimated. Chi-squared tests and Fisher’s Exact tests were performed to
test the associations between categorical variables and Lung-RADS scores.
All statistical tests are two-sided, controlling for a Type I error probability
P1.03-032 IN VIVO IMAGING MODELS FOR PRECLINICAL of 0.05. Results: Compared to the NLST, UIHSP has a higher percentage of
SCREENING OF MOLECULAR TARGETED DRUGS AGAINST BRAIN AA’s (65% vs. 4.5%), rate of Lung-RADS 3 and 4, (30% vs 13.7%). UIHSP had a
METASTASIS LC rate 3x that of NLST on T0 scan (3% vs 1%). A diagnosis of emphysema on
LDCT scans was significantly associated with higher Lung-RADS scores (p =
Akihiro Nishiyama1, Kenji Kita2, Shoko Arai1, Shinji Takeuchi3, Tadaaki 0.0415). Patients who were diagnosed with emphysema detected on LDCT
Yamada4, Seiji Yano3 report had significantly higher Lung-RADS scores. 5 LC diagnoses in the first
1
Division of Medical Oncology Cancer Research Institute, Kanazawa University, 163 T0-scans (3%), 4 of 5 were AAs. Males were more likely to have Lung-RADS
Kanazawa/Japan, 2Kanazawa University, Kanazawa/Japan, 3Cancer Research
3 and 4 than females (OR=2.1, p=0.0353). Smoking-pack years demonstrated
Institute, Division of Medical Oncology, Kanazawa University, Kanazawa/Japan,
4 a positive correlation with higher Lung-RADS score (p=0.067). Conclusion:
Cancer Research Institution, Kanazawa University, Kanazawa/Japan
UIHSP compared to NLST demonstrated higher incidence of Lung-RADS 3 and
Background: Background: Molecular targeted drugs are generally effective 4 scores and diagnosis of LC at T0 LDCT scans. In addition this study has found
on tumors with driver oncogene, including EGFR, ALK, and NTRK1. However, a significant association between emphysema and higher Lung-RADS scores
patients with these oncogenes frequently experience progression of brain among UIHSP. These results support the conclusion from previous studies that
metastasis during the targeted drug treatment. Thus, it is essential to emphysema on LDCT is an independent risk factor for LC. Furthermore, the
results show a statistically significant correlation between gender and Lung- comparison, we estimated the standardized mortality rate ratio (SMR) using
RADS scores. These statistical associations make the case for the modification FVG regional standard rates. Results: There was a significant 59.3% (95%CI:
of USPSTF guidelines to fit the risk-profile of minority populations like UIHSP. 3.9-82.8) reduction in adjusted mortality for LC among ATOM002 participants
vs. nonparticipants. LC crude mortality was 99.4 per 100,000 person-year
Keywords: lung cancer, LDCT, Screening, Early Detection in participants (8 LC deaths) compared to 430.4 per 100,000 person-year in
nonparticipants (50 LC deaths). Mortality was also reduced for all causes
(HR=0.61; 95%CI 0.44-0.84), but not for all cancers (HR=0.97; 95%CI 0.62-1.50)
or malignant pleural mesothelioma (HR=0.86; 95%CI 0.31-2.41). Compared with
regional mortality rates, a trend towards reduced mortality for LC was found
SCREENING – among ATOM002 participants (SMR =0.55; 95%CI 0.24-1.09), in contrast to a
MONDAY, DECEMBER 5, 2016 statistically significant increase in the nonparticipants (SMR = 2.07; 95%CI
1.53-2.73). Conclusion: In our cohort, participation in the LDCT based screening
study was associated with reduced mortality for LC compared to empiric CXR
P1.03-034 IMPLEMENTING SMARTPHONE APPLICATION IN EARLY
based public health surveillance. To our knowledge, this is the first report
LUNG CANCER DETECTION AND SCREENING suggesting reduction in mortality for LC with LDCT screening in an asbestos
Zalan Szanto, Gabor Szalai, Laszlo Jakab, Andras Vereczkei exposed population. LDCT screening might therefore be a reasonable approach
Thoracic Surgical Department, University of Pécs, Pécs/Hungary for surveillance in these populations.
Background: The early detection of NSCLC cases is still the key point of the Keywords: asbestos, Screening, lung cancer, low-dose computed tomography
surgical treatment of lung cancer. Finding the symptomless patients require
the system of risk assessment, risk group selection and a controlled screening.
The modern communication path of the mobile devices are enabling us a
complete new communication and selection method wich can effectively
simplify the risk group identification and the suggestion of screening by the POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
Screening Centers. The aim of our study was to determine the effectivity of MONDAY, DECEMBER 5, 2016
a lung cancer risk assessment mobile application (LungScreen) in a localised
setting. Methods: A freely downloadable lung cancer risk assessment
application (LungScreen) were created for Android and iOS mobile platforms. P1.03-036 ADHERENCE TO ELIGIBILITY CRITERIA FOR LOW-DOSE CT
The application calculates and shows individual NSCLC risk based on Bach’s SCREENING IN AN ACADEMIC CENTER
protocol after collecting demographic data, smoking status, possible Jacob Bloom, Stuart Greenlee, David Madtes, Mikael Greenwood-Hickman,
environmental harms of the participant. Based on GPS coordinates the high Scott Ramsey, Bernardo Goulart
risk participant is navigated to the nearest Screening Center for further Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer
investigation. We analysed the records of the application in a test period of Research Center, Seattle/WA/United States of America
one year aided by an informative campaign in Hungary. Results: In one year
test period more than 70000 participants downloaded and completed the risk Background: The United States Preventive Services Task Force (USPSTF),
assessment test (Male/Female 58%/42%, Age range 9-92 years,mean age 38,2 Centers for Medicare and Medicaid Services (CMS), and the National
year). 14238 participants were active smokers, high risk criteria was calculated Comprehensive Cancer Network (NCCN) recommend low dose computed
in 1831 cases, in which further screening investigation were suggested. In our tomography (LDCT) lung cancer screening for high risk patients, defined
region (Baranya County) 158 LDCT screening were performed, with 32 positive as those between age 55-77 (CMS) or 55-80 (USPSTF), with ≥30 pack-year
findings wich required further investigations. In 9 cases Tumor Board decided smoking history who currently smoke or quit within the past 15 years. The
to indicate surgery (7 cases NSCLC, 2 cases benign lesion). All the procedures NCCN guidelines also recommend screening for patients over 50 years with
were performed with VATS. 8028 tests from 28 other countries (e.g. Germany, ≥20 pack-year smoking history and at least one additional lung cancer risk
France, UK, USA, Japan etc) Conclusion: Lung cancer risk assessment via mobile factor. To better understand community practices, we describe adherence to
devices allows free, fast and efficient way to select, manage and localize high screening eligibility criteria for the population screened at the Seattle Cancer
risk population for NSCLC. By omitting the complex recruitment process it can Care Alliance (SCCA). Methods: The SCCA developed a multidisciplinary LDCT
effectively fasten the screening trials and subsequently lower the financial screening program that executes LDCT screening orders when patients’ regional
needs. Giving immediate personalised feedback and individual direction to primary care providers deem them eligible for screening, and provides follow-up
diagnostic centers can facilitate early diagnosis of operable NSCLC cases. evaluations based on screening results. From a prospective registry study
of patients screened at the SCCA, we collected baseline sociodemographic,
Keywords: smartphone application, lung cancer screening, Early Detection smoking history, and clinical data to retroactively assess patients’ screening
eligibility based on USPSTF, CMS, and NCCN criteria, respectively. We define
adherence as the proportion of patients meeting at least 1 set of guidelines
criteria for screening and used univariate logistic regression to identify
potential sociodemographic predictors of adherence, excluding age and
SCREENING – smoking history. Results: Of 252 patients screened between 5/8/2012 and
MONDAY, DECEMBER 5, 2016 8/19/2015, 111 (44%) consented to participate in the study. Median age was 63,
67% were male, 89% were white, 99% were insured, median household income
was $75,000, 56% were current smokers, and median cigarette use was 36
P1.03-035 DOES SCREENING WITH LOW-DOSE COMPUTED pack-years. Of 106 patients with complete eligibility data, 61 (58%), 60 (57%),
TOMOGRAPHY (LDCT) OF ASBESTOS EXPOSED SUBJECTS REDUCE and 60 (57%) met the USPSTF, CMS, and NCCN screening criteria, respectively.
MORTALITY FOR LUNG CANCER (LC)? Seventy-nine (75%) patients met eligibility criteria for at least one guideline.
Gianpiero Fasola1, Ornella Belvedere2, Fabio Barbone3, Alessandro Follador 1, Of the 27 patients ineligible by any guidelines, 17 (63%) had <20 pack-years
Fabiano Barbiero3, Simona Rizzato1, Ciro Rossetto1, Elisa De Carlo1, Paolo smoking history and 5 (19%) were under age 50. White patients were more likely
Cassetti4, Stefano Meduri1, Francesco Grossi5 to meet eligibility for at least one guideline (Odds Ratio= 7.3; 95% CI = 1.9-27.8).
1
University Hospital of Udine, Udine/Italy, 2York Teaching Hospital, York/United Conclusion: In this single-center registry study, 25% of patients did not meet
Kingdom, 3University of Udine, Udine/Italy, 4 Monfalcone General Hospital, screening eligibility criteria when primary care providers were responsible for
Monfalcone/Italy, 5IRCCS Aou San Martino-Ist, Genova/Italy identifying screening candidates. In response to these results, the program
employed a coordinator to pro-actively review screening orders to confirm
Background: Our previous prospective non-randomized ATOM002 study guideline compliance. An opportunity exists to prioritize LDCT screening to high
showed that LDCT screening of asbestos exposed subjects can identify LC at risk patients through patient counseling, provider education and pro-active
an earlier, and potentially more curable, stage than chest radiographs (CXR) review of screening CT orders.
(Fasola et al, The Oncologist 2007). The ATOM002 participants were selected
from subjects enrolled in a surveillance program for asbestos exposed workers Keywords: screening eligibility, screening guidelines, Low-Dose Computed
at the Monfalcone Occupational Health Unit in the Friuli Venezia Giulia (FVG) Tomography (LDCT)
region, Italy. Here, we report a cohort mortality study of asbestos exposed
subjects from that surveillance program, comparing outcomes in the ATOM002
participants and contemporary nonparticipants. Methods: Within a cohort
of 2,433 asbestos exposed subjects, we compared mortality between the
ATOM study participants (who had additional baseline and 1 year LDCT) and POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
nonparticipants (n=926 and 1,507, respectively). The follow-up period spanned MONDAY, DECEMBER 5, 2016
the years 2002-2011. Cox models were performed to assess survival for all
causes, all cancers, LC and malignant pleural mesothelioma. Final models
estimating mortality hazard ratios (HR) were adjusted for smoking habits, age, P1.03-037 RADIO-GUIDED LOCALIZATION AND RESECTION OF
level of asbestos exposure and Charlson-Quan comorbidity index. For external SMALL OR ILL-DEFINED PULMONARY LESIONS

Domenico Galetta, Lorenzo Spaggiari POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING

SCREENING –
Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy MONDAY, DECEMBER 5, 2016
Background: Screening programs increased identification of small or

indistinct pulmonary lesions which are difficult to localize. We report our P1.03-039 IS IT NECESSARY TO REPEAT LUNG CANCER SCREENING
experience in their preoperative localization by radiotracer and resection. WITH LOW-DOSE CT(LDCT) IN FEMALE NEVER SMOKERS?
Methods: Patients with pulmonary nodule of subsolid morphology or
Hyae Young Kim1, Kyu-Won Jung2, Kun Young Lim1, Soo Hyun Lee1, Jae Kwan
smaller than 1 cm and/or deeper 1 cm below the visceral pleura underwent
Jun3, Byung-Ho Nam3, Jeongseon Kim3, Bin Hwangbo4, Yoo Sun Choi3, Hyemi
computer-tomography (CT)-guided injection of radiotracer technetium99m
Jo3, Jin Soo Lee4
macroaggregates in vicinity of the lesion. During surgery, a handheld gamma 1
Diagnostic Radiology, Center for Lung Cancer, National Cancer Center, Goyang-Si,
probe was used to detect hot spot where radioactive was localized and this
Gyeonggi-Do/Korea, Republic of, 2Korea Central Cancer Registry, National Cancer
area was resected. Results: From November 2007 to December 2013, 112 Center, Goyang-Si, Gyeonggi-Do/Korea, Republic of, 3National Cancer Center,
patients (58 men; median age 62 years) underwent preoperative radiotracer Goyang-Si, Gyeonggi-Do/Korea, Republic of, 4 Center for Lung Cancer, National
injection with a successful marking in all patients. Complications included 33 Cancer Center, Goyang-Si, Gyeonggi-Do/Korea, Republic of
pneumothoraces (29.4%) (one requiring chest tube placement), 23 (20.5%)
parenchymal hemorrhage soffusions, and 1 (0.9%) allergic reaction to contrast Background: Lung cancer (LC) screening is not recommended for low-risk
medium. In all cases, except for 2, gamma probe revealed pulmonary lesion. subjects, including never smokers. However, LDCT is often performed in Korea
Overall, 123 pulmonary nodules were localized and resected. Mean distance as a part of cancer screening program even for healthy female never smokers
from the pleura was 12 mm (range, 0 to 39 mm). Pulmonary resection was (FNS). To examine the role of LDCT screening in FNS, we estimated the risk of
performed by thoracoscopy in 70 (62.5%) cases, thoracotomy in 36 (32.1%), subsequent development of LC according to their initial LDCT findings and age
and converted thoracoscopy to thoracotomy in 6 (5.4%). Mean nodule size groups. Methods: This retrospective cohort study included FNS aged 40 to 79
was 9 mm (range, 3-24 mm). Histology showed 14 (11.4%) benign lesions and years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer
109 (88.6%) malignant lesions (85 primary lung cancers, and 24 metastases). diagnosis was identified from the Korea Central Cancer Registry Database
Conclusion: Radiotracer localization of pulmonary lesions is a simple and (Dec 2013) and vital status (Dec 2014) from Statistics Korea. LDCT findings
feasible procedure with a high rate of success. Optimal candidates are were reviewed using Lung Imaging Reporting and Data System (Lung-RADS).
patients with suspicious nodules detected by screening or incidental CT due LC risk and outcomes were analyzed according to initial LDCT findings and age
to high rate of nonsolid morphology and small size. groups using the national data up to 12 years after the LDCT. Results: There
were 4,365 FNS with mean age of 51.1±7.6 years (median F/U time = 9.7 years).
Keywords: radiology, lung tumor, Surgery Overall, twenty-two LCs (0.5%) were identified with an incidence rate of 52.58
(95% CI 34.62-79.86) per 100,000 person-years. The incidence rates were 8.53
(2.75-26.44), 75.16 (24.24-233.04), 0 and 1665.58 (1020.38-2718.72) in subjects
with category 1, 2, 3 and 4, respectively. The cumulative incidence is shown in
Fig 1. The incidence rates were 35.30 (95% CI 18.99-65.00) and 88.84
SCREENING – (50.45-156.44) in age with 40~54 years and 55~79, respectively. Three women
MONDAY, DECEMBER 5, 2016 among 16 classified into category 4 died of LC, while no death in those with
category 1, 2, or 3 [median time to LC diagnosis= 5.1 years (range, 2.8-8.8)]. Fig
1. Cumulative incidence of lung cancer according to lung-RADS
P1.03-038 APPROPRIATENESS OF LUNG CANCER SCREENING WITH
LOW DOSE COMPUTED TOMOGRAPHY
Louise Henderson1, Laura Jones1, Thad Benefield1, Dan Reuland2, Alison
Brenner3, Paul Molina1, M Rivera2
1
Radiology, The University of North Carolina, Chapel Hill/NC/United States of
America, 2Medicine, The University of North Carolina, Chapel Hill/NC/United States
of America, 3Cecil G. Sheps Center for Health Services Research, The University of
North Carolina, Chapel Hill/NC/United States of America
Background: Based on results of the National Lung Screening Trial, several

expert U.S. groups now recommend lung cancer screening (LCS) with
annual low-dose computed tomography (LDCT). The extent to which
LCS is performed according to guidelines is unknown. We evaluated the
appropriateness of LCS performed at a US academic medical center. Methods:
Chart abstractions were performed for all patients (N=174) undergoing LCS
at an academic medical center between 2/5/2015 and 4/30/2016. During the
data collection period, an active quality improvement (QI) project, aimed at
improving appropriate implementation of LCS, was underway in the internal
medicine (IM) department. Appropriate screening was defined as: 1) patient
age 55-77 years; 2) smoking history of 30+ pack-years; 3) current smoker or
quit less than 16 years ago; 4) asymptomatic for lung cancer; 5) not on daytime
oxygen; 6) documentation of shared decision making (SDM); 7) no severe
COPD; and 8) no heart failure. We evaluated characteristics associated with
Conclusion: Although, the effectiveness of lung cancer screening is in FNS still
LCS using multivariate logistic regression and report odds ratios (OR) and 95%
unclear, repeat LDCT seems to be unnecessary in those with category 1, 2 and
confidence intervals (95%CI). Results: The study population was between 44
3, at least within 5 years after initial LDCT.
and 85 years, was 68% white, 28% black, and 4% other race, and the majority
(56%) were male. Fifty-six percent of patients were former smokers, and Keywords: Lung-RADS, female never smoker, low-dose CT, lung cancer
most (83%) had smoked at least 30 pack-years. The majority of screenings screening
were ordered by family medicine and IM practitioners. Seventy percent of
screenings were classified as inappropriate. The most frequent reasons for
inappropriate screening were: inadequate or no SDM documentation (47%),
patient being symptomatic (19%), too low or missing pack-year data (17%),
patient quit smoking more than 15 years ago (13%), and having severe COPD POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
(13%). Thirty-five percent were classified as inappropriate based on two or MONDAY, DECEMBER 5, 2016
more criteria. The proportion appropriately screened increased from 10%
during the first third of 2015 to 34% in the first third of 2016. After adjusting
for patient race and sex, predictors of appropriate screening were having P1.03-040 BELIEFS SURROUNDING LUNG CANCER SCREENING
the order from an IM versus family medicine provider (OR=3.8, 95%CI:1.5-9.6) AMONG PHYSICIANS AND LAY POPULATIONS: RESULTS FROM THE
and having a more recent order date (order from first third of 2016 versus EDIFICE SURVEY
the first third of 2015 (OR=5.4, 95%CI:1.1-26.8)). Conclusion: Although a
Alexis Cortot 1, Sébastien Couraud2, François Eisinger3, Chantal Touboul4,
significant proportion of patients screened for lung cancer do not meet U.S.
Jean-Yves Blay5, Jérôme Viguier6, Christine Lhomel7, Xavier Pivot8, Jean-
appropriate eligibility criteria, this is improving. The QI project in the IM clinic
François Morere9, Laurent Greillier 10
addressed key factors affecting implementation of LCS, such as collection of 1
Hôpital Calmette, Lille/France, 2 Service de Pneumologie, Centre Hospitaliser
complete smoking history and training of nurses and providers, resulting in
Lyon Sud, Pierre Bénite/France, 3Institute Paoli Calmettes, Marseille/France,
improvements to the rate of appropriate LCS. 4
Kantarhealth, Paris/France, 5Centre Léon Bérard, Lyon/France, 6Hôpital
Bretonneau, Tours/France, 7Roche, Boulogne-Billancourt/France, 8 CHU Besançon,
Keywords: guidelines, appropriateness, Screening Hôpital Jean Minjoz, Besançon/France, 9Hôpital Paul Brousse, Villejuif/France,
10
Hôpital Nord, Marseille/France diagnosed were either stage I or II. Of the 11 individuals with biopsy proven
cancers, 7 had normal previous CTs, 4 had a pre-existing groundglass nodules
Background: The National Lung Cancer Screening Trial has shown that lung in the tumor location on the most recent exam. The overall prevalence of lung
cancer screening (LCS) with an annual low-dose chest CT-scan reduces specific cancer in this cohort is 15.2% (55/361) and it may increase. The detection rate
mortality in both former and current heavy smokers. However, organizational of LDCT to date is 7.2% (11/153). Conclusion: Lung cancer risk remains high
issues have yet to be solved before it can be systematically implemented. We despite several negative annual screening LDCT scans. Continued screening
investigated the perceptions of the population at large as well as those of beyond three years is recommended in high risk individuals.
physicians with regard to the efficacy of LCS, and target populations in terms
of tobacco use. Methods: The 4th French nationwide observational survey, Keywords: Low dose computed tomography, lung cancer, Screening
EDIFICE 4, was conducted by phone interviews of a representative sample of
1602 subjects, aged between 40 and 75 years, from June 12 to July 10, 2014. A
mirror survey was also conducted by phone among physicians between July 9
and August 8, 2014. Both surveys were conducted using the quota method on
representative samples of 1463 lay persons and 301 physicians with no history SCREENING –
of cancer. Results: For 53% of lay persons and 33% of physicians interviewed MONDAY, DECEMBER 5, 2016
(P<0.01), generalization of LCS is potentially an effective way to reduce lung
cancer mortality. For the majority of interviewees (58% of lay persons and
55% of physicians; difference not statistically significant [NS]), offering LCS P1.03-042 NODULE SIZE IS POORLY REPRESENTED BY NODULE
to the whole population would not encourage smokers to continue smoking. DIAMETER IN LOW-DOSE CT LUNG CANCER SCREENING
The table shows lay persons’ and physicians’ replies concerning possible Marjolein Heuvelmans 1, Rozemarijn Vliegenthart1, Peter Van Ooijen1, Harry
target populations within the whole population and among smokers. De Koning2, Matthijs Oudkerk1
1
Center for Medical Imaging North-East Netherlands, University of Groningen,
University Medical Center Groningen, Groningen/Netherlands, 2Public Health,
Erasmus University Medical Center, Rotterdam/Netherlands
Background: In lung cancer screening, at least one pulmonary nodule is found

in over 50% of participants, of which 99% is benign. As lung cancer probability
in low-dose computed tomography (CT) lung cancer screening usually is based
on nodule size and growth rate, accurate nodule size determination is of
major importance to decrease false positive screen results. Previous studies
showed that nodule size measurements based on semi-automated volume are
preferred over diameter measurements. Aim of this study was to determine
the correlation between nodule diameter and nodule size of nodules found
in low-dose CT lung cancer screening, and to directly compare it with semi-
automated volume measurements. Methods: We investigated baseline data
Conclusion: Lay persons are more inclined to suggest generalizing LCS to the of 2,240 solid nodules of intermediate size (volume 50-500mm3) in 1,500
whole population, independently of current smoking status or quitting issues. lung cancer screening participants. Nodule volume, x, y, and z diameter and
Lay persons and physicians alike agree with generalizing LCS to all smokers, minimum / maximum diameter in any direction were generated by semi-
regardless of their tobacco consumption. automated software (LungCARE, Siemens). Range in maximum axial and
mean nodule diameter per nodule volume category (50-100mm3, 100-200mm3,
Keywords: screening organisation, screening efficacy, opinion, target
200-300mm3, 300-400mm3, 400-500mm3) was determined. Semi-automated
population
nodule volume represented nodule size. Intra-nodule diameter variation
was defined as maximum minus minimum nodule diameter. Results: Median
participant age was 59 years, 14.1% were women. Median nodule volume
was 82.4 mm3 (interquartile range [IQR], 62.9–125.4 mm3). Median nodule
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING diameter was 6.1 mm (IQR, 5.4–7.2 mm) for mean diameter, and 6.6 mm (IQR,
SCREENING – 5.9–7.7 mm) for maximum axial diameter. Range in mean nodule diameter
MONDAY, DECEMBER 5, 2016 per volume category varied from 8.55 mm (3.0 – 11.5 mm) for nodules with
volume of 50-100 mm3 to 6.1 mm (7.2 – 13.3 mm) for nodules with volume of
P1.03-041 DO SEVERAL ROUNDS OF NEGATIVE SCREENING LOW 200-300 mm3; range in maximum axial diameter varied from 11.2 mm (7.3 –
18.5 mm) for nodules with volume of 200-300 mm3, to 7.0 mm (9.1 – 16.1 mm)
DOSE CT SCANS INFLUENCE THE RISK TO DEVELOP LUNG CANCER?
for nodules with volume of 400-500 mm3. Intra-nodule diameters varied by
Heidi Schmidt 1, John Kavanagh1, Geoffrey Liu2, Ming Tsao3, Frances Shepherd2 a median of 2.8 mm (IQR, 2.2-3.7 mm). Intra-nodule diameter variation for
1
Joint Department of Medical Imaging, University Health Network, Toronto/ smaller intermediate-sized nodules (50-200 mm3) was 2.8 mm (IQR 2.2-
ON/Canada, 2Princess Margaret Cancer Centre, Toronto/ON/Canada, 3Research, 3.5 mm), and was smaller than intra-nodule diameter variation for larger
Princess Margaret Hospital and Ontario Cancer Institute, Mg L/ON/Canada
intermediate-sized nodules (200-500 mm3; median 3.6 mm [IQR 2.5-5.1 mm],
Background: The purpose of this study was to assess whether several P<0.01). Conclusion: Nodule size is poorly represented by diameter, as a nodule
years of negative screening low-dose computed tomography (LDCT) scans has an infinite number of diameters, but only one volume. Therefore, use of
predict a subsequent lower risk of developing lung cancer. This would have nodule diameter measurements may lead to misclassification of lung cancer
implications for recommended intervals and duration of LDCT lung cancer probability. Median intra-nodule diameter variation was found to be higher as
screening. Methods: The cohort was an at-risk population who had previous the 1.5mm LungRADS cutoff for nodule growth.
negative screening LDCTs and had not been screened for at least 5 years.
Keywords: pulmonary nodule, computed tomography, Screening
Between 2003 and 2009, 4782 individuals had been enrolled in a lung cancer
screening study based on age and smoking alone. At this time, their risk
was re-calculated using a multifactorial assessment model, and they were
contacted in decreasing order of their re-calculated risk. An initial phone
interview assessed interim history, general health, interim diagnosis of lung POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
cancer or interim chest CT. Those participants without lung cancer or recent SCREENING –
CT were invited for a single LDCT (40mA, 135kV, 1mm axial reconstructions).
Subsequent investigation was recommended depending on the LDCT
findings: negative, no new or growing nodules (no further recommendation), P1.03-043 PRACTICAL DIFFICULTY OF LOW DOSE COMPUTERIZED
positive, low suspicion for malignancy (follow up CT in 3-6 months) or TOMOGRAPHY AS A LUNG CANCER SCREENING TOOL IN AN
positive, high suspicion for malignancy (referral to the local lung cancer rapid
ENDEMIC AREA OF TUBERCULOSIS
diagnostic assessment program). Results: To date, 361 individuals or family
members have been contacted. Fifty-five individuals had passed away (20 Natthaya Triphuridet, Sutida Singharuksa, Sirachat Vidhyakorn
from lung cancer), 24 were alive with lung cancer. 129 did not qualify for a Medicine, Chulabhorn Hospital, Bangkok/Thailand
LDCT scan (declined participation, or recent CT). A total of 153 have attended
Background: Low-dose computerized tomography (LDCT) is a current
for LDCT, on average 7 years after their last LDCT. Ninety-one (59%) studies
standard technique for lung cancer screening to reduce lung cancer death.
were reported as negative. Fourty-five (29%) LDCTs were positive with low
Clinical and radiographic finding for lung cancer can also be found in
suspicion and a follow up scan was recommended; in 13 cases nodules had
Tuberculosis(TB). No clear evidence of benefits from lung cancer screening has
resolved on follow up imaging, the remaining 32 are awaiting surveillance
been established in a high-risk population residing in an endemic area of TB.
LDCTs. Seventeen (11%) LDCTs were reported as positive with high suspicion;
Methods: A 5-year prospective lung cancer screening using LDCT enrolled 634
11 of those have a subsequently biopsy proven lung cancer and 6 are currently
former or current heavy smokers (>30 pack-years) aged 50-70 years without a
undergoing further investigations or LDCT surveillance. All lung cancers

history of active TB within a recent year between July 2012 and January 2014 POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
at Chulabhorn Hospital in Thailand. The results were classified as negative, MONDAY, DECEMBER 5, 2016
indeterminate, or positive for primary lung cancer. The preliminary data
demonstrated from three rounds of low-dose CT screening for lung cancer
(rounds T0, T1, and T2). Results: At initial screening LDCT, 3.5% had positive P1.03-045 SCREENING FOR LUNG CANCER WITH EARLY CDT-LUNG
test (solid/part solid nodule>10·0 mm/volume >500 mm3 or consolidation, BLOOD BIOMARKERS AND COMPUTED TOMOGRAPHY
obstructive atelectasis, pleural effusion, or mediastinal lymphadenopathy). James Jett1, Debra Dyer2, Jeffrey Kern2, Donald Rollins2, Melanie Phillips2,
Most of participants with non calcified lung nodule(NCN)(s) had 2-4 nodules, James Finigan3
the higher proportion of multiple pulmonary nodules was observed in the 1
Oncology, National Jewish Health, Denver/CO/United States of America, 2National
larger size. Nine cases(1.4%) were proven lung cancer (56% stage I, 22% Jewish Health, Denver/United States of America, 3Oncology, National Jewish
stage II/III, 22% stage IV) within 12 months. All cases of stage I-II had 2-10 Health, Denver,co/CO/United States of America
lung nodules, while all stage III- IV lung cancers had single lung nodule. PPV
of positive LDCT test, NCN(s)>10 mm and GGN(s)>10 mm for diagnosis lung Background: The Early Cancer Detection Test (CDT)-Lung is a serum-based
cancer were 27.3%, 40%, and 75%, respectively. The incidence of lung cancer biomarker consisting of a panel of tumor-associated autoantibodies that
in T1 and T2 were 0.67% and 0.70%, respectively. Half of them had baseline has been shown to detect lung cancer. We hypothesized that this biomarker
lesions suspected inflammation/infection. The incidence of active pulmonary when used in combination with a low-dose CT (LDCT) in screening of an at-risk
TB in T1 and T2 was 0.50% and 0.52%, respectively. Conclusion: Despite a high population would increase the detection of early stage lung cancer. Methods:
burden of TB in Thailand, LDCT screening in heavy smokers could yield a high A prospective study of 1,600 subjects at high risk for lung cancer was designed.
rate of early stage of primary lung cancer in this population at risk and also Eligibility criteria included persons 50-75 years of age, current or former
high rate of active pulmonary tuberculosis. However, high prevalence of lung smokers of ≥ 20 pack years and ˂ 10 years since quit smoking. Those with a
nodules and high proportion of multiple pulmonary nodules of individuals history of lung cancer in first-degree relative(s) and any history of smoking
were major problems in diagnosis and staging lung cancer in endemic area of were included. Exclusion criteria were any history of cancer within 10 years
Tuberculosis. Regarding the high probability of malignancy in GGN diameter (except skin cancer), any use of oxygen, and life expectancy of < 5 years. Those
>10 mm and newly seen or progressive lesion of baseline lesion suspected of fitting inclusion criteria received the Early CDT-Lung blood test and a LDCT.
inflammation/infection, nodule management protocol would be adapted in A nodule of ≥ 3mm was considered as a positive scan. The Early CDT-Lung test
this population. was considered positive if any one of the seven autoantibodies was positive.
Telephonic follow-up was conducted over two years. Results: From May 2012
Keywords: lung cancer screening, low dose CT, Pulmonary Tuberculosis through June 2016, 1235 individuals were enrolled. The cohort median age was
59 years with 55% female and 45% male gender distribution. Fifty-two per
cent were current smokers while 48% were former smokers. Seventy-one per
cent of the LDCTs were negative for any lung nodule while 29% were positive.
The Early CDT-Lung biomarker was positive in 88 (7%) of participants. In those
SCREENING – with a positive LDCT (n=352), the biomarker was positive in 30 (8.5%). As of
MONDAY, DECEMBER 5, 2016 June 30, 2015, there have been seven confirmed lung cancers: two limited
stage small cell, two Stage IB adenocarcinoma (ACA), and three Stage IA (two
ACA and one squamous cell). The Early CDT-Lung blood test was positive in 2 of
P1.03-044 EUS-GUIDED SAMPLING OF MEDIASTINAL LYMPH
the 7 (29%) total cancers, both stage 1A. Early CDT-Lung was positive in 2 of 5
NODES AND ABDOMINAL LESIONS IN LUNG CANCER (40%) Stage IA/B lung cancers in total. Early CDT-Lung was negative in the two
Toyoaki Hida1, Yuko Oya1, Kosuke Tanaka1, Hiromi Furuta1, Naohiro small cell cancers. There are 58 Early CDT-Lung biomarker positive individuals
Watanabe1, Tatsuya Yoshida1, Junichi Shimizu1, Yoshitsugu Horio1, Kazuo with a LDCT without nodules. (NCT01700257) Conclusion: The Early CDT-Lung
Hara2, Yasushi Yatabe3 biomarker was more likely to be positive in patients with nodules and lung
1
Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya/Japan, cancer cases, particularly early stage lung cancer. Accrual to the study and
2
Gastroenterology, Aichi Cancer Center Hospital, Nagoya/Japan, 3Department of follow-up of 58 biomarker positive but LDCT negative participants continues.
Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya/Japan
Keywords: Screening, LDCT, auto-antibodies
Background: Endobronchial ultrasound-guided transbronchial needle
aspiration (EBUS–TBNA) was introduced to provide access to mediastinal
and hilar lymph nodes. However, it is difficult to use EBUS to approach the
aortopulmonary window and paraesophagaeal stations. Transesophageal
endoscopic ultrasound (EUS) was introduced to provide access to this area. POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
In addition, transgastroduodenal endoscopic ultrasound can evaluate MONDAY, DECEMBER 5, 2016
abdominal lesions. Methods: Endoscopic ultrasound fine needle aspiration
(EUS-FNA) was performed under conscious sedation with the administration
of intravenous midazolam and pethidine hydrochloride. It was performed P1.03-046 SELECTION OF SUBJECTS AT HIGH-RISK FOR LDCT LUNG
with a convex array echoendoscope connected to an ultrasound scanning CANCER SCREENING USING A MOLECULAR PANEL: RESULTS BY THE
system. Lymph nodes of paraesophageal, subcarinal, lower paratracheal, ITALUNG BIOMARKER STUDY
subaortic, and upper paratracheal regions were evaluated from esophagus.
Francesca Carozzi1, Laura Carrozzi2, Fabio Falaschi3, Andrea Lopes Pegna4,
Left adrenal gland and right adrenal gland were evaluated from stomach
Mario Mascalchi5, Giulia Picozzi6, Francesco Pistelli2, Ferruccio Aquilini2,
and duodenum, respectively. Abdominal lesions were also evaluated from
Cristina Ocello7, Luana Greco1, Cristina Sani1, Marco Peluso1, Simonetta
stomach and duodenum. After obtaining tissue via EUS-FNA, the tissue was
Bisanzi1, Eugenio Paci8
reviewed immediately (rapid on-site cytopathological evaluation: ROSE) 1
Prevention Laboratory Unit, Institute for Cancer Prevention and Research (Ispo),
by a cytopathologist. Subsequent punctures in the same patient were not
Florence/Italy, 2Cardio-Thoracic and Vascular Dept, University Hospital of Pisa,
performed before confirming the results of ROSE so as to minimize the Pisa/Italy, 3Diagnostic Radiology, University Hospital of Pisa, Pisa/Italy, 4Formerly
complications. Results: As to the lymph node level, the lower mediastinum at Cardio-Thoracic-Vascular Dept., Careggi Hospital, Florence/Italy, 5“Mario
and the aortopulmonary window are particularly important for detection by Serio”Department of Experimental and Clinical Biomedical Sciences, University of
transesophageal EUS, whereas pretracheal and hilar lymph nodes are out of Florence, Florence/Italy, 6Diagnostic Imaging Unit, Institute for Cancer Prevention
reach because of the interposition of air from the trachea and bronchi. EUS and Research (Ispo), Florence/Italy, 7Clinical Descriptive Epidemiology Unit,
was chosen to assess the posterior mediastinum nodes (#5, 7, 8, or 9) but not Institute for Cancer Prevention and Research (Ispo), Florence/Italy, 8Formerly
the anterior ones. A final diagnosis was obtained by EUS-FNA in 76 patients. at Clinical Descriptive Epidemiology Unit, Institute for Cancer Prevention and
Research (Ispo), Florence/Italy
The lesions sampled were mediastinal lymph nodes (n=64; #5, 7, 8, or 9),
abdominal lymph nodes (n=8), and adrenal gland (n=4). Conclusion: Repeat Background: Low Dose Computer Tomography (LDCT) screening has been
tumor biopsies from patients with acquired resistance were initially obtained shown effective in reducing overall and lung cancer mortality, but there are
through research efforts to ascertain mechanisms of resistance, but are now still concerns for efficiency and the cost/harm benefit ratio.reduce costs.
recommended to help select second-line therapies. However, such biopsies are Subjects enrolled in trials evaluating LCDT as a test for the early detection
associated with both risk and discomfort and may not always supply enough of lung cancer represent the ideal population in which to study the possible
tumor tissue for genetic analyses. Although EUS–FNA does not provide access use of molecular markers in a combined approach of screening. Methods: Out
to pretracheal and hilar lymph nodes, EUS-FNA is an accurate, safe, and of 1406 subjects randomised in the intervention arm of the ITALUNG study
minimally invasive modality for evaluating mediastinal lymphadenopathy and and attending at baseline test, 1356 were enrolled, after specific consent,
abdominal lesions in patients suspected of having lung metastases. in the ITALUNG biomarker study. Screen detected lung cancers detected
over the 4-years of screening (N=36 out of 38 in ITALUNG active arm) and 481
Keywords: biopsy, lymph node, EUS, Genetic analysis
randomly selected subjects without lung cancer at end of the study follow
up, were included in this analysis . DNA in plasma was quantified at baseline
by Real Time PCR; microsatellite instability (MSI) and loss of heterozygosity
(LOH) was assessed in blood and sputum. ITALUNG Biomarker Panel (IBP) was
considered as positive if MSI /LOH and/or DNA Plasma values (cutoff 5 ng / ml) stage lung cancers were detected without excessive testing or complications.
were positive. Results: The IBP results are shown in Table 1. Accuracy measure
were estimated and showed high sensitivity for baseline screen-detected Keywords: lung cancer, histoplasmosis, Screening, community
cases (94.4%) with a specificity of 60.0% (ROC Area:77%). Sensitivity and
specificity were 66.7% and 60.1% for lung cancers screen detected at repeated
LDCT (ROC Area: 63.4%).
SCREENING –
P1.03-048 A STRUCTURED LUNG CANCER SCREENING PROGRAM

FACILITATES PATIENT AND PROVIDER COMPLIANCE
Jared Christensen1, Jennifer Garst2, Momen Wahidi3, Catherine Hogan4, Hilary
Crittenden4, Susan Bruce2, Thomas D’Amico5, Betty Tong5
1
Radiology, Duke University Medical Center, Durham/NC/United States of America,
2
Medical Oncology, Duke Cancer Center Raleigh, Raleigh/NC/United States of
America, 3Medicine, Duke University Medical Center, Durham/NC/United States of
America, 4Duke Cancer Institute, Durham/NC/United States of America, 5Surgery,
Duke University Medical Center, Durham/NC/United States of America
Background: In the United States, both private insurers and Medicare provide
coverage for low-dose computed tomography (LDCT) screening for lung
cancer. Medicare has defined specific criteria for coverage to include “lung
Conclusion: The IBP showed good accuracy for the identification of screen cancer screening counseling and shared decision making visit”1. Currently, in
detected baseline lung cancers, with a very high sensitivity and a specificity of many institutions, it is possible for LDCT screening to be performed without
about 60%. The analysis of IBP of the baseline sample showed low prediction documentation of these discussions. We hypothesize that performing LDCT
at repeated test. IBP was confirmed as a potentially valid tool for baseline screening in the context of a structured lung cancer screening program
selection of high-risk subjects, saving about the 60% of the tests. Low results in improved compliance with coverage regulations. Methods: Medical
predictive capacity of screen detected cases at repeated tests needs further records of patients undergoing LDCT screening at our institution between
investigation. January 1, 2015 and June 30, 2016 were reviewed. Chart abstraction included
eligibility criteria and documentation of shared decision making, discussion
Keywords: high-risk, lung cancer, Screening, biomarker of adherence to annual screening and discussion of tobacco cessation/
continued abstinence. Results: Of the 591 patients who had LDCT screening in
the defined time period, 223 (37.7%) were seen in the Lung Cancer Screening
Clinic and 368 (62.3%) had studies ordered by other providers. Within the
Lung Cancer Screening Clinic (LCSC) cohort, 202/223 (90.6%) met Medicare
SCREENING –
eligibility and 17/223 (7.6%) met National Comprehensive Cancer Network
MONDAY, DECEMBER 5, 2016 (NCCN) “Category 2” criteria for lung cancer screening. In the “other provider”
(OP) cohort, 281 (76.4%) met Medicare eligibility and 24 (6.5%) met NCCN
“Category 2” criteria for screening (p<0.0001). Current smokers were more
P1.03-047 COMMUNITY-BASED LOW-DOSE COMPUTED likely to have documented discussion of tobacco cessation counseling (99.2%
TOMOGRAPHY (LDCT) LUNG CANCER SCREENING IN THE US vs. 64.2%, respectively; p<0.0001). Similarly, patients seen in the LCSC were
HISTOPLASMOSIS BELT: ONE YEAR FOLLOWUP more likely to have documentation of shared decision making than those in
Emilia Porubcin1, Judy Howell2, Steven Cremer3 the OP cohort (97.3% vs. 19.3%, respectively; p<0.0001).
1
Rivermont Collegiate, Bettendorf/IA/United States of America, 2Unitypoint Health
Trinity, Moline/IL/United States of America, 3 Advanced Radiology, Moline/United Table 1. Compliance with Medicare criteria for LDCT screening.
States of America
LCSC (n = 223) OP (n = 368) p-value
Background: LDCT lung cancer screening has been incorporated into most
major American medical societies’ screening guidelines. However, its Medicare-eligible for
202 (90.6%) 281 (76.4%)
performance in a non-tertiary care community setting with a high prevalence screening NCCN “Category
17 (7.6%) 4 25 (6.8%) 62 <0.0001
of fungal infections has not been sufficiently studied. Methods: Beginning 2” Do not meet criteria for
(1.8%) (16.8%)
in April 2013, high-risk adults ages 55-80 with at least a 30 pack-year smoking lung cancer screening
history, including former smokers who had quit within the previous 15 years, Former smoker, quit
were prospectively evaluated with an LDCT scan performed at our community 99 (44.4%) 124 181 (49.2%) 187
within 15 years Current 0.2958
hospital (UnityPoint Health Medical Center in Quad Cities, Illinois). Standard (55.6%) (51.8%)
smoker
National Lung Screening Trial exclusion criteria were followed with minor
modifications. All participants’ scans were evaluated using Lung-RADS Documented Tobacco 123/124
version 1.0 assessment categories. An oncology nurse navigator contacted and Cessation Counseling 119/187 (63.6%) <0.0001
(99.2%)
(current smokers)
monitored all participants. CTs were interpreted by a local radiology group,
with two radiologists spearheading the program and ensuring consistent Mean time spent in
interpretations. Results: As of June 2016, we present data on 466 evaluable tobacco cessation 23 minutes 5 minutes 0.0075
participants (compared to 176 from one year ago), 234 of whom were men counseling
(50%). The median age of the studied population remains 64 years (range 55- 182/187
Documentation of shared
80). Screening adherence has dropped from 97% to 91%, with 40 participants 68/353 (19.3%) <0.0001
decision making (97.3%)
lost to followup. 27 participants have completed all required phases of the
screening. 192 participants (41%) had positive baseline screening tests. 26 of Conclusion: LDCT screening conducted in the context of a dedicated lung
those participants (6% of the total population) required further evaluation cancer screening clinic facilitates compliance with Medicare criteria and
with PET scans. 15 of these PET scans were followed by invasive procedures, improves patient education and decision-making. Opportunities exist for
including lung biopsy. 13 biopsy-proven malignancies (3%) were detected those providing LDCT to improve the elements of patient education that are
as a direct result of the screening. 12 malignancies were NSCLCs, of which 9 essential to LDCT screening.References 1. https://www.cms.gov/medicare-
were early-stage (stages I-II). The thirteenth malignancy, a stage I Marginal coverage-database/details/nca-decision-memo.aspx?NCAId=274
Zone Non-Hodgkin Lymphoma of the lung, was confirmed by a lung wedge
biopsy. Of the other two participants requiring invasive diagnostic procedure, Keywords: lung cancer screening, low-dose CT
one had a biopsy “negative for malignancy” and the other was diagnosed
with histoplasmosis. No biopsy-related complications occurred. Twelve of
thirteen participants with biopsy-proven malignancies are still alive and doing
well. One participant died secondary to an advanced NSCLC detected by the
screening program. Conclusion: This report represents an update on, to our SCREENING –
knowledge, the first community hospital-based study evaluating the results MONDAY, DECEMBER 5, 2016
of LDCT lung cancer screening in an area of the United States endemic for both
histoplasmosis and blastomycosis. Only one case of histoplasmosis has been
confirmed by invasive diagnostic procedure. A significant number of early P1.03-049 SMOKING PATTERNS IN A PREDOMINANTLY AFRICAN
AMERICAN POPULATION UNDERGOING LUNG CANCER SCREENING

Cherie Erkmen1, Shelby Sferra2, Callan Goldman2, Larry Kaiser 1, Verdi Disesa1, Percutaneous needle aspiration (n=11), endoscopic sampling (n=10), and
Grace Ma2 surgical biopsy/resection (n=4) were performed as the first invasive diagnostic
1
Thoracic Surgery, Temple University Hospital, Philadelphia/PA/United States of procedure. The outcomes of this initial sampling were cancer (n=15), non-
America, 2Center for Health Disparities, Temple University Hospital, Philadelphia/ diagnostic (n=7), benign (n=2), and infection (n=1). Three patients without
PA/United States of America an initial diagnosis underwent additional non-surgical biopsy attempts.
Overall, surgical resection was performed in twelve patients (6 after previous
Background: Patients within the National Lung Screening Trial (NLST) diagnostic procedure, 2 after previous non-diagnostic procedure, and 4
undergoing low-dose computed tomography (LDCT) lung cancer screening as initial procedure). Final outcomes were cancer (n=16), non-diagnostic
(LCS) with abnormal results were more likely to quit smoking (Tammemagi procedure (n=4), non-caseating granulomatous inflammation (n=2), benign
et al.). However, these results may not be generalizable to underserved, diagnosis after wedge resection (n=2), and infection (n=1). Conclusion: Within
ethnic minorities. Despite high incidence and mortality of smoking-related a nurse practitioner led, multidisciplinary, lung cancer screening program, a
lung cancer among African Americans (AAs), few efficacy smoking cessation small proportion of patients undergo invasive diagnostic testing, despite a
trials in the context of LDCT-LCS include a large representation of AAs. Thus, rather high prevalence of potentially actionable nodules. Within the NLST
we studied smoking patterns in a predominantly AA population undergoing population receiving computed tomography, 6.1% underwent invasive
lung cancer screening. Methods: In a predominantly AA population we testing with 43% undergoing testing that ultimately did not result in a
studied those undergoing LDCT-LCS (n=146). These patients received shared cancer diagnosis. Within our multidisciplinary program, 4.8% underwent
decision making, LDCT-LCS, results and smoking cessation in a single visit. invasive testing with 36% undergoing testing not ultimately resulting in a
Patients self-reported smoking status six months following LDCT. Results: cancer diagnosis. The utilization of multidisciplinary teams during the biopsy
Of 146 patients receiving lung cancer screening, 100 (68%) are AAs, 30 (21%) decision-making process may help decrease the number of non-diagnostic
Caucasians, 14 (10%) Hispanics and 2 (1%) Asians. Smoking history was a procedures. Further research is needed to help identify tools that improve
mean of 49 pack years, median of 42 pack years with 60% current smokers. patient selection for invasive testing in lung cancer screening programs.
Of the 88 active smokers, 86 received greater than 10 minutes of smoking
cessation counseling, 61 received a prescription for smoking cessation Keywords: lung cancer screening, Multidisciplinary team, Diagnostic
medications, and 60 agreed to follow up smoking cessation appointments. sampling, lung cancer
The overall quit rate was 11% (10 out of 88 active smokers). Quit rate for
smokers who declined medical assistance was 4% (1 out of 28). Smokers who
attended follow up visits in addition to receiving a personalized combination
of smoking cessation medications had a quit rate of 33% (5 out of 15). Quit
rate was 20% for people with normal LDCT, Lung-RADS category 1 (8 out of POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
40) and 5% for people with benign appearing nodules, Lung-RADS category MONDAY, DECEMBER 5, 2016
2 (2 out of 41). None of the 3 people with nodules requiring further follow
up, Lung-RADS category 3, or the 4 people with nodules suspicious for
cancer Lung-RADS category 4, quit smoking within 6 months of their LDCT. P1.03-051 MEDICALLY UNDERSERVED AND GEOGRAPHICALLY
Conclusion: In a predominantly AA population, 60% of screened LDCT-LCS REMOTE INDIVIDUALS MAY BE UNDERREPRESENTED IN CURRENT
were active smokers, only 11% quit despite a rigorous smoking cessation LUNG CANCER SCREENING PROGRAMS
program. Different from the NLST population, our findings indicate that Candice Wilshire 1, Bretta Mccall1, Hannah Modin1, Joelle Fathi1, Christopher
patients without suspicious nodules were more likely to quit than those with Gilbert2, Brian Louie3, Ralph Aye3, Alexander Farivar3, Eric Vallieres4, Jed
suspicious nodules. The causes of these differing results are unknown. We Gorden2
theorize that the differences may be due to biological, cultural, psychological 1
Interventional Pulmonolgy and Thoracic Surgery, Swedish Medical Center
and socioeconomic factors. We suggest that future research should aim and Cancer Institute, Seattle/WA/United States of America, 2Interventional
to examine these factors to identify barriers and facilitators to changing Pulmonolgy, Swedish Medical Center and Cancer Institute, Seattle/WA/United
smoking behaviors among those undergoing LDCT-LCS. States of America, 3Thoracic Surgery, Swedish Cancer Institute, Seattle/WA/United
States of America, 4Thoracic Surgery, Swedish Medical Center and Cancer Institute,
Keywords: delivery of health care, Disparity of health care, lung cancer Seattle/WA/United States of America
screening, Smoking Cessation
Background: The National Lung Screening Trial demonstrated a 20% reduction
in lung cancer mortality and ushered in lung cancer screening (LCS). Study
centers included 33 academic, mostly urban-based sites, which may
underrepresent low socioeconomic remote populations with minimal health
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING care access. United States Census Bureau 2014 data demonstrated that
SCREENING –
smoking is concentrated among adults with low income and education, and
without private medical insurance; components of medically underserved/
shortage area designations. We sought to assess the representation of
P1.03-050 OUTCOMES AFTER THE DECISION TO BIOPSY: RESULTS underserved communities in our hospital-based Lung Cancer Screening
FROM A NURSE PRACTITIONER RUN MULTIDISCIPLINARY LUNG Program (LCSP). Methods: We reviewed individuals referred to our LCSP from
CANCER SCREENING PROGRAM 2012-2016, consisting of two separate screening sites located within
metropolitan King County, Washington. Each individual’s county and distance
Christopher Gilbert1, Joelle Fathi2, Candice Wilshire 2, Brian Louie3, Ralph
from the LCS site was calculated. Individual’s residence designation as a
Aye3, Alexander Farivar3, Eric Vallieres4, Jed Gorden1
1 geographic medically underserved/shortage area was determined. Definitions
Interventional Pulmonolgy, Swedish Medical Center and Cancer Institute, Seattle/
include: medically underserved area [MUA; healthcare resources deficient
WA/United States of America, 2Interventional Pulmonolgy and Thoracic Surgery,
Swedish Medical Center and Cancer Institute, Seattle/WA/United States of region], medically underserved population [MUP; area with economic/
America, 3Thoracic Surgery, Swedish Cancer Institute, Seattle/WA/United States of cultural/linguistic barriers to primary care services], health professional
America, 4Thoracic Surgery, Swedish Medical Center and Cancer Institute, Seattle/ shortage area [HPSA; primary care physician shortage]. Results: We identified
WA/United States of America 599 referred individuals, median age 64, from 13/39 counties (King County and
12 clustered, surrounding counties). Overall, <20% of the referred population
Background: Lung cancer screening programs are increasing in popularity resided in underserved/shortage areas and <55% of the designated
after results from the National Lung Screening Trial demonstrated geographic underserved/shortage areas in the 13 counties had patient
improvement in mortality after screening with low dose computed referrals (Table). Of those referred, 85% resided in King County, 17% in a MUA
tomography. Current guidelines recommend the availability of and 65% of the MUAs had patient referrals. Two percent of the referral
multidisciplinary care and evaluation; however, reported outcomes from population resided in a remote county, Clallam, where ≥70% of referred
multidisciplinary team decision making to proceed with diagnostic sampling households were in underserved/shortage areas.
in lung cancer screening remains sparse. Methods: A retrospective review
of patients enrolled in the Swedish Cancer Institute Lung Cancer Screening
Program from January 2013 to March 2016 was performed. The program is run
by an independently practicing nurse practitioner, with a multidisciplinary
team consisting of radiologists, interventional pulmonologists, and thoracic
surgeons. Positive screening results (nodules >6mm) with the potential need
to pursue diagnostic sampling were reviewed in a multidisciplinary fashion.
Basic demographics and procedural outcomes after the decision to biopsy
were obtained. Results: A total of 516 patients were enrolled within the lung
cancer screening program from 2013 – 2016. Nodule(s) >6mm were identified
in 164 (31.8%) patients. Subsequently, 25 (4.8%) patients underwent some
form of invasive testing. The mean age of this population was 66.2 (SD-6.7)
years with 56% (14/25) being female and mean pack years of 50.8 (SD-19.5).
Conclusion: The majority of individuals referred reside within 10 miles of the Methods: As we previously reported, a randomly selected sample of 1384
LCS site. Less than 20% reside in designated underserved/shortage areas and primary care physicians in Los Angeles County was surveyed between January
<55% of underserved/shortage areas are represented. Creative and and October 2015, using surveys sent by mail, fax, and email. The response
coordinated approaches, like Telemedicine, will be required to address the rate was 18%. Training background, years in practice, practice type, and
potential lack of LCS services in underserved/shortage areas and facilitate respondent demographics were collected. We analyzed results based on
individuals remaining in their communities. the response to a question on whether the USPSTF recommends the use of
LDCT to screen high-risk individuals for lung cancer. Results: One hundred
Keywords: lung cancer screening, Medically underserved area/population, seventeen (47%) PCPs responded that the USPSTF recommends LDCT for
Health professional shortage area, Geographically remote LCS. Of PCPs who were aware of USPSTF recommendations, 94% responded
that CT was somewhat or very effective at reducing lung cancer mortality
among individuals meeting eligibility criteria, compared with 79% who were
unaware (p=0.013). 27% of those aware of the recommendations thought
chest X-ray (CXR) was effective at reducing lung cancer mortality compared
SCREENING – with 62% of unaware PCPs (p=0.001). A similar number of PCPs in each group
MONDAY, DECEMBER 5, 2016 ordered CXR for screening over the past 12 months, but a larger proportion of
PCPs aware of guidelines ordered LDCT (69% vs 36%, p <0.001) and initiated
a discussion on screening (84% vs 59%, p<0.001) over the past 12 month. 14%
P1.03-052 THE EFFECT OF ROUNDING ON RATE OF POSITIVE
of PCPs aware of guidelines reported that benefits of LCS were not clear to
RESULTS ON CT SCREENING FOR LUNG CANCER them compared with 43% of those unaware of guidelines (p<0.001). Both
Kunwei Li1, Rowena Yip1, Ricardo Avila2, Claudia Henschke1, David Yankelevitz1 groups of PCPs reported similar scores when questioned on other barriers to
1
Radiology, ICAHN School of Medicine, New York City/NY/United States of America, screening such as insurance coverage, risks of LCS, and cost to society. There
2
Accumetra, Rexford/NY/United States of America were no differences between groups by practice size, training background,
years in practice, or PCP demographics. Conclusion: Awareness of USPSTF
Background: Effective management of small pulmonary nodules to reduce
recommendations for lung cancer screening is associated with the perception
frequency of false positives has been one of the most challenging issues
of benefit of LDCT and with increased utilization of LDCT for screening.
to implementation of screening. Measurement of size is important as it
Educational interventions for PCPs may improve adherence with LCS
determines whether a nodule is positive result and also whether growth
recommendations.
has occurred. Lung-RADS v.1 guideline requires nodule measurement to be
rounded to the nearest whole number, it is not specified whether individual Keywords: cancer screening, survey research, lung cancer, low-dose CT
length and width measures should also be rounded prior to rounding
the diameter. An alternative approach is the one used in I-ELCAP where
measurements were recorded to one decimal place. This study explored how
rounding would affect the frequency of positive results both for baseline and
annual rounds. Methods: Using data collected from CT screenings of 21,136 POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
I-ELCAP participants, we evaluated four different approaches for calculating MONDAY, DECEMBER 5, 2016
the nodule diameter (D) based on measurements of the length (L) and width
(W) listed below: 1) Measurement of L and W to one decimal place (x.x) and
calculation of D without rounding; 2) rounding D to the nearest integer; 3) P1.03-054 QUANTITATIVE ACCURACY AND LESION DETECTABILITY
rounding the L and W measurements to the nearest integer before calculating OF LOW-DOSE FDG-PET FOR LUNG CANCER SCREENING
D with no further rounding; and 4) rounding the calculated D determined by Ivan Tham1, Joshua Schaefferkoetter2, Anne Therese Sjoeholm2, Maurizio
method 3 to the nearest integer. Threshold of positive results was 6.0 mm for Conti3, John Tam4, Ross Soo5, David Townsend2
baseline round and 4.0 mm for annual repeat rounds of screening. Frequency 1
National University Cancer Institute Singapore, Singapore/Singapore, 2 A*star/
of positive results in the baseline and annual repeat rounds were compared. nus Clinical Imaging Research Centre, Singapore/Singapore, 3Siemens Healthcare
Results: For baseline screening using the current I-ELCAP definition (Method Molecular Imaging, Knoxville/TN/United States of America, 4Department of
1), the rate of positive results was 10.2%. Using method 2, 3 and 4, positive Surgery, National University of Singapore, Singapore/Singapore, 5Medical
rates were 12.8%, 10.5% and 13.2%, respectively. Use of rounding would Oncology, National University Cancer Institute Singapore, Singapore/Singapore
have increased the frequency of positive results by 25.7%, 3.0%, and 28.9%,
respectively. Of 85,877 repeat screenings, the rate of positive results was Background: Low-dose computed tomography (CT) screening for high-risk
8.0% using method 1. Using method 2, 3 and 4, positive rates were 9.7%, patients can reduce lung cancer mortality, but false-positivity rates are
8.3% and 9.8%, respectively. Use of rounding would have increased the high. Positron emission tomography (PET)/CT is more accurate compared
frequency of positive results on repeat screenings by 20.5%, 3.2%, and 22.3%, to CT alone, but typically is associated with a higher radiation exposure. We
respectively. Conclusion: Regardless of where the rounding occurred, it results investigate a low radiation dose PET/CT solution without compromising
in more nodules designated as positive. This effect is most pronounced when quality. Methods: Twenty lung cancer patients were scanned with PET/
the rounding occurs in average diameter, and since frequency of nodules CT after an uptake period of 60 min, following injection of 5.9±0.14 mCi
increases as size decreases, small nodules are therefore the most frequent 18F-Fluorodeoxyglucose. All were scanned with 2 beds covering the lungs at
cause for positive results and rounding can lead to large increases in positive 10 min each, resulting in 120±25 x106 mean true coincident counts per bed.
rates. Reduced doses were simulated by randomly discarding events in the PET list
mode according to 9 predefined true count levels, from 20 to 0.25 x106. For
Keywords: CT screening, nodule measurement, positive results, rounding each patient & simulated dose, the highest possible number of independent
numbers realizations was generated & reconstructed, up to 50. The reconstruction
algorithm was OP-OSEM, using TOF and PSF, with 2 iterations, 21 subsets
& 5mm smoothing, producing 400x400 image matrices with voxel size
2.04x2.04x2.03mm. At each simulated dose, lesions consistent with those of
early lung cancer were identified & classified by metabolic volume, signal-
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING to-background contrast, mean & max SUV, lesion-to-background SNR, &
SCREENING –
MONDAY, DECEMBER 5, 2016 Hotelling observer SNR. Bias & stability of the lesion activity measurements
were evaluated across all simulated dose levels, and detectability was
determined by various human-trained, numerical observer models. Results:
P1.03-053 THE EFFECT OF PRIMARY CARE PHYSICIAN KNOWLEDGE Twelve isolated lung lesions (mean volume 2.61±2.86 cm3 on CT) were studied
OF LUNG CANCER SCREENING GUIDELINES ON PERCEPTIONS AND in detail. Analyses of bias & reproducibility in the lesion activity values
UTILIZATION OF LOW DOSE CT showed that measurements were stable until the count levels approached
Dan Raz 1, Geena Wu2, Martin Consunji2, Rebecca Nelson1, Heeyoung Kim1, extreme conditions. Bias in the lesion VOI mean & max SUV were relatively
Canlan Sun3, Virginia Sun4, Jae Kim5 negligible until true count level was decreased to 1 million. Variance on
1 reproducibility of lesion values showed a more dramatic trend, but standard
City of Hope, Duarte/United States of America, 2Thoracic Surgery, City of Hope
National Medical Center, Duarte/CA/United States of America, 3City of Hope, deviation was still around 10% at 5 million counts. Conclusion: We show that
Duarte/CA/United States of America, 4Division of Nursing Research & Education, simulated images with accurate lesion characteristics can be obtained at 1/12
Department of Population Sciences, City of Hope, Duarte/CA/United States of of a typical radiotracer dose.
America, 5Division of Thoracic Surgery, Department of Surgery, City of Hope,
Duarte/CA/United States of America Keywords: low dose, lesion detectability, PET/CT, lung cancer screening
Background: Lung cancer screening with low-dose computed tomography

(LDCT) is recommended by the U.S. Preventive Services Task Force (USPSTF)
in high-risk patients, but a minority of eligible people is screened. It is
unknown whether knowledge of USPSTF recommendations among primary
care physicians (PCP) impacts perceived benefits and utilization of LDCT.

POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING to date with 100 lung cancer diagnoses within our lung screening program.
SCREENING –
In 2014, funding (LUNGevity and Robert E Wise grants) was obtained for
biospecimen collection from subjects enrolled in our institutional LDCT
screening program. Initial prospective collection of biospecimens was slower
P1.03-055 LUCAS DA: A LUNG CANCER SCREENING DECISION AID than anticipated due to various factors. After review of the process, a number
TO IMPROVE SCREENING DECISIONS of adjustments were made, which significantly increased enrollment. This
Jamie Studts 1, Kory Brinker 1, Stacey Tannenbaum2, Margaret Byrne2 included implementation of a multidisciplinary taskforce consisting of
1 research and clinical staff committed to patient outreach and participation.
University of Kentucky, Lexington/KY/United States of America, 2Public Health
Sciences, University of Miami, Miami/FL/United States of America To date, samples from approximately 1420 subjects have been collected.
Of these, 268 (19%) were found to have newly detected IPNs measuring
Background: Although lung cancer (LC) continues to be one of the leading 6-20mm on LDCT, and 28 samples were from patients with subsequent
causes of cancer morbidity and mortality world-wide, the NLST trial showed diagnoses of lung cancer. Conclusion: Successful coordination of biospecimen
that low dose computed tomography (LDCT) screening can substantially collection within a lung screening program is complex, but achievable with
reduce mortality in specific high-risk populations. However, most individuals multidisciplinary coordination, and has great potential to help further
are not making informed decisions which take into account the risks of stratify patients that may or may not benefit from invasive diagnostics and
screening although US guidelines advocate for informed decision-making. We therapy. We demonstrate an established lung screening program that is
report preliminary results of a web-based interactive LC decision aid (LuCaS successfully accruing to a prospective diagnostic study and share specific
DA) on LC screening knowledge and decision making compared to the US recommendations for how to successfully accrue in other programs.
National Cancer Institutes’ web-pages on LC screening. Methods: Individuals
in the study (n=50; from rural Kentucky and SE Florida, USA) had an elevated Keywords: biospecimen, blood sample, Lung Screening, Indeterminate
risk for lung cancer (n=50) due to smoking. Participants completed a baseline pulmonary nodule
survey and were randomized to viewing the LuCaS DA or the NCI website.
After 2 weeks, participants completed an online survey. Surveys collected
information on: demographics, health status, smoking history, knowledge of
CT screening, decisions about being screened for lung cancer, and decisional POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
conflict about screening. Results: Participants were 52.6 (SD 5.1) years old SCREENING –
on average; were majority female (77.1%), White (62.0%), and non-Hispanic MONDAY, DECEMBER 5, 2016
(83.7%), and reported have some insurance coverage (88.0%). Most were
current daily smokers (70.2%), and overall had smoked an average of 27.9
P1.03-057 ASSESSMENT OF LUNG CANCER RISK- REGIONAL
(SD 7.7) years. Mean Decisional Conflict overall participants was 39.3 (SD
RESPIRATORY DISEASE SCREENING REPORT IN JILIN, CHINA
13.5) at baseline and 34.4 (SD 11.1) at 2 week follow up, with no differences
between the arms. The percentage of participants show stated that they had Jie Zhang, Yan Xu, Peng Gao, Guang Meng, Qi Wang, Jun Li, Xue Lv, Yu Hao,
made a decision about screening increased slightly from 32.7% at baseline Hong Zhou
to 37.5% at follow up. Preparedness for making a decision about screening Respiratory Medicine, Second Affiliated Hospital of Jilin University, Changchun/
(measured POST only) showed no differences between the arms. There were China
some increases in knowledge about CT screening and knowledge about LCS
Background: Both morbidity and mortality of lung cancer ranks first in China.
guidelines from initial to 2-week follow up. Finally, a qualitative exploration
According to the “2012 cancer registration report of China”, Northeast China
of the LuCaS DA showed that it had high levels of acceptability. Conclusion:
is a high prevalence area of lung cancer, so early diagnosis of lung cancer
DAs can facilitate informed decisions about participation in cancer screening,
is particularly important. Based on this, we made the regional survey in
and US policies have required their use. This is the first study that we are
Changchun city. (1) To investigate the incidence of pulmonary nodules and
aware of that assesses the use and effects of a lung cancer screening decision
lung cancer in Changchun city. (2)To provide the foundation of large data
aid. These preliminary results show that the LuCaS DA can improve some
study on early screening of lung cancer and disease control. Methods: Carry
outcomes, but not consistently more than the NCI webpages. Additional
out the investigation of the people over 50 years of age in 10 communities in
analyses will include the full sample of participants, evaluate a broader array
Changchun of Jilin Province (A total of 1461 people), including questionnaire,
of decision and behavioral outcomes, and consider longer term outcomes of
pulmonary function tests and low-dose spiral CT examination. The disease
the LuCaS DA.
assessment and patient management are based on “Diagnosis and treatment
Keywords: decision aids, Lung cancer creening, decision-making of pulmonary nodules in Chinese expert consensus”. Results: The percentage
of lung disease in the investigated population was 25.67%, and the
constitution of the lung disease included: 30.67% of the lung nodules, 37.07%
of chronic obstructive pulmonary disease, 18.67% of inflammation, 5.6% of
the lung, 2.13% of pulmonary interstitial fibrosis, 2.13% of pleural effusion
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING and 3.73% of other lung diseases. The number of pulmonary nodules was 115,
SCREENING –
accounting for 7.87% of the total number of screening, 89 cases of solitary
nodules, 26 cases of multiple nodules. A total of 4 patients with lung cancer
were confirmed by pathology, including 2 cases of adenocarcinoma, 1 cases of
P1.03-056 IMPLEMENTATION OF A PROSPECTIVE BIOSPECIMEN squamous cell carcinoma and 1 case of mucinous carcinoma of the lung. All of
COLLECTION STUDY IN AN ESTABLISHED LUNG CANCER the cancer cases were solitary nodules, and accounted for 3.48% of the total
SCREENING PROGRAM samples. Among them, 3 patients are male with a history of smoking, and 1
is female without any history of smoking. According to the nodule size, the
Jacob Sands 1, Katrina Steiling2, Travis Sullivan3, Sebastian Flacke3, Kimberly
diameters of nodule in 3 cases are greater than 8mm and 1 case is less than
Rieger-Christ3
1 4mm. According to the quality of nodules, 3 cases are solid and mixed nodules,
Oncology, Lahey Hospital & Medical Center, Burlington/MA/United States of
and 1 case is ground-glass opacity. Conclusion: (1)Smoking is a risk factor for
America, 2Boston Medical Center, Boston/United States of America, 3Lahey
Hospital & Medical Center, Burlington/MA/United States of America lung cancer. (2) Solid and mixed character nodules in pulmonary nodules and
larger diameter nodules are more likely to develop into cancer, so they should
Background: Complexities such as addressing indeterminate pulmonary be strengthened management. (3) Low-dose spiral CT is helpful for early
nodules (IPNs) are an inherent part of a lung screening program, and defining diagnosis of lung cancer.
which individuals will benefit from invasive intervention is not always
known. With the goal of combining non-invasive biomarkers with imaging Keywords: Low-dose spiral CT, lung cancer, pulmonary nodules
to more definitively stratify patients, we initiated an investigational
biospecimen collection process into our lung screening program. Ultimately,
these biomarkers may improve specificity within the screening population,
thereby reducing the overall cost and potential morbidity from false positive POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
results of low-dose computed tomography scan (LDCT) screening. Studies SCREENING –
like this are important to the ongoing improvement of lung cancer screening. MONDAY, DECEMBER 5, 2016
Methods: NCCN high-risk individuals enrolled in a high volume clinical lung
screening program were introduced to our IRB approved research biospecimen
P1.03-058 COST-EFFECTIVENESS OF CT SCREENING IN THE EARLY
study at the time of the scheduling of their LDCT. Patients were consented,
DETECTION OF LUNG CANCER
and routine biospecimens were collected by research staff at the time of
their LDCT scan, including nasal epithelial brushings, buccal swabs and Tomasz Szczęsny 1, Małgorzata Kanarkiewicz2, Janusz Kowalewski3
1
blood. When available, additional biospecimens consisting of bronchial Department of Thoracic Surgery and Tumors, Franciszek Lukaszczyk Memorial
airway brushings and tumor samples were collected from subjects who Oncological Center in Bydgoszcz, Bydgoszcz/Poland, 2Department of
underwent diagnostic interventions for suspicion of malignancy. Results: Pharmacology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in
Torun, Bydgoszcz/Poland, 3Department of Thoracic Surgery and Tumors, Collegium
Since 2012 there have been 3856 patients enrolled and 8776 LDCT scans
Medicum, Nicoalus Copernicus University in Torun, Bydgoszcz/Poland Keywords: Evaluation, high risk lung cancer screening
Background: Screening using computerized tomography of the chest for an

early detection of lung cancer has been performed worldwide since decades,
but only two years ago, after proving in a prospective randomized study that
it prolongs survival of the study population, it received the recommendation POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
SCREENING –
of scientific societies. However, the issue of cost-effectiveness of this MONDAY, DECEMBER 5, 2016
screening remains open. Methods: A review of several cost-effectiveness
analyses of lung cancer screening with low-dose CT available in the literature
was performed. We also conducted our own cost-effectiveness analysis on P1.03-060 LUNG CANCER SCREENING: A QUALITATIVE STUDY
the basis of epidemiological data and data from the National Health Fund EXPLORING THE DECISION TO OPT OUT OF SCREENING
concerning the type, number and cost of medical procedures reimbursed Lisa Carter-Harris 1, Susan Brandzel2, Joshua Roth3, Karen Wernli2, Diana
for lung cancer patients. Results: The results of cost-effectiveness analyses Buist2
carried out in different countries are equivocal and depend mainly on the 1
School of Nursing, Indiana University, Indianapolis/IN/United States of America,
inclusion and exclusion criteria, methods of analysis and prices of medical 2
Group Health Research Institute, Group Health, Seattle/WA/United States of
procedures. More recent analyses, performed in different countries, indicate America, 3Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson
high profitability of this screening. In our study, the cost of early detection of Cancer Research Center, Seattle/United States of America
one lung cancer using CT scan is comparable to the cost of a detection of one
breast cancer using mammography and is about 3,400 Euro. The incremental Background: Lung cancer screening (LCS) with annual low-dose computed
cost-effectiveness ratio (ICER) in our analysis is about 1180 Euro / life year tomography is relatively new for long-term smokers in the US supported by a
gained. Conclusion: As the widely accepted limit of cost-effectiveness is US Preventive Services Task Force Grade B recommendation. As LCS programs
three times the gross national product per capita / life year gained, lung are more widely implemented and providers engage patients about LCS, it is
cancer screening with low-dose CT in Poland should be considered highly critical to understand what influences the decision to screen, or not, for lung
cost-effective. In future screening programs, high cost-effectiveness can be cancer. Understanding LCS behavior among high-risk smokers who opt out
achieved by strict adherence to inclusion and exclusion criteria. To ensure provides insight, from the patient perspective, about the shared decision-
this, screening should be performed either as prospective observatory non- making (SDM) process. This study explored LCS-eligible patients’ decision to
randomized clinical trials or in dedicated screening centers. To ensure low opt out of LCS after receiving a provider recommendation. New knowledge
level of false positive and false negative results, radiologists in screening will inform intervention development to enhance SDM processes between
centers should be equipped with software for measuring and monitoring the high-risk smokers and their provider, and decrease decisional conflict about
volume of pulmonary nodules. LCS. Methods: Semi-structured qualitative interviews were performed
with 18 LCS-eligible men and women who were members of an integrated
Keywords: cost-effectiveness analysis, lung cancer screening, ICER, cancer healthcare system in Seattle about their decision to opt out of screening.
screening Participants met LCS criteria for age, smoking and pack-year history. Audio-
recorded interviews were transcribed verbatim. Two researchers with cancer
screening and qualitative expertise conducted data analysis using thematic
content analytic procedures. Results: Participant mean age was 66 years (SD
6.5). Majority were female (61%), Caucasian (83%), current smokers (61%).
SCREENING –
Five themes emerged: 1) Knowledge Avoidance; 2) Perceived Low Value;
MONDAY, DECEMBER 5, 2016 3) False Positive Worry; 4) Practical Barriers; and 5) Misunderstanding.
Representative thematic example quotes are presented in the Table below.
P1.03-059 ORGANIZED HIGH RISK LUNG CANCER SCREENING IN

Knowledge Avoidance
ONTARIO, CANADA: A MULTI-CENTRE PROSPECTIVE EVALUATION
Martin Tammemägi1, Joanne Hader2, Monica Yu2, Kiran Govind2, Erin Svara2, “It’s fear of the unknown…if I know, you have to follow through and do more
Marta Yurcan2, Beth Miller2, Gail Darling2 and more.”
1
Health Sciences, Brock University, St. Catharines/Canada, 2Cancer Care Ontario, Perceived Low Value
Toronto/ON/Canada
“It could show me if I had lung cancer…what are they going to do?...screening
Background: Guidelines published in Ontario Canada in 2013, recommend doesn’t really make any difference...”
screening individuals at high risk of lung cancer with low-dose computed
False Positive Worry
tomography through an organized program. Cancer Care Ontario, Ontario’s
provincial cancer agency, is implementing a prospective evaluation of “I did schedule one…then after I read the print out, I canceled it…the false
organized high risk lung cancer screening (HRLCS) in a 2-year, multi-centre positives were so high. I thought why… that would be so stressful…”
pilot. The pilot evaluation aims to inform: · Recommendations to Ontario’s
Practical Barriers
Ministry of Health and Long Term Care regarding the potential for a
provincial program · Optimal program design and requirements for effective “I really didn’t have time to get over there.”
implementation. Methods: The process to establish a robust evaluation plan
Misunderstanding
for the HRLCS pilot included the development of a logic model, evaluation
objectives and evaluation questions. Input from a multidisciplinary panel of “I wasn’t hurting or having any problems breathing…wasn’t a top priority for
experts, including clinicians, epidemiologists, and administrators guided the me” [reflecting misunderstanding of the concept of screening]
development of the evaluation plan. A modified Delphi technique facilitated
panel input on the proposed evaluation questions, which were drafted based Conclusion: Many screening-eligible smokers opt out of LCS. Participants in
on the logic model and evaluation objectives, and aligned to the steps in the our study provided new insights into why some patients make this choice.
screening pathway. Panel members rated the importance of each evaluation LCS is effective in early lung cancer detection among high-risk patients.
question through an online survey using a 5-point Likert scale, and proposed However, LCS has associated risks and harms making the SDM process critical.
changes or additional questions. A question was retained if >75% of panel Understanding why people decide not to screen will enhance future efforts
members rated it as important or very important. A facilitated discussion post to improve knowledge transfer from providers to patients about the risks and
survey enabled a review of survey results to confirm consensus on the final benefits of LCS and ultimately enhance SDM about screening.
set of evaluation questions. Results: The survey was completed by all panel
Keywords: health behavior, qualitative, decision making, lung cancer
members. Of 32 evaluation questions proposed, 31 were rated as important
screening
or very important by more than 75% of respondents. Endorsed questions
addressed both screening processes and key outcomes, and included, for
example: · Did recruitment strategies engage individuals representative of
the eligible population? · Did the follow-up processes occur as intended? · Did
screening identify early stage lung cancers? Panel discussion led to retention POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
of the single question that did not meet the threshold, and the addition of SCREENING –
one new question to the evaluation plan. Given consensus was achieved, a
second round modified Delphi survey was not required. Conclusion: Using
an expert panel and modified Delphi technique was an effective method to P1.03-061 PATIENT MOTIVATIONS FOR PURSUING LOW-DOSE
obtain consensus on the pilot evaluation questions. Endorsed evaluation CT LUNG CANCER SCREENING IN AN INTEGRATED HEALTHCARE
questions will frame the development of measures and indicators to be
SYSTEM: A QUALITATIVE EVALUATION
assessed throughout the pilot. This comprehensive evaluation strategy will
inform the design and implementation of a high quality organized HRLCS Joshua Roth1, Susan Brandzel2, Lisa Carter-Harris3, Diana Buist2, Karen
screening program. Wernli2

1
Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer whether LDCT screens could decrease healthcare costs is yet insufficiently
Research Center, Seattle/United States of America, 2Group Health Research explored. The objectives of the present study was to investigate whether
Institute, Group Health, Seattle/WA/United States of America, 3School of Nursing, LDCT screening is capable to reduce the lung cancer mortality by at least
Indiana University, Indianapolis/IN/United States of America 20% and analyze the healthcare costs of the lung cancer LDCT screening in
China. Methods: The present study is a randomized controlled trial of LDCT
Background: Low-dose CT (LDCT) lung cancer screening for heavy smokers was
screening for lung cancer versus usual care. Eligible participants were those
given a ‘B’ rating by the U.S. Preventive Services Task Force (USPSTF) in 2013,
aged 45–70 years, and with either of the following risk factors: 1) history of
and gained widespread insurance coverage in the U.S. in 2015. Little is known
cigarette smoking ≥ 20 pack-years, and, if former smokers, had quit within the
about patient motivations for pursuing lung cancer screening outside of
previous 15 years; 2) malignant tumors history in immediate family members;
clinical trials because it is a relatively new covered service. The objective of
3) personal cancer history; 4) professional exposure to carcinogens; 5) long
this study was to understand some of the major factors that motivated
term exposure to second-hand smoke; 6) long term exposure to cooking
patients to pursue LDCT lung cancer screening in an integrated healthcare
oil fumes. All the participants were randomized into a screening arm with
system. Methods: We conducted a semi-structured qualitative interviews
three rounds of alternate years LDCT screens and a control arm with three
with 20 adult men and women who were members of an integrated healthcare
rounds of alternate years questionnaire inquiries. Management of positive
system in Washington State about their choice to receive LDCT lung cancer
screening test was carried out by a prespecified protocol. Results: From
screening. Participants met USPSTF screening criteria for age and smoking
November 2013 to November 2014, 5933 participants were enrolled in our
history. Trained staff contacted a total of 25 randomly selected eligible
trail, of which 2933 were assigned to LDCT screening arm, and 3000 to control
participants and completed 20 interviews (80% response rate) in the Fall of
arm. In the first screening round, 2892 participants (98.6%) undergo LDCT
2015. The interviews were recorded, transcribed, and three investigators used
after randomization. At baseline 742 subjects (25.7%) showed noncalcified
inductive content analysis to identify themes about motivations for pursuing
nodules (NCN) larger than 4 mm. 69 cases were highly suspected of lung
screening. Results: Participant mean age was 68 years, 40% were male, 90%
cancer according to the suggestion of three experienced experts. The highly
were Caucasian, and 35% were current smokers. Analysis of interview
suspected cases were accounting for 9.30% of all NCN subjects and 2.39%
transcripts identified 6 primary themes (Table 1) that were common
of all the screening arm participants. By March 2016, 26 cases underwent
motivations for pursuing LDCT lung cancer screening: 1) early-detection
surgical resections, including 23 lung adenocarcinoma, 1 lung squamous cell
benefit, 2) limited understanding of LDCT harms, 3) relatively low radiation
carcinoma and 2 benign lesions, representing a positive lung cancer detection
dose, 4) trust in the referring clinician, 5) friends and family with advanced
rate with low-dose CT screening of 0.83%(24/2892). Among all the lung cancer
cancer, and 6) low out-of-pocket cost.
cases, 23/24 (95.8%) had stage I disease, and 1/24 (4.2%) had stage II disease.
The second round screening was still ongoing since May 2016. Conclusion:
Screening with LDCT increases the detection rate of early stage lung cancers
(stage I and II) in a high risk population.
Keywords: lung cancer screening, low-dose CT, high risk population

SCREENING –
P1.03-063 QUANTITATIVE IMAGING FEATURES PREDICT INCIDENCE

LUNG CANCER IN LOW-DOSE COMPUTED TOMOGRAPHY (LDCT)
SCREENING
Dmitry Cherezov1, Samuel Hawkins1, Dmitry Goldgof 1, Lawrence Hall1,
Yoganand Balagurunathan2, Robert Gillies3, Matthew Schabath4
1
University of South Florida, Tampa/FL/United States of America, 2Moffitt Cancer
Center, Tampa/FL/United States of America, 3Radiology and Cancer Imaging,
Moffitt Cancer Center, Tampa/FL/United States of America, 4 Cancer Epidemiology,
H Lee Moffitt Cancer Center and Research Institute, Tampa/FL/United States of
America
Background: Although the NLST demonstrated a benefit of LDCT screening

for reducing lung cancer and all-cause mortality, LDCT screening identifies
large numbers of indeterminate pulmonary nodules and there are limited
clinical decision tools that predict probability of cancer development. Using
data and images from the NLST, we extracted quantitative imaging features
Conclusion: The participants in our study were motivated to obtain lung from nodules of baseline positive screens (T0) and delta features from T0 to
cancer screening based on perceived benefit of early-detection, an absence first follow-up (T1) and performed analyses to identify imaging features that
of safety concerns, social factors, and low expense. Our findings provide new predict incidence lung cancer. Analyses were stratified by nodule size since
insights about patient motivations for pursuing LDCT screening, and can be guidelines in the U.S. have increased the size threshold for positivity to 6 mm.
used to improve lung cancer screening shared decision-making processes. Methods: We extracted 438 features from T0 nodules, and delta features
from T0 to T1, including size, shape, location, and texture information.
Keywords: false-positive, qualitative, Screening, computed tomography
Nodules were identified for 170 cases that were diagnosed with incidence lung
cancer at the first (T1) or second (T2) follow-up screen and for 328 controls
that had three consecutive positive screens (T0 to T2) not diagnosed as lung
cancer. The cases and controls were split into a training cohort and a testing
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING cohort and classifier models (Decision tree-J48, Rule Based Classier-JRIP,
SCREENING – Naive Bayes, Support Vector Machine, Random Forests) that were stratified
MONDAY, DECEMBER 5, 2016 by nodule size (< 6 mm, 6 to 16 mm, ≥ 16 mm) were used to identify the most
predictive feature sets. Results: The training cohort consisted of 83 cases
P1.03-062 LUNG CANCER SCREENING WITH LOW-DOSE CT IN and 172 controls and a testing cohort of 77 cases and 135 controls. Within
and across each cohort, there were no significant differences in demographic
CHINA: STUDY DESIGN AND BASELINE RESULTS FROM THE FIRST
and clinical covariates. Training and testing was first performed using three
ROUND SCREENING ARM difference nodule size groups (< 6 mm, 6 to 16 mm, and ≥ 16 mm) which
Huimin Wang1, Yanwei Zhang1, Jiajun Teng1, Qunhui Chen1, Jianding Ye1, Jiatao revealed for < 6 mm a final model of 5 features (AUROC=0.75), 6 to 16 mm a
Lou1, Rong Shi2, Liyan Jiang1, Aiqin Gu1, Yizhuo Zhao1, Bo Jin1, Xueyan Zhang1, final model with 10 features (AUROC=0.73), and ≥ 16 mm a final model with
Jianlin Xu1, Yuqing Lou1, Fangfei Qian1, Wenjia Yang1, Baohui Han1 10 features (AUROC=0.83). Finally, we combined the two larger groups and
1
Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai/China, found for ≥ 6 mm a final model with 10 features with an AUROC of 0.84 (95% CI
2
Shanghai Jiao Tong University, Shanghai/China 0.8-0.87), Sensitivity of 60% (95% CI 0.50-0.71), and Specificity of 95% (95% CI
0.92-0.99). Conclusion: In this analysis we revealed a set of highly informative
Background: Lung cancer screening with low-dose CT (LDCT) was shown to
imaging features that predicts subsequent development of incidence lung
reduce lung cancer mortality by 20% in the National Lung Screening Trial.
cancer among individuals presenting with a ≥ 6 mm nodule. These imaging
However, several other trails have reported that there was no reduction
features could be scored in the clinical setting to improve nodule management
in lung cancer mortality with a LDCT screening strategy. Meanwhile,
of current size-based screening guidelines.
Keywords: NLST, Radiomics, LDCT, lung cancer screening and small cell lung cancer (SCLC) in our Institution, where we are a regular
contributor of a subset of cases for the IASLC TNM staging revision projects.
Methods: Data was collected from the Queensland Cancer Control Analysis
Team (QCCAT) Queensland Oncology Online (QOOL) registry of NSCLC or SCLC
cases presented to The Prince Charles Hospital (TPCH) between 2000 and
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING 2015. It was validated against Queensland Integrated Lung Cancer Outcomes
SCREENING –
MONDAY, DECEMBER 5, 2016 Project (QILCOP) registry with case identification number, first name, last
name, and date of birth. Cases were classified according to IASLC TNM
revisions 7th edition and then according to the proposed TNM revisions and
P1.03-064 CHEST X-RAY (CXR) SCREENING IMPROVES LUNG stage groupings where data available. Kaplan-Meier curves were plotted and
CANCER (LC) SURVIVAL IN THE PROSTATE LUNG COLON AND OVARY survival differences tested with Log-Rank test using SPSS Statistics ver. 23.
(PLCO) RANDOMIZED POPULATION TRIAL (RPT) Results: The entire study population consisted of three thousand six hundred
John Paul Flores 1, Alejandro Moreno-Koehler2, Matthew Finkelman3, Jaime and thirty-seven cases. One thousand three hundred and ninety-two non-
Caro4, Gary Strauss2 surgical patients had complete clinical staging and one thousand and fifteen
1
Hematology/Oncology, Tufts Medical Center, Boston/United States of America, patients with pathological staging were identified. Median survival in clinical
2
Hematology/Oncology, Tufts Medical Center, Boston/MA/United States of staging by the 7th edition showed progressive reduction in median survival
America, 3Biostatistics, Tufts School of Dental Medicine, Boston/MA/United States with increasing Stage (IA:1480, IB:714, IIA:715, IIB:391, IIIA:399, IIIB285, IV:196;
of America, 4Evidera, Waltham/MA/United States of America days) which was similar in the proposed 8th edition staging noting small
numbers in IA1 (IA1:1385, IA2:2098, IA3:1004, IB:801, IIA:550, IIB:589, IIIA:448,
Background: The effectiveness of CXR-screening for LC was estimated in IIIB285, IIIC:265, IVA:218, IVB:106; days). A similar pattern was reflected in
the context of performing a cost-effectiveness analysis of LC-screening pathological staging 7th edition TNM staging (IA:3725, IB:3486, IIA:1796,
comparing CT, CXR, and no screening. CXR-screening has long been considered IIB:1209, IIIA:841, IIIB:587, IV:869; “days) and in the proposed 8th edition
ineffective because no RPT has demonstrated a LC mortality reduction. staging (IA1:1929, IA2:3586, IA3:3804, IB:3640, IIA:2977, IIB:1796, IIIA:949,
However, CXR-screening has been shown to produce a significant survival IIIB:723, IVA:869; “days”). Log-Rank test in all the survival curves were <0.001.
advantage not attributable to overdiagnosis or other screening biases Conclusion: The proposed 8th edition TNM classification appears to be a more
(JCO:20,1973,2002). The lung portion of the PLCO trial, which compared CXR refined predictor of prognosis. However, our cohort only had small sample
to no screening, reported no LC mortality reduction after 13-years follow-up sizes for Stage I cases, which need validation and further hazard ratio and
(JAMA,306,1875,2011). However, that analysis included all LCs diagnosed multivariate analysis is recommended. Acknowledgements: patients and staff
over 13-years, despite the fact that the active screening period lasted at TPCH and UQTRC
only 3-years. LC survival was not reported. Since screening is exceedingly
unlikely to provide any advantage to individuals diagnosed many years after Keywords: 8thedition, validation, Staging, survival
active screening is discontinued, and because sojourn time associated with
CXR-screening is estimated to be up to 4 years, we evaluated outcomes of
LCs diagnosed within 7-years of randomization in PLCO. Methods: PLCO
randomized 77,445 subjects to an experimental group (EG) undergoing
a prevalence CXR and 3 annual incidence CXRs and 77,456 others to an POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
STAGING –
unscreened control group (CG). Using Kaplan-Meier methods in the intent- MONDAY, DECEMBER 5, 2016
to-screen analysis of PLCO data, LC survival and mortality were calculated
for all LCs diagnosed during the 13-year follow-up, as well as those diagnosed
within 7 years of randomization. LC incidence and mortality were compared P1.03-066 INCORPORATION OF A MOLECULAR PROGNOSTIC
with Fisher’s exact test. Survival was compared with the log-rank test. All CLASSIFIER IMPROVES CONVENTIONAL NON-SMALL CELL LUNG
p-values are two-sided. Results: After 13-years, 1,838 and 1,737 lung cancers CANCER TNM STAGING
were detected in EG and CG, respectively (RR=1.06; 95%CI 0.99-1.13; p=0.09). Johannes Kratz1, Nancy Cook2, Gavitt Woodard1, Kirk Jones3, Matthew
Median survival was 13.2-months vs. 11.5-months, and 5-year survival was Gubens4, Thierry Jahan4, Il-Jin Kim1, Biao He5, David Jablons1, Michael Mann5
24% vs. 19% in EG and CG respectively (p=0.0008). There were 1,217 and 1,203 1
Thoracic Surgery, University of California, San Francisco/CA/United States of
LC deaths, indicating no LC mortality reduction (RR=1.01; 95%CI: 0.93-1.09; America, 2Department of Epidemiology, Brigham and Women’s Hospital, Boston/
p=0.77). Within 7-years of randomization, 1,072 and 1,022 lung cancers were AL/United States of America, 3Pathology, University of California, San Francisco,
detected in EG and CG, respectively (RR=1.05; 95%CI 0.96-1.14; p=0.27). Median San Francisco/United States of America, 4Hematology and Oncology, University
survival was 15.4-months vs. 11.5months, and 5-year survival was 27% vs. 18% of California, San Francisco, San Francisco/CA/United States of America, 5Thoracic
in EG and CG, respectively (p<0.0001). Among these cases, there were 764 Surgery, University of California, San Francisco/United States of America
and 811 LC deaths, indicating a trend toward reduced LC mortality that was
Background: Tumor size, nodal spread, and distant metastases form the
not statistically significant (RR=0.94; 95%CI:0.85-1.04; p=0.24) Conclusion: In
basis of current non-small cell lung cancer staging. Despite undergoing a
PLCO, randomization to CXR-screening produced a significant improvement in
major revision in 2009, the poor outcomes of early-stage lung cancer patients
LC survival. This survival advantage cannot be attributed to any conventional
relative to other solid tumors such as breast and colorectal cancer suggests
screening bias including overdiagnosis. The benefit is diminished when lung
that further improvement to our ability to stage non-small cell lung cancers
cancers diagnosed well beyond the active screening interval are included in
is needed. In this study, we demonstrate the benefit of integrating a clinically
the analysis.
validated molecular prognostic signature into conventional TNM staging.
Keywords: Screening, survival, mortality, chest X-ray Methods: A new staging system integrating a 14-gene molecular prognostic
classifier with TNM descriptors was developed using 332 patients with stage
I-IIIB non-squamous, non-small cell lung cancer resected at the University of
California, San Francisco. This staging system was subsequently validated
on a separate multi-institutional international cohort of 1379 patients
with stage I-IIIB disease. Reclassification measures were used to assess for
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/
improvements in calibration and discrimination beyond conventional TNM
SCREENING staging. Results: In the validation cohort, 78.2% of patients were reclassified
Staging – using the new staging system. 73% of these patients were reclassified more
MONDAY, DECEMBER 5, 2016 accurately. The new staging system demonstrated improved measures of
model fit including the modified Nagelkerke’s R 2 statistic as well as the
c-index. In addition, incorporation of the molecular classifier resulted in a
P1.03-065 COMPARISON OF THE PROPOSED IASLC 8TH TNM LUNG Net Reclassification Improvement of 16.6% (95%CI 7.9-25.2%) and a relative
Integrated Discrimination Improvement of 27.9% (95%CI 6.4-49.4%). Kaplan-
CANCER STAGING SYSTEM TO THE 7TH EDITION
Meier analysis of overall survival after surgical resection demonstrated
Joseph Hwang1, Barbara Page1, David Flynn2, Linda Passmore3, Elizabeth superior survival curve separation with the addition of the molecular
Mccaul3, Ian Yang 3, Morgan Windsor 1, Rayleen Bowman3, Rishendran Naidoo1, classifier. Figure 1. Kaplan-Meier analysis of overall survival from time of
Tracy Guan1, Shoni Philott1, Michael Blake1, Kwun Fong4 surgical resection (A: TNM staging, B: TNMB staging).
1
Lung Cancer Research, Thoracic Medicine, The Prince Charles Hospital, Chermside/
Australia, 2The Prince Charles Hospital, Chermside/QLD/Australia, 3Department
of Thoracic Medicine, the Prince Charles Hospital, Chermside/QLD/Australia,
4
The Prince Charles Hospital, University of Queensland Thoracic Research Centre,
Brisbane/Australia
Background: We performed a validation study of the proposed International

Association for the Study of Lung Cancer (IASLC) 8th tumour, node, metastasis
(TNM) and grouping revisions on the non-small cell lung cancer (NSCLC)

Oncology Research Group, Multidisciplinary Thoracic Oncology Program, Baptist

Cancer Center, Memphis/TN/United States of America
Background: We compared the prognostic impact of 8E to 7th Edition(7E),

using sequentially-defined surgical quality cohorts. Methods: We analyzed
curative-intent resections for non-small cell lung cancer from 2009-2016 in a
population based cohort from 4 Dartmouth Referral Regions in 3 US states.
Patients were re-staged by 8E criteria. Survival analyses used Kaplan-Meier
estimates and Proportional Hazards models with adjusted hazard ratios(aHR)
controlling for age, histology, grade, and comorbidities. Results: 548 of 2226
patients were stage-redistributed: 525(24%) up, 23(1%) down-staged. The
largest shifts were from IB to IIA (76/522 [15%]);IIA to IIB (238/251[95%]);
IIB to IIIA (88/217 [41%]); IIIA to IIIB (59/277[21%]). We found no difference
in unadjusted survival in patients upstaged to IIA compared with those
remaining in IB (p=0.55). Patients upstaged from IIB to IIIA had similar survival
to those remaining IIB (p=0.4884), but were similar to patients already IIIA
by 7E (p=0.8152). However, patients upstaged from IIIA to IIIB had worse
survival than those remaining in IIIA (p=0.0360). Sub-classification of IA had
no prognostic value when comparing IA1 vs. IA2 (p=0.74), but patients in IA3
had significantly worse survival than those in IA2 (p=0.0177). 5-year survival
estimates for IA1/IA2/IA3 were 65%, 68%, and 61% in our cohort, compared to
92%, 83%, and 77% in the IASLC database. Adjusted models indicate 8E stage
as a significant prognostic factor (p<0.0001), with increasing hazards of death
with each progressive stage beyond IA2 (Table 1). This result was reasonably
consistent as the quality of resection increased incrementally from: All
Patients, excluding margin-positives, excluding margin-positives and pNX
resections, excluding margin-positives and resections without mediastinal
nodes(MedNX).
3-Year
IASLC 8th- 5-Year Survival
Survival
Edition Estimate
Estimate
Stage (95% CI)
(95% CI)
0.80(0.69-
IA1(N=91) 0.65(0.48-0.77)
0.88)
0.80(0.75-
IA2(N=454) 0.68(0.62-0.73)
0.84)
0.71(0.65-
IA3(N=312) 0.61(0.54-0.68)
0.76)
0.67(0.63-
IB(N=509) 0.55(0.49-0.60)
0.72)
0.66(0.53-
IIA(N=81) 0.61(0.48-0.72)
0.76)
0.59(0.53-
IIB(N=375) 0.45(0.39-0.52)
0.64)
0.50(0.43-
IIIA(N=302) 0.41(0.34-0.48)
0.56)
0.39(0.26-
IIIB(N=62) 0.29(0.18-0.42)
0.52)
0.44(0.26-
IV(N=40) 0.44(0.26-0.61)
0.61)
Adjusted
Hazard
Ratios by
Conclusion: Incorporation of a molecular classifier of tumor biology offers Quality
substantial improvements to conventional TNM staging and encourages Parameters
application of molecular prognostic classifiers into the refinement of TNM
Exclude Exclude
staging systems for other solid tumors. All Exclude
Margin+/ Margin+/
Patients Margin+
Keywords: Prognosis, NSCLC, Staging, Molecular pNX MedNX
(N=2195) (N=2090)
(N=1939) (N=1656)
IA1 1.00 1.00 1.00 1.00
IA2 0.83 0.83 0.70 0.75
STAGING – IA3 1.12 1.11 1.00 1.13
IB 1.30 1.26 1.11 1.23
IIA 1.34 1.27 1.11 1.25
P1.03-067 VALIDATION OF THE IASLC 8TH EDITION (8E) TNM
CLASSIFICATION FOR NON-SMALL CELL LUNG CANCER BY THE IIB 1.72 1.69 1.56 1.69
QUALITY OF SURGICAL RESECTION IN A US COHORT IIIA 2.40 2.31 2.11 2.45
Matthew Smeltzer 1, Nicholas Faris2, Carrie Fehnel2, Cheryl Houston-Harris2,
IIIB 3.73 3.21 2.95 3.41
Meredith Ray1, Yu-Sheng Lee1, Meghan Meadows1, Edward Robbins2, Sam
Signore3, Chris Mutrie2, Raymond Osarogiagbon2 IV 3.76 3.43 2.62 3.11
1
Epidemiology and Biostatistics, University of Memphis School of Public Health,
Memphis/TN/United States of America, 2Multidisciplinary Thoracic Oncology Conclusion: 8E was generally supported by our data, although modifications
Program, Baptist Cancer Center, Memphis/TN/United States of America, 3Thoracic for Stage IA1-IIB patients were not fully evident, even in high-quality
resections. The survival disparity with IASLC data suggests that unidentified Methods: Database of 479 metastatic non-small cell lung cancer (NSCLC)
confounding factors are impairing survival in this early-stage US NSCLC patients, treated between 2009 and 2011, all tested for EGFR mutations, was
cohort. retrospectively reviewed to categorize them into one of the new sub-groups
according to new M descriptors. Medical records of 355 patients, among them
Keywords: IASLC 8th Edition, 8th Edition, TNM, Staging 89 with EGFR mutations (EGFR-m), had sufficient information that allowed
appropriate new categorisation. Results: After a median follow up of 53.9
months, median overall survival (mOS) of EGFR-m patients (20.6 months)
was significantly longer than mOS of patients without EGFR mutations
(8.3 months, p<0.001). Patients with the smallest disease burden (M1b
STAGING – sub-group) had the longest mOS among EGFR wild type patients (EGFR-wt)
MONDAY, DECEMBER 5, 2016 and EGFR-m patients, 14.4 months and 41.1 month, respectively. However,
due to small number of patients in M1b subgroup, the difference was not
statistically significant (p=0.08). In spite of widespread metastatic disease
P1.03-068 IMPACT OF POSITIVE PLEURAL LAVAGE CYTOLOGY OR
in M1c EGFR-m patients, they had longer mOS than M1b EGFR-wt patients
MALIGNANT EFFUSION ON SURVIVAL IN PATIENTS HAVING LUNG with the lowest disease burden, 18.8 vs 14.4 months, respectively. Conclusion:
RESECTION FOR NSCLC EGFR mutational status has probably more important impact on mOS than
Tomohiro Obata1, NAOYA YAMASAKI1, YUKA KITAMURA2, GO the number of metastasis or number of metastatic sites in NSCLC. Our results
HATACHI2, TAKURO MIYAZAKI1, KEITARO MATSUMOTO1, TOMOSHI indicate that further analysis is warranted to address this issue.
TSUCHIYA1, KAZUHIRO TABATA3, TAKESHI NAGAYASU1
1
Surgical Oncology, Nagasaki Graduate School of Medicine, Nagasaki/Japan, EGFR-
2
Surgical Oncology, Nagasaki University, Nagasaki/Japan, 3Department of M descriptor EGFR-m
wt
Pathology, Nagasaki Graduate School of Medicine, Nagasaki/Japan
mOS mOS
n n p
Background: Pleural lavage cytology (PLC) is the microscopic study of cells (months) (months)
obtained from saline instilled into and retrieved from the chest during surgery
M1a 17 22.3 61 10.7 0.022
for NSCLC. PLC is not reflected in the 7th TNM classification of lung cancer by
the Union for International Cancer Control (UICC),although it is known that M1b 5 41.1 32 14.4 0.080
PLC-positive means worth prognosis.
M1c 67 18.8 173 6.6 <0.001
The reason is that information regarding the treatment of PLC-positive
all 89 20.6 266 8.3 <0.001
patients is still limited. On the other hand, malignant effusion is categorized
M1a, and reflect the grade of malignancy more. The aim of this study is to Keywords: new TNM classification, M descriptor, EGFR mutational status,
evaluate the possibility of being an established independent predictor of survival
prognosis and the efficacy of intrapleural chemotherapy (IPC) in PLC-positive
patients. Methods: 1,165 of the 1,473 lung cancer patients who underwent
surgery had undergone PLC before thoracotomy, following by a complete
resection (PLC-positive:41 patients) and 16 patients with malignant effusion
were evaluated. The treatment was performed for 16 patients with malignant POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
effusion and 27 patents with PLC-positive. After pulmonary resection, IPC STAGING –
was performed after surgery, and the pleural cavity was filled with cisplatin
with a normal saline solution. The disease-free survival (DFS) and the overall
survival (OS) of the patients were evaluated. Results: The pathological P1.03-070 THE IMPACT OF ADVANCES IN SYSTEMIC STAGING ON
diagnosis showed that 41 patients (2.8 %) were positive for (or suspected THE RATE OF METACHRONOUS AND SYNCHRONOUS METASTASES
to have) malignancy in their PLC. The univariate analysis showed that only IN PATIENTS LUNG CANCER
T category and Lymph node metastasis were significant predictors of a
Ugur Yılmaz1, Lawrence Marks2, Kyle Wang 3
PLC-positive status. The 5-year overall survival in PLC-positive patients was 1
Radiation Oncology, Ege University Faculty of Medicine, Izmir/Turkey,
37 % and that in PLC-negative patients was 75 %. The univariate (p<0.01) 2
Departments of Radiation Oncology, Medicine and Radiology, University of North
analyses showed that the status of PLC was significantly associated with Carolina, Chapel Hill/United States of America, 3Radiation Oncology, University of
the overall survival. Correction for differences in survival were obtained in North Carolina Hospitals, Chapel Hill/NC/United States of America
the earlier stages than stage IIIA . Twenty-six of the 42 PLC-positive patients
underwent IPC. The median survival time of the IPC group was 47.0months Background: To quantify the impact of advances in systemic staging (i.e.
and that of those without IPC was 17.4 monthes (p<0.01), respectively. But, from CT-based to PET-based over the last ≈ 20 years) on the rate of distant
there are no significant differences between these groups with respect of metastases detected at their time of initial diagnosis (synchronous) and
DFS and reccurent site. Conclusion: PLC should be considered in all patients sometime after initial diagnosis (metachronous) in patients with lung cancer.
with NSCLC suitable for resection. A positive result can be an independent Methods: The Surveillance, Epidemiology, and End Results (SEER) data base,
predictor of adverse survival especially in early stages. IPC may improve the representing 10 % of the US population was used to analyze lung cancers from
OS in PLC-positive NSCLC patients and patients with malignant effusion, and 1988-2008. (a) The fraction of patients with overt synchronous metastases
a further prospective evaluation regarding this therapy is warranted. at diagnosis was noted. (b) Among patients without overt metastasis at
diagnosis, their 5-year mortality rate was taken as an estimate of their rate of
Keywords: intrapleural chemotherapy, PLC, malignant effusion metachronous metastasis (as most deaths were due to distant metastases).
(c) The overall rate of metastases (synchronous + metachronous) amongst
all patients was computed. (d) The fraction of all metastases detectable
at initial diagnosis (synchronous / [synchronous + metachronous]) was
computed. Rates were computed for patient cohorts diagnosed in different
STAGING – time intervals from 1988-2008, to reflect the use of different systemic staging
MONDAY, DECEMBER 5, 2016 methods over the 20-year interval. Results: (a) The rate of synchronous
metastatic disease slowly increased from ≈ 53% in the earlier years to ≈
55% in 2008. (b) Among patients without overt metastasis at diagnosis,
P1.03-069 EGFR MUTATIONS HAVE GREATER INFLUENCE ON
the rate of metachronous metastatic disease slowly decreased from ≈ 73%
SURVIVAL THAN PROPOSED M DESCRIPTORS OF NEW TNM in the earlier years to ≈ 62% in 2008. (c) If one assumes that most of the
CLASSIFICATION FOR LUNG CANCER metachronous metastatic lesions were present (but covert) at the time of the
Karmen Stanic 1, Martina Vrankar2 initial diagnosis of the primary disease, then one can estimate that ≈ 83-87%
1
Department of Radiotherapy, Institute of Oncology, Ljubljana/Slovenia, of patients have micro/macro metastatic disease at presentation (this rate
2
Radiotherapy, Institute of Oncology, Ljubljana/Slovenia is basically unchanged over time, but small changes over time may reflect the
impact of systemic chemotherapy). (d) Among all patients with metastatic
Background: The forthcoming 8th edition of TNM staging system for lung disease, ≈ 60.4% of metastatic lesions were detectable clinically or with CT
cancer proposes revision of M descriptor. No changes of M1a category at the time of diagnosis in the pre-PET era, vs. ≈ 66.6% of these lesions being
is suggested, while further sub-classification of M1b category into M1b detectable clinically or with CT and/or PET in the PET era. Conclusion: The
(single distant metastatic lesion in single organ) and M1c (multiple distant addition of PET appears to have a small but measurable impact on the rates
metastatic lesions) is proposed. The limitations of new classification due of synchronous and metachronous metastasis, resulting in stage migration
to lack of information on EGFR and ALK status that significantly impact from metachronous to synchronous (i.e. from covert to overt) metastases at
treatment response and outcome have been pointed out, however no further the time of diagnosis. The addition of PET to the pre-treatment evaluation
analysis addressing this issue has been published. Here we report the impact increases the ability to detect metastatic disease by ≈ 6% (from 60.4 to
of EGFR mutation status on survival in view of new TNM classification system. 66.6%).

Keywords: PET, synchronous and metachronous metastasis calcification or high attenuation >70 household unit (HU) at unenhanced
CT were regarded as being positive for malignancy. All patients underwent
hilar and mediastinal lymph nodes dissection according to the AJCC lymph
node map (nodal stations 2R, 4R, 7, 8 and 9 for a right-sided tumour; 4L, 5,
6, 7, 8 and 9 for a left-sided tumour) after resection of the main tumour.
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING Histologic nodal assessment results were used as reference standards. Of
STAGING – these 55 patients, 10 (20%) had a past history of pulmonary tuberculosis as
determined by clinical or imaging studies. Results: Of 230 mediastinal nodal
stations evaluated in 46 patients, 5(2%) stations in 4(8%) patients proved to
P1.03-071 IMPACT OF VISCERAL PLURAL INVASION TO T be malignant by histopathologic assessment. Mean number of lymph node
DESCRIPTORS: BASED ON THE FORTHCOMING EIGHTH EDITION OF stations evaluated were 5. On a per-nodal station basis, the overall sensitivity,
specificity, accuracy, PPV, NPV of PET-CT were 60%, 97%, 96%, 38%,99% for
TNM CLASSIFICATION FOR LUNG CANCER
mediastinal lymph nodes staging(N2) respectively. Conclusion: Integrated
Mikiko Suzuki, Takeshi Matsunaga, Kazuya Takamochi, Shiaki Oh, Kenji PET-CT provides high specificity and high accuracy, but low sensitivity for
Suzuki mediastinal staging of NSCLCs. The high specificity is achieved at the expense
Department of General Thoracic Surgery, Juntendo University School of Medicine, of sensitivity by interpreting calcified nodes or nodes with high attenuation
Tokyo/Japan at CT, even with high FDG uptake at PET, as benign in a tuberculosis-endemic
region.
Background: According to the forthcoming eighth edition of TNM
classification, T descriptors and M descriptors will be subdivided. Visceral Keywords: NSCLC, PET CT, Mediastinal lymphnode staging
plural invasion of lung cancer has been known as a non-size-based T2
descriptor. However, the definition still lacks in detail, and its validation
is not included. Methods: We retrospectively reviewed 1250 patients, who
underwent curative surgical resection for non-small cell lung cancer at
Juntendo University Hospital, between January 2008 and December 2014.
Patients with pathologic N1 or N2 disease were excluded. We subdivided STAGING –
tumor size based on the eighth edition of TNM classification. Cumulative MONDAY, DECEMBER 5, 2016
survival rates were evaluated by the Kaplan–Meier method. Statistical
differences in survival status were evaluated using the log-rank test. Results:
P1.03-073 PREDICTORS FOR PATHOLOGICAL N1 AND N2 DISEASE IN
In tumor size of 0-4cm, overall survival was significantly different between
pl0 and pl1-pl2 in each tumor size; 0-1cm (p<0.0001), 1-2cm (p=0.001), 2-3cm CLINICAL N1 NON-SMALL-CELL LUNG CANCER
(p=0.007), 3-4cm (p=0.012). In tumor size of over 4cm, overall survival was not Takayuki Fukui, Toshiki Okasaka, Koji Kawaguchi, Koichi Fukumoto, Shota
different between pl0 and pl1-pl2 in each tumor size; 4-5cm (p=0.825), 5-7cm Nakamura, Shuhei Hakiri, Naoki Ozeki, Kohei Yokoi
(p=0.311), over 7cm (p=0.272). In tumor size of 4-5cm with pl0-pl2, a five-year Thoracic Surgery, Nagoya University, Nagoya/Japan
survival rate was 60%. In tumor size of 0-4cm with pl0-pl1, a five-year survival
rate was not significant difference with in tumor size of 4-5cm with pl0-pl2; Background: Patients with clinical N1 (cN1) non-small-cell lung cancer (NSCLC)
0-1cm 50% (p=0.799), 1-2cm 71% (p=0.169), 2-3cm 70% (p=0.370), 3-4cm 67% is usually considered to be candidates for curative resection. However,
(p=0.609). Conclusion: In pathologic N0M0 disease, there was no prognostic they sometimes have unexpected mediastinal nodal involvement (pN2).
difference between tumor size of 0-4cm with pl1-pl2 and 4-5cm with any pl. In To avoid futile pulmonary resection, accurate preoperative evaluation of
this study, tumors 4cm or less with visceral plural invasion become classified nodal status would be necessary. The purpose of this study was to identify
as T2b, and tumors larger than 4cm but 5cm or less also become classified as predictors for lymph node metastasis in cN1 NSCLC patients. Methods: We
T2b regardless of visceral plural invasion. retrospectively reviewed data on the clinicopathological and radiological
features of 170 patients with cN1 NSCLC who had undergone complete
Keywords: visceral plural invasion, the eighth edition of TNM classification for resection at Nagoya University Hospital between 2004 and 2015. Hilar and/
lung cancer or intrapulmonary lymph nodes with ≥ 1.0 cm in the short axis on computed
tomography or with high accumulation of [18F]Fluorodeoxyglucose (FDG)
in positron emission tomography compared with that of the adjacent
mediastinal tissue were considered as cN1 in our institution. The association
between clinicoradiological variables and nodal status was analyzed to
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING identify predictors for lymph node metastasis. Results: The cohort consisted
STAGING – of 125 males and 45 females, ranging in age 39 to 84 years. There were 62
(36%) adenocarcinomas, 82 (48%) squamous-cell carcinomas, 10 (6%) large-
cell carcinomas, and 16 (10%) other types of cancers. The breakdown by
P1.03-072 MEDIASTINAL LYMPHNODES STAGING BY PET CT FOR pathological N category was 61 (36%) pN0, 72 (42%) pN1, and 37 (22%) pN2
RESECTABLE NON-SMALL CELL LUNG CANCER IN A TUBERCULOSIS patients. Among pN2 patients, only three showed negative N1 lymph nodes
(skip pN2 metastasis). Female gender, adenocarcinoma histology, middle
ENDEMIC COUNTRY
or lower lobe orign and positive N1 lymph node (pN1) were significantly
Vinayakumar J R 1, Sunil Kumar 1, Surayanarayana Deo1, Rakesh Kumar2, associated with pN2 by univariate analysis. Logistic regression analysis
Prabhat Malik 3, Chandrashekhara Sh4, Deepali Jain5, Nootan Shukla1 showed that the female and pN1 were significant predictor for pN2 with the
1
Surgical Oncology, Irch, All India Institute of Medical Sciences(Aiims), New Delhi/ odds ratio of 3.0 and 13.1, respectively (P = 0.02 and 0.0001, respectively).
India, 2Nuclear Medicine, All India Institute of Medical Sciences, New Delhi/India, In addition, using the 63 patients extracted from our cohort of this study,
3
Medical Oncology, Irch, All India Institute of Medical Sciences(Aiims), New Delhi/
we sought the predictor of pN1. The maximum size of the lymph node
India, 4Radiodiagnosis, Irch, All India Institute of Medical Sciences(Aiims), New
Delhi/India, 5Pathology, All India Institute of Medical Sciences, New Delhi/India and standardized uptake value of the FDG were significant factor for pN1
with the cut-off value of 1.3 cm and 4.28, respectively. Conclusion: Female
Background: Integrated 18 fluorine fluorodeoxyglucose (18F-FDG) PET-CT gender and pN1 was significantly assosiated with pN2 in cN1 NSCLC patients
has shown somewhat variable sensitivity and specificity for nodal staging of our cohort. The large size and a high accumulation of FDG of hilar or
in tuberculosis endemic areas. This variation mainly because PET scans intrapulmonary lymph node might predict the pN1.
show falsely increased 18F-FDG uptake in inflammatory nodes, which may
be observed in lymph nodes containing calcification or showing higher Keywords: lymph node, Non-small-cell lung cancer, cN1
attenuations than those of surrounding great vessels on unenhanced CT
scans. TB is a major health problem in India, incidence is around 2.1 million
cases annually.The purpose of the study was to evaluate the efficacy of
PET-CT for mediastinal nodal staging in non-small cell lung cancer (NSCLC)
patients in a tuberculosis-endemic country. Methods: Prospective assessment POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
STAGING –
of the diagnostic efficacy of integrated PET-CT for detecting mediastinal MONDAY, DECEMBER 5, 2016
nodal metastasis was performed from February 2012 to February 2016. A
total 160 patients underwent surgery for pathologically proven NSCLC.
Patients who received chemotherapy or radiotherapy prior to surgery were P1.03-074 COMBINED USE OF PET/CT AND CLINICAL FEATURES
excluded from study. Thus assessment of the diagnostic efficacy of integrated YIELDS A HIGHER DIAGNOSTIC RATE OF MEDIASTINAL LYMPH
PET-CT for detecting nodal metastasis was performed in 46 patients (Male NODE METASTASIS IN LUNG ADENOCARCINOMA
to Female ratio:4; mean age- 55 years). Patients underwent an integrated Miao Huang, Shaolei Li, Yue Yang
PET-CT examination and subsequent surgical nodal staging. One radiologist
Thoracic Surgery Ii, Peking University Cancer Hospital and Institute, Beijing/China
and 1 nuclear medicine specialist together prospectively evaluated PET-CT
datasets.Nodes showing greater 18F-FDG uptake at PET without benign Background: The aims of this study were to investigate the correlation
between 8F-fluorodeoxyglucose (FDG) uptake of the primary tumor and Nuclear Medine, Pet & Ultrasound, Westmead Hospital, Earlwood/NSW/Australia
mediastinal lymph node metastasis (MLNM) in lung adenocarcinoma, and
to improve the diagnostic capability of tumor FDG uptake and other risk Background: In patients with pulmonary malignancies, 18FDG uptake in
factors in predicting occult MLNM preoperatively. Methods: We reviewed mediastinal nodes is a sensitive but non-specific indicator of metastatic
360 consecutive pulmonary adenocarcinoma patients who underwent disease. The pattern of tracer uptake may improve the predictability of
preoperative PET/CT scan and subsequent surgery. Resected tumors were such findings. Methods: To retrospectively i) compare 18FDG-PET scans and
classified according to the 2011 IASLC/ATS/ERS classification. Univariate and EBUS findings in patients with documented pulmonary malignancies; and,
multivariate analysis were conducted to evaluate the associations between ii) compare the pattern of 18FDG uptake in mediastinal nodes in patients
clinicopathological variables and MLNM. The receiver operating characteristic with / without documented mediastinal node metastases. Methods: 62
(ROC) curve analysis was performed to quantify the predictive value of these patients with documented pulmonary malignancies underwent 18FDG-
factors. Results: Of all the 360 patients, 54 were pathological N2 diseases. PET scintigraphy followed by EBUS within the ensuing 3 weeks. One-two
On univariate analysis, CEA level, nodule type, nodal SUVmax, tumor nodes were assessed in each patient, determined by 18FDG-PET findings
SUVmax, size, location and histologic subtype were associated with MLNM. and accessibility of the FDG-positive nodes. The mediastinal nodal status
On multivariate analysis, CEA≥5.0 ng/ml (p < 0.001), solid nodule (p = 0.012), from each procedure was compared. Results: EBUS resulted in mediastinal
tumor SUVmax ≥ 3.7 (p < 0.027), nodal SUVmax ≥ 2.0 (p < 0.001) and centrally nodal status downgrading in 25 (40%) patients. No upgrading was noted.
located tumors (p = 0.035) were independent risk factors that associated with Downgrading most likely occurred when there several non-enlarged lymph
MLNM. The area under the ROC curve (AUC) for tumor SUVmax in predicting nodes of similar 18FDG-avidity distributed randomly and bilaterally in
MLNM was 0.764 and AUC of nodal SUVmax was 0.730. The combined use of the mediastinum, often with bilateral hilar uptake (17 of 25 patients).
five factors yielded a higher AUC of 0.885 for N2 disease. The tumor SUVmax Further, only 2 of 19 patients exhibiting such a pattern of mediastinal tracer
among histologic subtypes differed significantly (p < 0.001). Conclusion: distribution were found to have lymph node metastases (10%), and both had
Primary tumor SUVmax of PET/CT was shown a good predictor for MLNM metastatic disease elsewhere on the PET scan. 21 of 23 patients with positive
in patients with lung adenocarcinoma, and the underlying mechanism may EBUS findings demonstrated discrete 18FDG-avid lymph nodes ipsilaterally,
attribute to the close association between tumor FDG uptake and IASLC/ with minimal-to-no 18FDG-avid nodes contralaterally. EBUS findings in 14
ATS/ERS adenocarcinoma subtypes. The combined use of tumor SUVmax (23%) patients were inconclusive, despite multiple sampling. Enlarged,
with factors like nodal SUVmax, solid nodule, centrally located tumor and rounded lymph nodes with avid FDG uptake (SUV>4) were also more likely
increased CEA level improved the diagnostic capacity for predicting N2 to harbour metastatic disease. Conversely, a Hounsfield unit of >55 was
disease preoperatively. associated with benign disease. Conclusion: The pattern of mediastinal 18FDG
uptake was highly predictive of metastatic disease, and may circumvent the
Keywords: histologic subtype, lung adenocarcinoma, PET/CT, Mediastinal need for EBUS evaluation. Prospective analysis of these parameters will be
lymph node metastasis undertaken.
Keywords: FDG-PET, Mediastinum, Staging, EBUS

STAGING –
MONDAY, DECEMBER 5, 2016 POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
STAGING –
P1.03-075 PREDICTIVE FACTORS FOR MINIMAL PLEURAL DISEASE
DETECTED AT THORACOTOMY OR POSITIVE LAVAGE CYTOLOGY
P1.03-077 ANALYSIS OF THE EARLY CDT-BLOOD BIOMARKER FOR
Akira Sakurada1, Fumihiko Hoshi2, Yoshinori Okada1
1
LUNG CANCER IN HIGHER VS. LOWER RISK COHORTS
Institute of Development, Aging and Cancer, Sendai/Japan, 2Tohoku University
Hospital, Miyagi/Japan Melanie Ohillips1, Donald Rollins2, Debra Dyer 1, Jeffrey Kern1, James Jett1,
James Finigan1
Background: Minimal pleural disseminations and malignant pleural effusion is 1
National Jewish Health, Denver/United States of America, 2National Jewish Health,
eventually diagnosed at the therapeutic thoracotomy. Pleural lavage cytology Denver/AL/United States of America
is another prognostic factor which is available through surgery. Although
CT image have become high quality, prediction of such pleural disease is still Background: The Early Cancer Detection Test (CDT)-Lung Cancer Screening
difficult. To establish predictive markers for minimal pleural disease before (LCS) Study is a prospective, lung cancer screening study testing the
surgery will be useful for planning strategy for the patients with minimal hypothesis that a serum biomarker consisting of a panel of seven cancer-
pleural disease. Methods: 115 patients who underwent pulmonary resection associated autoantibodies, in combination with a low-dose CT (LDCT),
in our hospital from January 2010 to December 2011 were retrospectively would increase detection of early stage lung cancer. We analyzed nodules
analyzed for their clinicopathological information such as tumor marker CT rates and lung cancer in “higher risk” individuals who meet the USPSTF LCS
image, and histology. 65 were male and 50 female. Histology was squamous criteria (http://www.uspreventiveservicestaskforce.org/Page/Document/
cell carcinoma, adenocarcinoma, and other histology for 32, 78, and 5 cases, UpdateSummaryFinal/lung-cancer-screening) and “lower risk” individuals
respectively. Clinical staging according to WHO 7th edition stage IA, IB, IIA, IIB, who do not meet these criteria. Methods: The EarlyCDT LCS study eligibility
and IIIA for 62, 31, 11, 3, and 8 cases, respectively. CT findings such as pleural criteria included persons 50-75 years of age, current or former smokers of ≥ 20
indentation and contact of tumor on pleura were carefully measured on pack years, former smokers have ˂ 10 years since quit smoking. Additionally,
thin-slice CT sections with 0.5-1mm pitch. P value less than 0.05 was regarded those with a history of lung cancer in first-degree relative(s) and any history of
as statistically significance. Results: Eight cases were positive for pleural smoking were also included. Exclusion criteria included any history of cancer
disease, one for malignant effusion, 2 for minimal dissemination, and 6 for within 10 years (except skin cancer), any use of oxygen, or life expectancy < 5
pleural lavage cytology. By statistical analysis regarding association between years. The EarlyCDT-Lung test was considered positive if any one of the seven
clinicopathological factors pleural disease, statistical positive factor was autoantibodies was positive. Results: From May 2012 through June 2016,
tumor diameter and CEA positivity (P=0.037 and 0.01, respectively), but tumor 1235 individuals were enrolled (final target 1600). The median age was 59
contact on pleura did not reach statistical significance (p=0.07). Pleural years, 55% were female and 45% were male. Fifty-two per cent were current
indentation and histologic type was not statistically significant. Conclusion: smokers while 48% were former smokers. Fifty-three percent of participants
Based on current study, tumor diameter and serum CEA level could be possible were higher risk and 47% were lower risk. The EarlyCDT-Lung was positive in
predictive factors for minimal pleural disease. Upon limited number of 8% of higher risk individuals and 6% of lower risk individuals. Thirty-five per
patients, further study will be needed. cent of higher risk individuals had nodules on LDCT while 27% of lower risk
participants had nodules on LDCT. The EarlyCDT-Lung blood test was positive
Keywords: pleural dissemination, pleural lavage cytology, CT, malignant in 91 patients, 77 were higher risk and 34 were lower risk. There were 7 lung
effusion cancers, all in the higher risk group, resulting in a lung cancer rate of 1.07% in
the higher risk group. The median pack years of individuals with lung cancer
was 60 and the median age was 64 years. Two of the 7 lung cancer patients
were positive for the EarlyCDT test. The relative risk of lung cancer in patients
with a positive EarlyCDT test was 5.5 for the entire cohort and 4.5 for the
POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING higher risk group for lung cancer. Conclusion: There were more total nodules in
STAGING –
MONDAY, DECEMBER 5, 2016 the higher risk group compared to the lower risk group. There were more lung
cancers in the higher risk group compared with the lower risk group. A positive
EarlyCDT test is associated with an increased risk of lung cancer.
P1.03-076 NODAL STAGING OF PATIENTS WITH PULMONARY
MALIGNANCIES - THE PREDICTIVE VALUE OF DIFFERENT PATTERNS Keywords: LDCT, Screening, biomarker
OF MEDIASTINAL 18FDG-PET ACTIVITY
Socrates Angelides, Andrew Markewycz

POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING well as lesion features were collected. Descriptive statistics were tabulated
STAGING –
and chi-square statistical analysis performed. Results: 57.44% of the patients
were female, with average age of 67 years (35-91) and 65.42% had history of
smoking. Lesion size varied from 0.8 cm to 15.6 cm, with average of 3.9 cm.
P1.03-078 SIZE MATTERS...BUT DON’T UNDERESTIMATE THE 83.51% were spiculated, 78.72% solid, 12.23% presented intralesional low
POWER OF MORPHOLOGY attenuation (<20HU), 11.17% were associated with perilesional atelectasis and
Annemie Snoeckx 1, Damien Desbuquoit1, Maarten Spinhoven1, Annelies 19.14% with pleural effusion. 63.83% had known metastasis at the time of
Janssens2, Patrick Lauwers3, Michèle De Waele3, Christel De Pooter4, Patrick the procedure, 29.78% had systemic treatment before the biopsy. Specimens
Pauwels5, Jan Van Meerbeeck6, Paul Parizel1 were successfully used for NGS in 80.52% of cases. Overall adequacy of biopsy
1 specimens for analysis of gene mutations requested was 87.76%. Conclusion:
Department of Radiology, Antwerp University Hospital and University of Antwerp,
Edegem/Belgium, 2Department of Thoracic Oncology, Antwerp University Hospital The overall success rate of percutaneous image guided lung cancer biopsies for
and University of Antwerp, Edegem/Belgium, 3Department of Thoracic and Vascular clinically requested genetic mutation analysis was 87.76%.
Surgery, Antwerp University Hospital and University of Antwerp, Edegem/Belgium,
4
Departement of Radiotherapy, Gza Hospital Sint-Augustinus, Wilrijk/Belgium, Keywords: Percutaneous lung biopsy, Single gene sequencing, next
5
Department of Pathology, Antwerp University Hospital and University of Antwerp, generation sequencing
Edegem/Belgium, 6Thoracic Oncology, University Hospital of Antwerp, Edegem/
Belgium
Background: The detection of solitary pulmonary nodules has increased STAGING –
due to the widespread use of Computed Tomography (CT) and will increase MONDAY, DECEMBER 5, 2016
even more in the future when lung cancer screening will be embedded in
daily practice. In addition to the clinical information, size is one of the most P1.03-080 THE SUVMAX RATIO OF TWO TUMORS ON PET/CT
important parameters to assess the likelihood of malignancy. Although there
MAY DIFFERENTIATE SEPARATE PRIMARY LUNG CANCERS AND
is a considerable overlap in imaging characteristics of benign and malignant
solitary pulmonary nodules, the power of morphology –even in small nodules-
INTRAPULMONARY METASTASES
should not be underestimated. The aim of this pictorial essay is to give an Yi Liu1, Yanhua Tang2, Xiangyang Chu1, Zhiqiang Xue1, Ping Yang 3, Po Zhao4, Jie
overview of the wide range of morphologic characteristics and to address Gao4, Guangyu Ma5
1
the available evidence on sensitivity and specificity of these characteristics. Thoracic Surgery, The Chinese People’s Liberation Army General Hospital, Beijing/
Methods: Cases presented were collected during the Multidisciplinary Thoracic China, 2Radiology, The Chinese People’s Liberation Army General Hospital, Beijing/
Oncology Tumor Board between January 2014 and May 2016. All malignant China, 3Health Sciences Research, Mayo Clinic, Rochester/MN/United States of
America, 4Pathology, The Chinese People’s Liberation Army General Hospital,
cases have histopathologic proof, whereas benign lesions were included when
Beijing/China, 5Nuclear Medicine, The Chinese People’s Liberation Army General
the benign nature was suggested after follow-up, negative PET-scan and/or Hospital, Beijing/China
multidisciplinary consensus. Results: With regard to margin characteristics,
spiculation is highly suggestive of a malignant nature. It is the only feature that Background: Differentiation between separate primary lung cancers and
is incorporated as ‘morphologic’ variable in most risk prediction models. Other intrapulmonary metastases (IM) has significant therapeutic and prognostic
features however may also be strong indicators of malignancy. Lobulation, implications in lung cancer patients with multiple pulmonary nodules. In this
halo sign, pleural indentation, vascular convergence sign and pitfall sign retrospective study, we investigated the diagnostic ability of ratio (MSR)
are frequently encountered in malignant nodules. The nodule-bronchus and differences (MSD) of maximum standardized uptake values (SUVmax)
relationship can give additional information regarding the nature of the between two tumors in discriminating separate primary lung cancers from
nodule, with signs such as air bronchogram, bubble like lucencies and bronchus metastases. Methods: We evaluated 5641 lung cancer patients between
cutoff sign being indicative of a malignant nature. In cavitated nodules, a March 2009 and March 2016 at the Chinese People’s Liberation Army General
very thin wall might indicate a benign cause, whereas a very thick wall is more Hospital. Patients underwent PET/CT and pathology confirmed as multiple
common in malignant nodules. Calcification is typically seen in benign nodules, lung cancers were included. Patients with ground glass opacity lung cancers
but depending on the calcification pattern a malignant etiology cannot be or underwent preoperative radiotherapy or chemotherapy were excluded. All
excluded. The presence of fat is a relative reliable sign of benignity. Thin- lung cancers tissues were reassessed and discriminated from separate primary
section CT will enable detection of subtle findings. Nodules rarely present with lung cancer to metastases by two pathologists independently according to
only one characteristic and combination of findings can definitely increase comprehensive histological assessment criteria, which was proposed by IASLC
the likelihood of a correct diagnosis. Conclusion: The management of solitary lung cancer staging project as pathologic definition to distinguish multiple
pulmonary nodules involves both clinical and imaging assessment. Although a primary lung cancers from metastatic in the forthcoming eighth edition
great overlap exists in morphologic features of benign and malignant nodules, TNM classification of lung cancer. The MSR and MSD were determined and
thorough knowledge and recognition of subtle morphologic findings will aid in compared in diagnosing separate primary lung cancers. Receiver-operating
early detection of nodules with a high likelihood of malignancy and will avoid characteristic (ROC) curve analysis was performed to determine the area
unnecessary follow-up and delay in diagnosis and treatment. under the curve (AUC), sensitivity and specificity with an optimal cut-off
value. Example of MSR and MSD deduction was given in Figure. 1.
Keywords: morphology, lung cancer, solitary pulmonary nodule, computed
tomography

STAGING –
P1.03-079 ADEQUACY OF PERCUTANEOUS LUNG BIOPSY FOR

ASSESSING CLINICALLY REQUESTED GENETIC MUTATIONS IN LUNG
CANCER
Sharjeel Sabir, Livia Maria Frota Lima
MD Anderson Cancer Center, Houston/TX/United States of America
Background: Percutaneous lung biopsy is used to assess for the presence of

actionable genetic mutations in EGFR, BRAF and KRAS. ALK mutation was
assessed separately through FISH, which was not assessed in this study.
Sequencing can be performed with next generation sequencing (NGS) or
single gene sequencing (SGS). Methods: A retrospective study with 188
consecutive histologically diagnostic CT guided lung biopsies sent for NGS
were performed between 2013 and 2014. Procedures were performed using
19 gauge guiding cannula, 20 gauge side-cutting core needles and 22 gauge
Chiba FNA needles. Patients in whom 2 or more gene mutation analyses
were requested had their biopsy specimen analyzed for adequate tumor
cellularity (>20% tumor) and if adequate had DNA extracted and sequenced
with a 50-gene multiplex platform (Ion Torrent Personal Genome Machine).
If the material was not adequate for NGS, the requested genes mutation
analyses were performed with SGS. Demographics, procedure technique as
Results: Totally 24 patients with 24 pairs-tumor (18 primary, 6 metastases) method is becoming increasingly popular. Therefore, we aimed to evaluate
were included. The area under the curve of MSR (AUC, 0.843; 95% CI, 0.637- the accuracy same as false-negative and false-positive results of PET/CT
0.958; p=0.001) was significantly higher than MSD (AUC, 0.685; 95% CI, when compared to histopathological diagnoses at Vilnius university hospital
0.465–0.857; p=0.240) with p value 0.022. The optimal cut-off value for MSR Santariskiu klinikos (VUL SK). Methods: A retrospective analysis included 15
and MSD was 1.61 (83.33% sensitivity, 83.33% specificity) and 1.94 (83.33% NSCLC patients who underwent preoperative PET/CT scan and postoperative
sensitivity, 66.67% specificity). Conclusion: The MSR from PET/CT may histopathological analysis for the N staging at VUL SK. PET/CT N stage
helpful in differentiating separate primary lung cancers from intrapulmonary was compared with gold standard histopathological N stage to assess the
metastases and larger studies were needed to confirm this result. sensitivity, specificity, positive and negative predictive values for N staging
of NSCLC. Results: There were 15 patients (11 men (73,3%), 4 women (26,7%))
Keywords: diagnosis, Maximum Standardized Uptake Values, Separate with average age of 66,1±10,2 years included into the study. Ten patients
primary lung cancers, Intrapulmonary metastases (66,7%) were staged N>0 by PET/CT, histopathological analysis confirmed
4 diagnoses (40%), other 6 diagnoses (60%) were considered false positive.
Five patients (33,3%) were staged N0 by PET/CT, histopathological analysis
confirmed 3 diagnoses (60%), other 2 diagnoses (40%) were false negative.
Estimated specificity of PET/CT for N staging of NSCLC was 25%; sensitivity
STAGING – – 57,14%, positive predictive value – 40%, negative predictive value – 60%.
MONDAY, DECEMBER 5, 2016 Conclusion: Despite many advantages, PET/CT still has limited value staging
NSCLC. Significant number of inaccuracies in N staging may occur evaluating
inflammatory lymph nodes. The necessity of histologic confirmation of
P1.03-081 SYNCHRONOUS TRIPLE MALIGNANT TUMORS OF THE
N stage in stage I-IIIa NSCLC is crucial as these patients may have surgical
LUNG: A CASE REPORT OF TWO LUNG ADENOCARCINOMAS, AND treatment combination and better outcomes.
MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA
Xun Wang 1, Hongqing Zhao2 Keywords: PET/CT, NSCLC, Staging
1
Nanjing Medical University Wuxi No.2 People’s Hospital, Wuxi/China, 2Nanjing
Medical University Wuxi No.2 People’s Hospital, Wuxi/China
Background: Synchronous primary malignant tumors are relatively rare. The

accurate diagnosis remains challenging. Methods: We report a case of POSTER SESSION 1 - P1.03: RADIOLOGY/STAGING/SCREENING
STAGING –
synchronous triple primary tumors of the right lung in a 64-year-old male MONDAY, DECEMBER 5, 2016
patient in whom each tumor presented distinct CT imaging findings.
Abnormal nodules were found in the lung (one in right upper lobe and another
in the right lower lobe). Almost 2 years later, Chest CT revealed that the P1.03-083 ADVANCES IN SURGICAL STAGING OF NSCLC
nodule in the right lower lobe had grown. After complete resection, Prakash Balakrishnan, SEAN GALVIN, BARRY MAHON, JOHN
pathological sections revealed the similar pathological features of two RIORDAN, JAMES MCGIVEN
adenocarcinomas. As the L858R mutation within exon 21 of the EGFR gene Cardiothoracic Surgery, Wellington Regional Hospital, Wellington/New Zealand
was identified in the lower lobe tumor but not in the upper-lobe tumor, we
diagnosed as double primary lung adenocarcinomas. We performed the right Background: Staging of mediastinal lymph nodes in NSCLC defines the extent
lower lobe tumor. Pathological examination revealed a combined of thoracic malignancies & the disease process. It is based on the American
adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Joint Committee for Cancer (AJCC), TNM staging system, which describes
the best anatomic extent of the disease. This defines operability & surgical
resectibility, neoadjuvant therapy & prediciting prognostic survivability.
Methods: A well-conducted literacture search & review undertaken. All papers
or studies in the last 10 years were identified and studied. Results: Surgical
& non-surgical staging methods were identified, compared and analysed for
their sensitivity & specificity. Size, location & characteristics of tumour, local
invasion or extension, lymphadenopathy & metastatic disease spread were
identified as parameters. Conclusion: Early accurate staging improves overall
outcomes if therapeutic interventions are well-organised & excuted in a
timely fashion. Careful selection of staging methods is crucial.
Keywords: NSCLC, Staging, Surgical staging

Results: This is the first case of triple malignant tumors (two lung STAGING –
adenocarcinomas, and MALT lymphoma) reported in the literature. Conclusion: MONDAY, DECEMBER 5, 2016
Because of its rarity, MALT lymphoma should be considered in the differential
diagnosis when we encounter abnormal nodules in patients with synchronous P1.03-084 IMPLICATIONS OF 8TH EDITION TNM PROPOSAL:
malignant tumors of the Lung. Mutational analysis of the EGFR gene provided
INVASIVE VS. TOTAL SIZE FOR T DESCRIPTOR IN PT1A-2BN0M0
important information not only in decision-making of selection of
chemotherapeutic agent but also in the diagnosis of double primary cancers.
LUNG ADENOCARCINOMA
Takashi Eguchi1, Koji Kameda1, Shaohua Lu2, Zachary Tano1, James Huang1,
Keywords: EGFR mutation, lung adenocarcinoma, Synchronous Triple David Jones1, Prasad Adusumilli1, William Travis3
Malignant Tumors, mucosa-associated lymphoid tissue lymphoma 1
New York/NY/United States of America, 2Department of Pathology, Memorial
Sloan Kettering Cancer Center, New York/NY/United States of America, 3Dept of
Pathology, Memorial Sloan Kettering Cancer Center, New York/NY/United States of
America
STAGING – Background: The aim of this study was to conduct a clinicopathological
comparative analysis of total tumor versus invasive tumor size in pT1a-2bN0M0
nonmucinous lung adenocarcinomas. Methods: Resected pT1a-2bN0M0 lung
P1.03-082 18F-FDG PET/CT VALUE STAGING NSCLC EXTENSION TO adenocarcinomas (1995-2012) based on 8th edition of TNM classification using
THE LYMPH NODES, SINGLE CENTER EXPERIENCE total (N=1475) and invasive tumor size (N=1482) were included. Recurrence free
probability [RFP] and lung cancer-specific survival [LCSS]) were compared
Ruta Vosyliute 1, Gabija Visockyte1, Donatas Vajauskas2
between both pT-staging systems using Kaplan-Meier method. Results: Use of
1
Faculty of Medicine, Vilnius University, Vilnius/Lithuania, 2Radiology and Nuclear invasive size for the T descriptor increased the number of pT1a tumors by 2 fold
Medicine Center, Nuclear Medicine and Molecular Imaging Department, Vilnius
compared to use of total tumor size (316 vs. 161), with no difference in RFP and
University Hospital Santariskiu Klinikos, Vilnius/Lithuania
LCSS (RFP, 82% vs. 80%; LCSS, 94% vs. 93%). Use of invasive rather than total
Background: Non small-cell lung carcinoma (NSCLC) is the most common size also showed better stratification of lymphatic/vascular invasion and
type of lung cancer. Correct clinical and pathological lymphnode (N) staging high-grade histological subtypes according to increasing pT stage. RFP and
is critical for choosing the best treatment. Positron emission tomography/ LCSS in invasive-size-based pT2b were lower than those in total-size-based
computed tomography (PET/CT), being non-invasive pre-operative diagnostic pT2b (RFP, 44% vs. 60%; LCSS, 69% vs. 77%). Conclusion: In pT1a-2bN0M0

nonmucinous lung adenocarcinoma, the 8th edition TNM proposal to use as surgical specimen with histological type of adenocarcinoma and NSCLC
invasive rather than total size for the pT descriptor gives better prognostic NOS (Not Otherwise Specified) were routinely analyzed independent of the
discrimination by capturing a larger number of patients with favorable tumor stage and clinical characteristics (reflex testing) for these genetic
prognosis (pT1a) and providing better stratification for pT2b. alterations. Since January 2010 the EGFR mutation detection was performed
with the EGFR Mutation Test Kit from ROCHE on a COBAS4800. Since August
2011 tumor tissue was analyzed for EML4-ALK with a two-step procedure.
First an immunohistochemical staining was done with the Ventana anti
ALK(D5F3), OptiView DAB IHC DetectionKit and OptiViewAmplifikationKit®
and further on positive cases were tested by PCR (AmoyDx®EML4-ALK
FusionGeneDetectionKit) or ALK FISH (dual colour breakapart FISH/Abbott
Vysis®). Since January 2014 the tumor tissue was analyzed for ROS1 with a
two-step procedure. First an immunohistochemical staining was done with
ROS1 D4D6, cell signaling® and further on positive cases were tested by PCR
(AmoyDx®ROS1 GeneFusionDetectionKit) or ROS1 FISH (ROS1-6q22.1 dual
colour breakapart probe ZytoVision®). BRAF testing was performed with the
cobas®4800BRAF V600Mutation Test from Roche since March 2016. Results:
An EGFR Mutation was found in 340 out of 2776 patients (12.2%). 253 patients
(9.1%) carried an activated mutation (Exon 19 Deletion, Exon 21 L858R). EML4-
ALK positive translocation was found in 100 out of 2212 patients (4.5%).
ROS1 positive translocation was found in 5 out of 1060 patients (0.5%). BRAF
mutation was found in 3 patients out of 40 (7.5%). Conclusion: Frequency of
these genetic alterations in Austrian patients with NSCLC was quite similar to
other Caucasian peers. Therefore reflex testing is recommended independent
of any clinical characterization.
Keywords: Non-small-cell lung cancer, Target therapy
POSTER SESSION 1 - P1.04: PULMONOLOGY –

P1.04-002 POSITIVE AIRWAY PRESSURE-ENHANCED CT TO

IMPROVE VIRTUAL BRONCHOSCOPIC NAVIGATION
Marta Diez-Ferrer 1, Debora Gil2, Elena Carreño3, Susana Padrones1, Samantha
Aso1, Vanesa Vicens1, Noelia Cubero1, Rosa Lopez-Lisbona1, Carles Sanchez2,
Agnes Borras2, Jordi Dorca1, Antoni Rosell1
1
Respiratory Medicine, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat/
Spain, 2Computer Vision Center, Bellaterra/Spain, 3Radiology, Hospital Universitari
de Bellvitge, L’Hospitalet de Llobregat/Spain
Background: A main weakness of virtual bronchoscopic navigation (VBN)

is unsuccessful segmentation of distal branches approaching peripheral
pulmonary nodules (PPN). CT scan acquisition protocol is pivotal for
segmentation covering the utmost periphery. We hypothesize that
application of continuous positive airway pressure (CPAP) during CT
acquisition could improve visualization and segmentation of peripheral
bronchi. The purpose of the present pilot study is to compare quality of
segmentations under 4 CT acquisition modes: inspiration (INSP), expiration
(EXP) and both with CPAP (INSP-CPAP and EXP-CPAP). Methods: In 10
patients 320-detector row CT scans with slice thickness of 0.5 mm were
performed in the 4 modes. In first 5 patients a pressure ranging 6-10 cmH2O
was applied for 3 min immediately before CT acquisition (CPAP6-10).
In following 5 a pressure of 10 cmH2O was applied, followed by 3 min of
expiratory maneuvers and non-CPAP acquisitions (CPAP10). Segmentations
Keywords: TNM staging, T factor, Invasive adenocarcinoma, Tumor size were obtained and measurements manually calculated with a VBN
system (LungPoint, Broncus Technologies, Inc., Mountain View, CA, USA).
Comparisons for the inspiratory and expiratory models were made upon main
airways area (proximal trachea, distal trachea and main bronchi) and distance
of the path to the nodule (DIST-PN). Also, 2 random bronchi per lobe were
selected and the number of bifurcations (BIF) and distance (DIST) from carina
to the very end of the selected bronchi were manually counted and median
MONDAY, DECEMBER 5, 2016 calculated. Statistical analyses with R-3.2.3. Results: See table 1.
P1.04-001 EGFR, EML4-ALK, ROS 1 AND BRAF TESTING IN AUSTRIAN

PATIENTS WITH NSCLC: A MULTICENTRE STUDY
Sophia Holzer 1, Maximilian Hochmair 1, Ulrike Setinek2, Dagmar Krenbek2,
Hannah Fabikan1, Rosemarie Rumbold1, Andrea Mohn-Staudner 1, Klaus
Kirchbacher3, Madeleine Arns1, Tatjana Bundalo4, Kurt Patocka5, Otto
Burghuber 1
1
Otto Wagner Hospital, Department of Respiratory and Critical Care Medicine,
Vienna/Austria, 2Pathological-Bacteriological Institute, Otto Wagner Hospital,
Vienna/Austria, 3Wilhelminenspital, Department Medicine Ii, Vienna/Austria,
4
Landeskrankenhaus Hochegg, Department of Pneumology, Grimmenstein/Austria,
5
Krankenhaus Hietzing, Department of Pneumology, Vienna/Austria
Background: Targeted therapy is becoming increasingly important and

has improved the overall survival for patients with NSCLC. EGFR and BRAF
mutations, EML4-ALK and ROS1 translocations are current allocatable targets.
The incidence of these druggable targets in Austria is unknown. Methods:
Tumor tissue from bronchoscopy, CT- and ultrasound guided biopsies as well
Conclusion: A tendency towards enlargement and improved segmentation of Background: The bronchoscopic cryosurgery with carbon dioxide is a
airways is seen with the use of CPAP in both levels of pressure. However, the groundbreaking tool in the diagnostic treatment of respiratory diseases.
power of this pilot study is limited and larger studies might be encouraged. It has shown to be of great usefulness at a reasonable cost, with multiple
Funded by La MaratóTV3-20133510, FIS PI09/90917, DPI2015-65286-R, 2014- indications and few side effects. We described the experience in an oncology
SGR-1470, PROD-2014-00065, FUCAP and SEPAR. institution in Colombia. Methods: Medical histories, Bronchoscopies and
images were reviewe from patients subjected to Bronchoscopic Cryosurgery.
Keywords: Thorax CT, diagnosis, Peripheral Pulmonary Nodule The procedures were performed at the “High-Tech Western Oncologist Clinic”
in Pereira, Colombia with a highly trained medical staff from this clinic
and from Neumovida Clinic from Armenia. Rigid and flexible Bronchoscopy
video was made, and the equipment used in the cryotherapy was the Erbe
Cryo 2 with the cryoprobe of 1.9 and 2.4 mm. Results: 71 patients were
MONDAY, DECEMBER 5, 2016 found, 44 men, 27 women. Tracheal Recanalization to 11 patients, Bronchial
Cryorecanalization to 24, Bronchial Cryobiopsy to 13, Tracheal Cryobiopsy
to 7 and Pulmonary Cryobiopsy to 16 patients. Cryorecanalization was
P1.04-003 INCIDENCE OF NON-CASEATING GRANULOMAS performed to 15 patients with tumors in the right lung and 9 in the left lung.
DIAGNOSED IN PET AVID MEDIASTINAL/HILAR NODES IN PATIENTS Permeabilization of the Bronchial lumen was achieved to 22 patients at the
WITH KNOWN BREAST CANCER same time the Bronchoscopy was being done. In 2 patients with Bronchial
Tracy Webb1, Ioana Bonta2, Patricia Thompson3, Christopher Parks2, Rabih Obstruction the same procedure was achieved a week later. Pulmonary
Bechara2, Daniel Miller4 re-expansion and symptomatic control were achieved in 31 patients.
1
Emory University, Atlanta/GA/United States of America, 2Center for Advanced
Permeabilization of the bronchial lumen was achieved in 2 patients but not
Oncology - Thoracic, Cancer Treatment Centers of America, Newnan/United States pulmonary re expansion. Silicone prosthesis were implanted to 9 patients
of America, 3Hematology Oncology, Cancer Treatment Centers of America, Newnan/ with Tracheal lesions and 18 patients with Bronchial lesions. Differences
United States of America, 4Thoracic Surgery, Wellstarr Health Network, Marietta/ between genders were not shown. There were not any important clinical
GA/United States of America complications associated with the procedures. Moderate bleeding with
the pulmonary biopsy was control locally. In general the post operative
Background: Breast cancer is known to metastasize to the lung.. Most breast evolution of the patients was satisfactory. Conclusion: The Bronchoscopic
malignancies are clinically staged using radiographic modalities (e.g. PET Cryosurgery has clear indications in patients with Central Airway Tumors,
scans). Importantly, many inflammatory disorders will present similar lymph just as the diagnostic, therapeutic and palliatives purposes and in patients
node FDG-uptake on PET- as that of metastasized breast cancer. The latter with interstitial compromise of presumable neoplasic or infectious origin. In
confuses the treatment for individuals within whom both undiagnosed our casuistry, the objective was achieved in all the patients that underwent
autoimmune disorders and breast cancer co-occur. We aim to examine the the procedures such as tracheobronchial recanalization and extraction of
frequency of non-caseating granulomas diagnosed in PET avid mediastinal/ tracheal, bronchial or pulmonary tissue with a significant symptomatic
hilar nodes in patients with known breast cancer. Methods: Between March improvement with a low risk and low morbidity
2013 and December 2015, 46 patients diagnosed with breast cancer were
staged by PET-CT. Those with positive result in the mediastinum/hilum Keywords: bronchoscop, recanalization, lung, cryosurgery
underwent linear endobronchial ultrasound (EBUS) for pathologic diagnosis
and ensuing treatment Results: Of the 46 patients with avid mediastinal/hilar
adenopathy, 31 (67%) had malignant cytology on EBUS; the remaining 15 had
positive PET but negative cytology for malignancy. Twelve of the 15 patients
with false positive PET had reactive lymph nodes, and 3 had non-caseating POSTER SESSION 1 - P1.04: PULMONOLOGY –
granulomas on cytology (table 1). . Table 1: Results from EBUS Procedure and
Resulting Percentage Following Identification of Sarcoid-like Symptoms
P1.04-005 EFFICACY OF PHOTODYNAMIC THERAPY COMBINED
Total Number of WITH A GUIDE SHEATH METHOD IN LUNG CANCER PATIENTS WITH
Percentage of Percentage
patients in study: Number of
total (all PET among negative
ENDOBRONCHIAL STENOSIS
n=46 with positive patients Masafumi Misawa, Fumi Suzuki, Satoshi Yamawaki, Ryuta Tsuzuki, Ayumu
positive patients) patients
PET Otsuki, Kei Nakashima, Satoshi Noma, Masahiro Aoshima
Positive EBUS 31 67.40% Pulmonary Medicine, Kameda Medical Center, Kamogawa/Japan
Negative EBUS 12 26.10% 80% Background: Photodynamic therapy (PDT) using a second generation of
photosensitizier, talaporfin sodium was useful for the curative or palliative
Negative/ treatment of lung cancer. However, it is required for interventional
Non-caseating 3 6.50% 20% pulmonologist to perform accurate PD-laser irradiation in some lung cancer
granulomas EBUS case. We hypothesized that all-direction type PD-laser probe covered with
a guide sheath (GS) (GS-PDT) made it possible to secure its probe and fix its
Twenty percent of the patients with negative cytology and positive PET had
position in the endobronchial lesion, to enhance the effect of PDT by avoiding
non-caseating granuloma, and 6.5 % of all patients with positive PET had
direct contact with the tumor lesion, thus preventing its probe from contact
non-caseating granulomas. Conclusion: Conclusion: This study represents
with blood. Methods: We evaluated the efficacy and safety of this irradiation
the largest cohort of breast cancer patients, where the incidence of non-
technique for the lung cancer patients with endobronchial stenosis. Before
caseating granulomas is investigated in PET-positive mediastinal/hilar nodes.
the procedure, we evaluated the extent of tumor lesion by auto-fluorescence
We conclude that PET may not be sufficient for staging the mediastinum
video-bronchoscope (BF TYPE-F260, Olympus, Japan). As a photosensitizer,
in patients with breast cancer and, in selected patients, pathologic staging
talaporfin sodium (Laserphyrin, Meiji Pharma, Japan) was administered
should be done. In addition, the finding of non-caseating granulomas in these
at 40mg/m2 intravenously 6 hours before irradiation. PDT was performed
patients may either indicate an incidental diagnosis of early stage sarcoidosis,
by using video-bronchoscope (EB-530T, FUJI MEDICAL, Japan) to visualize
or an inflammatory reaction to the current treatment (sarcomatoid
PD-laser light clearly by adjusting FICE (Flexible spectral Imaging Color
reaction). We also suggest that these patients should be followed for any
Enhancement) mode. We irradiated 664nm laser light to the target bronchus
manifestations of sarcoidosis.
with endobronchial stenosis utilizing an all-direction type laser probe covered
Keywords: sarcoid, sarcomatoid, mediastinal lymphadenopathy with a GS (disposable K203 guide sheath kit, Olympus, Japan) at each dose of
100J/cm2 (150mW) for 11 minutes and 7 seconds under fluoroscopic guidance.
After one month, we evaluated the endoscopic efficacy of this method.
Results: Between December 2014 and April 2015, we performed GS-PDT for
three patients with pathologically diagnosed lung cancer, 1 squamous cell
POSTER SESSION 1 - P1.04: PULMONOLOGY – carcinoma, 1 adenocarcinoma and 1 small cell carcinoma. Stage IA squamous
cell carcinoma patient with endobronchial stenosis underwent definitive
therapy. Stage IA adenocarcinoma patient with endobronchial wall spread of
P1.04-004 BRONCHOCOPIC CRYOSURGERY WITH CARBON DIOXIDE; tumor to proximal respiratory tract underwent a combination of induction
EXPERIENCE IN AN ONCOLOGY CLINIC IN COLOMBIA chemo-radiotherapy followed by sleeve left upper lobectomy as for definitive
therapy to reduce the extent of lung resection. Stage IIIA limited-stage
Jaime Sanchez Vallejo1, Jaime Echeverri2, Juan Carlos Rojas Puentes3, Antonia
small-cell lung cancer patient with the stenosis of right main and upper
Angel Henao4
lobe bronchus underwent palliative therapy to improve oxygenation and
1
Quindio, Universidad Del Quindio, Armenia/Colombia, 2Oncólogos Del Occidente to prevent obstructive pneumonia. One month after GS-PDT, we confirmed
S.A., Pereira/Colombia, 3Oncólogos Del Occidente, Pereira/Colombia, 4Universidad
the endoscopic response (1 complete response, 2 partial response). No PDT-
Javeriana, Cali/Colombia
related complications occurred. Conclusion: New GS-PDT method was safe

and could be an effective technique to accurately irradiate the lung cancer adenocarcinoma (8 pts, mOS 3.64 m), small cell lung cancer (4 pts, mOS 1.18 m)
patients with endobronchial stenosis. and NOS (3 pts, mOS 1.80 m). Squamous cancer stage IIIB (22 pts, mOS 5.18 m)
had better prognosis than stage IV (10 pts, 3.47 m), all differences were not
Keywords: Photodynamic therapy, Guide sheath, Lung cancer, Endobronchial significant. Conclusion: Y stent insertion is an effective palliative procedure
stenosis in malignant stenosis of central airways. Tumours in this localisation have
generally bad prognosis. In present study, squamous lung cancer was the most
frequent one and had longer survival than other types of cancers. Study was
supported by grant AZV 16-32318A
POSTER SESSION 1 - P1.04: PULMONOLOGY – Keywords: central malignant stenosis - Ystent - prognosis
P1.04-006 SECOND PRIMARY LUNG CANCER: FIVE YEARS OF A

SINGLE CENTER EXPERIENCE IN ITS DIAGNOSIS AND TREATMENT
Fatmir Caushi1, Danjela Xhemalaj2, Hasan Hafizi3, Ilir Skenduli2, Jona Shkurti2, MONDAY, DECEMBER 5, 2016
Arjan Mezini3, Zyber Pupla3, Alban Hatibi2
1
Thoracic Surgery, University Hospital of Lung Diseases, Tirana/Albania, 2Thoracic
Surgery, University Hospital of Lung Diseases, Tirana/Albania, 3Pneumology,
P1.04-008 TUMOR PENTAPLICITY - CASE REPORT
University Hospital of Lung Disease “Shefqet Ndroqi”, Tirana/Albania Petra Smičková
The Department of Respiratory Medicine, The University Hospital of Olomouc,
Background: Second primary lung cancer (SPLC) constitute an important Olomouc/Czech Republic
dimension of the burden of cancer survivorship that needs to be taken into
account when defining strategies for surveillance, prevention and counseling. Background: Metachronic tumor duplicity is a relatively common
In last three decades the incidence of SPLC in patients that had a history of phenomenon, often related to mutagenic effects of some types of antitumor
a prior cancer out of the respiratory system is estimated 2-8%. Relative risks therapy. However, idiopathic tumor multiplicity is rare. We present the
of SPLC may be smaller than previously reported may benefit from increased case report of a patient, who developed five different malignant tumors in
surveillance. The goal of this study was to give an overview of SPLC regarding fifteen years horizon. Methods: Case report Results: 66-year old patient was
patients’ primary malignancy, their stage of lung cancer presentation and diagnosed renal cell carcinoma in year 2001 with subsequent nephrectomy.
bringing to the light some possible risk factors. Such data will be helpful in During follow-up, a coin lesion was recognized on chest x-ray, histologically
calculation of the risk for SPLC as well as handling of risky patients for a better and radiologically verified as stage IA pulmonary adenocarcinoma. Patient
survival. Methods: This is a retrospective study for a period of 5 years where underwent successful right lower lobectomy. In 2010 colorectal carcinoma
all the data that was gathered from clinical cartels of patients with lung was diagnosed followed by non-invasive papillocarcinoma of urinary bladder
cancer were analyzed using Pearson Chi-Square. Results: SPLC represents 2% in 2012. All these tumors were treated curatively. In 2014 a new mass appeared
of all lung cancers diagnosed during the period of study. The prior diagnose on chest x-ray. Repeated bronchoscopy failed to obtain valid histological
of cancer for this patients was breast cancer in 46% of cases, cervix cancer sample. The positron emission tomography revealed malignancy suspicion
in 40% of cases and the other diagnosis 14% of cases. All the patients have and excluded the disseminated disease. Surgical resection was performed.
been under oncologic treatment with radio or chemotherapy. 20% of these Peroperative histology reported carcinoma of uncertain type and surgeon
patients have been smokers prior to first malignancy. The average age of decided for completion of pulmonectomy. However, final histological
the patients with SPLC was 55 years old. The ratio male to female was 1:10. report showed small-cell lung cancer (pT2apN2Mx). Despite adjuvant
The most frequent hystotipe found was adenocarcinoma in 60% of cases chemotherapy given the patient developed distant metastases and died
meanwhile in all cases with a prior squamous cell cancer of cervix was found subsequently due to tumor progression in February 2016. Conclusion: Tumor
squamous cell carcinoma as SPLC. The average period of time from the pentaplicity is a clinical situation with rare occurrence. Our patient didn´t
prime cancer to the SPLC was 3.7 years. 73% of cases with SPLC underwent receive chemotherapy until 2010 (adjuvant chemotherapy after radical
an anatomical resection of the tumor. Conclusion: This study shows that colorectal carcinoma surgery), so there could be no influence of the first
patients with the higher risk for a SPLC are premenopausal women with three malignancies therapy. We did not find tumor occurrence in the family,
breast cancer and cervical cancer. Changes in the prevalence of risk factors no external risk factor, the patient fits in none of defined hereditary cancer
and diagnostic techniques may have affected more recent risks. The relative predisposition disorder. Detection of common driver mutations in all five
risk of developing SPLC in smokers is unclear. SPLC after oncologic treatment tumors is running. The long term survival is supporting the idea of a careful
is an issue that raises many questions. follow up and shows advances in current oncological treatment.
Keywords: second primary lung cancer

P1.04-009 BACTERIAL POPULATION DYNAMICS IN COLONIZATION
OF AIRWAY STENTS IN PATIENTS WITH CANCER
P1.04-007 Y STENTS IN MALIGNANT TUMOURS - LONG TIME
Marta Diez-Ferrer 1, Laura Calatayud2, Cristina Lopez-Delgado1, Rosa Lopez-
FOLLOW UP AND SURVIVAL
Lisbona1, Noelia Cubero1, Nikos Koufos1, Sara Marti2, Carmen Ardanuy2, Jordi
Vitezslav Kolek, Renata Zittova Dorca1, Josefina Liñares2, Antoni Rosell1
Dept. of Respiratoty Medicine, University Hospital, Olomouc/Czech Republic 1
Respiratory Medicine, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat/
Spain, 2Microbiology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat/
Background: Stent insertion is one of the standard methods of therapeutic Spain
bronchology. Stents can be applied to trachea or bronchi. Y stents are inserted
to the tracheobronchial area around tracheal bifurcation. The most frequent Background: Stent placement is an increasingly used treatment for malignant
indications are the central malignant tumours, less frequently benign tracheobronchial stenosis. The main complication related to airway stents is
stenosis, phistulla or tracheomalatia. The prognosis of central stenosing bacterial colonization causing chronic cough and sputum, halitosis, recurrent
tumours is usually unfavourable with no specific data available. Methods: bronchial infections, pneumonia and even sepsis. The main objectives were to
464 stents were inserted in our institution, out of them 120 were of Y type. describe potentially pathogenic bacteria (PPM) involved in stent colonization
The results of Y stent insertion in malignant tumours during the period 2001- and to analyze PPM dynamics during follow-up. Methods: Prospective study
2015 were evaluated. Survival of patients was compared according to sex, in patients with malignant stenosis treated with stent placement. Bronchial
age, tumour origin, histology and stage. Results: 80 Y stents were inserted washings (BW) were performed before and at least 1 month after stent
in 50 men and 30 women, mean age in the time of diagnosis was 61.6 year, placement. Qualitative cultures of PPM isolated in BW were performed.
in the time of stent insertion 62.8 year. There were 53 bronchial cancers, Statistical analyses with R-3.2.3. Results: Total of 65 patients, 56 (86%) men,
6 tracheal cancers, 12 oesophageal cancers, 3 laryngeal cancer, 2 thyroid mean age 64 (±10) y/o, 58 (89%) current or former smokers, 2 (3%)
cancers, and 1 breast cancer, 2 lymphomas, and 1 thymoma. Since diagnosis bronchiectasis, 28 (43%) COPD. Cancers were: primary lung cancer (n=52, 80%)
the mean survival (MS) was 26.39 months, median of overall survival (mOS) followed by thyroid (n=4, 6%), esophagus (n=2, 3%) and other (n=7, 11%);
was 10.89 (95% CI 8.10- 13.67) months. Since stent insertion MS was 18.09 m stenosis were located in trachea (n=14, 21%), main carina (n=16, 25%) and main
and mOS was 3.48 (95% CI 2.72-4.23) m. There were no statistically significant bronchi (n=35, 54%); and stent types included metal (n=30, 46%) and silicone
differences according to sex, age and type of tumour (p >0.05): tracheal (n=35, 54%). Isolated PPM in BW (table 1). Airway colonization was absent in
cancer - mOS 6.07 m, lung cancer - mOS 3.64 m, oesophageal cancer - mOS 2.49 14 (21.5%) and present in 79%, of which it was persistent in 33 (50.8%) and
m, other tumours - mOS 3.54 m. Among lung cancers squamous cancer was intermittent in 16 (24.6%). Only 2 (3.1%) became negative. Median time until
the most frequent type (34 pts, mOS 4.20 m) and had better prognosis than colonization was 35 days (IQR 28-116), with no significant differences between
stent types or location. Metintas1

1
Lung and Pleural Cancers Research and Clinical Center; Medical Faculty
Department of Chest Diseases, Esogu, Eskisehir/Turkey, 2Esogu Medical Faculty
Department of Public Health, Lung and Pleural Cancers Research and Clinical
Center, Eskisehir/Turkey, 3Lung and Pleural Cancers Research and Clinical
Center and Medical Faculty Department of Chest Diseases, Eskisehir Osmangazi
University, Eskisehir/Turkey, 4Lung and Pleural Cancers Research and Clinical
Center, Eskisehir Osmangazi University, Eskisehir/Turkey
Background: To determine demographic, clinical and survival data of elderly

lung cancer patients. Methods: We evaluated 2,637 patients with lung cancer
between January 1990 and October 2010. Elderly patients were defined as
those 65 years or older. The patients were classified into two groups: younger
and older group. The demographic, clinical and survival data of the groups
were compared. Results: 998 (37.8%) patients were in the older group and
1,639 (62.2%) were in the younger group. The female patients rate (9.1% vs
7.8%; p=0.238) and other cancer history (4.4% vs 3.3%; p=0.101), and family
cancer history rate (p=0.664) were similar between two groups. Illiterate
patients rate (20.1% vs 16.6%; p<0.001), occupational risks (9.2% vs 12.8%;
p=0.005), current smoker and exsmoker rate (p<0.001), asbestos exposure
rate (p=0.005), COPD prevalence (15.1% vs 8.6%; p<0.001), and two or more
comorbidity rate (21.1% vs 10.1%; p<0.001) of older group was higher than
younger group. The symptom duration of the groups were 96.4 days and
92.8 days, respectively (p=0.359). Systemic complaints and extrapulmonary
intrathoracic spread complaints of older group were higher than younger
group (p<0.001 and p=0.025). Karnosfky performance status was lower in
older group than younger group (79.3 vs 82.2; p<0.001). Radiological findings
Conclusion: The majority of patients with malignant stenosis treated with
of asbestos exposure was higher in the older group than younger group (6.9%
airway stents develop early and persistent colonization by PPM, regardless of
vs 4.1%; p=0.002). There was no difference between the groups in terms of
stent type.
histology and stage (p=0.078 and p=0.254). The independent etiological
Keywords: Airways stenosis, Tracheobronchial stents, Microbiology risk factors of lung cancer in elderly patients were lower educational status,
smoking, COPD and male gender by multivariable logistic regression analysis.
The median survival was 8.0 ± 0.36 months (95% CI: 7,288-8,712) for older
group and 9.0 ± 0.27 months (95% CI: 8,477-9,523) for younger group (log-
Rank: 4.567; p=0.033). The factors affecting survival in the both groups stage,
POSTER SESSION 1 - P1.04: PULMONOLOGY – Karnofsky performance status and treatment by Cox regression analysis.
Conclusion: These data indicate that lung cancer had different risk factors and
short survival in elderly patients. These features should be considered in the
P1.04-010 NEUTROPHIL TO LYMPHOCYTE, PLATELET TO management of these patients.
LYMPHOCYTE RATIOS AND SYSTEMIC INFLAMMATION IN LUNG Keywords: elderly patients, lung cancer
CANCER STAGES
Erhan Ionela Mihaela1, Dumitrache-Rujinski Stefan2, Stroescu Carmen2,
Bogdan Miron2
1
Marius Nasta Institute of Pulmonology, Marius Nasta Institute of Pulmonology,
Bucharest/Romania, 2Umf Carol Davila, Bucharest/Romania POSTER SESSION 1 - P1.04: PULMONOLOGY –
Background: Lung cancer is associated with systemic inflammation which
seems to influence the prognostic of the disease. Different affordable P1.04-012 SINGLE CENTER EXPERIENCE WITH NIVOLUMAB
methods may be used to evaluate the systemic inflammation: erythrocyte
ADMINISTRATION IN NSCLC PATIENTS FROM EAP PROGRAM
sedimentation rate (ESR), Neutrophil to lymphocyte ratio (Ne/Ly), Platelet
to lymphocyte ratio (Pl/Ly). The aim of the study is to assess the relation Milos Pesek 1, Jana Durova2, Gabriela Krakorova2
1
between TNM lung cancer stages and the systemic inflammation estimated Faculty Hospital, Charles University in Prague, Plzeň/Czech Republic, 2Faculty
by Ne/Ly, Pl/Ly and ESR. Methods: Patients with lung cancer were classified Hospital, Dept. of Pneumology and Phtis., Plzeň/Czech Republic
according to 7th TNM lung cancer staging in two groups: Group A (I, II and IIIA)
Background: Immunotherapy using monoclonal antibody against PD-1
and Group B (IIIB, IV). A complete blood count (CBC) and ESR were determined.
receptor (nivolumab) offers another possibility to improve tumor control in
Ne/Ly and Pl/Ly ratios were calculated for all patients. The results were
patients with advanced squamous (SQ) and non-squamous (NSQ) NSCLC.
compared between the two groups. Results: 73 consecutive patients (22 in
Methods: We present first experience with nivolumab in Early Access
Group A and 51 in group B) were analyzed. In Group A (16 males), the mean
Program (EAP). Nivolumab tolerability, safety data, frequency of therapeutic
age was 63,73 ± 7,69 years, the median Ne/Ly: 2,86 (0,88-8,36), median Pl/
responses and ADRs will be presented in 42 patients with advanced SQ and
Ly: 128,81 (21,62-416,67) and median ESR: 10 mm/h (10-120). In Group B (48
NSQ NSCLC. Results: 22 patients with SQ-NSCLC entered EAP, 3 patients
males), the mean age was 65,06 ± 10,09 years, the median Ne/Ly: 4,46 (0,70-
did not start therapy (2 early deaths and 1 refusal) and 19 patients received
25,6), median Pl/Ly: 204,48 (3,38-651,25) and median ESR: 40 mm/h (3-120).
treatment (16 males, 3 females). Therapy was discontinued in 9 patients
The values of Ne/Ly, Pl/Ly were significantly higher (p: 0,009 respectively p:
(7x disease progression, 2x serious ADR). Therapy is currently withold in 4
0,007) in Group B versus Group A, but no statistically significant difference
patients due to management of ADRs and 7 patients continue to receive
was observed for ESR values. Conclusion: We found a relation between TNM
nivolumab. 5 patients died (26%) with median follow up of 9 months in this
lung cancer stages and the systemic inflammation assessed by neutrophil to
group. 20 patients with NSQ histology were included in EAP, 2 patients from
lymphocyte (Ne/Ly) and platelet to lymphocyte (Pl/Ly) ratios. The values of
this group died before initiation of therapy and 1 patient did not receive
Ne/Ly, Pl/Ly ratios were significantly higher in nonresectable stages (IIIB, IV).
nivolumab due to worsening of her performance status. 17 patients were
Erythrocyte sedimentation rate (ESR) seems not to be an appropriate method
treated with at least one dose of nivolumab (10 males, 7 females). Therapy was
to evaluate this relation.
discontinued in 8 patients (7x disease progression, 1x due to gastrointestinal
Keywords: lung cancer, systemic inflammation toxicity with grade 3 diarrhea). Treatment is currently withold in 6 patients
due to management of ADRs and 4 patients continue to receive nivolumab.
5 patients (29%) in this group died with median follow up of 5 months. So
far, we have seen 7 partial remissions in all 36 treated patients with NSCLC
(19%) which corresponds to data from registration studies of nivolumab.
Disease stabilization was reported in other 7 patients giving the disease
POSTER SESSION 1 - P1.04: PULMONOLOGY – control rate of 38%. As expected from nivolumab mechanism of action,
adverse drug reactions are usually immune related. Serious ADRs were rarely
observed including neurological toxicity (difficulty to swallow and diplopia),
P1.04-011 DEMOGRAPHIC, CLINICAL AND SURVIVAL diarrhea, pneumonitis and skin toxicity (lichen ruber planus). Conclusion:
CHARACTERISTICS OF LUNG CANCER AMONG ELDERLY PATIENTS In general, patients from EAP program were more pretreated compared to
IN TURKEY patients in registration studies (therapy allowed in 3rd and 4th line), also
patients with PS2 were included (only PS 0 and 1 in the trials). Treatment with
Guntulu Ak 1, Selma Metintas2, Senay Yilmaz3, Filiz Bogar4, Muzaffer

nivolumab was well tolerated and it brings the benefit for some patients of the impact of using an artificial airway under GA on diagnostic yield was
after 1-3 lines of previous anticancer therapy. Although serious ADRs are determined using multivariate logistic regression. Continuous variables are
relatively rare, management of side effects requires good cooperation with presented as means (± SD) and categorical variables are reported as counts
the patients as well as cooperation with highly specialized departments and percentages. For all tests, two-sided P values < 0.05 were considered
(gastroenterologists, endocrinologists, dermatologists). statistically significant. Results: Patients in the GA group were older (65
years versus 57.6, p= 0.005), had a higher age-adjusted Charlson comorbidity
index, (3.7 versus 1.9, p < 0.001) and a higher ASA classification (3 versus 2
p=0.004). Average lymph node size was smaller in the artificial airway group
(16.2 mm versus 20.7mm, p = 0.01). Despite these differences, the diagnostic
POSTER SESSION 1 - P1.04: PULMONOLOGY – yield was the same (61.4 % in each group). In multivariate analyses, female
sex and lymph node size were the only predictors of a diagnostic EBUS-TBNA.
OR 3.3, 95 % CI, 1.23 – 9.1 for female gender, (p= 0.02) and 1.1, 95 % CI, 1.00 –
P1.04-013 DIAGNOSTICS AND TREATMENT OF ALK-POSITIVE NSCLC 1.18 for lymph node size (p= 0.04). Diagnoses made were: adenocarcinoma of
PATIENTS - A SINGLE CENTER EXPERIENCE the lung 42.6 %, Sarcoidosis 16.7 %, Small cell lung cancer 14.8 %, Squamous
Milos Pesek 1, Petr Grossmann2, Petr Mukensnabl3, Gabriela Krakorova4 cell carcinoma 11.1 %. Conclusion: EBUS-TBNA performed under general
1 anesthesia through an artificial airway was not associated with an increased
Dept. of Pneumology and Phthiseology, Charles University in Prague, Plzeň/Czech
diagnostic yield, and therefore concious sedation should be considered
Republic, 2Molecular Pathology Laborartory, Bioptic Laboratory, Ltd, Plzeň/Czech
Republic, 3Dept. of Pathology, Faculty Hospital, Plzeň/Czech Republic, 4Dept. of where appropriate, with general anesthesia reserved for those patients who
Pneumology and Phthiseology, Faculty Hospital, Plzeň/Czech Republic are older, and with a higher perioperative risk. More research assessing the
determinants of a positive diagnosis including physician pretest likelihood
Background: ALK positive advanced NSCLC patients could get significant and PET/CT avidity are needed to improve diagnostic outcomes.
benefit of targeted therapy. In Czech Republic, targeted therapy is payed
just as second-and more line treatment, required positive FISH result of Keywords: EBUS-TBNA, moderate sedation, Diagnostic yield, lung cancer
ALK-positive NSCLC tumour. Methods: We investigate ALK-rearrangement in
selected group of NSCLC patients starting from January 2011 via fluorescence
in situ hybridization (FISH) with the Vysis ALK Break Apart FISH Probe Kit
(Abbott Molecular). We evaluate frequence of positive and inconclusive
results. In the group of ALK positive patients we evaluate clinical behaviour MONDAY, DECEMBER 5, 2016
of tumours and effectivity and side effects of ALK inhibitors. Results:
From January 2011 till June 2016, 798 nonsquamous NSCLC tumour samples
were evaluated by FISH method. 20 (3.2 %) of evaluable 660 samples were P1.04-015 CLINICAL APPLICATION OF VIRTUAL NAVIGATED
positive, 138 tumour samples were clasified as ALK break inconclusive (17.3 BRONCHIAL INTERVENTION
%). ALK break positive group of patients consist of 13 men and 7 women, Naohiro Kajiwara, Junichi Maeda, Koichi Yoshida, Masaru Hagiwara, Tetsuya
median age 68.5 years. 17 of them were adenocarcinomas, in two there were Okano, Masatoshi Kakihana, Tatsuo Ohira, Norihiko Ikeda
adenosquamous histology and in one NSCLC-NOS was found. The limit of ALK Department of Surgery, Tokyo Medical University, Tokyo/Japan
positivity was 10 % positive cells, the range of our positive results were 10 – 72
%. 6/20 patients were treated by crizotinib. Two of them received second ALK Background: Removal of endobronchial tumor is considered the first
inhibitor ceritinib after failure of crizotinib, those patients are alive and well treatment of choice to improve respiratory status to dilate and maintain the
5 and 8 years from diagnosis of adenocarcinoma st. IV. Three patients died airway. In patients with inoperable tumors we frequently regard endoscopic
before they could get an access to targeted therapy, seven others with low treatment as the first treatment of choice, but the indications and decisions
PS died before start of targeted therapy, in three others there is not actual regarding the method require careful consideration. We reported the
need for targeted treatment. One patient on crizotinib died after 11 months indications and efficacy of virtual navigated bronchial intervention for the
of targeted treatment, two other died after one month of treatment, in one treatment of bronchial tumors. To select safer and precisely approach for
patient targeted therapy was refused due to intolerance. Conclusion: Patients patients with bronchial tumors, we evaluate virtual navigated bronchial
suffering from advanced ALK rearranged NSCLC should have perspectives intervention using a high-speed 3-dimensional (3D) image analysis system,
of long lasting tumour response on ALK inhibitors. ALK rearrangement Synapse Vincent (Fuji Photo Film Co., Ltd., Tokyo, Japan). Methods: We set
investigations should be done in nonsquamous NSCLC routinely. In our out to clarify, based on retrospective evaluation of routine work-up data
departments, we have relatively high frequency of inconclusive ALK testing in our charts and patient treatment data, the efficacy of virtual navigated
results. However, it is not easy to get adequate tissue sample from routine bronchial intervention for the treatment of different types of bronchial
investigations. Positive results are found most frequently in adenocarcinoma tumors, yet representative of the spectrum of conditions we encounter, in
patients. We consider due to rapid progression of ALK positive tumours on order to provide a guide to techniques available in interventional bronchology
chemotherapy that targeted therapy should be realised as a first line option. for obstructive lesions. All computed tomography (CT) must satisfy several
conditions necessary to analyze images by Synapse Vincent. Synapse Vincent
Keywords: NSCLC; ALK translocation; crizotinib; ceritinib provides more information not only concerning tumor size and shape, but
also whether the tumor invades surrounding tissue and the extent of airway
and vessel involvement. Constructed images are displayed on a monitor,
which can be utilized for deciding the simulation and interventional strategy
and for navigation during interventional manipulation. Results: In these
MONDAY, DECEMBER 5, 2016 cases, Synapse Vincent was used to determine the best planning of virtual
navigated bronchial intervention. The feasibility and safety of Synapse
Vincent in performing useful preoperative simulation and navigation of
P1.04-014 DIAGNOSTIC YIELD IN PATIENTS UNDERGOING interventional procedures lead to the safer, more precise, and less invasive for
ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSBRONCHIAL the patient, and easy to construct an image, depending on the purpose, in 5-10
NEEDLE ASPIRATION FOR DIAGNOSIS OF LUNG CANCER minutes using Synapse Vincent. Moreover, if the lesion is in the parenchyma
Sunkaru Touray 1, Rahul Sood1, Carlos Martinez-Balzano1, Jonathan Holdorf 1, or sub-bronchial lumen, it helps to perform simulation with virtual skeletal
Anne Lim2, Andres Sosa1, Paulo Oliveira1, Scott Kopec1 subtraction to estimate potential lesion movement. By using virtual
1
Pulmonary Allergy & Critical Care Medicine, University of Massachusetts Medical navigated system for simulation, bronchial intervention was performed with
School, Worcester/United States of America, 2Internal Medicine, Saint Vincent no complications safely and precisely. Conclusion: Preoperative simulation
Medical Center, Worcester/MA/United States of America using virtual navigated bronchial intervention reduces the surgeon’s stress
levels, particularly when highly skilled techniques are needed to operate on
Background: Endobronchial Ultrasound-Guided Transbronchial Needle lesions. This task, including interventional simulation and navigation both
Aspiration (EBUS-TBNA) is an established diagnostic tool in the evaluation pre- and during manipulation, could lead to greater safety and precision.
of lung cancer with a variable diagnostic yield, ranging from 62 % - 93 %1–4. These technological instruments should be helpful for bronchial intervention
Although the procedure can be performed under moderate sedation (MS) or procedures, and are also excellent devices for educational training.
general anesthesia (GA) 5, the impact of sedation type on the diagnostic yield
has yielded variable results with some authors reporting a higher yield with Keywords: Interventional bronchology, Virtual navigation system
deep sedation6, whereas others note no difference between MS and GA 5.
We present findings of a retrospective study that looked at the diagnostic
yield using an artificial airway under GA compared to conscious sedation
through a natural airway in patients undergoing EBUS-TBNA . Methods:
Demographic information on age, sex, race and co-morbidities were used to MONDAY, DECEMBER 5, 2016
compute an age adjusted Charlson Co-morbidity index for each of 88 patients.
Pathology reports were reviewed and an EBUS-TBNA was determined to be
diagnostic if any of the sampled lymph nodes yielded a diagnosis. Assessment P1.04-016 EBUS PLUS FLUOROSCOPY-GUIDED BIOPSY COMPARED
TO FLUOROSCOPY-GUIDED TBB FOR OBTAINING SAMPLES OF Keywords: lung cancer, survey, effecting factors, surgery
PERIPHERAL PULMONARY LESIONS
Jian Ye
Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou/China
Background: Early detection of peripheral pulmonary nodules and MONDAY, DECEMBER 5, 2016
histopathologic diagnosis of biopsy samples of the nodules are key to
improving survival rates of lung cancer. Steady improvement in bronchoscopic
procedures during the past few decades enable detection and biopsy of much P1.04-018 OCCURRENCE OF TRIPLE MULTIPLE MALIGNANCIES
smaller nodules. We report a meta-analysis of recent reports comparing the WITH LAST LUNG SQUAMOUS CELL CARCINOMA - CASE REPORTS
diagnostic yields of endobronchial ultrasonography plus fluoroscopically- Anna Doboszyńska, Anna Romaszko
guided transbronchial biopsy with that of fluoroscopically-guided Department of Pulmonary Medicine and Infectious Diseases, University of Warmia
transbronchial biopsy without the use of endobronchial ultrasonography. and Mazury, Olsztyn/Poland
Methods: We searched Medline, the Cochrane Library, PubMed, and
Google Scholar and found five articles that met our inclusion criteria. One Background: The incidence of multiple primary tumors (MMPNs) ranges
of those articles did not strictly meet our criteria, in that it was deficient from 0.73 to 11.7%. Most often occur double malignancies - 3-5%, much less
in quantitation, but we included it because it contained other relevant triples - 0.5%. The aim of the study is to describe the three cases of triple
information. Results: Meta-analysis from the 4 studies revealed a higher metachronous multiple malignancies, the last of which was a squamous
positive diagnostic yield in the group with endobronchial ultrasonographic cell carcinoma of lung in all three patients. Methods: A retrospective
guidance in addition to fluoroscopy than the group diagnosed with only analysis of all medical histories (1163) patients who were hospitalized in
conventional fluoroscopic guidance to the lesion, for large and small lesions. the Pulmonary Hospital Hospital in Olsztyn, Poland in the period from
Conclusion: Obtaining transbronchial biopsy samples for histopathological January 2013 to October 2015, with a diagnosis of at least one neoplasm
diagnosis is enhanced by addition of endobronchial ultrasonography to was performed. We selected only these patients who were diagnosed with
conventional fluoroscopic guidance; this is especially important for patients histologically confirmed three independent malignancies. Results: The
with small peripheral lung lesions who benefit greatly from early diagnosis. incidence of tumors of triple malignancies was 0.52%. Of all cases of triple
malignancies, we selected 3 cases - 2 men and 1 woman, whose last-growing
Keywords: endobronchial ultrasound, Lung biopsy, peripheral pulmonary cancer, histopathologically confirmed, was squamous cell lung cancer. Case
lesion, fluoroscopy-guided No. 1 - 54-year-old man with COPD (GOLD 2), who gave up smoking, melanoma
of the scalp treated surgically and by chemotherapy (6xDTIC) at the age of
19, Hodgkin NS II at the age of 38 treated with 6xABVD, at the age of 53 years
diagnosed with squamous cell carcinoma of the left lung in stage T2N1M0.
Due to the low value of spirometry disqualified from surgery, qualified for
MONDAY, DECEMBER 5, 2016 radiotherapy. Case No. 2 67-year-old man with a history of hypertension, colon
cancer at the age of 56, after a laryngectomy because of laryngeal squamous
cell carcinoma at the age of 63, diagnosed with asymptomatic squamous
P1.04-017 THE SURVIVAL OF OUR PATIENTS DIAGNOSED WITH cell carcinoma of the right lung in a stage T2N0M0 at the age of 65. Case No.
LUNG CANCER IN 2013 3 74-year-old woman with atrial fibrillation, stable ischemic heart disease,
Sedat Altin1, Cengiz Ozdemir2, Celalettin Kocaturk 3, Murat Kiyik2, Nur Urer4, tongue cancer at the age of 67, and its recurrence in the age of 72, after a right-
Mehmet Gunluoglu5, Kaan Kara2, Serap Hastürk2, Yusuf Baser6, Mehmet sided mastectomy and chemotherapy for breast cancer at the age of 69, at the
Bedirhan3, Ibrahim Dincer3 age of 74 diagnosed with squamous cell carcinoma of the left lung. The average
1 age of first cancer was 47, the second 57 years, the third 64 years. Conclusion:
Pulmonary Diseases, Yedikule Chest Diseases and Chest Surgery Hospital,
Istanbul/Turkey, 2Pulmonary Diseases, Yedikule Chest Diseases and Thoracic 1. Lung cancer often occurs as a subsequent malignancy 2. Another primary
Surgery Training Hospital, Istanbul/Turkey, 3Thoracic Surgery, Yedikule Chest malignancy may develop even 30 years later, and therefore the possibility of
Diseases and Thoracic Surgery Training Hospital, Istanbul/Turkey, 4Pathology, development the third or another cancer should be considered for all cancer
Yedikule Chest Diseases and Thoracic Surgery Training Hospital, Istanbul/ patients. 3. Development of synchronous or metachronous neoplasms should
Turkey, 5Chest Surgery, Medipol University Faculty of Medicine, Istanbul/Turkey, be considered in any case in patients with previous oncological treatment.
6
Radiation Oncology, Yedikule Chest Diseases and Thoracic Surgery Training
Hospital, Istanbul/Turkey Keywords: case report, triple metachronous multiple malignancies, multiple
maliganacies, Squamous cell lung cancer
Background: Lung cancer is an important health problem. To investigate
the survival of our patients diagnosed in our hospital with lung cancer and
the situations that effect. Methods: Using the data processing and archive
system of our hospital, patients were examined who had operated with C34
code in 2013. The rates of survival were calculated using Kaplan-Meier Method POSTER SESSION 1 - P1.04: PULMONOLOGY –
and compared with Long-rank method. The influence of age on survival was MONDAY, DECEMBER 5, 2016
analysed with Cox’s proportional hazards regression model. For multivariate
analysis Cox’s proportional hazards regression model also used. The level of
P1.04-019 FINAL ANALYSIS OF LUNG MICROBIOME FROM PATIENTS
P<0.05 accepted as significant. Results: 1563(83.5%) of 1871 patients were
UNDERGOING BRONCHOSCOPY
male and 308 of the were female and their average age were found as 62.5
years, the average age in male was 62.7 while 61.4 in female. Median age was Glen Weiss 1, Jill Cocking2, Cherae Bilagody2, Heidie Hornstra3, Emily
62. The rate of M/F was calculated as 5.1, but there were no difference in Kaufman2, Daniel Nader4, J. Turner5, Sharad Chandrika6, J. Caporaso2, Paul
terms of the average age(p>0.05). We had 16 male and 11 female patients were Keim2, Brandy Harmon1, Heather Barilla1, Talima Pearson2
1
about 27(1.4%), under the age of 40. As a histological type, 717(38.3%) were Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear/
squamous carcinoma, 692(37%) were adenocarcinoma, 288(15,4%) were small AZ/United States of America, 2Northern Arizona University, Flagstaff/AZ/United
cell, 174(9.3%) unidentified cell malign carcinoma. While with 42.8% in male States of America, 3Northern Arizona University, Flagstaff/United States of
America, 4Southwestern Regional Medical Center, Cancer Treatment Centers of
squamous carcinoma was frequent, adenocarcinoma with 57.8% in female was
America, Tulsa/AL/United States of America, 5University of Tennessee Graduate
frequent. The average survival was calculated as 18 months, median survival School of Medicine, Knoxville/AL/United States of America, 6Western Regional
as 12 months (95& Cl 11-13 months) and the rate of 2 years survival as 33,4%. Medical Center, Cancer Treatment Centers of America, Goodyear/United States of
While surgical treatment were applied to 380 patients (20.3%), chemotherapy America
were applied to 1100 patients(58,8%) and palliative care were applied to
302(16,1%) patients. The 2 years survival time was found significantly high Background: Recent studies have demonstrated diversity in the lung
in patients received surgical treatment.(73% in spite of 23.3%)(p<0.0001). microbiomes of chronic obstructive pulmonary disease and healthy
While the 2 years survival of patients receiving chemotherapy was calculated individuals. Lung microbial communities may not just serve as a predictor
as 25,6%, the patients receiving palliative care was 20,5%(p=0.08).The of cancer development, but also as a target of pharmacological cancer
median survival time was found 28,4 months in patients receiving surgical prevention strategies. We sought to characterize the lung microbiome
treatment, patients receiving chemotherapy 14 months and palliative care diversity within patients with lung cancer for comparison to those with
was 11.5 months .The patients received neoadjuvan therapy lived 31months. other cancers and those without cancer. Methods: Signed informed consent
Evaluation made as multivariate analyses; age, gender, with histological was obtained from patients ages ≥18 years undergoing a clinically indicated
type, the tretament variables one by one were found effective on survival bronchoscopy. A bronchial lavage (BAL) was collected for research purposes
as p=0.0001 level. Conclusion: It was obtained that the patients diagnosed after completing routine bronchoscopic procedures. Samples were prepped
with lung cancer in our hospital, after they diagnosed they lived averagely 16 and DNA was extracted and 515F/806R 16S rRNA primers used to amplify
months. The patients received surgical treatment with 73%,with 2 years time Variable Region 4. Amplicons were sequenced and grouped into 100%
survival lived significantly more than the other treatments. operational taxonomic units (OTUs) using vsearch. Taxonomy was assigned, a
phylogenetic tree was constructed, and sequences aligned for phylogenetic

diversity calculations, including Faith’s Phylogenetic Diversity and weighted RESULTS OF A RETROSPECTIVE ANALYSIS

and unweighted UniFrac. OTUs that were significantly different across sample Sofia Tsagouli1, Emmanouil Kapetanakis1, Christos Kampolis2, Periklis
categories were identified using DESeq2. Results: There were 137 unique BAL Tomos3, Konstantinos Potaris4, Elias Kainis1, Ioannis Gkiozos1, Kostas Syrigos1
samples collected. One patient had an adverse research procedure event that 1
Medical School, University of Athens, Athens/Greece, 2Laiko Athens General
resolved after temporary supplemental oxygen and overnight observation. Hospital, Athens/Greece, 3 Attikon University Hospital, Athens/Greece, 4Sotiria
BALs were from 68 non-small cell lung cancer (NSCLC), 12 small cell lung cancer Athens General Hospital, Athens/Greece
(SCLC), 52 other cancers, and 5 non-cancer patients. 58 NSCLC were current/
former smokers (average 43 pack-years), while all the SCLC were current/ Background: Medical thoracoscopy is a minimally invasive procedure
former smokers (average 56 pack-years). 22 other cancers were current/former utilized mainly by pulmonologists for the diagnosis and management of
smokers (average of 27 pack-years). Overall, 51 samples (37.2%) had sufficient pleural effusions. The aim of this study was to evaluate the efficacy and
sequencing reads (>20,000) for subsequent analyses. There were multiple safety of medical thoracoscopy when performed by a combined team of
bacterial taxonomic groups in each sample, however, phylogenetic diversity pulmonologists and thoracic surgeons in a tertiary university hospital.
was low compared to other body sites. There were no statistical differences Methods: This is a retrospective cohort analysis of all patients with pleural
in alpha/beta diversity between ever-smokers and never-smokers, NSCLC effusion who underwent medical thoracoscopy at “LAIKO” Athens General
vs SCLC, lung cancer vs non-cancer, and location of BAL collection (upper vs Hospital from June 2013 to December 2014. Results: Our study population
lower airways and right vs left lung). There were a number of statistically included 36 patients, 18 males and 18 females, with a mean age of 61 years.
significant differences by taxonomy (False Discovery Rate adjusted p<0.01 All patients were submitted to medical thoracoscopy for the diagnostic
and listing genus only). Adenocarcinoma vs non-adenocarcinoma had more evaluation of pleural effusion. Twenty-six patients (26/36, 72.2%) presented
Streptococcus and Veillonella; less Haemophilus. For NSCLC vs SCLC, Rothia with an undiagnosed pleural effusion, six (16.7%) with known malignant,
was more prevalent in SCLC. BALs from the upper airways had more prevalent recurrent pleural effusion, three (8.3%) with parapneumonic effusion/
Streptococcus. BALs from the right lung had more prevalent Capnocytophaga empyema and one (2.8%) with idiopathic pleural effusion due to nephritic
and Parvimonas; less Moraxella and Selenomonas. Conclusion: We report syndrome. Eighteen patients (18/36, 50%) underwent drainage and pleural
significant taxonomic differences by tumor type and location of BAL sampling biopsy, 9 patients (9/36, 25%) underwent drainage, pleural biopsy and talc
and overall low phylogenetic diversity. Future validation of this work can be pleurodesis, 6 patients (6/36, 16.7%) underwent drainage and talc pleurodesis
used to modify bacterial colonization in a lung cancer prevention strategy or due to known malignant pleural effusion and 3 patients (3/36, 8.3%)
for early diagnostics/therapeutics. underwent drainage of their parapneumonic effusion/empyema. Among
all patients (n=27) who underwent diagnostic pleural biopsy, 2 patients
Keywords: bronchial lavage, microbiome, Cancer, characterization (7.4%) were diagnosed with primary non-small cell lung cancer, 4 (14.8%)
with malignant pleural mesothelioma, 3 (11.1%) with metastatic disease of
non-thoracic primary origin and 3 (11.1%) with lymphoma, while 1 patient
each (3.7%) was diagnosed with tuberculosis, systemic lupus eryhtematosus,
chronic inflammation, chronic pleural fibrosis and nephritic syndrome. In 3
MONDAY, DECEMBER 5, 2016 patients (3/27, 11.1%) the biopsy was negative. Medical thoracoscopy was
non-diagnostic in one patient only (1/27, 3.7%), thus producing a diagnostic
yield of 97.3%. With the notable exception of one patient (1/36, 2.8%) who
P1.04-020 MANAGEMENT OF LUNG CANCER IN PATIENTS WITH died due to empyema and subsequent sepsis, the remaining post procedural
PAST PULMONARY TUBERCULOSIS AND THEIR POSSIBLE complications were mild, and included subcutaneous emphysema in 6 cases
CAUSATIVE LINK (6/36, 16.7%) and minor bleeding in 3 cases (3/36, 8.3%). Conclusion: When
Fatmir Caushi1, Jona Shkurti2, Danjela Xhemalaj2, Ilir Skenduli2, Arjan Mezini2, performed by a combined team of pulmonologists and thoracic surgeons
Hasan Hafizi2, Alban Hatibi2, Irma Bani2 in a tertiary level hospital, medical thoracoscopy is a relatively safe and
1
efficacious technique for the diagnosis and management of pleural effusions
Surgery, University Hospital of Lung Diseases, Tirana/Albania in patients unable to undergo or not requiring surgical intervention.
Background: Lung cancer and tuberculosis cause significant morbidity and Keywords: medical thoracoscopy, pleural effusion, pleural biopsy,
mortality worldwide. In the past, it was well known that lung cancer is a pulmonologists
specific epidemiological successor of pulmonary tuberculosis (PTB) and that
it often develops in scars caused by PTB. In recent years, the relevance of
the two diseases has drawn attention in terms of the close epidemiological
connection and chronic inflammation-associated carcinogenesis. Although
studies have found a relationship between PTB and lung cancer, results for MONDAY, DECEMBER 5, 2016
the long-term risk and the role of confounding factors remain inconclusive.
Therefore, it is important to delineate the relationship between PTB and lung
cancer. Methods: Clinical files of all patients diagnosed with lung malignancy P1.04-022 USE OF ALTERNATIVE THERAPY IN PATIENTS WITH LUNG
between 2011 and 2016 were investigated retrospectively in terms of patient CANCER
characteristics, definite histopathological diagnosis and stage of tumor, Kristina Krpina, Marko Jakopović, Mihovil Roglic
operation methods, and associated complications. Results: Mean age was KBC Rebro, Zagreb/Croatia
56.4 years. Past PTB was detected in 3% of operated carcinoma patients and
in 6% of all patients diagnosed with lung malignancy. Central lung cancer Background: Background: Lung cancer has the highest mortality among all
was diagnosed in 80% of cases and peripheral in 20%. Epidermoid cancer was malignant diseases due to advanced stage of diseases at diagnosis, but also
diagnosed in 51% of cases, adenocarcinoma in 24% and adenoepidermoid due to modest response to therapy. For that reasons an increasing proportion
carcinoma in 25%. All cases of operable lung cancers were in stage I and of population use alternative therapy. Most often those are drugs that
II, while inoperable lung cancers were in stage IIIB and IV. Lobectomy was are alleged immunomodulators However, for systemically administered
performed in 100% of the operated cases. None of the patients received complementary and alternative medicine (CAM), there are significant risks
anti-TB treatment preoperatively or postoperatively because by the time they of adverse drug interactions with conventional treatments, which may
were diagnosed with lung cancer, their sputum culture for M.Tuberculosis result in either increased drug toxicity or therapeutic failure. Methods:
had converted negative. No postoperative mortality or reactivation of TB Methods: We performed a retrospective analysis of alternative therapies
was seen. Conclusion: PTB is an important risk factor for lung cancer, possibly used during oncology treatment in lung cancer. Data were collected from
related to chronic inflammation and shared risk factors. Our study adds to medical documentation. Total of 246 patients diagnosed with lung cancer
the evidence that implicates chronic inflammation and pulmonary scarring at Department of pulmonary diseases Jordanovac were tracked during a
in the etiology of lung cancer. However, further studies are needed to clarify two-year period. General information, sociodemographic characteristics and
whether there is a direct causative link between PTB and lung cancer. Surgery alternative therapies were extractes from documentation and statistically
is the method of choice in treatment of lung cancer in subjects with past PTB analised. Results: Results: Total of 76 out of 246 patients (31%) admitted to
history. using alternative therapy. Women use it more often than male (38% vs 28%).
No difference was observed according to age o geographic location. Yet there
Keywords: lung cancer, tbc was a small, but significant difference according to level of education. Among
patient with university degree 36% used alternative therapy in contrast to
30% among those with high school education. Use of chemotherapy and
advanced stage of disease correlated with more frequent CAM use (58%
vs 42%). Most often used alternative therapy was aronia (46%) and then
MONDAY, DECEMBER 5, 2016 cannabis and its derivatives (mostly oil) in 36% of patients, while beta-glucan
(11%) and other comprised smaller percentages. Conclusion: Conclusion: Use
of alternative therapies is increasing among patients with lung cancer and it
P1.04-021 MEDICAL THORACOSCOPY FOR THE is imperative for physicians to know about this. So far there is no scientific
DIAGNOSIS AND MANAGEMENT OF PLEURAL EFFUSIONS:
or clinical evidence for positive effects of this therapy, but it is known that it rare in PNC patients and most frequently observed in PLCNC. Patients with
can collide with chemotherapy. Because of that it is imperative to expand our carcinoid had a superior survival than PLCNC and SCLC.
knowledge of use of alternative therapy, as well as its effects.
Keywords: large cell neuroendocrine carcinoma, pulmonary neuroendocrine
carcinoma, genomic aberration

P1.04-023 THROMBOMODULIN INHIBITS THE GROWTH AND
ANGIOGENESIS OF HUMAN LUNG CANCER VIA BLOCKING VEGFR2-
P1.04-025 THE IMPACT OF EMERGENCY PRESENTATION ON
MEDIATED JAK/STAT3 SIGNALING PATHWAY
1 2
SURVIVAL OF LUNG CANCER PATIENTS
Yang Yi , Shun Lu
1 Marko Jakopovic 1, Dzubur Fedza2, Lela Bitar 1, Ivona Markelić1, Fran Seiwerth1,
Oncology, Shang Hai Chest Hospital, Shanghai/China, 2Oncology, Shanghai Chest
Hospital, Shanghai/China
Ana Hecimovic2, Branka Čučević1, Ivica Mazuranic2, Gzim Redzepi2, Andrea
Vukic Dugic2, Mateja Jankovic2, Miroslav Samarzija3
1
Background: Angiogenesis has been an attractive target for drug therapy Department for Respiratory Diseases “Jordanovac”, University Hospital Center,
because of its key role in the growth and metastatic spread of malignant Zagreb/Croatia, 2University Hospital Centre Zagreb, Zagreb/Croatia, 3Department
tumor. Thrombomodulin has been shown to possess anti-inflammatory for Respiratory Diseases “Jordanovac”, University Hospital Centre Zagreb, Zagreb/
and vascular endothelial protection activities. However, its roles in tumor Croatia
angiogenesis are unknown. The aim of this study was to investigate the roles
Background: A significant proportion of lung cancer patients are diagnosed
of thrombomodulin in tumor angiogenesis and its anticancer activities.
through emergency department (ED), which is usually associated with
Methods: ex vivo aortic ring angiogenesis sprouting assay was used to
poorer prognosis. We investigated the assocation between diagnosis of lung
detect neo-vascularization. Western blotting was performed to examine
cancer after presentation through emergency department due to symptoms
STAT3 signaling cascade. Results: Thrombomodulin significantly inhibited
associated to lung cancer. Methods: Medical charts of patients with lung
human umbilical vascular endothelial cell (HUVEC) proliferation, migration
cancer patients newly diagnosed in Department for Respiratory Diseases
and tube formation in vitro and blocked vascular endothelial growth factor
Jordanovac, University Centre Zagreb in years 2012 and 2103 were reviewed.
(VEGF)-triggered neo-vascularization. VEGF receptor (VEGFR) 2 mediated-
Overall survival was calculated and was compared between groups. Results:
Janus Kinase 2/STAT3 signaling pathway was significantly inhibited by
The medical charts of 951 males and 407 females, mean age 64 years (males
thrombomodulin in endothelial cells. In addition, the constitutively activated
64.5, females 62) were reviewed. 292 out od 1359 patients (21,5%) were
STAT3 protein, and the expression of STAT3-dependent target genes,
diagnosed with lung cancer after initial presentation through ED. The most
including cyclin D1, c-Myc, Bcl-xL, and VEGF were also down-regulated in
common reasons for ED admissions were hemopytsis (in 31% of patients),
response for thrombomodulin in human lung cancer cells. Consistent with the
pneumonia (16%), brain metastasis (15%), dyspnea (10%) and superior vena
above findings, thrombomodulin inhibited tumor cell cycle progression and
cava syndrome in 8% of patients. There were no differences in histology
induced cell apoptosis in vitro. Conclusion: Therefore, our provided the first
subptypes between two different routes of presentation (most common
evidence that thrombomodulin inhibited tumor angiogenesis and growth via
histology subtype was adenocarcinoma followed by squamous histology).
inhibiting VEGFR2-mediated JAK/STAT3 signaling pathway with the potential
Significantly higher proportion of patients diagnosed after initial diagnosis
of a drug candidate for cancer therapy.
through ED were at presentation in stage IV (61 vs 44%, p<0.0001), poorer
Keywords: Thrombomodulin; tumor angiogenesis; VEGF2; STAT3 signaling performance status (ECOG 3-4 vs ECOG 0-1, p<0.0001), significantly less
patients underwent surgical resection (14 vs 5%, p<0.0001) and radiotherapy
(56 vs 73%, p<0.0001). Median overall survival (mOS) was significantly
lower in patients diagnosed through ED (6.0 vs 10.0 months, p<0.0001). In
patients with non-small cell lung cancer (NSCLC) results were similar (mOS
POSTER SESSION 1 - P1.04: PULMONOLOGY – 6.0 vs 10.0 months, p<0.0001). In patients with small cell lung cancer (SCLC)
MONDAY, DECEMBER 5, 2016 mOS was also significantly worse (7.0 vs 9.0 months, p<0.0001) in patients
diagnosed through ED. Conclusion: Higher stage, reduced access to surgical
P1.04-024 MOLECULAR PROFILING AND SURVIVAL OF PRIMARY resection and radiotherapy, and significantly lower overall survival regardless
of histology subtypes among lung cancer patients who presents through
PULMONARY NEUROENDOCRINE CARCINOMA WITH COMPLETELY
emergency department, stress out the importance of earlier diagnosis of lung
RESECTION cancer patients so that initial presentation through emergancy department
Guangyuan Lou, Zhengbo Song, Yiping Zhang can be reduced.
Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China
Background: According to the 2015 World Health Organization classification

of lung tumors, pulmonary Large cell neuroendocrine carcinoma (PLCNC) is
grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary POSTER SESSION 1 - P1.04: PULMONOLOGY –
neuroendocrine carcinoma(PNC) for the common features of neuroendocrine MONDAY, DECEMBER 5, 2016
characteristics . Molecular profiles and prognosis of primary pulmonary
neuroendocrine carcinoma(PNC) are not well investigated currently. We P1.04-026 COEXISTING LUNG CANCER AND INTERSTITIAL LUNG
conducted present study to evaluate genomic abnormality and survivals in
DISEASE: A CHALLENGE IN CLINICAL PRACTICE
patients with primary PNC. Methods: Tumor samples of PNC after completely
resection from Zhejiang Cancer Hospital were collected from 2008 to 2015. Ana Linhas, Daniela Machado, Sara Conde, Sérgio Campainha, Ana Barroso
Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF, Centro Hospitalar Vila Nova de Gaia/espinho, Vila Nova de Gaia/Portugal
HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival
Background: Lung cancer (LC) risk is increased in patients with interstitial
analysis was evaluated using the Kaplan-Meier method. Results: Totally, 108
lung disease (ILD), and the two diseases sometimes occur concomitantly.
patients with pathologic confirmed PNC were enrolled. Samples included
Cigarette smoking is a recognised risk factor for development of both
52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients
pathologies but the aetiology and pathogenesis of LC in patients with ILD is
were found to harbor genomic aberrations (11.1%). The most frequent gene
still unclear. The benefit of chemotherapy or radiotherapy for LC in cases of
abnormality was PIK3CA (n=5,4.6%),followed with EGFR (n=3,2.8%), KRAS
ILD remains unknown. Objective: To analyse characteristics and outcomes of
(n=2,n=1.9%), ALK (n=1,0.9%), RET (n=1,0.9%). No ROS1,BRAF,NRAS and HER2
patients with ILD and LC. Methods: A retrospective analysis of all patients
mutations were observed. The frequencies of gene aberrations in PLCNC,
presenting with concomitant ILD and lung cancer to our centre, between
SCLC and carcinoid were 15.4%,6.8% and 8.3%,respectively. Sixty-seven
1st January 2011 and 30th June 2016, was performed. Diagnosed lung cancer
patients were with recurrence or metastasis after surgery, including 32
patients with suspected ILD, but not confirmed, were excluded, as well as
PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among
patients who developed ILD in the setting of lung cancer therapy. Clinical,
the 32 patients with PLCNC, none received molecular targeted treatment,28
radiological and pathological characteristics of this cohort were described.
received first-line chemotherapy,including 18 of etoposide/platinum regimen
Outcomes were also reported. Results: Eleven patients were included (mean
and 10 of other platinum-based treatment. The progression free survival in
age 63±12years). Most patients were men (82%) and heavy smokers (64%
patients with etoposide/platinum regimen was longer than patients with
had a smoking history >30pack/year). The majority ILD cases were related
non-etoposide/platinum treatment (4.8 vs.3.4 months,P=0.019) . Survival
to connective tissue disease (45%) and combined pulmonary fibrosis and
difference was observed among the PLCNC,SCLC and carcinoid group (37.0 vs.
emphysema (CPFE) (18%). The most prevalent lung cancer histological type
34.0 vs.not reached, P=0.035), but no difference existed between the PLCNC
was adenocarcinoma (45%); most patients were diagnosed at advanced
and SCLC group (P=0.606). Conclusion: Common genomic abnormality is
stages (63%) and mainly during the clinical and radiological follow-up for

the fibrosis. The mean time from the onset of ILD to the onset of LC was 39.4 POSTER SESSION 1 - P1.04: PULMONOLOGY –
months. On chest CT, the tumours were predominantly peripheral. Surgical
resection was performed in 3 patients with stage I or II LC; chemotherapy and/
or radiotherapy were given to 6 patients with advanced disease (stage III and P1.04-028 COLLECTION OF ICHOM-DEFINED PATIENT-REPORTED
IV). One patient was refused for radiotherapy due to considerations of the OUTCOME MEASURES (PROMS) DURING ROUTINE LUNG CANCER
adverse effects on the prognosis. The median survival since the diagnosis of
TREATMENT: A PILOT STUDY
LC was 6.7months. Two patients died of respiratory failure due to progression
of pneumonitis after the therapy and three patients died due to progression Jan Van Meerbeeck 1, Lesley De Backer2, Annelies Janssens3, Birgitta
of LC. Conclusion: Patients with LC and ILD might benefit from chemotherapy Hiddinga3, Greetje Vanhoutte2
1
and radiotherapy, but pre-existing ILD could influence negatively the Thoracic Oncology, Antwerp University Hospital, Edegem/Belgium, 2Oncology,
prognosis. Therapy for LC should be considered in patients presenting both LC University Hospital, Edegem/Belgium, 3Thoracic Oncology, University Hospital,
Edegem/Belgium
and ILD and interdisciplinary evaluation of therapeutic options is mandatory.
When planning radiotherapy it is important determinate the radiation Background: PROMs -including symptoms, health related quality of life,
pneumonitis risk. More studies are needed to clarify the role of LC treatment well-being and functional status- are commonly measured in clinical trials.
in the management of ILD patients. They are used in a variety of ways, including therapy decisions on individual
Keywords: lung cancer, interstitial lung disease, lung cancer treatment, patient level or research into disease progression. Optimizing how patients
outcomes feel is a goal of good oncology practice and a quality performance indicator of
care. Therefore it is important to implement the collection of PROMs during
routine lung cancer treatment without disturbing the routine workflow.
The International Collaboration on Health Outcomes Measures (ICHOM)
has proposed a standard set of uniform PROMs for lung cancer (Mak et
POSTER SESSION 1 - P1.04: PULMONOLOGY – al, ERJ 2016). Methods: A pilot study is set up to establish an operational
MONDAY, DECEMBER 5, 2016 workflow and to identify trouble shooting to the collection of PROMs in
standard of care. Self-reporting by the patient is conducted via a web-based
interface using questionnaires and individual case-mix variables according
P1.04-027 CHANGES IN PULMONARY FUNCTION IN LUNG CANCER
to the ICHOM standard set. At baseline, during treatment and in follow up
PATIENTS AFTER THORACIC SURGERY
patients receive electronic invitations. Computer-inexperienced patients
Ana Linhas, Sérgio Campainha, Sara Conde, Ana Barroso have the opportunity to complete paper forms. Results: A gap analysis was
Centro Hospitalar Vila Nova de Gaia/espinho, Vila Nova de Gaia/Portugal done and a swim lane algorithm constructed which will be presented at the
meeting. From February 2016 onwards, 24 patients were screened of whom
Background: Surgery is considered the first line treatment for patients with 11 consented. The other 13 patients were screen failures because of language
resectable early non-small cell lung cancer (NSCLC). Many of these patients barrier, previous therapy start or mental confusion. From the enrolled
present limited lung function which is caused by a common etiologic factor patients, 2 are currently in follow up and 5 patients choose to complete
- cigarette smoking. The evaluation of pulmonary function preoperatively PROMs on paper forms. Updated results on compliance and outcome in 50
is important to identify candidates at risk of postoperative respiratory patients will be brought at the meeting. Conclusion: Participants’ profile
complications and may assist in operability decision. However, lung function reflect a tertiary setting hospital with many referrals and patients, unable
after surgical resection may be affected by several factors. Objective: To to complete the PROM’s. To optimize the inclusion rate, several adaptations
evaluate changes in pulmonary function after thoracic surgery, in patients in the implementation workflow have been introduced. Although the
with solitary nodules or lung cancer. Methods: Retrospective study of registration of PROMs is not very time-consuming, real-time monitoring
patients diagnosed with operable lung cancer and solitary nodules followed requires a user-friendly online tool and dedicated staff. Lessons from this
in our centre between 1st January 2011 and 31th December 2014. Patients pilot study will be applied when rolling out other ICHOM standard sets.
presenting pulmonary function tests (PFTs) until one year after surgery were
included. Patients without PFTs after surgery were excluded. Results: Forty Keywords: Pilot, PROM, ICHOM
three patients were included. The results are presented in the table:
Mean age 62±9 years

Gender 67,4% (n=29) male
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
Indications for surgery Adenocarcinoma Translational Research & Biomarkers –
44,2%(n=19) 14%(n=6)
Carcinoid tumour Squamous cell carcinoma
11,6% (n=5) 25,6% (n=11) MONDAY, DECEMBER 5, 2016
Solitary pulmonary nodule
Clinical staging in lung cancer patients IA IB 43,7% (n=14) 15,6% (n=5)
IIA IIIA 12,5% (n=4) 18,7% (n=6) P1.05-001 CREATION AND EARLY VALIDATION OF PROGNOSTIC
Location of the lesion Superior right lobe MIRNA SIGNATURES FOR SQUAMOUS CELL LUNG CARCINOMA BY
34,9% (n=15) 25,6% (n=11)
Superior left lobe THE SPECS LUNG CONSORTIUM
Neoadjuvant chemotherapy Neoadjuvant David Harpole 1, Raphael Bueno2, William Richards3, David Beer4, Karla
20,9% (n=9) 4,7 (n=2) Ballman5, Ming Tsao6, Frances Shepard6, Daniel Merrick7, Adriaan Van
radiotherapy
Bokhoven7, Wilbur Franklin7, Ramaswamy Govindan8, Mark Watson8, David
Open surgery Video-assisted thoracic surgery R. Gandara9, Guoan Chen10, Zhengming Chen11, Lucian Chirieac3, Herman
83,7% (n=36) 16,3%(n=7)
(VATS) Chui6, Carlo Genova12, Mary-Beth Joshi13, Ashley Kowalewski7, Mark Onaitis1,
Comorbidities Chronic Obstructive Pulmonary Christopher Rivard7, Thomas Sporn13, Fred R. Hirsch7
30,3% (n=13) 4,7% (n=2) 1
Department of Surgery, Duke University Medical Center, Durham/NC/United
Disease (COPD) Ischemic Heart Disease (IHD)
States of America, 2Division of Thoracic Surgery, Brigham and Women’s Hospital/
Smoking habits Smoker Ex-smoker Non- 37,2% (n=16) 32,6% (n=14) Harvard Medical School, Boston/MA/United States of America, 3Brigham and
smoker 30,2% (n=13) Women Hospital, Boston/MA/United States of America, 4University of Michigan,
Ann Arbor/MI/United States of America, 5Biostatistics and Epidemiology, Weill
The mean values of FVC (L), FEV1 (L), FEV1/FVC and DLCO decreased after Cornell University, New York/NY/United States of America, 6Princess Margaret
surgery (p=0.010, p=0.001, p=0.011 and p=0.037, respectively). FVC (L) and Hospital, Toronto/ON/Canada, 7Division of Medical Oncology, University of
FVC (%) values decreased more significantly in patients submitted to Colorado Anschutz Medical Campus, Aurora/CO/United States of America, 8School
pneumonectomy (p=0.004 and p=0,047). There was, though, an improvement of Medicine, Washington University, St. Louis/MO/United States of America, 9Uc
Cancer Center, University of California Davis, Sacramento/CA/United States of
of FVC (%) in patients submitted to VATS and wedge resection (p=0.005 and
America, 10 6304 Cancer Center, U. of Michigan, University of Michigan, Ann Arbor/
p=0.034). FEV1 (L) mean values increased in patients submitted to wedge MI/United States of America, 11Weill Cornell University, New York/NY/United States
resection (p=0.017) and decreased in patients submitted to pneumonectomy of America, 12U.O.S. Tumori Polmonari, IRCCS San Martino-Ist Istituto Nazionale Per
(p=0.04). There was no significant association between histological type, La Ricerca Sul Cancro, Genova/Italy, 13Duke University Medical Center, Durham/NC/
clinical stage, local of the lesion, COPD and CVD and lung function parameters United States of America
before and after surgery. Conclusion: The postoperative pulmonary function
varied according to the type of surgery, therefore the surgical procedure Background: Despite overall favorable prognosis for operable early stage
adopted may help us predict changes in lung function after lung surgery. non-small cell lung cancer, predicting outcome for individual patients has
Clinicians should be aware of these changes when determining the surgical remained challenging. Small retrospective studies have reported potential
method, especially in high-risk patients. non-coding micro(mi)RNAs that might have prognostic significance; however,
these studies lacked statistical power and validation. To refine these
Keywords: lung cancer, Thoracic Surgery, pulmonary function test, outcomes initial findings to clinical application, the investigators have undertaken
a collaborative, structured evaluation of multiple signatures putatively
prognostic for lung squamous cell carcinoma (SCC) under a NCI/SPECS EGFR mut-
(Strategic Partnerships fo Evaluating Cancer Signatures) award. The study 90.6% 82.8% 92.6% 85.9%
(N = 392)
design specifies a primary validation cohort comprising institutional cases,
and additional validation cohorts of Cooperative Group cases, all profiled via Subtypes 0.385 0.507
a common pipeline. Methods: Completely resected SCC (confirmed by central
Ex 21 L858R
pathology review) meeting clinical (Stage I-II; complete 3-year follow-up) 84.8% 79.6% 95.2% 90.0%
(N = 224)
and specimen quality criteria (Tumor cellularity ≥ 50%;necrosis ≤ 20%) were
submitted by 6 institutions. Clinical, pathological and outcome data were Ex 19 del
84.7% 74.3% 97.5% 95.8%
uploaded to a central database. Lysates from 5 um sections of FFPE SSC tumor (N = 164)
samples were run on the HTG EdgeSeq Processor (HTG Molecular Diagnostics,
Tucson, AZ) using the miRNA whole transcriptome assay in which an excess of Conclusion: Positive EGFR mutation status is a favorable prognostic factor
nuclease protection probes (NPPs) complimentary to each miRNA hybridize in patients with surgically resected lung adenocarcinomas. However, EGFR
to their target. S1 nuclease then removes un-hybridized probes and RNA mutation subtypes (exon 21 L858R point mutation or exon 19 deletions) have
leaving behind only NPPs hybridized to their targets in a 1-to-1 ratio. Samples no prognostic impact.
were individually barcoded (using a 16-cycle PCR reaction to add adapters and
molecular barcodes), individually purified using AMPure XP beads (Beckman Keywords: progonostic factor, EGFR, lung adenocarcinoma
Coulter, Brea, CA) and quantitated using a KAPA Library Quantification
kit (KAPA Biosystems, Wilmington, MA). Libraries were sequenced on
the Illumina HiSeq platform (Illumina, San Diego, CA) for quantification.
Standardization and normalization was provided to the project statistical POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
core for validation of two pre-existing signatures and generation of new TRANSLATIONAL RESEARCH & BIOMARKERS –
models (MCP clustering). Results: Among 224 cases with miRNA data, median MONDAY, DECEMBER 5, 2016
age was 70 (43-92), 143 (64%) male, with 67% former (67%) and current (26%)
smokers. All patients were completely resected stage I or II. . At follow-up, 59 P1.05-003 COEXPRESSION OF CD8A AND PD-L1 FREQUENTLY
(26%) had documented recurrence and 129 (58%) were deceased. To date, we
OBSERVED IN RESECTED NSCLC TUMORS FROM SMOKERS
have been unable to validate the previous models, but have created a novel
signature of three miRNAs (see Figure) that is being validated in the second Aaron Lisberg 1, Robert Mckenna2, Judy Dering1, Hsiao-Wang Chen1, Naeimeh
phase of the project using an independent, blinded multi-institutional cohort. Kamranpour 1, Dongmei Hou1, Maria Velez1, Robert Cameron3, Jay Lee3, Steven
Conclusion: The Squamous Lung Cancer SPECS Consortium has established Dubinett3, Dennis Slamon1
1
well-annotated and quality-controlled resources for validation of prognostic Translational Oncology Research Laboratory, UCLA Medical Center, Santa Monica/
miRNA signatures. A new candidate 3-miRNA signature has been identified for CA/United States of America, 2 St John’s Health Center, Santa Monica/CA/United
States of America, 3David Geffen School of Medicine at UCLA, Los Angeles/CA/
further development as a clinically useful biomarker.
Keywords: Squamous cell lung cancer, gene expression signature
Background: With the approval of anti-programmed cell death-1 (PD-1)
therapy in advanced non-small cell lung cancer (NSCLC), identifying patients
with early stage disease most likely to benefit from therapy has become a
priority. It has been hypothesized that patients whose tumors show evidence
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC of PD-1 mediated T cell exhaustion, via the presence of both tumor infiltrating
TRANSLATIONAL RESEARCH & BIOMARKERS – lymphocytes (TILs) and PD-L1 expression, are more likely to respond to
anti-PD-1 therapy (Teng et al, 2015). The current study utilized microarray
analysis to evaluate the relationship between both clinicopathologic features
P1.05-002 THE PROGNOSTIC IMPACT OF EGFR MUTATION STATUS and overall survival (OS) with tumor microenvironment (TME) composition.
AND MUTATION SUBTYPES IN PATIENTS WITH SURGICALLY Methods: Gene expression microarray analysis was performed using the
Agilent Whole Human Genome 4x44K 2-color platform for 319 NSCLC and 15
RESECTED LUNG ADENOCARCINOMAS
normal resection specimens. The reference sample was an equal mixture of
Kazuya Takamochi, Shiaki Oh, Takeshi Matsunaga, Kenji Suzuki 258 of the NSCLC samples. Rosetta Resolver and Statistica 13.0 were used
Juntendo University School of Medicine, Tokyo/Japan for analysis. Samples with PD-L1 expression levels greater or unchanged from
reference level were classified as positive, while those significantly lower [log
Background: EGFR mutation status is a well-established predictor of the
(ratio)<0 and p<0.01] than the reference were classified as negative. CD8a
efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer.
expression was used as a surrogate for TILs as previously described by Ock
Recently, the differences in EGFR mutation subtypes were also reported to be
et al. (2016), and categorized in the same manner as PD-L1. Relationships
associated with the efficacy of EGFR TKIs. However, the prognostic impact of
between TME composition and clinicopathologic features were evaluated
EGFR mutation status and mutation subtypes remains controversial. Methods:
with the chi-square test. Survival analysis was performed using the Kaplan-
We retrospectively reviewed 945 consecutive patients with surgically resected
Meier method and compared using the log-rank test. Results: In the 319
adenocarcinomas who had their EGFR mutation status analyzed between
NSCLC samples the incidence of a Type I TME (+CD8a/+PD-L1) was 45%, Type
January 2010 and December 2014. Overall survival (OS) and recurrence-free
II TME (-CD8a/-PD-L1) 12%, Type III (-CD8a/+PD-L1) 25%, and Type IV (+CD8a/-
survival (RFS) were analyzed in three cohorts (all patients, pathological stage I
PD-L1) 18%. When assessing for survival, patients with a PD-L1 negative/CD8a
patients, and patients with exon 21 L858R point mutation or exon 19 deletions)
positive (Type IV) TME had improved OS compared to patients with PD-L1
using Kaplan-Meier methods and Cox regression models. Results: The median
negative/CD8a negative (Type II) TME (p=0.02). When assessed for smoking,
follow-up time was 42 months. The results for EGFR mutation status, mutation
ever smokers were more likely to evidence a PD-L1 positive/CD8a positive
subtype, and the comparison data of OS/RFS are summarized in the attached
(type I) TME compared to never smokers, 49% vs 32%, while never smokers
Table. Positive EGFR mutation status was significantly associated with longer
more frequently evidenced a PD-L1 positive/CD8a negative (Type III ) TME
OS/RFS in all patients and was also associated with longer OS in pathological
compared to ever smokers, 37% vs 22% (P=0.05). Interestingly, 75% of normal
stage I patients. However, no significant differences were observed in OS/
lung samples evidenced a PD-L1 positive/CD8a positive microenvironment.
RFS between patients with exon 21 L858R point mutation and those with
Conclusion: Evidence of both TILs and PD-L1 expression was observed in the
exon 19 deletions. In a Cox regression model for OS, the EGFR mutation status
majority of normal lung specimens and also more frequently in tumors from
was a significant prognostic factor that was independent of well-established
smokers compared to non-smokers. Patients whose tumors showed evidence
prognostic factors such as age, pathological stage, vascular invasion,
of CD8a, but not PD-L1, had improved OS compared to patients without
lymphatic permeation, and serum CEA level.
evidence of either. Future studies will utilize immunohistochemistry to
corroborate these findings and investigate other components of the TME.
3y-RFS 5y-RFS P 3y-OS 5y-OS P
Keywords: Immunotherapy, PD-L1, Tumor Infiltrating Lymphocytes (TILs),
All Pts 0.009 < 0.001 tumor microenvironment
EGFR mut+
84.6% 76.7% 95.2% 89.0%
(N = 423)
EGFR mut-
78.8% 71.2% 84.9% 76.5% POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
(N = 522)
TRANSLATIONAL RESEARCH & BIOMARKERS –
p stage I Pts 0.102 < 0.001 MONDAY, DECEMBER 5, 2016
EGFR mut+
93.4% 85.4% 98.2% 94.5% P1.05-004 SURFACTANT PROTEIN C IS A PROGNOSTIC MARKER IN
(N = 352)
RESECTED NON-SMALL CELL LUNG CANCER

Ivan Macía1, Juan Moya1, Gemma Aiza2, Ricard Ramos1, Ignacio Escobar 1, Conclusion: Underexpression of SFTPC in tumour samples was independently
Francisco Rivas1, Anna Ureña3, Gabriela Rosado3, Pau Rodríguez-Taboada3, associated with worse prognosis.
Samantha Aso4, Susana Padrones4, Carlos Déniz1, Ernest Nadal5, Gabriel
Capella6 Keywords: Surgery, prognostic marker, lung development, non-small cell lung
1 cancer
Thoracic Surgery, Hospital Universitari de Bellvitge. Idibell, Institut D’Investigació
Biomèdica de Bellvitge., L’Hospitalet de Llobregat/Spain, 2Laboratori de Recerca
Translacional, Hospital Duran I Reynals. Institut Català D’Oncologia, L’Hospitalet
de Llobregat/Spain, 3Thoracic Surgery, Hospital Universitari Joan Xxiii, Tarragona/
Spain, 4Respiratory Department, Hospital Universitari de Bellvitge. Idibell, Institut
D’Investigació Biomèdica de Bellvitge., Barcelona/Spain, 5Department of Medical POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
Oncology, Hospital Duran I Reynals. Institut Català D’Oncologia., L’Hospitalet/ MONDAY, DECEMBER 5, 2016
Spain, 6Programa de Càncer Hereditari, Institut Català D’Oncologia, L’Hospitalet de
Llobregat/Spain
P1.05-005 PROGRAMMED DEATH-LIGAND 1 (PD-L1) IN RESECTED
Background: The lung cancer cells express genes involved in key points of
LUNG ADENOCARCINOMAS (LA) IN A UNIVERSITY HOSPITAL
the lung development. The objective of this study was to determine the
prognostic value of expression of embryonic markers in tumour tissue María Álvarez, Sandra Vicente, Ana Cebollero, Isabel Pajares, Esther Millastre,
samples from patients with surgically-treated non-small cell lung cancer Jorge Hernando, Teresa Puértolas, Ramiro Álvarez, Miguel Artal Cortés,
(NSCLC). Methods: Study based on 129 primary tumour samples from 102 Antonio Antón
patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza/Spain
Expression of the following markers was evaluated by mRNA RT-qPCR assay:
CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the Background: The role of monoclonal antibodies inhibiting of the Programmed
tumour and lung samples. Statistical analyses included chi-squared tests, Death-1 and its ligand (PD-1/ PD-L1) pathway have been described in advanced
non-parametric tests, Kaplan Meier curves, log-rank and Cox regression disease. The knowledge of the role of this pathway in early stages of lung
tests. Results: Patients’ characteristics were: mean age 67 ± 8 years, cancer is still limited. We assessed the incidence of PD-L1 expression
squamous carcinoma (49%), adenocarcinoma (43%), pathological staging: in tumour cells of samples of resected lung adenocarcinomas and its
I: 56%, II: 32%, III: 11% and IV: 1%. 18% received adjuvant chemotherapy, prognostic role. Methods: A retrospective analysis of patients (p) with lung
1% radiotherapy and 7% both. CEACAM5 and MYCN were overexpressed in adenocarcinomas radically resected at our Institution between 2004 and
tumour samples related to lung samples (p<0,05), FGFR2b showed similar 2011 has been conducted. PD-L1 was determined by Immunohistochemistry
expression and FRS2, SFTPC, SHH, SHP2 and SOX17 were underexpressed (SP263, Ventana® assay). A cut-off value of 5% of positive tumour cell was
(p<0,05). The squamous carcinomas expressed more FGFR2b, FRS2 and chosen. Results: 112 tumours from 107 p were included. Median age was 62
SFTPC (p<0,10), while adenocarcinomas expressed more CEACAM5 (p>0,05). years. 81% were male, 88% had exposure smoking, baseline performance
Lymph node involvement was associated with SHH underexpression (p<0,05), status was 0 – I – II (62,5% - 26,8% - 10,7%) and pathological stage was I – II – III
intratumoral vascular invasion with CEACAM5 or FGFR2b underexpression – IV (49,1% - 26,8% - 23,2% - 0,9%). Fourteen p (12%) expressed PD-L1>5%. They
(p<0,05) and relapse with SHH (p<0,05) or SFTPC (p=0,09) underexpression. were mostly male (71%), smokers (93%), baseline performance status was
Kaplan-Meier curves of SFTPC were plotted in figure 1. Underexpression of 0 – 1 – 2 (64% - 29% - 7%), the most common histological subtype was poorly
SFTPC in the tumour sample was associated with a 7-fold (7.3; 1.3-40.9) greater differentiated adenocarcinoma (64%) and pathological stage was I – II – III
active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of (28% - 21% - 50%). One p (7,7%) harboured EGFR mutation, none (0%) were
death. Underexpression of SHP2 was associated with a shorter disease-free ALK positive and 6 p (46,2%) had a K-RAS mutation. With a follow-up of 52
survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression months median disease free survival (DFS) was 49 months and overall survival
of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for (OS) 58 months. Median DFS was shorter in p with expression of PD-L1 (27
SHH, p=0.07 for OS). Combining markers did not provide any additional months) that in negative tumours (49 months) (p=0,45). Median OS showed a
information. similar pattern (32 vs 66 months respectively) also favouring PD-L1 negative
p (p=0,05). Conclusion: In our series, patients with resected adenocarcinomas
expressing PD-L1 in >5% of cells showed a worse disease free and overall
survival than patients without such expression.
Keywords: lung adenocarcinoma, early lung cancer, PD-L1

P1.05-006 IDENTIFICATION OF MIRNAS AND MRNAS ASSOCIATED

WITH METASTASIS IN EARLY-STAGE NON-SMALL CELL LUNG
CANCER (NSCLC)
Shirley Tam1, Nhu-An Pham1, Shingo Sakashita2, Ethan Kaufman1, Melania
Pintilie1, Ni Liu1, Geoffrey Liu1, Frances Shepherd1, Ming Tsao1
1
Princess Margaret Cancer Centre, University Health Network, Toronto/ON/Canada,
2
Department of Pathology, Univerysity of Tsukuba Hospital, Tsukuba/Japan
Background: Early-stage NSCLC patients whose tumours can form primary

xenografts (XG) in immune deficient mice have significantly shorter
disease-free survival and are at a greater risk of early metastasis compared
with patients whose tumours do not form xenografts (non-XG). Genomic
and proteomic characterization of XG and non-XG-forming primary patient
tumours may reveal clinically relevant genetic aberrations that are associated
with early metastasis. Methods: miRNA-seq and RNA-seq data of 100
early-stage NSCLC patients with known engraftment status were acquired.
The cohort includes 62% adenocarcinoma (ADC) and 38% squamous cell
carcinoma (SQCC). Least absolute shrinkage and selection operator (LASSO)
was applied to identify features associated with XG status using integrated
miRNA and mRNA abundance profiles. Gene Ontology (GO) annotation was
subsequently performed to elucidate biological processes that may be altered
between the two patient groups. Results: Using miRNA and mRNA data
alone, ADC patients were classified as XG and non-XG with 88.7% and 95.2%
accuracy. The integration of these two data types classified the patients
with 100% accuracy using 20 features (7 miRNAs and 13 mRNAs). While less
is known regarding the roles of the identified miRNAs in lung ADC, several of
the genes have been suggested to affect the metastatic ability of lung cancer
cells; these include PITX1, GPNMB and KRT14. In SQCC, both the miRNA and
mRNA data alone and the integrated profiles were able to classify patients
into XG and non-XG-forming groups with 100% accuracy. However, the roles POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
of the selected features (1 miRNA and 11 mRNAs) in the metastasis of SQCC MONDAY, DECEMBER 5, 2016
are not well defined. GO annotation of the identified mRNAs in ADC revealed
enrichment of biological processes related to B cell differentiation, wound
healing and regulation of the immune response and signalling pathway, while P1.05-008 DETECTION OF EGFR MUTATIONS IN PULMONARY VEIN
catabolic and metabolic processes were enriched in SQ. Conclusion: The use of AND PERIPHERAL BLOOD PLASMA CELL-FREE DNA FOR ANALYSIS
single-dimensional data to classify patients into different prognostic groups OF SURGICAL TREATMENT IN EARLY-STAGE NSCLC
may not be sufficient in the presence of heterogeneous patient populations.
Chengliang Yang 1, Dan Yang1, Bo Dong2, Xin Meng2, Yong-Yu Liu3
Integrative analysis of multi-omic data can provide greater insights into 1
Department of Thoracic Oncology, Shenyang Tenth People’s Hospital & Shenyang
clinically relevant genetic aberrations, which can be used to improve the
Chest Hospital, Shenyang/China, 2Laboratory of Lung Cancer, Shenyang Tenth
molecular classification of NSCLC. People’s Hospital & Shenyang Chest Hospital, Shenyang/China, 3Department of
Thoracic Surgery, Shenyang Tenth People’s Hospital & Shenyang Chest Hospital,
Keywords: mRNA, patient-derived xenografts, miRNA, Prognosis Shenyang/China
Background: Free circulating DNA (cfDNA) has been known for several
decades. These small DNA fragments are released into the circulation from
nucleated cells through necrosis, apoptosis and/or active secretion. Use
TRANSLATIONAL RESEARCH & BIOMARKERS – of blood plasma cfDNA to detect mutations has spread widely as a form
MONDAY, DECEMBER 5, 2016 of liquid biopsy. However, it remains unclear which types of samples are
appropriate for detecting tumor cell-free DNA in these biopsies. We compared
the abundance of EGFR mutations in peripheral blood and pulmonary vein
P1.05-007 ANALYSIS OF RNA SEQUENCING DATA ALONG WITH PET plasma cell-free DNA from patients with early-stage NSCLC. Methods: In this
SUV-MAX CAN DISCOVER NOVEL GENE SETS WHICH CAN PREDICT study, primary lung tumors and matched presurgery peripheral blood plasma
SURGICAL OUTCOME OF NSCLC samples and intraoperative pulmonary vein blood samples were collected
Yoohwa Hwang1, Yoo Jin Jung1, Sae Bom Lee1, Yoon Ho Kim1, Kwanyong Hyun2, from patients with early-stage NSCLC (n=89). We detected EGFR mutations
Samina Park2, Hyun Joo Lee2, In Kyu Park2, Chang Hyun Kang2, Young Tae Kim2 (exon19 deletion, L858R, G719X, S768I and T790M) in 89 early-stage lung
1
Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul/ cancer samples using droplet digital PCR (ddPCR) and amplification refractory
Korea, Republic of, 2Department of Thoracic and Cardiovascular Surgery, Seoul mutation system (ARMS). EGFR mutation abundance was determined and
National University Hospital, Seoul/Korea, Republic of analyzed to reveal potential impact of samples types. Results: Presurgery
peripheral blood plasma samples (n=89) and intraoperative pulmonary vein
Background: Recent development of NGS technology provides a better blood samples (n=89) matched tumor tissue samples (n=89) were analyzed
understanding on the molecular mechanism of the cancer. A comprehensive for EGFR mutations using ddPCR and ARMS respectively. Of the 41 EGFR
analysis algorism of NGS data along with various clinical phenotypes and mutations detected in tumor tissues by ARMS, 37 of the corresponding
clinical outcome may lead discovery of novel molecular mechanism of cancer mutations were detected in presurgical peripheral blood plasma cfDNA and
biology. It has been suggested that the preoperative SUV of the PET-CT intraoperative pulmonary vein cfDNA, whereas 4 mutations were found
is related to the aggressiveness of the cancer. We hypothesized that the in plasma from patients with EGFR wild-type tumors (sensitivity 80.49%,
identification of genes that were related to the PET SUV-max would lead a specificity 91.67%).Free circulating DNA was identified in the plasma of
discovery of novel genes which could predict long-term outcomes of patients pulmonary venous blood and peripheral blood in thirty-seven patients. Of the
of non-small cell lung cancer. Methods: We set a 51 adenocarcinoma and a 101 37 cases of EGFR mutation positive plasma samples, ddPCR identified a higher
squamous cell carcinoma patients cohort, whose cancer and normal tissue mutation abundance of pulmonary venous samples than peripheral blood
whole transcriptome sequencing data were available. The RNA sequencing (1.05% vs. 0.12%, p = 0.007). Conclusion: This study demonstrates accurate
fastq files were aligned on the reference genome (http://grch37.ensembl. mutation detection in plasma using ddPCR, and that cfDNA can be detected
org/) and the differential expressions were analyzed using tuxedo protocol in presurgical peripheral blood and intraoperative pulmonary vein in patients
(TopHat 2.0, Cufflinks 2.2.1). Visualizations of differential expressions with early-stage lung cancer. Our results suggest that pulmonary venous blood
were presented with CummeRbund R-package. Results: Based on the can be obtained from the resected specimen, thus facilitating the detection
preoperative PET-CT SUV-max, patients were classified as “Low” (SUV≤3), of cfDNA. Future studies can now address whether monitoring the change
“Intermediate” (SUV 3-10), and “High” (SUV>10) groups. Using the tuxedo RNA of EGFR mutation abundance after surgery identifies patients at risk for
analysis tools, we selected 31 genes which showed significantly different recurrence, which could guide therapy decisions for individual NSCLC patients.
expression of RNAs between “Low” and “High” groups in adenocarcinoma and
between “Intermediate” and “High” groups in squamous cell carcinoma. By Keywords: plasma, pulmonary vein, lung cancer, cell-free DNA
comparing expression levels of those 31 genes according to the development
of recurrence, we could identify two sets of genes (COL2A1, BPIFB2, RYR2,
F7, HPX, AC022596.6 and H19 for adenocarcinoma; BPIFB2, AC022596.6,
ANKRD18B, GCLC, HHIPL2, COL2A1 and DPP10 for squamous cell carcinoma)
which were related to the development of recurrence.
Conclusion: Our results suggest that it is necessary to set a comprehensive

analysis algorithm of the NGS data along with various clinical phenotypes of
the patients, for the discovery of clinically meaningful molecular mechanisms
of the cancer.
Keywords: NSCLC, transcriptome, NGS, recurrence

POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC aberrant promoter methylation of ESR1 and CDH13 genes may be associated
with inferior survival, showing promise as a useful prognostic biomarker in
patients with NSCLC.
P1.05-009 CLINICAL VALUE OF CIRCULATING TUMOR CELL IN THE

DIFFERENTIAL DIAGNOSIS OF SOLITARY PULMONARY NODULE
Lin Wang, Lihua Qiao, Wenjun Yu, Jiatao Lou POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
Shanghai Chest Hospital, Shanghai/China TRANSLATIONAL RESEARCH & BIOMARKERS –
Background: The diagnosis of lung cancer suffers from the lack of accurate,
noninvasive and early diagnostic tests. Low-dose helical computed
tomography (LDCT) identifies millions of solitary pulmonary nodules (SPN)
P1.05-011 COMPARATIVE ANALYSIS OF TTF-1 COPY NUMBER
annually, many of which are undiagnosed as either malignant or benign. ALTERATIONS AND PROTEIN EXPRESSION IN PATIENTS WITH NON-
When removed surgically, 18%-25% of the nodules are benign, which leads to SMALL CELL LUNG CANCER
unnecessary treatment procedures for surgeons, stress and panic for patients Katsuhiro Yoshimura1, Yusuke Inoue1, Nobuya Kurabe2, Tomoaki Kahyo2,
and waste of medical resources for government. Therefore, an accurate Akikazu Kawase3, Masayuki Tanahashi4, Hiroshi Ogawa5, Naoki Inui6,
noninvasive test that can discriminate benign SPN from malignant is urgently Kazuhito Funai3, Kazuya Shinmura2, Hiroshi Niwa4, Takafumi Suda1, Haruhiko
needed. Circulating tumor cells (CTCs) are cells shed from either primary or Sugimura2
secondary tumors that migrate into the circulatory system and exist at the 1
Second Division, Department of Internal Medicine, Hamamatsu University School
early stage of cancer. In recent years, CTC has become the research hotspot of Medicine, Hamamatsu/Japan, 2Department of Tumor Pathology, Hamamatsu
because of its great significance in the early diagnosis of cancer, disease University School of Medicine, Hamamatsu/Japan, 3First Department of Surgery,
monitoring, prognosis evaluation and guiding individualized treatment. Hamamatsu University School of Medicine, Hamamatsu/Japan, 4Division of
In this study, we evaluated the application value of CTC in the differential Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital,
Hamamatsu/Japan, 5Department of Pathology, Seirei Mikatahara General Hospital,
diagnosis of SPN. Methods: Peripheral blood samples were collected from
Hamamatsu/Japan, 6Department of Clinical Pharmacology and Therapeutics,
134 patients with solitary pulmonary nodule in Shanghai Chest Hospital from Hamamatsu University School of Medicine, Hamamatsu/Japan
September 2013 to January 2015, including 80 patients with malignant nodule
and 54 with benign nodule. CTC levels of the above subjects were detected Background: TTF-1 (also known as NKX2-1) is located at chromosome
by LT-PCR (ligand-targeted polymerase chain reaction, LT-PCR) assay, and 14q13.3. TTF-1 is a master regulator for the development of normal lung,
serum CEA and CYFRA21-1 were detected by flow fluorescence assay. Results: and is also both a lineage oncogene and a suppressor gene in non-small
The CTC levels of malignant SPN patients were significantly higher than that cell lung cancer (NSCLC). TTF-1 expression is associated with a favorable
of benign SPN patients (P<0.001). The area under the Receiver Operating prognosis. In contrast, the clinical significance of increased TTF-1 gene
Characteristic (ROC) curves of CTC and CEA were 0.817(95% CI: 0.743~0.891) dosage has yet to be fully elucidated. We explored the relationship of
and 0.613(95% CI: 0.508~0.718) respectively, while the CYFRA21-1 had no TTF-1 copy number alterations with TTF-1 protein expression as well as
significant meaning in the differential diagnosis of SPN. The positive and patients’ prognoses in a relatively large cohort. Methods: We assessed
negative predictive value (PPV and NPV) in differential diagnosis of SPN for TTF-1 gene copy number and protein expression in microarrayed 636
CTC were 89% and 74%. Then the patients were divided into three groups NSCLC, including 421 adenocarcinomas and 173 squamous cell carcinomas
according to the nodule diameter to evaluate the diagnostic value of CTC in (SCCs), and 42 other histologies, using fluorescent in situ hybridization and
SPN with different size. For SPN with diameter less than 8 mm, the PPV and immunohistochemistry. TTF-1 copy number alterations were divided into
NPV of CTC were 86% and 57%; For SPN with diameter between 8 mm and three categories; amplification (TTF-1/CEP14 ≥2), polysomy (TTF-1/CEP14
20 mm, the PPV and NPV of CTC were 88% and 81%; For SPN with diameter <2 and TTF-1 signals ≥4 copies per nucleus), and disomy (the others). Their
greater than 20 mm, the PPV and NPV of CTC were 92% and 68%. Conclusion: associations with clinical data were retrospectively analyzed. Results:
Compared with traditional tumor marker, CTC detection could provide more Among the entire cohort, TTF-1 amplification and polysomy were observed
clinical value in differential diagnosis of solitary pulmonary nodule. in 5.6% (36/636) and 8.3% (53/636), respectively. Tumors with copy number
alterations (amplification and polysomy) were detected in 14.5% (61/421)
Keywords: Circulating tumor cell, differential diagnosis, lung cancer, solitary among adenocarcinomas, 9.3% (17/173) among squamous cell carcinomas, and
pulmonary nodule 26.2% (11/42) among other histologies (P = 0.012). TTF-1 expression was almost
exclusively observed in adenocarcinomas (P < 0.001). In the adenocarcinoma
cohort, the frequency was 6.7% (28/421) for TTF-1 amplification and 7.8%
(33/421) for polysomy. TTF-1 positivity was 84.8% (357/421). A multivariate
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC Cox hazards model analysis demonstrated that TTF-1 amplification was
TRANSLATIONAL RESEARCH & BIOMARKERS – an independent worse prognostic factor (hazard ratio (HR), 3.84; 95%
MONDAY, DECEMBER 5, 2016 confidence interval (CI), 2.18-6.71) for overall survival, but TTF-1 expression
was adversely an independent better prognostic factor (HR, 0.49; 95% CI,
P1.05-010 ABERRANT PROMOTER METHYLATION OF ESR1 AND 0.28-0.85). In the SCC cohort, there were few cases of TTF-1 amplification
(1.7%, 3/173), polysomy (8.1%, 14/173), and TTF-1 expression (3.7%, 10/273).
CDH13 GENE ARE AN INDEPENDENT PROGNOSTIC MARKER IN
Interestingly, any case of adenocarcinoma and SCC with TTF-1 amplification
SURGICALLY RESECTED NON-SMALL CELL LUNG CANCER harbored positive TTF-1 expression. Conclusion: Both TTF-1 amplification
Milica Kontic 1, Dragana Jovanovic2, Svetlana Bojic3, Heather Nelson4, Simona and TTF-1 expression were more common in adenocarcinoma. However,
Ognjanovic5 they had distinct prognostic roles: TTF-1 amplification was an independent
1
Clinical Centre of Serbia, Belgrade/Serbia, 2Clinic for Pulmonology, Clinical Centre poor prognostic factor in adenocarcinoma, whereas TTF-1 expression was a
of Serbia, Belgrade/Serbia, 3Institute for Medical Statistics and Informatics, favorable prognostic factor.
Belgrade/Serbia, 4 Masonic Cancer Center, Division of Epidemiology and Community
Health, University of Minnesota, Minneapolis/MN/United States of America, 5Mayo Keywords: gene copy number, TTF-1, prognostic marker, amplification
Graduate School, Mayo Clinic, Rochester, Rochester/MN/United States of America
Background: Aberrant promoter hypermethylation of tumor suppressor genes

are promising markers for lung cancer diagnosis and prognosis. The purpose of
this study was to determine the correlation between the aberrant promoter POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
methylation of multiple genes and 5-year survival rate in patients with TRANSLATIONAL RESEARCH & BIOMARKERS –
nonsmall cell lung carcinoma (NSCLC) after a surgical resection. Methods:
Primary tumor samples (n=65) and corresponding nonmalignant lung tissues
(n=65) were obtained from NSCLC patients who underwent curative surgery. P1.05-012 THE IMPACT OF EGFR MUTATIONS ON THE PROGNOSIS
The methylation status of seven genes (SOX1, RASSF1A, HOXA9, CDH13, OF PATIENTS WITH RESECTED STAGE I LUNG ADENOCARCINOMA
MGMT, ESR1 i DAPK) was quantified using bisulfite pyrosequencing. Cox
Jiro Kitamura, Luis Tapias, Douglas Mathisen, Michael Lanuti
proportional hazards models were used to analyze the associations between
gene methylation status and overall patient survival. Results: In the Cox Thoracic Surgery, Massachusetts General Hospital, Boston/United States of
America
proportional hazards model, ESR1 methylation in tumor tissue was associated
with significantly poorer survival, with hazard ratio of 1.09 (95% confidence Background: Recent studies have reported that epidermal growth factor
interval 1.02-1.16, p=0.01). This effect was independent of TNM stage, which receptor (EGFR) mutations are potential predictive factors for prognosis as
was also a predictor of survival. We also found that aberrant methylation in well as for the response to the treatment of EGFR tyrosine kinase inhibitors in
CDH13 gene in tumor tissue was associated with inferior survival in surgically patients with advanced lung adenocarcinoma. However, the prognostic role of
resected NSCLC pateints. In contrast, there were no significant survival EGFR mutations has not been well studied in treatment-naïve stage I lung
differences noted between the methylation-positive and methylation- adenocarcinoma. In this study, we evaluated the pure prognostic value of
negative tumors for the other genes tested. Conclusion: Our study shows that EGFR mutations in patients with stage I lung adenocarcinoma who underwent
complete resection. Methods: We retrospectively reviewed the medical known as Cancer Stem Cells (CSCs), which are able to grow as spheroids
records of treatment-naïve patients who underwent complete resection of (suspension culture). The aim of the study was to obtain tumorspheres
stage I lung adenocarcinoma between January 2008 and December 2014. from lung cancer cell lines and to use them as an in vitro platform for drug
Mutation testing was performed on resected tumor using multiplex (SNaP screening. Methods: Cells from lung cancer cell lines (A549, H1650, PC9, H460
Shot) polymerase chain reaction assay. Survival curves were generated with and H358) were grown in monolayer and as spheroids. Cultured cells were
Kaplan-Meier method and compared using a log-rank test. A Cox proportional used: (i) to compare the cytotoxic effect of anticancer drugs in adherent
hazards model was used for multivariate analysis. Results: Of 583 patients, vs lung-tumorspheres (ii) to perform a high-throughput screening with a
127 (21.8%) patients had EGFR-mutations. Median follow up period after commercial chemical library (Prestwick) and (iii) to analyze the citotoxicity
surgery was 36.9 months (range: 0.1-95.8). Patients with EGFR mutations of specific inhibitors of Wnt, Hedgehog and Notch pathways. Briefly, cells
showed a better 5-year recurrence-free survival (RFS, 89.4% vs 77.8%, were plated at the desired density in 200 μl of medium in 96-well plates and
p=0.0053) and 5-year overall survival (OS, 99.1% vs 87.7%, p=0.0044) than compounds were added at 4 different concentrations (n=3). Cell viability was
those with EGFR wild-type (Figure). Multivariate analysis demonstrated that measured after 48 and 72h, using MTS Assay. Cell viability was normalized
the presence of EGFR mutation (HR=0.4875, p=0.0388) and pathological stage to the respective mock-treated control cells and presented as percentage of
0 or IA (HR=0.4590, p=0.0016) were independent prognostic factors for better control. Results: Cells cultured in serum-free conditions were able to form
RFS. The presence of EGFR mutations (HR=0.1878, p=0.0443), lobar resection spheroids, such as stem-like cells. Under these culture conditions, classical
(HR=0.4076, p=0.0123), and ECOG performance status 0 (HR=0.4061, anticancer drugs (cisplatin, paclitaxel, vinorelbine and pemetrexed) exhibited
p=0.0259) were independent prognostic factors for better OS. mild or null cytotoxic effects on A549, H1650, PC9, H460 and H358 spheroids.
Moreover, we performed a high-throughput screening with Prestwick library
and remarkably, three compounds reduced the number of viable cancer cells.
As regards ‘stemness’ inhibitors, Wnt (IWP2 and XAV939) and Hedgehog
inhibitors (Vismodegib) show high activity against tumorspheres (p<0.05),
suggesting them as possible therapeutic strategies in NSCLC Conclusion:
Our data suggest that lung-tumorspheres showed resistance to classical
anticancer drugs, strengthening its possible use as a short-term culture
platform for a simple, and cost- effective screening to investigate novel
therapeutic approaches. In this setting, some compounds were identified as
promising therapeutic agents on lung tumorspheres, but confirmatory data
are still necessary. This project was supported by [RD12/0036/0025] from
RTICC, SEOM 2012, [PI12-02838 and PI15-00753] from ISCIII

P1.05-014 STEMNESS GENE EXPRESSION PROFILE OF

TUMORSPHERES FROM NON-SMALL CELL LUNG CANCER
Alejandro Herreros Pomares1, Silvia Calabuig Fariñas2, Ester Munera
Maravilla1, Ana Blasco3, Aminta Isabel Martinez4, Eva García Del Olmo4, Eloisa
Jantus-Lewintre5, Carlos Camps6
1
Molecular Oncology Laboratory, General University Hospital Research
Foundation, Valencia/Spain, 2Molecular Oncology Laboratory, General University
Hospital Research Foundation; Department of Pathology, Universitat de València,
Valencia/Spain, 3Department of Medical Oncology, General University Hospital
of Valencia, Valencia/Spain, 4Department of Thoracic Surgery, General University
Hospital of Valencia, Valencia/Spain, 5Fundación Investigación Hospital General
Universitario, Valencia/Spain, 6Molecular Oncology Laboratory, General University
Hospital Research Foundation; Department of Medical Oncology, General
University Hospital of Valencia; Department of Medicine, Universitat de València,
Conclusion: Patients harboring an EGFR-mutation in completely resected Valencia/Spain
stage I lung adenocarcinoma had a much improved prognosis compared to
Background: Lung cancer features like chemoresistance, tumor progression or
those patients whose tumors expressed EGFR wild-type. The presence of an
metastasis have consolidated lung cancer as the first cause of death cancer-
EGFR mutation was a significant positive prognostic factor in this cohort.
related worldwide. Cancer stem cells (CSCs) are small subpopulations of stem-
Keywords: lung cancer, EGFR, survival, Early-stage like cells that have been associated to these traits, constituting a promising
target, but remaining largely unknown. In this study, we isolated CSCs from
lung cancer cell lines and tumor tissue of resectable NSCLC patients using a
sphere-forming assay and analyzed their gene expression profile. Methods:
The investigation was carried out on cells from seven NSCLC tumor samples
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC and six cell lines (H1650, H1993, H358, A549, PC9, H460) grown in monolayer
MONDAY, DECEMBER 5, 2016 and as spheroids. The expression of CSC-markers (CD133, EPCAM1, ALDH1A1,
CD166, ABCG2, CD44, MUC1, BMI1, THY1), pluripotency promoters (KLF4,
OCT4, NANOG, SOX2, MYC, CCND1), cell cycle regulators (CDKN1A, CDKN2A,
P1.05-013 LUNG TUMORSPHERES AS A PLATFORM FOR TESTING MDM2, WEE1), invasiveness-related genes (CDH1, VIM, SNAI1, MMP2, MMP9,
NEW THERAPEUTIC STRATEGIES IN NON-SMALL CELL LUNG CEACAM5, ITGA2, ITGA6, ITGB1), Notch pathway (NOTCH1, NOTCH2, NOTCH3,
CANCER JAG1, DLL1, DLL4, NUMB, HEY1, HES1), Wnt pathway (WNT1, WNT2, WNT3,
Ester Munera Maravilla1, Alejandro Herreros Pomares1, Silvia Calabuig WNT5A, CTNBB1, DKK1, FZD7) and Hedgehog pathway (SMO, PTCH1, SHH,
Fariñas2, Eva Escorihuela1, Elena Duréndez1, Aminta Isabel Martinez3, Miguel GLI1) components were analyzed by quantitative real time PCR (RTqPCR).
Martorell4, Ana Blasco5, Eloisa Jantus-Lewintre 6, Carlos Camps7 ACTB, CDKN1B and GUSB genes were used as housekeeping controls for the
1 relative expression calculation. Results: Lungspheres showed significantly
Molecular Oncology Laboratory, General University Hospital Research
higher expression of the CSC-markers EPCAM1, CD44 and ALDH1A1 (p= 0.028,
Foundation, Valencia/Spain, 2Molecular Oncology Laboratory, General University
Hospital Research Foundation; Pathology Department, Universitat de València, p= 0.021 and p= 0.043, respectively) and the quiescence promoter CDKN1A
Valencia/Spain, 3Department of Thoracic Surgery, General University Hospital (p= 0.021) in comparison with their paired-monolayer cells. The epithelial
of Valencia, Valencia/Spain, 4Department of Pathological Anatomy, General to mesenquimal transition (EMT) inducer, SNAI1, as well as integrins ITGA2,
University Hospital; Department of Pathology, Universitat de València, Valencia/ ITGA6 and ITGB1 were overexpressed in tumorspheres (p= 0.011, p= 0.018, p=
Spain, 5Department of Medical Oncology, General University Hospital of Valencia, 0.016 and p= 0.013, respectively). Regarding the Notch signaling pathway,
Valencia/Spain, 6Fundación Investigación Hospital General Universitario, Valencia/ most ligands (JAG1 and DLL4) and receptors (NOTCH1 and NOTCH2) analyzed
Spain, 7Molecular Oncology Laboratory, General University Hospital Research
had increased expression in spheroids (p= 0.021, p= 0.028, p= 0.038 and p=
Foundation; Department of Medical Oncology, General University Hospital of
0.036, respectively). In Wnt pathway, we found higher expression levels of
Valencia; Department of Medicine, Universitat de València, Valencia/Spain
WNT3, CTNBB1 and GSK3B (p= 0.021, p= 0.008 and p= 0.021, respectively)
Background: Resistance to treatment is one of the causes influencing the high in tumorspheres. No significant results were found for the rest of genes
mortality of lung cancer. This feature seems to be linked to a subpopulation analyzed. Conclusion: Lung cancer spheroids from primary tumors and cell

lines showed increased levels of genes related to CSCs properties. Genes cancer based on a blood test for detection of BARD1 antibodies. Results:
belonging to Notch and Wnt signaling pathways were found to be more Modeling values from 200 samples, shows a distinction of lung cancer and
expressed in tumorspheres, suggesting that these pathways could be healthy controls with high sensitivity and specificity (AUC=0.961; Figure 1).
interesting lung-CSC targets. This work was supported in part, by grants Splitting the samples randomly and repeatedly into training sets and
RD12/0036/0025 from RTICC, and PI12-02838/PI15-0753 from ISCIII. validation sets, confirmed an average AUC=0.964 for the training sets and
AUC=0.861 for the validation sets. ROC curves for early and late stage lung
Keywords: non-small cell lung cancer, biomarker, Gene Expression, Cancer cancers showed no difference in their AUCs. The BARD1 lung cancer test is
stem cell highly specific and does not cross-react with other cancers. Conclusion: Lung
cancer has a very long latent phase and is often discovered at an advanced and
untreatable stage. Currently the detection by low dose CT scan is relatively
expensive and not very specific. Therefore a blood test, such as the BARD1 test
could i) help to detect cancers earlier, in particular by screening of risk groups,
TRANSLATIONAL RESEARCH & BIOMARKERS – and ii) become a diagnostic aid in combination with CT scan.
P1.05-015 GENOMIC CHARACTERISATION OF NON-SMALL CELL

LUNG CANCER IN AN AUSTRALIAN POPULATION
Brielle Parris 1, Darryl Irwin2, Marissa Daniels1, Louise Franz2, Felicia Goh1,
Linda Passmore3, Elizabeth Mccaul3, Deborah Courtney3, Rayleen Bowman3,
Ian Yang 3, Kwun Fong 3
1
University of Queensland Thoracic Research Centre, the Prince Charles Hospital,
Chermside/QLD/Australia, 2 Agena Bioscience, Herston/QLD/Australia, 3Department
of Thoracic Medicine, the Prince Charles Hospital, Chermside/QLD/Australia
Background: Lung cancer is a heterogeneous disease with poor prognosis.

Genomic variants may predict sensitivity to targeted drug therapies or
assist in prognostication. We sought to determine the frequency of driver
mutations and gene rearrangements in non-small cell lung cancer (NSCLC) and
evaluate the feasibility of the MassARRAY system for multiplexed mutational
profiling. Methods: A cohort study of 419 fresh-frozen NSCLC tumours was
performed (AC, n=370; SCC, n=39; ASC, n=7; LCC, n=3). High-throughput
and multiplexed mutational profiling was performed using the MassARRAY
genotyping system (Agena Bioscience) (n=419). The OncoFOCUS+KIT panel
was used for detecting genomic variants in EGFR, BRAF, KRAS, NRAS and KIT
(n=413) and the LungFusion panel for fusion genes involving ALK, RET and
ROS1 (n=371). Clinico-pathological associations were evaluated using Fisher’s
exact test for categorical data, and T test for continuous data. A p-value
of <0.05 (two-tailed) was considered statistically significant. Results: At Keywords: Early detection, lung cancer, biomarker
least one genomic variant was detected in 196 (46.8%) cases (n=419). EGFR
mutations were identified in 42 cases (10.2%), KRAS in 133 (32.3%), BRAF
in 11 (2.7%), NRAS in 4 (1.0%) and no KIT mutations were detected. Gene
rearrangements involving ALK, RET and ROS1 were identified in 2 (0.5%), 1
(0.3%) and 5 (1.3%) cases respectively. Based on current clinical guidelines POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
for NSCLC, 28 patients would qualify for tyrosine kinase inhibitor therapy, TRANSLATIONAL RESEARCH & BIOMARKERS –
and 4 for targeted therapy available for other cancers (BRAF V600E). EGFR
mutations were significantly associated with adenocarcinoma histology
and female never smokers (p<0.001) and KRAS mutations predominated in P1.05-017 THE PROGNOSTIC IMPACT OF EGFR, KRAS AND TP53
smokers (p<0.001). Conclusion: Driver mutations were detected in 46.8% of SOMATIC MUTATIONS IN CURATIVELY RESECTED EARLY-STAGE
NSCLC cases resected at TPCH. Rapid, multiplexed mutation testing can guide LUNG ADENOCARCINOMAS
treatment as well as assist in patient stratification for clinical trials.
Bonnie Gould Rothberg 1, Rahul Das2, Laura Jackson1, Heather Lazowski1,
Keywords: Epidermal growth factor receptor, Anaplastic lymphoma kinase, Yalai Bai3, Daniel O’Neill2, Sophia Roberts2, Jonathan Rothberg2, Roy Herbst1,
non-small cell lung cancer, multiplex genotyping Anthony Kim4, Daniel Boffa4, David Rimm3, Frank Detterbeck4, Lynn Tanoue5
1
Internal Medicine, Section of Medical Oncology, Yale University School of
Medicine, New Haven/CT/United States of America, 2The Rothberg Institute
for Childhood Diseases, Guilford/CT/United States of America, 3Department of
Pathology, Yale University School of Medicine, New Haven/CT/United States of
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC America, 4Surgery, Section of Thoracic Surgery, Yale University School of Medicine,
TRANSLATIONAL RESEARCH & BIOMARKERS – New Haven/CT/United States of America, 5Internal Medicine, Section of Pulmonary,
MONDAY, DECEMBER 5, 2016 Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven/
CT/United States of America
P1.05-016 CIRCULATING BARD1 ANTIBODIES FOR EARLY Background: As the 5-year survival among individuals undergoing curative-
DETECTION OF LUNG CANCER intent resection for early-stage lung cancer approaches 50%, identification of
Irmgard Irminger-Finger 1, Maxim Pilyugin1, Andrea Bianco2, Balazs Hegedus3, prognostic biomarkers useful for risk stratification is a priority. While somatic
Sylvain Sardy4, Pascaline Descloux5, Geoffrey Laurent5 mutation profiling drives treatment choice in advanced disease, its usefulness
1
University Hospitals Geneva, Geneva/Switzerland, 2 Second University of Naples, among early-stage patients is not well-established. Methods: From May 2011
Naples/Italy, 3Medical University Vienna, Vienna/Austria, 4University of Geneva, through December 2014, The Yale Lung Cancer Biorepository enrolled 192
Geneva/ACT/Switzerland, 5University of Western Australia, Perth/WA/Australia individuals who underwent curative-intent complete resection for Stage
IA-IIIA adenocarcinoma. Demographics and lifestyle choices were ascertained
Background: In a study of more than 100 NSCLC cases we previously showed by interview using validated questionnaires. Pathologic characterization of
that the expression of BARD1 isoforms is correlated with poor patient index tumors, including CLIA Laboratory-assayed EGFR/KRAS status, was
survival. BARD1 is a tumor suppressor acting with BRCA1 as ubiquitin ligase. extracted from the medical record. A custom targeted resequencing panel
BARD1 has also functions in mitosis and poly(ADP)-ribose signaling for DNA covering all coding exons from 93 lung adenocarcinoma-related genes was
repair. In cancer cells BARD1 isoforms are generated by alternative splicing. designed. Buffy coat-derived germline DNA and tumor DNA, extracted from
SNP affecting splicing and cancer predisposition were identified in the FFPE surgical specimen, were sequenced on the Ion Torrent platform
neuroblastoma. The alternatively spliced isoforms lack tumor suppressor with >90% of the assayed amplicons achieving >30x coverage in both tumor
functions and act as oncogenes. As the domain composition of cancer- and germline from each case. Somatic nonsynonymous tumor variants
associated isoforms predicts altered tertiary structures, we investigated were identified using the Torrent Variant Caller. Bivariate associations were
whether BARD1 isoforms act as cancer antigens. Methods: ELISA assays were evaluated by Chi-square or ANOVA. Survival analyses were conducted using
performed to detect antibodies generated against BARD1 isoforms in the Cox modeling. Results: 181/192 (94.3%) participants underwent EGFR/KRAS
serum of lung cancer patients. We used BARD1 protein fragments and short somatic mutation profiling with 43 EGFR mutations and 71 KRAS mutations
peptides for capturing autoimmune antibodies. Using fitted Lasso logistic detected. EGFR mutations were more common among well- and moderately-
regression methods, we developed an algorithm for the prediction of lung differentiated lesions (p=0.06) and among never or former light smokers
(p=0.0007). Seventy-two percent of EGFR and 81.7% of KRAS mutations were CXCL13 (P<0.0001) for the comparison of 4th quartile with 1st quartile. When
found among female patients (p=0.0008). The joint distribution between analysis was restricted to never smokers (196 patients/196 controls), MDC/
smoking and gender favored EGFR mutations among female never/former CCL22 and BLC/CXCL13 were still significantly associated with early stage
smokers, KRAS mutations among female ever-smokers and EGFR/KRAS lung adenocarcinoma risk (OR; 95% CI; P: 0.37; 0.21-0.66; P<0.0001 for MDC/
wild-type status among male ever-smokers (p=0.0002). After adjustment CCL22 and 2.78; 1.48-5.22; P =0.001 for BLC/CXCL13). Additionally, significance
for AJCC 7th edition Tstage, Nstage and presence of lymphovascular invasion, persisted after restricting analysis to 159 stage IA lung adenocarcinoma
KRAS mutations (HR=2.14; 95% CI:1.04-4.43; p=0.04) but not EGFR mutations patients and 159 matched controls for MDC/CCL22 (OR; 95% CI; P: 0.37; 0.21-
(p=0.63) were prognostic for poorer disease-free survival. Targeted 0.66; <0.0001) and BLC/CXCL13 (2.78; 1.48-5.22). Furthermore, elevated BLC/
resequencing data is available on 148 cases. The nonsynonymous mutation CXCL13 was associated with a 2.90-fold (95% CI: 1.03-8.17; P=0.037) increased
burden ranged from 0-7 with 84% of cases having ≤3. In addition to KRAS and risk of subcentimeter lung adenocarcinoma, and there was an increasing trend
EGFR, frequent mutations were noted in p53 (n=40; 27.0%), STK11 (n=10; 6.8%) for BLC/CXCL13 with the progression of subcentimeter lung adenocarcinoma.
and PIK3CA (n=7; 4.7%) with 4 genes mutated in 6 cases. TP53 mutations Conclusion: Our findings demonstrated that MDC/CCL22 and BLC/CXCL13
were associated with high nonsynonymous mutation burden (p<0.0001) and were independently associated with the significant risk of early stage lung
the joint distribution with EGFR/KRAS status revealed the highest burden adenocarcinoma, and this association persisted even in non-smokers and in
among KRASmut /TP53mut (3.94±1.57) followed by EGFRmut /TP53mut (3.07±1.61) stage IA patients. Moreover, BLC/CXCL13 was identified to play a carcinogenic
and EGFR_KRASwt /TP53mut (2.20±1.40; p<0.0001). Conclusion: KRASmut, like role in the progression of lung adenocarcinoma.
EGFRmut, is associated with female gender but only KRASmut is prognostic
following curative-intent resection. Elevated mutation burden observed Keywords: Early Stage Lung Adenocarcinoma, Subcentimeter lung
among KRASmut /TP53mut may offer novel therapeutic options following adenocarcinoma, Inflammatory biomarkers, Prospective study
recurrence.
Keywords: recurrence-free survival, TP53, KRAS, Somatic mutation


P1.05-020 OPPOSING PROGNOSTIC ROLES OF CD73 AND A2A
ADENOSINE RECEPTOR IN NON-SMALL-CELL LUNG CANCER
Yusuke Inoue 1, Katsuhiro Yoshimura2, Nobuya Kurabe1, Tomoaki Kahyo2,
P1.05-018 LNCRNA16 IS A POTENTIAL BIOMARKER FOR EARLY- Akikazu Kawase3, Masayuki Tanahashi4, Hiroshi Ogawa5, Naoki Inui6,
STAGE LUNG CANCER THAT PROMOTES CELL PROLIFERATION BY Kazuhito Funai3, Kazuya Shinmura2, Hiroshi Niwa7, Takafumi Suda1, Haruhiko
REGULATING THE CELL CYCLE Sugimura2
1
Nan Wu, Huange Zhu, Liyi Zhang, Yue Yang, Xing Wang Second Division, Department of Internal Medicine, Hamamatsu University School
Department of Thoracic Surgery Ii, Peking University Cancer Hospital & Institute, of Medicine, Hamamatsu/Japan, 2Department of Tumor Pathology, Hamamatsu
Beijing/China University School of Medicine, Hamamatsu/Japan, 3First Department of Surgery,
Hamamatsu University School of Medicine, Hamamatsu/Japan, 4Division of
Background: Early diagnosis of lung cancer greatly reduces mortality; Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital,
however, the lack of suitable plasma biomarkers presents a major obstacle. Hamamatsu/Japan, 5Department of Pathology, Seirei Mikatahara General Hospital,
Hamamatsu/Japan, 6Department of Clinical Pharmacology and Therapeutics,
Recent studies showed that long noncoding RNAs (lncRNAs) play important
Hamamatsu University School of Medicine, Hamamatsu/Japan, 7Thoracic Surgery,
roles in cancer initiation and development. Methods: Here, we identify Seirei Mikatahara General Hospital, Hamamatsu/Japan
differential expressed lncRNAs by using custom designed microarray on 20
lung cancer samples and evaluate the expression by Real-time PCR (qRT-PCR) Background: CD73 (otherwise known as ecto-5’-nucleotidase) is an important
on 118 lung cancer samples.The role of lncRNA16 in lung cancer was studied molecule in the adenosine pathway because it generates adenosine by
in vitro and in vivo, utilizing the lung cancer cell line PC9 ,A549 and xenograft enzymatically dephosphorylating extracellular AMP, which results in
mouse models. Results: lncRNA16 (ENST00000539303) expression level was immunosuppressed niche within the tumor microenvironment. A2A
highly in lung cancer (80/118) and in plasma (32/42) of lung cancer patients. adenosine receptor (A2AR) acts as a predominant receptor for adenosine
In early stage, lncRNA16 expression levels were significantly higher compare in immune cells and can also be expressed in lung tumor cells. However, the
to that in adjacent matched normal tissues (Figure 1C-1F) . Importantly, this clinical impact of the adenosine pathway in non-small-cell lung cancer (NSCLC)
increase was mirrored in plasma samples of early stage lung cancer patients has yet to be uncovered, although the pathway has been shown to have a
(Figure 2A) . Our study reveals that knockdown of lncRNA16 inhibited pivotal role in the regulation of anti-tumor immunity and is considered as
proliferation of PC9 cells in vitro and also inhibited tumor growth in xenograft one of the promising future treatment targets. Methods: We investigated
mouse models. Specifically, we show that lncRNA16 promotes G2/M transition CD73 and A2AR protein expression profiles using immunohistochemistry
through regulating cyclin B1 transcription. Conclusion: In conclusion, in tissue microarrays containing 642 resected NSCLC specimens. The
lncRNA16 was identified as a potential biomarker for lung cancer diagnosis, expression levels were assessed using the H-score method that ranged from
as it displayed significantly elevated levels in cancer patient over baseline. 0 to 300, and cutoffs were determined using the minimum P-value method
Furthermore, we showed that the false-negative rate is significantly lower for overall survival (OS). The associations between their expression levels
compared to markers those widely used for lung cancer assessment. and clinicopathological and molecular characteristics as well as patients’
prognoses were retrospectively analyzed. Results: The median age of
patients was 68 years old (range, 23–88) and 440 (68.5%) patients were
male. 438 (68.2%) patients had smoking history and 420 (65.4%) patients
had adenocarcinoma histology. Significantly higher expression of both CD73
TRANSLATIONAL RESEARCH & BIOMARKERS – and A2AR was observed in female than male, in never smokers than ever
MONDAY, DECEMBER 5, 2016 smokers, and in adenocarcinomas than squamous cell carcinomas. Among
adenocarcinomas, both high CD73 and A2AR expression were significantly
associated with TTF-1 positivity and EGFR mutations. ALK-positive
P1.05-019 TWO INFLAMMATORY BIOMARKERS MDC/CCL22 adenocarcinomas showed significantly higher expression levels of CD73 than
AND BLC/CXCL13 ARE INDEPENDENTLY ASSOCIATED WITH THE ALK-negative tumors. High CD73 expression was an independent indicator of
SIGNIFICANT RISK OF EARLY STAGE LUNG ADENOCARCINOMA a poor prognosis for NSCLC patients in multivariate Cox regression analyses
Yanwei Zhang1, Keke Yu1, Song Hu1, Yuqing Lou1, Chunxing Liu2, Jianlin Xu1, for OS (hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.38–3.47) and
Rong Li1, Xueyan Zhang1, Huimin Wang1, Baohui Han3 disease-specific survival (DSS) (HR, 2.97; 95% CI, 1.78–4.95). Contrary, high
1
Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai/China, 2Huadong A2AR expression was an independent favorable predictor of prognosis
Sanatorium, Wuxi/China, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, for OS (HR, 0.69; 95% CI, 0.49–0.97) and DSS (HR, 0.51; 95% CI, 0.33–0.79).
Shanghai/China Among adenocarcinomas, high CD73 expression was an independent poor
prognostic marker for OS (HR, 2.73; 95% CI, 1.61–4.63) and DSS (HR, 4.57; 95%
Background: This prospective study was designed to investigate the CI, 2.54–8.23), whereas high A2AR expression was an independent favorable
association between multiple inflammatory biomarkers in circulation and prognostic marker for DSS (HR, 0.56; 95% CI, 0.32–0.98). Conclusion: Both
the risk for early stage lung adenocarcinoma. Methods: We measured 10 CD73 and A2AR expression was associated with TTF-1-positive and EGFR-
inflammatory biomarkers in 228 early stage lung adenocarcinoma patients mutant adenocarcinoma. Nonetheless, they had opposing prognostic
and 228 age, sex and smoking matched healthy controls by using the significance in resected NSCLC.
Luminex bead-based assay. Results: Only two biomarkers were significantly
associated with early stage lung adenocarcinoma risk after Bonferroni Keywords: adenosine, CD73, Prognosis, A2AR
correction: the multivariate odd ratio or OR (95% confidence interval or CI)
was 0.29 (0.16-0.53) for MDC/CCL22 (P<0.0001) and 4.17 (2.23-7.79) for BLC /

POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC to 2 years. In addition, 1 patient with a benign lung disease were included
in this study. Results: CTCs were isolated independent from tumor stages
and even in quite early cases CTCs could be detected. Moreover, a difference
between CTC occurrence before and after surgery was seen and a correlation
P1.05-021 CIRCRNAS: POTENTIAL NOVEL BIOMARKERS FOR THE between CTC enumeration and clinical lack of recurrence could be detected.
EARLY DETECTION OF LUNG CANCER Conclusion: The GILUPI CellCollector® overcomes blood volume limitations of
Ruby Lin1, Glen Reid2, Luciano Mutti3, Anthony Ryan4, Siobhan Nicholson5, other diagnostic approaches and thereby increases the diagnostic sensitivity
Niamh Leonard5, Vincent Young6, Ronan Ryan6, Stephen Finn7, Sinead Cuffe8, of CTC analysis. Future implementation into clinical practice may improve
Steven Gray9 early detection, prognosis and therapy monitoring of cancer patients. Besides
1 enumeration, captured CTCs are ready for molecular characterization and will
University of Sydney, Concord/ACT/Australia, 2 Asbestos Diseases Research
Institute, Sydney/Australia, 3School of Environment & Life Sciences, University of help to establish more personalized treatment regiments since knowledge of
Salford, Salford/United Kingdom, 4Dept. of Clinical Medicine, Trinity Translational the molecular make-up of the cancer cells to be defeated is an indispensable
Medicine Institute (Ttmi), Dublin/Ireland, 5Histopathology, Labmed Directorate, prerequisite to use targeted therapies efficiently.
Dublin/Ireland, 6Cardio-Thoracic Surgery, Sacc Directorate, Dublin/Ireland, 7Dept.
of Histopathology and Morbid Anatomy, Trinity College Dublin, Dublin/Ireland,
8
Oncology, Hope Directorate, Dublin/Ireland, 9Thoracic Oncology Research Group,
Labmed Directorate, Dublin/Ireland
Background: Lung cancer is the leading cancer killer globally. Cancers such as TRANSLATIONAL RESEARCH & BIOMARKERS –
colon, breast, and prostate all have relatively reliable early detection tests. MONDAY, DECEMBER 5, 2016
In contrast, lung cancer does not. If caught early, lung cancer has a much
better prognosis. Non-invasive or minimally invasive tools to improve early P1.05-023 INDUCTION OF PATIENT-DERIVED XENOGRAFT
detection of lung cancer represents a critical unmet need. Analysis of the
FORMATION AND CLINICAL SIGNIFICANCE FOR PD-L1 IN LUNG
human transcriptome indicates that a mere 2% of the genome corresponds
to protein coding transcripts, yet ~ 75% of the genome is transcribed. It is
CANCER PATIENTS
now well established that these non-coding RNAs (ncRNAs) play important Panpan Zhang, Yuanyuan Ma, Jiahui Si
regulatory functions within the cell and their expression are often altered in Department of Thoracic Surgery Ii, Peking University Cancer Hospital & Institute,
cancer. Circular RNAs (circRNAs) are a species of ncRNAs. They are abundant, Beijing/China
conserved and demonstrate cell-type specific expression patterns. Moreover,
Background: The relevance of programmed cell death ligand 1 (PD-L1)
they are extremely stable with half-life’s greater than 48 hours, are resistant
to patient-derived xenograft (PDX) formation and clinicopathological
to degradation by RNA exonucleases, and have been shown to play important
characteristics in early stage lung cancer was studied Methods: Cell counting
roles in cancer. Taken together these suggest that circRNAs could potentially
kit-8 and flow cytometry were carried out to examine proliferation and
be important biomarkers in early lung cancer diagnosis. Methods: Total RNAs
apoptosis in PC9 and H520 cells transfected with siRNAs. Nod-scid mice were
isolated from a panel of matched normal/tumour NSCLC adenocarcinoma
used to establish PDX. Immunohistochemistry was done to investigate PD-L1
(Stage IA/IB) samples (n=6) were probed for circRNAs using the Arraystar
expression in tumor tissues. Results: Proliferation was reduced and apoptosis
circRNA microarray. Survival was assessed on linear mRNAs with associated
was induced when PD-L1 was inhibited in the cells. Higher PD-L1 expression
circRNAs using KM-Plot. Results: Interim analysis of the data has identified
rate was observed in the primary tumors with PDX formation than in the
n=206 circRNAs with a 2-fold difference in expression between their
tumors without PDX formation. Moreover, PD-L1 was found to be related to
matched normal vs. tumour counterparts. Principal Component Analysis
smoking, histological types, stages and overall survival in 209 of lung cancer
(PCA) demonstrated a clear separation of the samples (Tumour vs. Normal).
patients. Conclusion: This study suggests that PD-L1 promotes PDX formation
Self-Organizing Maps (SOMs) analysis generated distinctive SOMS clusters
ability and is an independent prognostic marker for the early stage lung
of circRNAs, while associated linear pathway enrichment for microRNA
cancer patients.
and transcriptional binding motifs identified several additional potential
networks. Moreover, an analysis of linear mRNAs associated with 10 circRNAs Keywords: PD-L1, Patient-derived xenograft, lung cancer, clinical significance
with altered expression in adenocarcinomas found that these mRNAs were
linked to overall survival, and that the majority were adenocarcinoma specific.
Conclusion: Altered levels of a number of circRNAs were associated with lung
adenocarcinoma. A separate cohort of squamous cell carcinomas is currently
being assessed for circRNAs. At present we are validating the expression of POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
these circRNAs in a larger cohort of specimens, and assessing whether or not TRANSLATIONAL RESEARCH & BIOMARKERS –
these are detectable in plasma/serum from the same individuals. Overall,
circRNAs may represent novel potential biomarkers for the detection of
NSCLC, and may provide additional critical basic knowledge regarding the P1.05-024 PREOPERATIVE NEURON-SPECIFIC ENOLASE TO
development and biology of NSCLC. ALBUMIN RATIO IS A PROGNOSTIC BIOMARKER FOR PATIENTS
WITH OPERABLE NON-SMALL-CELL LUNG CANCER
Keywords: circRNA, biomarker, Early Detection
Hong Ren1, Xiang Li2, Boxiang Zhang1, Yiwen Zhang1, Litao Yang1, Guodong
Xiao1, Xiao Gao1, Guanghong Huang1, Peili Wang1, Huangzhen Wang1,
Chengcheng Yang1, Sida Qin1
1
Department Two of Thoracic Surgery, The First Affiliated Hospital of Xi’An Jiaotong
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC University, Xi’An/China, 2The First Affiliated Hospital of Xi’An Jiaotong University,
TRANSLATIONAL RESEARCH & BIOMARKERS – Xi’An/China
Background: Neuron-specific Enolase (NSE) is a widely used tumor biomarker
P1.05-022 CIRCULATING TUMOR CELL ISOLATION TO MONITOR in small-cell lung cancer (SCLC) diagnosis, and serum albumin (Alb) levels are
commonly used as indicators of the nutritional status of cancer patients.
NSCLC PATIENTS OVER THE COURSE OF TREATMENT
However, the prognostic value of these markers in combination has not been
Julia Herrmann1, Jens Pfannkuche2, Thomas Lesser 1 examined. This study was designed to explore the value of the combination
1
Srh Wald-Klinikum Gera, Gera/Germany, 2Gilupi GmbH, Potsdam/Germany between NSE and Alb in non-small-cell lung cancer (NSCLC). Methods: We
retrospectively evaluated the prognostic value of the preoperative NSE
Background: Compared to the investigation of the primary tumor or a biopsy
to albumin ratio (NAR) in 319 patients with operable NSCLC. We analyzed
taken from a distant metastasis, the investigation of a patient’s blood is
associations among the NAR, clinicopathological characteristics, and
relatively simple, less invasive and can be performed repeatedly. Thus, CTC
inflammatory biomarkers. Univariate and multivariate analyses were
(circulating tumor cells) investigation can be used as a real-time marker for
performed to identify the clinicopathological characteristics associated
staging, disease progression and therapy responsiveness. Cancer mortality
with OS. Furthermore, we compared the prognostic value of the NAR with
might be reduced dramatically when the disease and its metastatic spread
other established prognostic indexes by evaluating the area under the curves
are detected and characterized early and can therefore be treated in an
(AUC). Results: The optimal NAR cutoff level was found to be 3.2×10 -7. We
optimal fashion. The GILUPI CellCollector® offers medical personnel at any
found that a higher NAR was associated with more advanced TNM staged
point-of-care with the unique opportunity to enrich these CTCs in vivo.
cancers (P=0.041) and higher tumor stage (P=0.011).The NAR was also
Here, we conducted a study using this effective device, to monitor CTC
associated with the inflammatory biomarker albumin/globulin ratio (AGR,
counts before as well as on different time points after surgery in non-small
P=0.032), but not the neutrophil/lymphocyte ratio (NLR, P=0.295) or platelet/
cell lung cancer (NSCLC) patients and further to characterize the CTCs on a
lymphocyte ratio (PLR, P=0.260). In multivariate analyses, the NAR was an
molecular level. Methods: In total, 20 NSCLC patients (different stages) were
independent prognostic factor for NSCLC patients (P<0.001). The AUC of the
screened for CTCs at different time points: preoperative, 30 minutes after
NAR was higher than the NLR, PLR or AGR at 24 and 36 months of follow-
tumor resection, 1 week postoperative as well as in 3-monthly intervals up
up. Conclusion: The preoperative NAR might be an independent prognostic
factor for patients with operable NSCLC, and a higher NAR indicates a poorer for searching potential biomarkers in lung cancer patient. Methods: EBC
prognosis. sample collected using specific device called R-tube, containing both the
volatile organic compounds (VOCs) and non-volatile organic compounds
Keywords: Non-small-cell lung cancer, Neuron-specific Enolase, albumin, (NVOCs), were obtained from patients with lung cancer (n = 20) and control
Prognosis healthy individuals (n = 5). The EBC samples were applied to high resolution
metabolomics (HRM) based LC-MS for comparison of metabolic differences
among healthy people and lung cancer patients in order to detect potential
biomarkers. The multivariate statistical analysis was performed, including a
false discovery rate (FDR) of q=0.05, to determine the significant metabolites
TRANSLATIONAL RESEARCH & BIOMARKERS – between the groups. 2-way hierarchical clustering analysis (HCA) was done
MONDAY, DECEMBER 5, 2016 for determining the classification of significant features between the control
healthy and lung cancer patients. The significant features were annotated
using Metlin database (metlin.scripps.edu/) and the identified features were
P1.05-025 PROGNOSTIC SIGNIFICANCE OF HEPATITIS B VIRUS TO
then mapped on the human metabolic pathway of the Kyoto Encyclopedia
STAGE IB NON-SMALL CELL LUNG CANCER PATIENTS IN CHINA of Genes and Genomes (KEGG). This study was approved by Korea University
Shun Lu, Ziming Li Guro Hosipital Institutional review board (KUGH14273) Results: Using
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong metablomics-wide associated study (MWAS), metabolic changes among
University, Shanghai/China healthy group and lung cancer patients were determined. The 2-way HCA
identified the different metabolic profile in lung cancer patients from healthy
Background: Hepatitis B virus (HBV) is considered to be a major cause of
control. The identified potential biomarkers are Acetophenone (m/z 103.0542,
hepatocellular carcinoma. However, little is known about the role of chronic
[M+H-H2O]+), P-tolualdehyde (m/z 138.0914, [M+NH4]+), 2,4,6-Trichlorophenol
HBV infection in other malignancies. We aimed to determine HBV infection
(m/z 218.9134, [M+Na]+) and 11(R)-HETE (m/z 343.2233, [M+Na]+). The
with other well established prognostic factors and performed multivariate
top 5 of affected KEGG pathways are Arachidonic acid metabolism,
survival analyses to evaluate its value in Chinese non-small cell lung cancer
Glycerophospholipid metabolism, Bile secretion, Inflammatory mediator
(NSCLC) patients. Methods: It is a retrospective evaluation of the impact of
regulation of TRP channels and Tyrosine metabolism. Conclusion: Our result
HBV infection status in 366 patients who underwent complete surgical
shows that Acetophenone, P-tolualdehyde, 2,4,6-Trichlorophenol and 11(R)-
resection for stage IB NSCLC NSCLC patients in Shanghai Chest Hospital from
HETE are significantly higher in lung cancer patients. Acetophenone and
1998 to 2008. All the patients were Shanghai Niece and all the stage IB NSCLC
2,4,6-Trichlorophenol are classified as a Group D human carcinogen approved
patients didn’t receive adjuvant chemotherapy. The patients’ blood samples
by US Environmental Protection Agency (EPA), while 11(R)-HETE is associated
were tested with chemiluminescent immunoassay for the presence of HBV
with Arachidonic acid metabolism and P-tolualdehyde is related to xylene
surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and
degradation pathway and degradation of aromatic compounds pathway. Our
antibodies against HBsAg (anti-HBs) before operation. Other variables in the
identified metabolites can be the potential biomarkers in EBC for the early
analysis included age, gender, history of smoking and pathologic type. HBsAg
and non-invasive detection of lung cancer.
positive was definite as HBV infection. Results:
Keywords: exhaled breath condensate, metabolomics, Liquid
chromatography (LC-MS/MS), lung cancer

P1.05-027 NOVEL PROGNOSTIC GENE EXPRESSION SIGNATURES

FOR SQUAMOUS CELL LUNG CARCINOMA: A STUDY BY THE SPECS
LUNG CONSORTIUM
Raphael Bueno1, William Richards2, David Beer3, Karla Ballman4, Ming Tsao5,
Frances Shepard5, Daniel Merrick6, Adriaan Van Bokhoven6, Wilbur Franklin6,
Ramaswamy Govindan7, Mark Watson8, David R. Gandara9, David Harpole10,
Zhengming Chen11, Guoan Chen12, Lucian Chirieac2, Herman Chui5, Carlo
Genova13, Mary-Beth Joshi10, Ashley Kowalewski6, Mark Onaitis10, Christopher
Rivard6, Thomas Sporn10, Fred R. Hirsch6
1
Division of Thoracic Surgery, Brigham and Women’s Hospital/ Harvard Medical
School, Boston/MA/United States of America, 2Brigham and Women’s Hospital,
Boston/MA/United States of America, 3University of Michigan, Ann Arbor/MI/
United States of America, 4Biostatistics and Epidemiology, Weill Cornell University,
51 HBV infection cases (13.93%) were positive in stage IB NSCLC. The 5-year
New York/NY/United States of America, 5Princess Margaret Hospital, Toronto/
overall survival of patients without or with chronic HBV infection were 71.25% ON/Canada, 6Division of Medical Oncology, University of Colorado Anschutz
and 50.98% (P=0.028). Multivariate analyses revealed that gender, chronic Medical Campus, Aurora/CO/United States of America, 7Medical Oncology,
HBV infection were significant predictive factors for overall survival (P< 0.05). Washington University School of Medicine, St. Louis/MO/United States of
Conclusion: The chronic HBV infection is a significant independent prognostic America, 8Washington University School of Medicine, St. Louis/MO/United States
factor in stage IB non-small cell lung cancer. of America, 9Uc Cancer Center, University of California Davis, Sacramento/CA/
United States of America, 10 Department of Surgery, Duke University Medical
Keywords: Hepatitis B Virus, non-small cell lung cancer Center, Durham/NC/United States of America, 11Weill Cornell University, New York/
NY/United States of America, 126304 Cancer Center, U. of Michigan, University of
Michigan, Ann Arbor/MI/United States of America, 13U.O.S. Tumori Polmonari, IRCCS
San Martino-Ist Istituto Nazionale Per La Ricerca Sul Cancro, Genova/Italy
Background: A multi-institutional squamous lung cancer consortium of

TRANSLATIONAL RESEARCH & BIOMARKERS – investigators is developing prognostic signatures through the US NCI Lung
MONDAY, DECEMBER 5, 2016 SPECS (Strategic Partnership for Evaluation of Cancer Signatures) program.
Six institutions contributed tumor specimens and published/unpublished
expression-based prognostic signatures for validation using standardized
P1.05-026 HIGH RESOLUTION METABOLOMICS ON EXHALED
sample cohorts (a primary validation cohort comprising institutional cases,
BREATH CONDENSATE TO DISCOVER LUNG CANCER’S BIOMARKER and additional validation cohorts from two prospective cooperative group
Chang Young Park1, Adnan Khan1, Aryo Pamungkas1, Eun Jung Sim2, Kyung Ho studies) and quality controlled assessment in independent laboratory and
Kang2, Sung Yong Lee 2, Youngja Hwang Park1 statistical cores. Here, we report on de novo prognostic signatures derived
1
College of Pharmacy, Korea University, Sejong City/Korea, Republic of, 2Korea using the pooled institutional dataset. Methods: Highly quality-controlled
University Medical Center, Seoul/Korea, Republic of cases of primary SCC from the pooled cohort (N=249) were analyzed to
generate de novo prognostic signatures from among the 147 genes comprising
Background: Early and non-invasive detection of lung cancer is a desirable
pre-existing signatures, and from among all profiled genes. Minimax Concave
prognostic tool for prevention of lung cancer at early stages. Previously,
Penalty (MCP) selection and Ward’s minimum variance clustering yielded
unusual human breath smell of lung cancer patients detected by trained
survival analyses with 2 clusters that were evaluated using Cox regression and
dogs played an important role in early detection of lung cancer. Which
bootstrap cross validation (bCV; 500 iterations). Results: Two significantly
suggests that exhaled breath condensate (EBC) is a promising source

prognostic models were generated (see Figure): Pooled Model A (PMA) was Houston/United States of America, 10Translational Molecular Pathology, The
the optimal 2-cluster model using probesets representing 6 genes selected University of Texas MD Anderson Cancer Center, Houston, Tx/United States of
from components of pre-existing signatures: CASP8, MDM2, SEL1L3, RILPL1, America, 11Thoracic, Head & Neck Medical Oncology, The University of Texas M. D.
LRR1, COPZ2. Pooled Model B (PMB) was the optimal 2-cluster model using Anderson Cancer Center, Houston/TX/United States of America, 12Thoracic/Head &
probesets representing 6 genes selected from among all those profiled: SSX1, Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston/
TX/United States of America
DIAPH3, LOC619427, CASP8, EIF2S1, HSPA13. PMA and PMB each remained
independently prognostic in multivariable analyses incorporating an a priori Background: The ICON study aims to perform a comprehensive
baseline model (age, sex, stage; c-index = 0.641). Conclusion: Two de novo immunogenomic characterization of early stage localized non-small cell
prognostic signatures were derived using a pooled multi-institutional cohort lung cancer (NSCLC) and lay the foundation for the identification of barriers
of SCC assembled for validation of pre-existing signatures. PMA and PMB to tumor immunity that may be targeted in future trials. Earlier work has
were each found to be independently prognostic, accounting for established demonstrated the prognostic significance of TIL in localized NSCLC. This
clinical predictors. Both now move forward, along with validated pre-existing work evaluates the functional status of T cells infiltrating the NSCLC tumors
signatures, to additional assessment of discrimination, calibration and clinical and their capacity to expand ex-vivo and perform effector function in the
usefulness using additional independent prospective US co-operative group first 22 patients enrolled. Methods: Patients enrolled on the ICON study
cohorts of cases. underwent surgery. Fresh tumor samples were mechanically disaggregated
and immediately stained for flow cytometry. Panels consisted of markers of T
cell subsets, differentiation status, T cell function, activation and exhaustion.
PD-L1 expression was assessed on malignant cells as well as CD68+ tumor-
associated macrophages (TAMs) by IHC. Fragments from the tumor tissue
were also placed in culture in media containing IL-2 for ex-vivo TIL expansion.
TIL cultures were maintained for 3-5 weeks and subsequently underwent
phenotypical and functional characterization. Results: Analysis of freshly
disaggregated tumor tissue (n=22) from NSCLC tumor or adjacent normal
tissue by flow cytometry demonstrated that effector CD8+ T cells found in the
tumor were less functional than T cells infiltrating normal tissue, revealed by
a decrease in the co-expression of the cytotoxic effector molecules perforin
and granzyme B (p=0.0004) together with an enhanced expression of the
inhibitory receptor PD-1 (p<0.0001). Immunohistochemistry analysis showed
PD-L1 expression on malignant cells and/or CD68+ TAMs on all tumor samples
except one, strongly suggesting that the PD-1/PD-L1 inhibitory axis was
engaged contributing to decreased T cell functionality. TIL could be expanded
from the majority of samples (68.2%, n=22). The degree of infiltration
predicted the ability to grow TIL ex-vivo (median CD3+ infiltrate of 15.25% of
live cells in disaggregated tumor tissue for samples from which TIL could be
grown versus 2.9% when TIL could not grow p = 0.015). Immunophenotyping
following expansion showed an enrichment in CD8+ aβTCR+ T-cells
expressing both perforin and granzyme B indicating that TILs propagated
with IL-2 regained functionality (p=0.016). Lastly, NSCLC TIL were rapidly
expanded using anti-CD3 antibody, feeder cells and IL-2 over two weeks (n=6)
and reached clinically relevant numbers for TIL ACT (range 381-1282 fold
expansion). Conclusion: Overall, while TILs present in NSCLC are functionally
inhibited, they can be expanded ex-vivo from most tumor samples and regain
a functional phenotype for potential use in adoptive T-cell therapy.
Keywords: NSCLC, TIL, Tumor infiltrating lymphocytes

SBRT –
P1.05-029 SABRTOOTH-A FEASIBILITY STUDY OF SABR COMPARED

TO SURGERY IN PATIENTS WITH PERIPHERAL STAGE I NSCLC
Keywords: gene expression signature, Squamous cell lung cancer
CONSIDERED TO BE AT HIGHER RISK FROM SURGERY
Kevin Franks 1, Michael Snee2, Babu Naidu3, David Sebag-Monterfiore4,
Matthew Callister5, Jonathan Ferguson6, Richard Booton7, Martyn Kennedy5,
Catherine Lowe8, Fiona Collinson9, Lucy Mcparland8, Rachel Naylor8, Jo
Webster8, Walter Gregory8, Janine Bestall10, Jenny Hewison10, David Baldwin11
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC 1
Clinical Oncology, Leeds Teaching Hospitals/University of Leeds, Leeds/United
MONDAY, DECEMBER 5, 2016 Kingdom, 2Clinical Oncology, Leeds Teaching Hospitals NHS Trust, Leeds/
United Kingdom, 3Institute of Inflammation and Ageing College of Medical and
Dental Sciences Centre for Translational Inflammation Research, University of
P1.05-028 PHENOTYPIC AND FUNCTIONAL PROFILING OF TUMOR- Birmingham, Birmingham/United Kingdom, 4Radiation Biology and Therapeutics,
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds/United
INFILTRATING LYMPHOCYTES (TIL) IN EARLY STAGE NON-SMALL Kingdom, 5Respiratory Medicine, St James’ University Hospital, Leeds/United
CELL LUNG CANCER (NSCLC) Kingdom, 6Department of Cardiothoracic Surgery, James Cook University Hospital,
Lorenzo Federico 1, Cara Haymaker 1, Marie-Andrée Forget1, Luis Vence2, Icon South Tees NHS Foundation Trust, Middlesborough/United Kingdom, 7Respiratory
Team3, Padmanee Sharma4, James Allison5, Bingliang Fang6, Jianjun Zhang7, and Allergy Research Group, Institute of Inflammation & Repair, the University
Heidi Wagner8, Elena Bogatenkova9, Ignacio Wistuba10, Boris Sepesi6, John of Manchester, University Hospital of South Manchester, Manchester/United
Kingdom, 8Leeds Institute of Clinical Trials Research (LICTR), University of Leeds,
Heymach11, Don Lynn Gibbons12, Chantale Bernatchez1
Leeds/United Kingdom, 9Leeds Institute of Clinical Trials Research, University
1
Melanoma Medical Oncology, MD Anderson Cancer Center, Houston/TX/United of Leeds, Leeds/United Kingdom, 10 Centre for Health Services Research, Applied
States of America, 2Immunology, MD Anderson Cancer Center, Houston/TX/United Health Co-Operative, Leeds Institute of Health Sciences, University of Leeds,
States of America, 3The University of Texas MD Anderson Cancer Center, Houston/ Leeds/United Kingdom, 11Department of Respiratory Medicine, Nottingham
United States of America, 4 Genitourinary Medical Oncology, MD Anderson Cancer City Hospital, Faculty of Medicine & Health Sciences, University of Nottingham,
Center, Houston/TX/United States of America, 5Immunology, The University of Nottingham/United Kingdom
Texas M.D. Anderson Cancer Center, Houston/United States of America, 6Thoracic
and Cardiovascular Surgery, UT MD Anderson Cancer Center, Houston/TX/United Background: Stereotactic Ablative Radiotherapy (SABR) is a well established
States of America, 7Department of Thoracic/head and Neck Medical Oncology, treatment for medically inoperable peripheral stage I NSCLC. Previous
The University of Texas MD Anderson Cancer Center, Houston/TX/United States
non-randomised evidence supports SABR as an alternative to surgery, but
of America, 8The University of Texas M.D. Anderson Cancer Center, Houston/TX/
high quality randomised control trial (RCT) evidence is lacking due to low
United States of America, 9The University of Texas M.D. Anderson Cancer Center,
recruitment. The UK SABRtooth study aims to see if a large RCT is feasible. survival, which may be indicative of the patient response to SABR, and will
Methods: The trial management group includes pulmonologists, thoracic need further evaluation. Performance status and tumour size were associated
surgeons, nurses, patient representatives, oncologists and statisticians. with a poorer overall survival.
Patients considered at higher-risk of operative mortality and morbidity
with a peripheral stage I (<5cm) NSCLC are eligible. Defining “higher-risk” Keywords: SABR, Early-stage lung cancer, outcomes
patients considers multiple criteria, but the final decision is left to the
individual tumour boards. Equipoise in presenting the two interventions
to patients was considered key. Bias is minimised by ensuring the initial
approach is by the pulmonologist with subsequent counseling by the research
nurse and randomisation occurring before consultation with a surgeon SBRT –
or oncologist . Patients who decline the trial or do not proceed with their MONDAY, DECEMBER 5, 2016
allocated treatment are invited to take part in qualitative interviews. The
trial is open in 4 thoracic oncology centres and their referral units. The aim
P1.05-031 PRIMARY RESULTS OF DOSE ESCALATED STEREOTACTIC
is to recruit on average 3 patients/month to demonstrate that a phase III
RCT would be feasible. Results: Following a launch meeting in April 2015 the
BODY RADIOTHERAPY FOR STAGE IA NON-SMALL CELL LUNG
trial opened in July (all centres opened October 2015). To help train research CANCER
staff with introducing the trial to patients, mock patient consultations were Takafumi Komiyama1, Kengo Kuriyama1, Kan Marino1, Shinnichi Aoki1,
recorded. Recruitment was initially slow. Specific research nurse meetings Masayuki Araya2, Hiroshi Onishi1
have taken place (December 2015 and June 2016) to understand the barriers 1
Radiology, University of Yamanashi School of Medicine, Yamanashi/Japan, 2Proton
to recruitment, centre-specific issues and provide additional education Therapy Center, Aizawa Hospital, Nagano/Japan
to improve nurses’ confidence in recruiting patients. Regular updates are
provided with monthly emails and In February 2016, the Chief Investigator Background: JCOG 0403 showed excellent overall survival in stereotactic
and Trial Manager visited each site to promote the trial and help with any local body radiotherapy (SBRT) for stage IA non-small cell lung cancer (NSCLC). In
barriers to recruitment. In response to feedback, changes to the protocol to Japan, 48Gy/4Fr for isocenter have been the standard dose fractionation of
aid patient recruitment, additional promotional and patient information SBRT for stage IA NSCLC. JCOG0702 showed that dose escalation of 55Gy for
provided and a video for patients were produced. The study has also been PTVD95% was feasible in SBRT for peripheral small (PTV volume 100cc or less)
presented at varioUS Oncology/thoracic meetings. As a result recruitment has NSCLC. Intensification of local treatment with dose escalation is considered
increased with 15 patients successfully randomised into the trial. Conclusion: to be one of the measures for improvement of overall survival. In 2011, we
Whether SABR is an alternative to surgery is a key question in stage I NSCLC. adopted dose escalated regimen (50Gy/4Fr for PTVD95%) for SBRT for stage
However, SABRtooth is a challenging study but with a novel trial design and IA NSCLC, expected improvement of local control and overall survival. The
continual adaptive feedback we hope to be able to meet recruitment targets purpose of this study was to review and report the primary results of dose
and demonstrate that a definitive phase III RCT is feasible. escalated SBRT for stage IA NSCLC. Methods: From August 2011 to April 2015,
31 patients with stage IA NSCLC were treated with dose escalated SBRT at the
Keywords: SABR, Surgery, Stage I NSCLC, Randomised Controlled trial University of Yamanashi. The patients’ ages ranged from 61 to 86 (median 79)
years. Twenty two patients were male, 9 were female. Performance status
was 0 in 26, 1 in 5 patients. Tumor histology was squamous cell carcinoma in 6
and adenocarcinoma in 23, other NSCLC in 2 patients. Clinical stage was T1a in
19, T2b in 12 patient. A multiple static ports radiation planned by a radiation
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC treatment planning system (Pinnacle3 Version 9.2-9.8) was performed with
SBRT –
MONDAY, DECEMBER 5, 2016 linac using 6MV x-ray beams. The Breath hold technique and CT image guided
set-up were used in all cases. A total dose of 50Gy was delivered in 4 fractions
over 4-5days. Radiation doses were prescribed to the 95% of planning target
P1.05-030 LUNG SABR FOR EARLY STAGE LUNG CANCER: volume (PTVD95%). (A superposition algorithm with heterogeneity correction
OUTCOMES AND TOXICITY OF 803 PATIENTS TREATED AT THE was used for dose calculations. Results: The follow-up period for all patients
LEEDS CANCER CENTRE was 3.3-43.1 (median 23.7) months. The overall survival rate at one year
Patrick Murray 1, Katy Clarke1, Kevin Franks2, Peter Dickinson1, John Lilley3, and two years were 87.1%, 79.3%, respectively. The local control rate at one
Michael Snee1, Pooja Jain1 year and two years were both 96.4%. Local recurrence, regional lymph node
1
Clinical Oncology, St James’ University Hospital, Leeds/United Kingdom,
metastases, and distant metastases were observed in 1, 4 and 3 patients,
2
Department of Clinical Oncology, Leeds Cancer Centre/University of Leeds, Leeds/ respectively. Regarding to the toxicities, grade 3 radiation pneumonitis were
United Kingdom, 3Radiotherapy Physics, St James’ University Hospital, Leeds/ observed in 3 patients. Grade 2 rib fracture were observed in 3 patients. There
United Kingdom were no Grade 4 or greater adverse events in the follow-up period. Conclusion:
The toxicity was considered to be acceptable. The local control effect was
Background: SABR is an established treatment for early peripheral stage non- considered to be sufficient. Longer follow- up durations are needed to validate
small cell lung cancer (NSCLC) in medically inoperable patients We present the clinical benefits of dose escalated SBRT for stage IA NSCLC.
the outcomes 803 patients, a large prospective series of patients, with a
minimum 12 months follow-up after undergoing SABR treatment in Leeds, Keywords: stereotactic body radiotherapy, dose escalation, Non-small cell
UK, between May 2009 and May 2015. Methods: Patients with a pathological lung cancer, overall survival
or clinical diagnosis of peripheral stage I lung cancer, and deemed medically
inoperable, were treated with SABR at the Leeds Cancer Centre, using a dose
fractionation of 54Gy/3#, 55Gy/5#, or 60Gy/8# depending on proximity of
organs at risk. Patient follow-up was assessed using an electronic patient
record and radiology reports. Survival analysis was performed using Kaplein- SBRT –
Meier estimation and log rank test was used to compare survival distibutions MONDAY, DECEMBER 5, 2016
including performance status, histology, tumour T stage, tumour location,
post-SABR fibrosis, and toxicity. Results: 803 patients were treated with
SABR and had at least 12 months follow-up. Mean age at treatment was 73.9 P1.05-032 QUALITY OF LIFE AFTER STEREOTACTIC BODY
years (39 to 94 years). Median follow-up was 23.3 Months, from time of last RADIOTHERAPY AND SURGERY IN PATIENTS WITH EARLY STAGE
treatment fraction to last medical contact or death. Median overall survival NON-SMALL CELL LUNG CANCER
estimate was 33.3 Months (95% C.I. 29.54-27.1 Months) 1 year OS – 80.1% (SE Elisabeth Kastelijn1, Sherif El Sharouni2, Frederik Hofman3, Pieter Zanen1,
1.4%), 3 year OS – 46.4% (SE 2%), 5 year OS – 29.5% (SE 2.6%) Local control Franz Schramel1
(LC) 1 year LC – 99.2% (SE 0.3%), 2 year LC – 97.2% (SE 0.7%), 3 year LC – 95.1% 1
Department of Pulmonology, St. Antonius Hospital, Nieuwegein/Netherlands,
(SE 0.9%) Both performance status and tumour size were associated with 2
Department of Radiotherapy, University Medical Centre, Utrecht/Netherlands,
a worse overall survival, Log rank p<0.001 (PS), p=0.035 (T stage). Toxicity 3
Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein/
Only 4 patients had documented grade 3 toxicity. 3 pneumonitis requiring Netherlands
admission, and 1 patient developed a bronchopulmonary fistula 2 years post-
treatment. 44 Patients had a rib fracture recorded, of these 16 patients were Background: Several studies have shown that the clinical outcomes after
symptomatic, and were treated with analgesia or neuropathic adjuncts. 156 stereotactic body radiotherapy (SBRT) are not inferior compared to surgery
patients had documented radiological pneumonitis (gd 1), with 331 developing in patients with early stage non-small cell lung cancer (NSCLC). Quality of life
fibrotic change in the treatment area. Of interest the presence of radiological (QoL) after treatment is an important parameter for patients which receives
pneumonitis and fibrotic changes was associated with an improved overall raising interest. We compared the QoL during the first year after treatment
survival, Log rank P=0.009 (Rad pneum), P<0.001 (Fibrosis). Conclusion: SABR in patients with early stage NSCLC. Methods: Patients diagnosed with early
for early stage lung cancer is a safe and effective treatment even in medically stage NSCLC and treated with SBRT or surgery in the Sint Antonius Hospital
inoperable patients, with excellent local control. In our cohort, we found between 2013 and 2015 were included. QoL assessments were performed
radiological pneumonitis and fibrosis was associated with an improved overall before treatment, and at three, six and 12 months after treatment. QoL was

evaluated by using the 30-item European Organization for Research and FF-SBRT group. The onset of distant failure was significantly delayed in the
Treatment of Cancer Quality of life Core questionnaire and its corresponding SF-SBRT compared to the FF-SBRT group. The majority of toxicities occurred
13-item lung cancer supplement. A linear mixed model was used to analyse late. Having SF-SBRT itself was not significantly associated with severe
the data and a change of more than five points was determined as minimal toxicity.
clinically important difference . Results: Ninety-three patients were included
(SBRT n = 39, surgery n = 54). Patients who underwent SBRT were significantly Keywords: Distant failure, Stereotactic body radiation therapy, Single
older, had a higher ECOG performance status and a lower pulmonary function. fraction, Central lung tumor
The compliance for SBRT and surgery at baseline were 97% and 98% (p = 0.8),
at three months 74% and 71% (p = 0.8), at six months 62% vs 78% (p = 0.1), and
at 12 months 45% and 73% (p = 0.04). The ECOG performance status was not POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
SBRT –
significantly different between the patients who were compliant and those MONDAY, DECEMBER 5, 2016
who were not compliant. During the 12 months after treatment different
significant changes were observed:
P1.05-034 NEUTROPHIL-TO-LYMPHOCYTE AND PLATELET-TO-
QoL remained stable in SBRT patients and increased in surgical patients (p = LYMPHOCYTE RATIOS AS PROGNOSTIC BIOMARKERS IN EARLY
0.012) NSCLC PATIENTS TREATED WITH SABR
Role functioning increased in SBRT patients and decreased in surgical Stephen Mckay 1, Karen Moore1, Jennifer Macphee1, Jonathan Hicks1, Graeme
patients (p = 0.005) Lumsden1, Vivienne Maclaren1, Philip Mcloone2, Stephen Harrow1
1
Beatson West of Scotland Cancer Centre, Glasgow/United Kingdom, 2Institute of
Cognitive functioning increased in SBRT patients and remained stable in Health & Wellbeing, University of Glasgow, Glasgow/United Kingdom
surgical patients (p = 0.045)
Background: Inflammation may play an important role in cancer progression.
Social functioning remained stable in SBRT patients and decreased in surgical High Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte
patients (p = 0.001) ratio (PLR) have been reported to be poor prognostic indicators in several
malignancies. In this study we quantify the prognostic impact of these
Pain increased in SBRT patients and decreased in surgical patients (p = 0.001) biomarkers for overall survival (OS) among early stage NSCLC patients
treated with Stereotactic Ablative Body Radiotherapy (SABR). Methods:
SBRT patients had a decrease in effect of pain medication and surgical
102 consecutive patients who received SABR between October 2011 and
patients had an increase in effect of pain medication (p = 0.0001).
May 2014 at the Beatson West of Scotland Cancer Centre (BWoSCC) were
Conclusion: We showed that in patients with early stage NSCLC treated with identified from a prospectively maintained electronic database. NLR and
SBRT or surgery the QoL scores showed different changes after treatment. PLR were derived from blood results obtained within 60 days prior to SABR.
In the light of the comparable clinical outcomes after both treatments these Receiver Operator Characteristic (ROC) curves were generated to calculate
QoL aspects should be discussed with the patient before making a treatment- the optimal thresholds for NLR and PLR. Results: The median age of patients
decision. was 72 (range 47-91) years. 60 (59%) were female. Maximum tumour diameter
ranged from 10-42mm (median 18mm). Median follow up was 37.1 months.
Keywords: early stage non-small cell lung cancer, stereotactic body Overall survival at 2 and 4 years was 75.5% (95%CI 65.9-82.7%) and 51.4%
radiotherapy, Surgery, quality of life (38.8-62.6%) respectively. There was strong association between NLR and
PLR levels (r=0.803, p<0.001). ROC Curves indicated a threshold value for
NLR of 3.155 (AUC 0.74) and PLR of 155.15 (AUC 0.70) respectively. Median
OS for ‘low’ NLR and PLR was not yet reached compared with 33.9 months
for ‘high’ NLR (p<0.0001) and 35.4 months for ‘high’ PLR (p=0.002). Multi-
SBRT –
variable analysis indicated a stronger independent effect of NLR (p<0.0001),
MONDAY, DECEMBER 5, 2016 whilst taking account of gender, age, tumour size, histological confirmation
and performance status. No association was found between elevated NLR
or PLR and loco-regional or distant recurrence. Conclusion: Neutrophil-to-
P1.05-033 COMPARISON OF SINGLE- AND FIVE-FRACTION Lymphocyte Ratio appears to be a prognostic biomarker for patients with
SCHEDULES OF STEREOTACTIC BODY RADIATION THERAPY FOR early stage NSCLC receiving SABR. Platelet-to-Lymphocyte ratio acts as a
CENTRAL LUNG TUMORS linear co-variant. We found no association between elevated NLR or PLR and
Sung Jun Ma, YUSEF SYED, CHARLOTTE RIVERS, JORGE A. GOMEZ loco-regional or distant recurrence.
SUESCUN, ANURAG K SINGH
Keywords: SABR, NSCLC
Radiation Medicine, Roswell Park Cancer Institute, Buffalo/NY/United States of
America
Background: Stereotactic Body Radiation Therapy (SBRT) is a treatment

option for patients with early-stage non-small cell lung cancer (NSCLC) who
are medically inoperable or decline surgery. The safety of 20 Gray (Gy) x 3 SBRT –
fractions of SBRT within 2 cm of the proximal bronchial tree is unclear. Here MONDAY, DECEMBER 5, 2016
we compare the clinical outcome of patients with centrally located lung
tumors who underwent either single fraction (SF)- or five-fraction (FF-) SBRT
at a single institution over 5 years. Methods: Between January 2009 and
P1.05-035 SABR FOR MEDICALLY INOPERABLE EARLY STAGE
October 2014, 11 out of 42 patients received 26-30 Gy in 1 fraction, while the NSCLC AT THE BEATSON WEST OF SCOTLAND CANCER CENTRE:
remaining 31 patients received 52.5-60 Gy (median 55 Gy) in 5 fractions. Data OUTCOMES AND TOXICITY
were retrospectively collected using an institutional review board-approved Stephen Mckay 1, Karen Moore1, Jennifer Macphee1, Jonathan Hicks1, Graeme
database. Kaplan-Meier method, competing risks method, and Cox regression Lumsden1, Vivienne Maclaren1, Andy Aitken2, David Stobo3, Gordon Cowell3,
model were used. Toxicities were graded using Common Terminology Criteria Philip Mcloone4, Stephen Harrow1
for Adverse Events version 4.0. R version 3.3.1 was used for statistical analysis. 1
Beatson West of Scotland Cancer Centre, Glasgow/United Kingdom, 2Radiotherapy
Results: After a median follow-up of 12 months for SF-SBRT and 17 months Physics Section, Department of Clinical Physics and Bio-Engineering, Beatson West
for FF-SBRT groups (p=0.64), 1-year overall survival rates for SF- and FF-SBRT of Scotland Cancer Centre, Glasgow/United Kingdom, 3Clinical Radiology, Victoria
groups were 82% and 87%, respectively. There was no statistically significant Infirmary, Glasgow/United Kingdom, 4Institute of Health & Wellbeing, University of
difference in overall survival (p=0.061), progression-free survival (p=0.47), Glasgow, Glasgow/United Kingdom
local failure (p=0.43), nodal failure (p=0.42), and distant failure (p=0.45) at
Background: SABR is now an established therapeutic option for patients
18 months. No primary tumor failure was seen in both groups at 18 months.
with medically inoperable early stage NSCLC. It is well tolerated and
Distant failure rates at 18 months were 9.1% for SF-SBRT group and 54.5%
associated with low rates of Grade 3+ toxicity. Here we present the outcomes
for FF-SBRT group. Among the patients with distant failure (n=4 in SF-SBRT
and toxicity data for the SABR service based at the Beatson West of
and n=6 in FF-SBRT), median time to distant failure was 29.5 months and
Scotland Cancer Centre (BWoSCC). Methods: All 102 consecutive patients
8.9 months for SF- and FF-SBRT groups, respectively (p=0.0095). 3 out of
(median age 72 (range 47-91) years, 60 (59%) female) who received SABR
11 patients in SF-SBRT group and 2 out of 32 patients in FF-SBRT group
between October 2011 and May 2014 at the BWoSCC were identified from a
experienced grade 3-4 toxicities. No grade 4-5 toxicities were observed in
prospectively maintained electronic database. Toxicity data was collected
the FF-SBRT group. SF-SBRT group showed higher cumulative incidence of
at pre-determined intervals in a dedicated follow-up clinic. Radiological
grade 3+ toxicity at 18 months (p=0.018). However, univariate analysis showed
evidence of pneumonitis was scored on follow-up CT imaging at 3 months
SF-SBRT alone was not a significant factor that increased risk for grade 3+
post-SABR. Outcomes were collated from electronic records. Results:
toxicities (HR=5.50, p=0.063). 4 out of 5 toxicities occurred at least 12 months
Median and minimum follow-up were 37.1 and 24.1 months respectively.
after SBRT. Conclusion: SF- and FF-SBRT showed no significant difference in
Histological confirmation of NSCLC was available for 33 (32.4%) patients.
overall survival and local control. No grade 4-5 toxicities were observed in our
Local and regional control rates at 2 years were 95.1% and 94.1% respectively. 58 GGNs were retrospectively reviewed. Results: Median age of the patients
8.8% of patients developed metastases within 2 years with a median time was 58 years (range, 33 – 75) and 34 patients (83.3%) were female. Median
to detection of metastases of 6.9 months. Overall survival (OS) at 1, 2, 3 preoperative follow-up duration of GGNs was 11 months (range, 3–114). In
and 4 years post-SABR was 88.2% (95%CI 80.2-93.1%), 75.5% (65.9-82.7%), spite of all patients were asymptomatic, the reasons of check-up the chest
59.8% (48.2-69.7%) and 51.4% (38.8-62.7%) respectively. No difference CT included to follow-up for other malignant disease in 29 patients (70.1%),
in OS was apparent between histologically confirmed and unconfirmed routine health check-up in 10 (25.0%), and to follow-up of other benign disease
subgroups (p=1.0). On multi-variable analysis, tumour size >= 20mm was in 2 (4.9%). Among a total 45 operations, preoperative CT-guided localization
negatively associated with OS (p=0.003) whilst gender, age, performance was performed in 31 operations (68.9%). Extents of resection included
status, deprivation index and histological confirmation were not associated. wedge resection in 29 patients (64.4%), segmentectomy in 7 (15.6%), and
Radiological scoring of post-SABR pneumonitis was available for 69 lobectomy in 9 (20.0%). Lymph node sampling or dissection was performed in
patients. A total of 33 of these patients (48%) had radiological evidence of 27 operations (60.0%). Among 58 resected GGNs, median diameter of GGNs
pneumonitis. No association between V5 or V20 and radiological pneumonitis was 8mm (range, 3-15mm), median number of resected GGN per operation
was identified. One death occurred that was potentially related to radiation was 2 (range, 1-5). The distribution of pathologic diagnosis included benign
pneumonitis. Otherwise, only 1 patient experienced grade 4 toxicity (fatigue) disease in 3 GGNs (5.2%), atypical adenomatous hyperplasia (AAH) in 4 (6.9%),
and 5 patients (4.9%) reported grade 3 toxicity (4x dyspnoea, 1x fatigue) adenocarcinoma in situ (AIS) in 17 (29.3%), minimally invasive adenocarcinoma
within 12 months of SABR. There were 4 instances of rib fracture with no (MIA) in 19 (32.8%), and invasive adenocarcinoma (IA) in 15 (25.9%). The
association with maximum chest wall dose. Conclusion: Within the Beatson diameter of GGNs classified into 3 categories (0 – 5mm, 6 – 10mm, 11 – 15mm)
West of Scotland Cancer Centre the use of SABR for early stage NSCLC is were associated with pathologic invasiveness (Cochran-Amitage test, p =
associated with high rates of loco-regional control. Our overall survival and 0.005). However, follow-up duration of GGNs classified into 3 categories
toxicity data compare favourably with published series. (3 - 12 months, 13 - 24 months, more than 25 months) was not associated
with diameter of GGNs (p = 0.453) or pathologic invasiveness (p = 0.893).
Keywords: SABR, NSCLC Among 18 GGNs tested, epidermal growth factor receptor (EGFR) mutations
were detected in 5 GGNs (27.7%). Conclusion: The prevalence of lung
adenocarcinoma (AIS, MIA, IA) was 87.9% in surgically resected pure GGNs
persistent more than 3 months and their diameter at CT scan less than 15 mm.
A diameter of GGNs diameter was associated with pathologic invasiveness.
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC Further studies are needed for persistent pure GGNs not affected by partial-
Surgery – volume effect of CT in non-selected patients.
MONDAY, DECEMBER 5, 2016 Keywords: lung, Adenocarcinoma, GGO, Surgery
P1.05-036 A PROPENSITY-MATCHED STUDY OF MULTI-PORT

VERSUS SINGLE-PORT VIDEO-ASSISTED THORACOSCOPIC
SURGERY FOR EARLY LUNG CANCER SURGERY –
1 1
Kyoji Hirai , Shingo Takeuchi , Jitsuo Usuda 2 MONDAY, DECEMBER 5, 2016
1
Division of Thoracic Surgery, Nippon Medical School Chiba Hokusoh Hospital,
Inzai/Japan, 2Thoracic Surgery, Nippon Medical School, Bunkyo-Ku/Japan
P1.05-038 PATTERNS OF RECURRENCE IN CURATIVELY RESECTED
Background: Several thoracic surgeons have already reported the beneficial STAGE I LUNG CANCER
effects of single-port (SP) video-assisted thoracoscopic surgery (VATS) for Kanghoon Lee, Dong Kwan Kim, Seung-Il Park, Yong-Hee Kim, Hyeong Ryul
the patients with lung cancer. We also analyzed surgical outcomes between Kim, Se Hoon Choi, Han Pil Lee, Byung Kwon Chong, Jin San Bok, Su Kyung
SP VATS and multi-port (MP) VATS, which was defined as surgery through 3-4 Hwang
ports alone, and showed the inhibitory effect of postoperative wound pain in Department of Thoracic and Cardiovascular Surgery, Asan Medical Center,
the SP VATS (Eur J Cardiothorac Surg 2015 ). In this study, we aimed to compare University of Ulsan College of Medicine, Seoul/Korea, Republic of
the effectiveness of SP and MP video-assisted thoracoscopic surgery for stage
I lung cancer. Methods: A total of 212 patients with non-small cell lung cancer Background: The patterns of recurrence after curative resection for
underwent lobectomy via SP and MP procedure between April 2008 and pathologically stage I non-small cell lung cancer(NSCLC) were investigated
June 2015 in our institute. We examined the a propensity-matched analysis, according to the cell type. Methods: The medical records of stage I NSCLC
perioperative variables and short-term outcomes of both operations. Results: patients who undergone curative resection at Asan Medical Center between
Propensity matching produced 80 pairs in each group. The clinical outcomes 2000 and 2009 were reviewed. Results: Total 940 patients with pathologically
of SP /MP group were as follows. The mean Fev1.0 and maximum size of proven stage I NSCLC were included. Patients with lepidic-type
tumor was 1.88±0.32/1.65±0.41 liter and 2.8±0.3/2.7±0.3 cm, respectively. adenocarcinoma(LTA) were 74, other adenocarcinoma(ADC) 580, and
The median operation time, intraoperative blood loss was 165±35/172±26 squamous cell carcinoma(SCC) 246. Median length of follow-up was 62
min. and 85±25/75±26 ml. The median drainage duration and postoperative months(3~189), median survival was 146 months, and median disease-free
hospital stay were 1.8±0.7/1.9±0.8 and 7.5±1.9/7.2 ±1.8 days and the mean survival(DFS) was 109 months. During follow-up, recurrence occurred in 221
number of dissected lymph nodes was 19.8±3.8/17.5± 3.1. The number of patients(23.5%). Number of recurrence is grouped by every 6 months.
days that was used with analgesic agents within a month after surgery was Incidence of recurrence was peaked within 2 years after resection, then
8.1±1.2/12.5±2.5 (P<0.05). Conversion rate to open thoracotomy was 3.9/3.6 gradually decreased thereafter. Recurrence LTA(AIS/MIA) group was
%. The overall 3-year disease free survival rate was 92/88%. As for mortality significantly rare(13.5%) throughout the all follow-up period(median DFI of
and morbidity, there was no significant difference in both groups. Conclusion: 60months), and its distribution shows relatively even distribution. Comparing
SP VATS lobectomy, showing alomost as effective as the MP VATS should be ADC and SCC, ADC seemed to show better 5-year OS in univariate
considered as a new treatment option for stage I lung cancer. analysis(p=0.003), but not in multivariate analysis. Furthermore, there were
no significant difference in 5-year DFS(p=0.331). ADC shows higher proportion
of distant metastasis, even though ADC group has lower T-stage. SCC shows
higher incidence of local recurrence.

SURGERY –
P1.05-037 HISTOPATHOLOGIC RESULTS OF SURGICALLY RESECTED

PURE GROUND-GLASS OPACITY LUNG NODULES
Geun Dong Lee 1, Chul Hwan Park2, Young Woo Do1, Sungsoo Lee1
1
Department of Thoracic Surgery, Gangnam Severance Hospital, Yonsei University
College of Medicine, Seoul/Korea, Republic of, 2Department of Radiology, Gangnam
Severance Hospital, Yonsei University College of Medicine, Seoul/Korea, Republic of
Background: Little is known about the histopathology of persistent

pure ground-glass opacity lung nodules (GGNs). Methods: We reviewed
preoperative chest computed tomography (CT) in patients who underwent
surgery for GGNs between Mar. 2015 and May 2016. A total of 58 surgically
resected pure GGNs persistent more than 3 months and their diameter at CT
scan less than 15 mm in 41 patients were included. Then pathologic reports of


SURGERY –
P1.05-040 PROGNOSTIC FACTOR OF NODE INVOLVEMENT PATTERN

IN COMPLETELY RESECTED PN1 SQUAMOUS CELL CARCINOMA
PATIENTS
Kenta Tane, Kenji Miura, Hiromichi Okuma, Yoshitaka Kitamura, Wataru
Nishio, Masahiro Yoshimura
Thoracic Surgery, Hyogo Cancer Center, Akashi/Japan
Background: In patients with non-small cell lung cancer, the degree of regional
lymph node involvement is an important prognostic factor. The prognostic
significance of lymph node involvement pattern is unclear in the seventh
edition of TNM classification. Squamous cell carcinoma (SCC) often arises in
the central way and directly invades intrapulmonary and hilar lymph nodes.
Conclusion: Recurrence of ADC occured within 2 years after resection, and In this study, we reviewed our population of operated SCC patients classified
shows higher proportion of distant metastasis(74.0% Vs. 57.2) even though as pathologically N1 (pN1) to evaluate the association between N1 lymph node
ADC group has lower T-stage. Most of recurrence of both ADC and SCC groups involvement patterns and the prognosis. Methods: From our institutional
were peaked within 2 years after resection. LTA group shows significantly database of 3,264 consecutive patients underwent surgical resection for
delayed pattern of recurrence. NSCLC at our hospital between January 1987 and December 2010, we examined
152 patients with completely resected pN1 squamous cell carcinoma. We
Keywords: recurrence, lung cancer performed reassessment of the data according to the seventh edition of TNM
classification of lung cancer. We divided the patients into two groups based
on lymph node involvement pattern; direct and separate pattern. The direct
pattern was defined as lymph node metastasis by the primary tumor directly
with continuity, separate pattern as metastasis without continuity. Survival
SURGERY – curves were generated by the Kaplan-Meier method and multivariate analysis
MONDAY, DECEMBER 5, 2016 was based on the Cox proportional hazards model. Results: In the lymph
nodes metastasis pattern, 75 (49%) patients were the direct group, 77 (51%)
patients were the separate group. The percentage of sleeve lobectomy was
P1.05-039 RECURRENCE AND SURVIVAL OUTCOME AFTER significantly higher in the direct group and lobectomy without bronchoplastic
SEGMENTECTOMY FOR NON-SMALL CELL LUNG CANCER: A LONG- procedure was higher in the separate group. The median follow-up period was
TERM FOLLOW-UP STUDY AT A SINGLE INSTITUTE 50 months. The 5-year survivals of the direct and separate group were 54%
Takamasa Koga1, Kosuke Fujino2, Kentaro Yoshimoto3, Koei Ikeda1, Yonosuke and 41% (p = 0.01). The 5-year survival of patients with the direct group was as
Sato4, Takaaki Ito4, Takeshi Mori1, Makoto Suzuki1 good as pN0 patients (p = 0.78). No survival difference between the separate
1
Thoracic Surgery, Kumamoto University Hospital, Kumamoto/Japan, 2Division of group and pN2 patients was noted (p = 0.06). Overall recurrence rate of the
Thoracic Surgery, Toronto General Hospital, Toronto/AB/Canada, 3Thoracic Surgery, direct group (44% [33/75]) was lower than the separate group (50% [39/77]),
Minami Kyushu Hospital, Aira/Japan, 4Department of Pathology and Experimental but there was no significant difference among them (p = 0.09). No significant
Medicine, Kumamoto University, Graduate School of Medical Sciences, Kumamoto/ difference was noted in recurrence pattern (distant or locoregional) when
Japan comparing the direct group or separate group (p = 0.27). By multivariate
analyses of survival, lymph node involvement pattern (p = 0.02) and lymphatic
Background: This study aimed to investigate the factors associated with
infiltration (p = 0.02) was independent prognostic factor. Conclusion: Lymph
long-term outcomes of segmentectomy for non-small cell lung cancer (NSCLC)
node involvement pattern of patients with pN1 squamous cell carcinoma is
carried out at a single institute. Methods: 179 patients with stage I NSCLC who
significant prognostic factor. Survival of the direct pattern is higher than the
underwent a segmentectomy between 2005 and 2009 were investigated.
separate pattern.
Histological classification was reassessed according to the criteria of the 2015
WHO. Results: 179 patients with stage I NSCLC (159 adenocarcinomas (ADCs), Keywords: lung cancer, Squamous cell carcinoma, lymph node involvement
14 squamous cell carcinomas (SQCs), 4 adenosquamous carcinomas, and 2 pattern, direct
typical carinoids) who underwent segmentectomy between 2005 and 2009
were investigated.The mean follow-up was 73 months. The 5-year overall
survival (5-OS) and 5-years disease-free survival (DFS) were 91.8% and 90.2%,
respectively. Seven cases of distant recurrence and 8 local-regional recurrence
occurred. Multivariate analysis revealed that lymphovascular invasion (LVI) POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
was the independent predictor of 5-OS (P=0.005), and part-solid GGO (GGO SURGERY –
ratio < 50%) and LVI were that for 5-DFS (P=0.043, P<0.001). Among invasive
ADC patients, micropapillary pattern (MIP) ≥ 5% was identified as an
independent predictor of recurrence (P=0.005) and survival (P=0.007). There P1.05-041 DYNAMICS OF BRAIN METASTASIS FOR CURATIVELY
were five local recurrences in patients with MIP more than 5 years after RESECTED STAGE I OR II NON-SMALL CELL LUNG CANCER PATIENTS
segmentectomy. Sumin Shin, Byung Jo Park, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Jae Ill
Zo, Young Mog Shim, Jhingook Kim
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of
Background: Development of brain metastasis results in a significant

impairment in overall survival. The aim of this study to investigate the
timing and manifestation of brain recurrence event during follow-up in
patients undergoing surgery for stage I or II non–small-cell lung cancer
(NSCLC). Methods: Between 2008 and 2012, medical records for patient who
underwent curative surgery for stage I or II NSCLC at our institution were
reviewed retrospectively. Event dynamics including brain metastasis, distant
metastasis and non-brain distant metastasis, based on the hazard rate,
were evaluated. Results: A total of 2389 eligible patients were identified. At
a median follow-up of 50.6 months (IQR, 37.8–60.3 months), 573 patients
developed recurrence. Among those, 457 patients had distant metastasis
including 70 patients had brain metastasis as the first relapse site. The hazard
rate curve for brain metastasis is similar from those of all distant metastasis
Conclusion: LVI was an independent predictor of the recurrence and overall and non-brain distant metastasis. The distinct surge was noted in 8.3
survival. In patients with invasive ADC, MIP≥5% was a multivariable predictor months in the brain metastasis. Subgroup analysis according to pathologic
of recurrence and overall survival. In the patients who underwent a stage revealed that patients with stage II have distinct surge in 10 months,
segmentectomy, 5 years without recurrence is not sufficient to conclude that while the surge of stage I patients is more gradual and low. Hazard rate for
patients with NSCLC is cured. brain metastasis is similar for each stage since 34months. Conclusion: Brain
recurrence dynamics of resected stage I or II early-stage NSCLC displays a
Keywords: non-small call lung cancer, NSCLC, early stage, segmentectomy
similar pattern compared to other distant metastasis. The overall risk reached
high less than 1 year postoperative period regardless of stage. Our findings identified. Numbers for other subtypes were small and therefor 3 year survival
would be helpful to make a strategy to surveillance for brain metastasis after was not always possible to calculate.
surgical resection for early stage NSCLC.
Survival by histological subtypes
Keywords: lung cancer, Surgery, recurrence, survival
No. of
Deaths 1 year 2 year 3 year
Histology
during survival survival survival
follow-up
SURGERY – Acinar (N=325) 93 90.5% 79.2% 68.3%
Glandular
5 94.1% - -
(N=17)
P1.05-042 TREATMENT STRATEGY OF LIMITED SURGERY FOR
EARLY LUNG CANCER Lepidic (N=133) 32 92.5% 84.4% 76.6%
Katsuo Kojima Micropapillary

1 - - -
Thoracic Surgery, Musashino Red-Cross Hospital, Musashino-Shi, Tokyo/Japan (N=3)
Mixed (N=26) 9 84.6% 71.3% -
Background: The standard surgical procedure for operable lung cancer is
lobectomy with lymph node dissection. However early lung cancer cases Papillary
11 78.9% 76.3% -
have been increasing in Japan and they have been able to be candidates (N=38)
for limited operation. We have predicted early lung cancer depending on
Solid (N=131) 50 81.7% 67.1% 59.7%
image findings and performed a limited operation positively. Methods: The
advisability of the limited operation is evaluated with computed tomography Unknown
10 93.5% 71.5% -
(=CT) and positron emission tomography (=PET) for the cases in which we (N=31)
have diagnosed a lung nodule as c-Stage IA by staging of lung cancer. We have
judged surgical indication for limited operation when the tumor diameter in Conclusion: A difference in survival can be seen between the three commonest
mediastinal window setting of high resolution CT is 5mm or less and SUVmax adenocarcinoma subtypes (Acinar, Lepidic and Solid) at 1, 2 and 3 years
level in tumor portion is 1.5 or less even if it exceeds 5mm. We decided the following surgical resection. Interpreting results on other sub-types is limited
orientation as follows: Wide wedge resection is performed for pure GGO by small numbers. Lepidic and Solid have the best and worst survival rates
(=ground glass opacity) based on expectation to be Adenocarcinoma in situ respectively. Limitations include a lack of adjustment for pathological stage
(=AIS). Segmentectomy with lymph node dissection is performed for mixed or co-morbidities and a lack of cancer-specific mortality data. Future studies
GGO to deal when it is difficult to distinguish whether that the lesion is may evaluate if the morphology of lung adenocarcinomas could have a role in
AIS, Minimally Invasive Adenocarcinoma (=MIA) or Invasive Carcinoma. We defining adjuvant and surveillance strategies.
examined whether each surgery method was appropriate compared with the
Keywords: NSCLC, Surgery, Adenocarcinoma, survival
postoperative pathological result. Results: Surgical treatment for lung cancer
was performed to 453 cases in our hospital between Apr.2010 and Jun.2016.
115 cases were diagnosed as early cancer suspected in preoperation by the
above criteria. Wide wedge resection was performed to 27 cases (31 lesions).
30 lesions were AIS and 1 lesion was MIA pathologically. We underwent left POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
S9 segmentectomy with lymph node dissection in addition for 1 case of SURGERY –
mucinous adenocarcinoma. Segmentectomy with lymph node dissection MONDAY, DECEMBER 5, 2016
was performed to 58 cases (61 lesions). 26 lesions were AIS, 29 lesions were
MIA, 5 lesions were invasive adenocarcinoma and 1 lesion was squamous P1.05-044 THE IMPACT OF IASLC 8TH EDITION UPDATES FOR
cell carcinoma pathologically. In all cases of invasive adenocarcinoma and T-CLASSIFICATION FOR LUNG CANCER IN A US POPULATION-BASED
squamous cell carcinoma, both lymph node metastasis and lymphovascular
SURGICAL RESECTION COHORT
invasion was negative, so we did not perform completion lobectomy in
addition. We performed lobectomy to 23 cases in spite of our expectation as Matthew Smeltzer 1, Nicholas Faris2, Carrie Fehnel2, Cheryl Houston-Harris2,
early cancer due to a lesion of the middle lobe, a lesion near pulmonary hilum Meredith Ray1, Yu-Sheng Lee1, Meghan Meadows1, Sam Signore2, Chris
or the request of the patients and pathological results were 7 AIS, 7 MIA and Mutrie2, Edward Robbins2, Raymond Osarogiagbon2
1
9 invasive adenocarcinoma with no lymphovascular invasion and no lymph Epidemiology and Biostatistics, University of Memphis School of Public Health,
node metastasis. Conclusion: We can operate for the appropriate extent of Memphis/TN/United States of America, 2Multidisciplinary Thoracic Oncology
resection for early lung cancer by making full use of image findings. Program, Baptist Cancer Center, Memphis/TN/United States of America
Keywords: limited resection, early lung cancer, segmentectomy, wide wedge Background: Accurate staging of non-small cell lung cancer (NSCLC) is vital for
resection prognostication and treatment selection. We evaluated the impact of the 8th
Edition TNM (8E) T-classification in a US regional NSCLC resection database.
Methods: Curative-intent NSCLC resections from 11 hospitals in 4 contiguous
Dartmouth Hospital Referral Regions within 3 US states from 2009-2016 were
re-staged based on 8E T-categorization. Survival analyses were conducted
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC using the Kaplan-Meier method and proportional hazards models with
SURGERY – adjusted hazard ratios (aHR) controlling for age, histology, grade, pN-
category, and comorbidities. M1 patients and those who received neoadjuvant
therapy were excluded. Results: The 2245 patients had a median age of 65,
P1.05-043 SURVIVAL FOLLOWING SURGICAL RESECTION OF LUNG were 48% female, 78% white, 21% black. The 961 pT1 (8E) distribution was 10%
ADENOCARCINOMA STRATIFIED ACCORDING TO MORPHOLOGICAL pT1a, 52% pT1b, and 39% pT1c. The 793 pT2 (8E) patients were 82% pT2a and
SUB-TYPE 18% pT2b. Of the 318 patients with pT3 (8E), 134 (42%) were pT2b based on the
7th Edition TNM (7E); of the 152 with pT4 (8E), 107 (70%) were pT3 based on 7E.
Haval Balata, Timothy Edwards, Charlene Tennyson, Philip Foden, Anshuman
There was no survival difference between pT1a and pT1b (p=0.83); pT1c had
Chaturvedi, Philip Crosbie, Richard Booton, Matthew Evison
worse survival than pT1b (p<0.01; Figure 1a). Of the 145 patients previously
University Hospitals of South Manchester, Manchester/United Kingdom classified as pT2b by 7E, 134 (92%) were upstaged to pT3. They had similar
survival to those classified as pT3 in 7E (p=0.75). Of the 296 patients
Background: Lung adenocarcinoma is the commonest histological sub-type
previously classified as pT3, 107 (36%) were upstaged to pT4. The upstaged
of Non-small cell lung cancer (NSCLC) and a leading cause of death worldwide.
patients had worse survival than 7E pT3 patients who were not upstaged,
Identifying factors that may influence survival or the risk of recurrence
although not statistically significant (aHR:1.32, Figure 1b). Adjusted models
following resection of lung adenocarcinoma may inform adjuvant strategies
confirm an increasing trend in the hazard of death with increasing stage, with
and the intensity of surveillance programs. The aim of this study was to assess
the exception of pT1b. (aHR: pT1a=1.00, pT1b=0.89, pT1c=1.15, pT2a=1.38,
the effect of morphological sub-type on survival following surgical resection.
pT2b=1.54, pT3=1.86, pT4=2.44).
Methods: Patients who underwent surgical resection for non-small cell lung
cancer between 2011 and 2014 at a tertiary thoracic surgical and lung cancer
centre were identified from pathological records (n=1387). Patients with
adenocarcinoma (n=705) were selected and the predominant morphological
subtyping was recorded. Survival data was obtained from national death
registries. Results: Of the 705 adenocarcinomas, Acinar (n=325), Lepidic
(n=133) and Solid (n=131) were the most frequent histological subtypes


Neoadjuvant and Adjuvant Chemotherapy –
P1.05-045 ADJUVANT CHEMOTHERAPY FOR PATIENTS WITH STAGE

IB NON SMALL CELL LUNG CANCER
Jia Wang, Yang Yue
Thoracic Surgery, Beijing Cancer Hospital, Beijing/China
Background: The prognosis of stage Ib non-small cell lung cancer (NSCLC)

remains poor, there’re much controversy over the necessity of adjuvant
chemotherapy to them. The aim of this study is to investigate the clinical
characters influencing prognosis of the stage Ib non-small cell lung cancer
(NSCLC) and to explore the indication of postoperative chemotherapy.
Methods: In total, 569 stage IB patients with NSCLC who underwent surgical
resection with or without adjuvant therapy were included in this study. Cox
proportional-hazards ratios were used to identify independent prognostic
factors for survival. Kaplan-Meier survival curves were calculated to estimate
survival rates. Results: Adjuvant chemotherapy, tumor size and performance
status were independent prognostic factors in the univariate and
multivariate analyses. Patients with tumor greater than 4 cm and patients
with good performance status benefitted from adjuvant chemotherapy.
On the contrary, to the patients with tumor less or equal to 4 cm or patients
without good performance status, giving adjuvant chemotherapy is not
better than giving surgery alone.
Conclusion: Adjuvant chemotherapy, tumor size and performance status were

closely correlated with survival in the stage Ib NSCLC, patients with tumor
greater than 4 cm and patients with good performance status benefitted
from adjuvant chemotherapy.
Keywords: lung cancer, adjuvant chemotherapy, stage IB
analysis independently corroborates the 8E re-classification for late stage

patients in the US. However, we found no survival differentiation between
tumors less than 2cm.
Keywords: Non-small cell, early stage, IASLC 8th Edition TNM
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC adverse events. Since there is limited information on the early mortality
NEOADJUVANT AND ADJUVANT CHEMOTHERAPY –
among patients undergoing adjuvant chemotherapy, we used the National
Cancer Data Base (NCDB) to calculate the percentage of deaths within
the first 6 months from starting chemotherapy. Methods: The NCDB was
P1.05-046 RANDOMIZED STUDY OF ADJUVANT DOCETAXEL VS. queried for patients aged 18 or older, diagnosed with stage IB to IIIA NSCLC
OBSERVATION FOR COMPLETELY RESECTED STAGE IB-IIIA NSCLC (AJCC 7th edition) from 2004 to 2012, who underwent surgery with negative
WITH 11 YEARS’ MEDIAN FOLLOW-UP margins followed by multi-agent chemotherapy, starting within 120 days
from the surgical resection. Patients who received radiation therapy were
Wen-Zhao Zhong 1, Xue-Ning Yang2, Hong-Hong Yan2, Ri-Qiang Liao2, Qiang
excluded. Age groups were divided into <50, 51-60, 61-70, 71-80 and >80
Nie2, Song Dong2, Ben-Yuan Jiang2, Qing Zhou2, Jin-Ji Yang2, Yi Long Wu2
1
years. Early mortality from months 1 to 6 were calculated and multivariate
Department of Pulmonary Oncology; Guangdong General Hospital & Guangdong
logistic regression was performed to identify clinical variables independently
Academy of Medical Sciences, Guangzhou/China, 2Guangdong Lung Cancer
Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, associated with mortality at six months from the date of initiation of
Guangzhou/China adjuvant chemotherapy. Results: A total of 19,791 patients met the eligibility
criteria. The median age was 65 (range 19-89). The percentage of deaths
Background: Although previous meta-analyses have verified the significance at 1, 2, 3, 4, 5 and 6 months were 0.6%, 1.3%, 1.9%, 2.6%, 3.3% and 4.2%
of adjuvant chemotherapy, the role of adjuvant carbopatin plus docetaxel(DC) respectively. The percentages of death at 6 months for each age group from
among patients with completely resected NSCLC with long periods of < 50 years to > 80 years were 2.7%, 3.2%, 4.1%, 5.3% and 7.8% respectively.
follow-up remains unclear. Methods: Eligible patients were randomly assigned Factors independently associated with increased 6-month mortality included
to 4 cycles of DC or observation after complete resection. The primary end increased age, male gender, higher Charlson-Deyo co-morbidity score (CDCS),
point was DFS; secondary ones were OS, the toxicity and safety of drugs. An type of surgery, length of stay (LoS) > 6 days and 30-day readmission (Table).
increase of 15% in 1-year survival rate (observation arm 70%) with a sample Conclusion: There is a high risk for early mortality among patients undergoing
size of 270 patients was considered significant. Results: This trial was adjuvant chemotherapy for NSCLC, particularly in patients older than 70, with
suspended prematurely in June 2005 due to the negative survival benefits high co-morbidity score and a more complicated post-operative period.
from chemotherapy in stage IB patients in the JBR10 trial. 82 patients were
enrolled between 2002 to 2005(43 and 39 in each arm).Two arms were Table. Multivariable analysis
well-balanced on age, gender, histology, smoking history and staging. Median
Variable OR (95% CI) P-value
follow-up was 11 years(10.5-13y). DFS was marginally significantly longer in DC
arm than observation (10.4 vs. 3.7y; HR=0.58; 95% CI, 0.33-1.03; P=0.06), as Age
was 5-year DFS rates(63% vs. 41%, P=0.057). No statistical significance ≤ 50 Reference Reference
existed in OS (NR vs. 7.1y; P=0.103) or 5-year survival rates(76% vs. 61%;
51-60 1.08 (0.74-1.60) 0.68
P=0.148). Multivariable analysis revealed patients receiving adjuvant
DC(HR=0.54, 95%CI 0.30-0.96, P=0.036) and with stage IB disease(HR=0.34, 61-70 1.33 (0.91-1.95) 0.15
95%CI, 0.19-0.61, P<0.001) bore lower recurrence risk. In DC arm, 84% of 71-80 1.59 (1.06-2.38) 0.03
patients received at least one cycle of DC, and 53% of patients finished four. > 80 2.27 (1.29-3.98) 0.004
Grades 3 adverse events occurred in 5%(2/43) in chemotherapy group. The
time-varying endpoints showed adjuvant DC could delay the recurrence and Gender
mortality in the first postoperative 5ys, while two arms tended to be Male Reference Reference
equivalent after 5ys. Female 0.70 (0.59-0.82) < 0.001
CDCS
0 Reference Reference
1 1.13 (0.95-1.34) 0.15
2 1.58 (1.26-1.98) < 0.001
Surgery
Sub-lobar Reference Reference
Lobectomy 0.72 (0.53-0.97) 0.03
Pneumonectomy 0.97 (0.68-1.39) 0.87
Stage
IB Reference Reference
II 1.29 (1.04-1.59) 0.02
IIIA 2.28 (1.81-2.87) < 0.001
LoS
≤ 6 days Reference Reference
Conclusion: This is the first randomized trial used DC as adjuvant > 6 days 1.24 (1.06-1.46) 0.008
chemotherapy suggesting a potentially significant role for completely 30-day readmission
resected early stage NSCLC with safety and compliance. Additionally, at least
10ys’ follow-up for each patient was vital to investigate the long-term time- No Reference Reference
varying recurrence and mortality pattern. Yes 1.54 (1.20-1.99) 0.001
Keywords: docetaxel, carboplatin, non-small cell lung cancer, adjuvant Keywords: non-small cell lung cancer, adjuvant chemotherapy
chemotherapy

POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC MONDAY, DECEMBER 5, 2016
P1.05-048 EFFECT OF ADJUVANT CHEMOTHERAPY ON THE

P1.05-047 EARLY MORTALITY IN PATIENTS WITH NON-SMALL CELL PATTERNS AND DYNAMICS OF RECURRENCES IN RESECTED STAGE
LUNG CANCER UNDERGOING ADJUVANT CHEMOTHERAPY II(N1) LUNG ADENOCARCINOMA
Daniel Morgensztern, Pamela Samson, Saiama Waqar, Lingling Du, Byung Jo Park 1, Yong Soo Choi1, Jung Hee Lee1, Hong Kwan Kim1, Jong Ho
Siddhartha Devarakonda, Ashiq Masood, Cliff Robinson, Varun Puri, Cho1, Jae Ill Zo1, Young Mog Shim1, Sumin Shin1, Myung-Ju Ahn2, Jin Seok Ahn2,
Ramaswamy Govindan Keunchil Park2, Jhingook Kim1
1
Washington University School of Medicine, St. Louis/MO/United States of America Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of, 2Division
Background: Although adjuvant chemotherapy improves survival in patients of Hematology-Oncology, Department of Medicine, Samsung Medical Center,
with completely resected non-small-cell lung cancer (NSCLC) compared Sungkyunkwan University School of Medicine, Seoul/Korea, Republic of
to surgery alone, it is also associated with potentially disabling or lethal

Background: Although the complete surgical resection in most cases of the

non-small cell lung carcinoma with N1 involvement is feasible, a considerable
number of patients develop recurrence and the disease course is highly
variable. Timing and pattern of recurrence are essential to explain strong
prognostic heterogeneity, however, research focusing on these subjects
have rarely been reported. We investigated the patterns of recurrences and
event rates over time in patients with completely resected N1-stageII lung
adenocarcinoma. Methods: We retrospectively reviewed the medical records
of 333 patients who underwent a complete surgical resection for N1-stage II
lung adenocarcinoma. Survival curves were generated using the Kaplan-Meier
method, and the event dynamics was estimated using the hazard function.
Results: The median recurrence-free survival was 36.8 months. The life table
survival analysis showed that the 1-year, 3-year and 5-year recurrence free
survival rates were 85.1%, 50.2% and 36.6%, respectively. Approximately
151(45.2%) patients experienced recurrence, and the patterns of recurrences
included loco-regional in 41 patients (27.2%), distant in 68 (45.0%), and
both in 42 (27.8%). Most commonly involved organs were the lung (n=77,
47.0%), followed by lymph nodes (n=41, 27.2%), bone (n=31, 20.5%), and brain
(n=30, 19.9%). There were 228 patients received adjuvant chemotherapy.
Patients treated with adjuvant chemotherapy showed better recurrence free
survival (chemotherapy group vs non-chemotherapy group; median survival
42.5 months vs 25.4 months), and post-recurrence survival(chemotherapy
group vs non-chemotherapy group; median survival 39.8 months vs 22.6 Conclusion: FDG-PET/CT may be used as a predictive tool to identify patients
months) compared to those of patients without adjuvant chemotherapy. with advantage of neoadjuvant EGFR-TKI treatment in resectable NSCLC.
The multivariate analysis revealed that adjuvant chemotherapy was
significantly correlated with recurrence free survival (p=0.004) and post Keywords: neoadjuvant, Surgery, EGFR-TKI
recurrence survival (p=0.001). Patients underwent adjuvant chemotherapy
had less distant (p=0.014) and less lung (p=0.045) recurrence, while there is
no difference in loco-regional (p=0.837) and brain (p=0.997) recurrence. The
recurrence hazard curve demonstrated similarly shaped and sized initial and
second peak at 16 and 24months, followed by a smaller peak at 40months. The NEOADJUVANT AND ADJUVANT CHEMOTHERAPY –
temporal distribution of the recurrence risk varied depending on adjuvant MONDAY, DECEMBER 5, 2016
chemotherapy. A visual inspection of the hazard curves suggested that the
patients without adjuvant chemotherapy exhibited earlier and higher first
P1.05-050 EXTERNAL VALIDATION OF A PROGNOSTIC MODEL
peaks with higher hazard rate over time. Conclusion: In the patients who
underwent completely resected N1-stageII lung adenocarcinoma, adjuvant
FOR SQUAMOUS-CELL LUNG CANCER AND IMPACT OF ADJUVANT
chemotherapy not only reduced the recurrence hazard, but also delayed TREATMENT IN >1,300 PATIENTS
the recurrence, altered pattern of recurrence and improved post-recurrence Emilio Bria1, Sara Pilotto1, Isabella Sperduti2, Giovanni Leuzzi3, Marco
survival. Chiappetta2, Felice Mucilli4, Giovanni Ratto5, Filippo Lococo6, Pier Luigi
Filosso7, Lorenzo Spaggiari8, Silvia Novello9, Michele Milella2, Paolo Visca2,
Keywords: recurrence dynamics, recurrence pattern, N1 adenocarcinoma, Antonio Santo1, Aldo Scarpa10, Maurizio Infante11, Giampaolo Tortora1,
adjuvant chemotherapy Francesco Facciolo2
1
University Oncology Unit, Department of Medicine, Verona/Italy, 2Regina
Elena National Cancer Institute, Rome/Italy, 3Istituto National Tumori, Milano/
Italy, 4University Hospital ‘Ss. Annunziata’, Chieti/Italy, 5 Aou ‘San Martino’ Ist,
Genova/Italy, 6Unit of Thoracic Surgery, IRCCS_Arcispedale Santa Maria Nuova,
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC Reggio Emilia/Italy, 7University of Turin, San Giovanni Battista Hospital, Torino/
Italy, 8European Institute of Oncology, Milano/Italy, 9Department of Oncology
- University of Turin, Thoracic Oncology Unit, Orbassano/Italy, 10 Department of
Pathology, Verona/Italy, 11 A.O.U.I. Di Verona, Chirurgia Toracica, Verona/Italy
P1.05-049 NEOADJUVANT ERLOTINIB TREATMENT IN PATIENTS
Background: A risk classification model able to powerfully discriminate the
WITH RESECTABLE NON-SMALL CELL LUNG CARCINOMA prognosis of resected squamous-cell lung cancer (R-SqCLC) patients (pts)
Matthijs Van Gool, Houke Klomp was developed (Pilotto JTO 2015). Herein, we validate the model in a larger
NKI-AVL, Amsterdam/Netherlands multicenter series of >1,300 R-SqCLC pts (AIRC project 14282). Methods:
R-SqCLC pts in 6 different institutions (01/2002 - 12/2012) were considered
Background: The value of neo-adjuvant therapy in patients with resectable eligible. Each patient was assigned with a prognostic score to identify the
non-small cell lung carcinoma (NSCLC) is limited. Recent advances in targeted individual risk of recurrence, on the basis of the clinico-pathological data
therapy have provided novel treatment options for NSCLC with promising according to the develop model (age, T-descriptor according to TNM 7th
results. The Epidermal Growth Factor Receptor (EGFR) is over expressed or edition, nodes, and grading). Kaplan-Meier analysis for disease-free/cancer-
may harbour activating mutations in adenocarcinoma in particular. Inhibition specific/overall survival (DFS/CSS/OS) was performed according to the
of EGFR with tyrosine-kinase inhibitor (TKI) therapy has a favourable outcome published 3-class risk model (Low: score 0-2; Intermediate: score 3-4; High:
in advanced stage patients with activating mutations. The purpose of this score 5-6). Harrell’s C-statistics was adopted for model validation. The effect
study was to prospectively evaluate 18F-FDG-PET metabolic response to of adjuvant chemotherapy (ACT) was adjusted with the Propensity Score
neoadjuvant erlotinib, in patients with resectable NSCLC. Methods: This (PS). Results: Data from 1,375 pts from 6 institutions were gathered (median
study was designed as a multicentre open-label phase II trial, performed in the age: 68 years; male/female: 86.8%/13.2%; T-descriptor 1–2/3–4: 73.3%/26.7%;
Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 nodes 0/>0: 53.4%/46.6%; stages I-II/III-IV: 71.7%/28.3%); 384 pts (34.5%)
weeks. Metabolic response evaluation was performed using FDG-PET/CT scan. underwent ACT. With a median follow-up of 55 months (95% CI 51-59), pts at
Tumour FDG uptake and changes were measured by standardized uptake Low-Risk had a significantly longer DFS in comparison with Intermediate- (HR
values (SUV). Metabolic response was classified using EORTC criteria. 1.67, 95% CI 1.40-2.01) and High-Risk (HR 2.46, 95% CI 1.90-3.19) pts, as well
Metabolic response was compared to the histopathological response and as for CSS (HR 1.79, 95% CI 1.48-2.17; HR 2.33, 95% CI 1.76-3.07) and OS (HR
survival. Results: From December 2006 until November 2010, 60 patients were 2.46, 95% CI 1.80-3.36; HR 4.30, 95% CI 2.92-6.33). C-statistics was 68.3 (95%
enrolled in this study. In 43 patients (18 male, 25 female), FDG-PET/CT scans CI 63.5-73.1), 68.0 (95% CI 63.2-72.9), and 66.0 (95% CI 61.6-71.1), for DFS, CSS
and histopathologic response monitoring were available. 14 patients (33%) and OS, respectively. 60-months DFS for Low-, Intermediate- and High-Risk
showed a metabolic response. Histopathologic examination showed a pts was 51.0%, 33.5% and 25.8%, respectively (p<0.0001). 60-months CSS
response in 13 patients (30%). In predicting histopathologic response for Low-, Intermediate- and High-Risk pts was 82.7%, 64.7% and 53.3%,
FDG-uptake showed an area under the curve of 72%. Metabolic responders respectively (p<0.0001). 60-months OS for Low-, Intermediate- and High-
show an improved overall and progression free survival in comparison to Risk pts was 56.7%, 37.9% and 30.9%, respectively (p<0.0001). A significant
patients without metabolic response. benefit in DFS was found in favor of ACT (p=0.005), with no difference in CSS
(p=0.57), although a trend in OS (p=0.16). Overall, no significant differences
for ACT were found in DFS, CSS and OS when survival was corrected with PS
analysis, although CSS and OS curves visually separate with a trend for ACT in
Intermediate- and High-Risk pts. Conclusion: The prognostic performance of
the previously developed model was validated in a larger R-SqCLC pts’ series.
Considering the overall dismal prognosis of such disease, the efficacy of ACT Saitama/Japan, 4Japan Lung Cancer Research Group, Fukuoka/Japan
requires to be clearly established for Intermediate- and High-Risk pts, as well
as that should be questioned for Low-Risk pts. Background: The Eighth Edition of the TNM Classification (TNM 8th) for
non-small cell lung cancer (NSCLC) proposes a more detailed classification of
Keywords: validation, ADJUVANT, squamous, Prognosis primary tumor diameter (T). Tegafur-uracil (UFT) improves survival in patients
with stage I adenocarcinoma of the lung based on the results of Japan Lung
Cancer Research Group (JLCRG: Kato H, et al. N Engl J Med. 2004). However, it
is controversial whether the effect of UFT on survival in each T category be the
same when TNM8th is adopted. Methods: This exploratory analysis was
performed on the subgroup of 979 eligible patients in JLCRG study. The hazard
MONDAY, DECEMBER 5, 2016 ratio and the 95% confidence interval (CI) for overall survival in each T
category of TNM 8th were estimated using stratified Cox proportional hazards
models, stratified by sex and age. The overall survival in each T category was
P1.05-051 SAFETY AND COMPLIANCE DATA OF THE PHASE III estimated by the Kaplan-Meier method. Results: The UFT group and the
STUDY OF ADJUVANT CHEMOTHERAPY IN COMPLETELY RESECTED observation group were reanalyzed based on the new classifications of T
P-STAGE I NON SMALL CELL LUNG CANCER: JCOG0707 category defined by TNM8th, T1a (T, ≤1 cm), T1b (T, >1 to ≤2 cm), T1c (T, >2 to ≤3
Hideo Kunitoh1, Hiroyuki Sakurai2, Masahiro Tsuboi3, Masashi Wakabayashi4, cm), T2a (T, >3 to ≤4 cm), T2b (T, >4 to ≤5 cm), and T3 (T, >5 to ≤7 cm). The major
Morihito Okada5, Kenji Suzuki6, Norihiko Ikeda7, Mitsuhiro Takenoyama8, prognostic factors did not differ significantly between these two groups in
Yasuhisa Ohde9, Makoto Takahama10, Katsuo Yoshiya11, Isao Matsumoto12, each T category. The benefits of UFT on overall survival varied in each T
Motohiro Yamashita13, Takashi Marutsuka14, Hiroshi Date15, Yasuki Saito16, category (Table 1).
Yoshinori Yamashita17, Norihito Okumura18, Shun-Ichi Watanabe19, Hisao
Asamura20
1
Medical Oncology, Japanese Red Cross Medical Center, Tokyo/Japan, 2Thoracic
Surgery, National Cancer Center Hospital, Tokyo/Japan, 3Nationa Cancer Center
Hospital East, Chiba/Japan, 4Jcog Data Center, Tokyo/Japan, 5Hiroshima University
Hospital, Hiroshima/Japan, 6Juntendo University School of Medicine, Tokyo/Japan,
7
Tokyo Medical University Center Hospital, Tokyo/Japan, 8National Kyushu Cancer
Center, Fukuoka/Japan, 9Shizuoka Cancer Center, Shizuoka/Japan, 10 Osaka City
General Hospital, Osaka/Japan, 11Niigata Cancer Center Hospital, Niigata/Japan,
12
Kanazawa University School of Medicine, Kanazawa/Japan, 13National Hospital
Organization Shikoku Cancer Center, Matsuyama/Japan, 14Kumamoto Chuo
Hospital, Kumamoto/Japan, 15Kyoto University Hospital, Kyoto/Japan, 16National
Hospital Organization Sendai Medical Center, Sendai/Japan, 17National Hospital
Organization Kure Medical Center, Kure/Japan, 18Kurashiki Central Hospital,
Kurashiki/Japan, 19National Cancer Center Hospital, Tokyo/Japan, 20 Keio University
School of Medicine, Tokyo/Japan
Background: Post-operative UFT (tegafur/uracil) has been shown to prolong

survival of Japanese patients (pts) with completely resected, pathological
(p-) stage I (T1> 2 cm) non small cell lung cancer (NSCLC). This trial aimed at
estimating the efficacy of S-1 (tegafur/gimeracil/oteracil) compared to UFT
as adjuvant therapy in this population. Methods: Eligible pts had undergone
complete resection with lymph node dissection for p-stage I (T1-2N0M0,
T1> 2 cm, by 5th Edition UICC TNM) NSCLC, within 56 days of enrollment. Pts
Conclusion: UFT tended to improve survival in each T category defined by
were randomized to receive either oral UFT 250mg/M2/d for 2 years (Arm
TNM8th, except for T1b, when compared to surgery alone.
A), or oral S-1 80mg/M2/d for 2 weeks followed by 1 week of rest, for 1 year
(Arm B). The initial primary endpoint was overall survival (OS). Based upon Keywords: tegafur-uracil, lung adenocarcinoma, TNM Classification,
the results of monitoring in Jun. 2013, which showed the combined OS of the postoperative adjuvant chemotherapy
2 arms better than expected (4-year OS of 91.6% vs. presumed 5-year OS of
70-76.5%), the study was judged to be underpowered. The study protocol was
amended so that the primary endpoint was relapse-free survival (RFS). With a
calculated sample size of 960, this study would detect the superiority of Arm
B over Arm A with power 79% and a one-sided type I error of 0.05, assuming POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
the 5-year RFS of 75% in Arm A and the hazard ratio of 0.75. Results: From MONDAY, DECEMBER 5, 2016
Nov. 2008 to Dec. 2013, 963 pts were enrolled: median age 66 (range: 33 to
80), male 58%, adenocarcinoma 80%, p-T1/T2 46%/54%. Only 2 pts received
pneumonectomy. All pts had completed protocol therapy. >Grade 3 toxicities P1.05-053 IMPACT OF GENDER DIFFERENCE ON ADJUVANT
(hematologic/nonhematologic) were observed in 15.9 (1.5/14.7) % in Arm CHEMOTHERAPY AFTER RADICAL RESECTION IN PATIENTS WITH
A, and in 14.6 (3.6/11.9) % in Arm B, respectively. In Arm A, 59.5% of the pts NON-SMALL CELL LUNG CANCER
completed protocol therapy, and 70.7% received UFT for >1 year, which was
Lu Yang 1, Xiaoyu Zhai2, Wang Ziping 3
comparable to prior studies. In Arm B, 54.7% completed protocol therapy, and 1
Department of Medical Oncology, Peking Union Medical College, Beijing/China,
69.9% received S-1 for > 6 months. There were 4 cases of on-protocol deaths, 2
Department of Medical Oncology, Cancer Hospital,chinese Academy of Medical
probably of cardio-vascular origin: 1 in Arm A and 3 in Arm B. Based on the Sciences & Peking Union Medical College, Beijing/China, 3Department of Medical
2nd interim analysis in Sep. 2015, the data and safety monitoring committee Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union
recommended the follow-up of pts without unmasking of treatment arms. Medical College, Beijing/China
Estimated combined 2-year OS and RFS were 97.3% and 89.6%, respectively.
Conclusion: Both post-operative adjuvant therapies were feasible, with Background: Gender was an important prognostic factor in patients with
similar compliances. Main results will be available in 2019. advanced non-small cell lung cancer (NSCLC). However, there are few studies
reporting the impact of gender difference on the efficacy of adjuvant
Keywords: Surgery, non small cell lung cancer, adjuvant chemotherapy, Phase chemotherapy (ACT) in NSCLC patients. Methods: 900 patients (584 men
III study and 316 women) who received post-operative ACT in the Cancer Hospital
of the Chinese Academy of Medical Sciences between 2001 and 2013 with
complete records in the database of the hospital were analyzed in this study
for analysis. The primary end point was disease-free survival (DFS) in terms
of gender. Survival analysis was performed using Kaplan–Meier estimates,
log-rank tests and Cox’s proportional hazards regression analysis. Propensity
MONDAY, DECEMBER 5, 2016 score matching (PSM) was used, and survival analysis of the match data were
carried out. Results: There was no significant difference in DFS between
the two groups in terms of gender before propensity score was matched
P1.05-052 AN EXPLORATORY ANALYSIS OF POSTOPERATIVE (105.857 weeks [95%CI 86.699, 125.015] vs. 95.714 months [95%CI 81.905,
ADJUVANT CHEMOTHERAPY WITH TEGAFUR-URACIL ON SURVIVAL 109.523], P=0.575). Furthermore, no significant impact of gender on DFS was
FOR LUNG ADENOCARCINOMA observed between the PS-matched groups (102.429 weeks [95%CI 80.078,
Masahiro Tsuboi1, Chikuma Hamada2, Harubumi Kato3, Mitsuo Ohta4 124.779] vs. 99.143 weeks [95%CI 66.539, 131.746], P=0.893). Conclusion: The
1
Nationa Cancer Center Hospital East, Chiba/Japan, 2Tokyo University of Science, results suggest that gender was not a prognostic factor on ACT after radical
Tokyo/Japan, 3Department of Thoracic Surgery, Niizashiki Central General Hospital, resected NSCLC. However, these conclusions are limited by the nature of this

retrospective study, and therefore prospective trials are required for further of these patients were reviewed carefully. The median age was 66.4 years
verification. with 512 stage IA and 281 stage IB. Histopathologically, there were 590
adenocarcinoma, 150 squamous cell carcinoma, 32 large cell carcinoma,
Keywords: gender, Non-small-cell lung cancer, adjuvant chemotherapy and 21 other histology cases. (Surgical procedure was segmentectomy,
lobectomy, and pneumonectomy for 46, 588, and 8 patients, respectively.
Clinicopathological factors such as smoking history, histology, pathological
vascular invasion (v), and lymphatic vessel invasion (ly) were analyzed.
Results: Recurrence occurred in 132 cases. Multivariate analysis showed
NEOADJUVANT AND ADJUVANT CHEMOTHERAPY – that T factor, v(+), ly(+), and smoking history have statistical significance
MONDAY, DECEMBER 5, 2016 with recurrence. n pT1a and T2a cases, there were no statistical significance
between recurrence and pathological ly(+) and/or v(+). But only in T1b cases,
ly(+) and/or v(+) had statistical significance with recurrence. Conclusion: We
P1.05-054 ADJUVANT CHEMOTHERAPY UPTAKE IN PATIENTS
identified that T factor, v, ly, and smoking history were predictive factors for
WITH NSCLC AFTER COMPLETE RESECTION: SINGLE INSTITUTION/ recurrence in stage IA and IB NSCLC patients. Because of good prognosis, pT1b
SINGLE AREA EXPERIENCE patients whose both v and ly were negative may not take UFT as adjuvant
Vitezslav Kolek 1, Ivona Grygarkova1, Juraj Kultan1, Petr Jakubec1, Marek chemotherapy.
Szkorupa2, Jiri Klein2, Cestmir Neoral2, Josef Skarda3, Tomas Tichy3, Zdenek
Kolar3 Keywords: NSCLC, stage IA and stage IB, recurrence
1
Dept. of Respiratoty Medicine, University Hospital, Olomouc/Czech Republic,
2
Dept. of Surgery, University Hospital, Olomouc/Czech Republic, 3Dept. of
Molecular Pathology, University Hospital, Olomouc/Czech Republic
Background: Adjuvant chemotherapy (AC) is recommended in patients (pts) POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
RECURRENCE –
with stages IB (tumour of ≥4 cm in diameter), IIA, IIB, and IIIA of non-small cell MONDAY, DECEMBER 5, 2016
lung cancer (NSCLC) after complete resection. According to metaanalyses it
prolongs survival of pts in good PS and age less than 75 years. The selection of
patients is influenced by the limited profit of AC, possible toxicity and the lack P1.05-056 INCREASED RISK OF POSTOPERATIVE RECURRENCE IN
of predictive biomarkers. There are only few retrospective studies describing EGFR-POSITIVE STAGE IA TO IB INVASIVE LUNG ADENOCARCINOMA
routine utilization of AC in specified areas. Presented AC uptake in stages II Masaoki Ito 1, Yoshihiro Miyata1, Kei Kushitani2, Tomoharu Yoshiya1, Yasuhiro
and III varies from 20 % to 24% in Canada and USA. . Methods: A retrospective Tsutani1, Kazuo Konishi1, Yukio Takeshima2, Morihito Okada1
study of AC uptake in pts with NSCLC from a Moravian region with 600.000 1
Department of Thoracic Surgery, Hiroshima University Hospital, Hiroshima/Japan,
inhabitants was conducted, evaluation period was 2006-2013. Treatment 2
Department of Pathology, Hiroshima University Hospital, Hiroshima/Japan
strategy of all patients was discussed by surgeons and pneumo-oncologists
on the interdisciplinary tumour boards before and after surgery. Uptake Background: Somatic mutations of EGFR represent one of the most frequent
and compliance of AC was evaluated according to age, sex, TNM stages, type genetic aberrations in lung adenocarcinoma and response to tyrosine kinase
of surgery and other cofactors. AC was given in regimens using doublets of inhibitors (TKIs) has been favourable in EGFR-positive and advanced lung
platinum with vinorelbine (rarely gemcitabine or paclitaxel). Vinorelbine was adenocarcinoma patients. The prognostic significance of EGFR mutations as
applied both intravenously (25 mg/m2) and orally (60 - 80 mg/m2). The choice oncogenic driver mutations in early-stage lung adenocarcinoma has yet to
of cisplatinum (80mg/m2) or carboplatinum (AUC 5) was based on patient be determined. We aimed to evaluate the oncological significance of EGFR
preference, PS and comorbidities. . Results: Out of all 1557 pts with lung mutations in early-stage lung adenocarcinoma Methods: Four hundred and
cancer, NSCLC was present in 1293 pts. 308 pts underwent curative-intent seventy-three consecutive lung adenocarcinoma patients who underwent
surgery and complete resection was achieved in 295 pts. 226 pts were pts with surgical resection for pathological N0M0 disease, between January 2007 and
stages IB, II and IIIA and AC was applied in 183 pts (80.1%), in 34 (18.6 %) pts December 2013, were retrospectively reviewed. The prognostic significance of
together with neoadjuvant chemotherapy. AC was not applied in 43 (19.9 %) EGFR mutation status was evaluated in 407 cases from these patients. Overall
pts after radical surgery due to worse PS, comorbidities, complications after survival (OS) and recurrence-free interval (RFI) curves were estimated using
surgery or patient´s refusal. The mean age of pts with AC was 65 years, 66,7% the Kaplan-Meier method and compared using a log-rank test. Univariate
were men, 48,9 % women, 49,9 % were current smokers, 40,0% ex-smokers and multivariate analyses were performed using a Cox proportional hazards
and 10,1 % non-smokers. Age, sex and smoking habits were not statistically model. Results: There was no statistical significance in the 5-year OS (89.3
different between pts with and without AC. Compliance with AC was very vs. 95.3%, P = .20, HR = 1.605) or RFI (86.5 vs. 93.5%, P = .06, HR = 1.956) rates
good, 82% of pts accomplished planned therapy. Conclusion: The optimal between the EGFR-positive (n=183) and EGFR-negative (n=224) groups.
uptake of AC in routine practice depends on the intensive communication Considering the risk of recurrence and positive EGFR mutation status, OS and
between the patient, surgeons and pneumoocologists. The individual decision RFI rates were subsequently calculated among specific histological subtypes.
is important in a context to the patients´ health status, tumour parameters After adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma
and the potential risk/ benefit of therapy. Study was supported by grant AZV (MIA), and invasive mucinous adenocarcinoma (IMA) cases were excluded,
16-32318A all analysed cases were ≤5.0 cm in tumour diameter and were classified as
pathological Stage IA-IB. Among specific histological subtypes, the 5-year
Keywords: non-small cell lung cancer - surgery - adjuvant chemotherapy RFI (81.5 vs. 92.4%, P = .04, HR = 2.160) but not OS rate (86.8 vs. 94.3%, P =
-utilization in practice .31, HR = 1.499) was significantly poorer in EGFR-positive cases compared
to EGFR-negative cases. Univariate analysis, excluding AIS, MIA, and IMA,
identified a pathological tumour size of >3.0 cm, a highly malignant subtype
(micropapillary or solid predominant adenocarcinoma), pleural/lymphatic/
vascular invasion, and a positive EGFR mutation status as significant negative
RECURRENCE – predictive factors for RFI. Multivariate analysis confirmed pleural invasion
MONDAY, DECEMBER 5, 2016 and a positive EGFR mutation status as independent negative predictive
factors for RFI. Conclusion: EGFR mutation status is a predictive factor for
postoperative recurrence in early-stage lung adenocarcinoma, with the
P1.05-055 RISK FACTORS OF POSTOPERATIVE RECURRENCE IN
exception of AIS, MIA, and IMA. The risk of recurrence should be considered
STAGE IA AND IB PATIENTS with EGFR mutation status and predominant histological subtype in resected
Fumihiko Hoshi1, Akira Sakurada1, Toru Hasumi2, Tetsu Sado2, Masafumi early-stage lung adenocarcinoma patients.
Noda1, Yasushi Matsuda1, Shunsuke Eba1, Hideki Mitomo1, Takeo Togo1,
Masato Katahira1, Yoshinori Okada1 Keywords: Early-stage, Surgery, EGFR, Adenocarcinoma
1
Tohoku University Hospital, Miyagi/Japan, 2 Sendai Medical Center, Sendai/Japan
Background: The 5-year survival rates of the patients with pathological stage
IA and IB NSCLC have been reported 86-93% and 67-84%, respectively. Among
stage I disease, patients with stage IA of tumor diameter over 20 mm as well POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
RECURRENCE –
as stage IB are recommended to take oral UFT as adjuvant chemotherapy for MONDAY, DECEMBER 5, 2016
2 years in Japan. Even after complete resection and such adjuvant therapy,
we still observe recurrence at a certain rate. Identifying clinicopathological
factors which is associated with recurrence would be beneficial to establish P1.05-057 PREDICTION OF EARLY RECURRENCE IN PATIENTS WITH
alternative strategy. The purpose of this study is to identify the predictive STAGE I AND II NON-SMALL CELL LUNG CANCER USING FDG PET
factors for recurrence in the patients with stage I NSCLC. Methods: A total QUANTIFICATION
of 742 stage I NSCLC patients who underwent complete resection in our Michael Arvanitakis1, Irene Burger2, Seraina Steiger3, Beate Sick4, Walter
hospital from 1996 to 2012 were retrospectively analyzed. Medical records Weder 1, Sven Hillinger 1
1
Thoracic Surgery, University Hospital, Zürich/Switzerland, 2Nuclear Medicine therapy were prognostic factors for PRS. In the patients who underwent
and Radiology, University Hospital, Zürich/Switzerland, 3Radiology, University treatment for recurrence, bone metastasis and treatment with EGFR TKIs
Hospital, Zürich/Switzerland, 4Engineering, Biostatistics, Zurich University of were independent prognostic factors. Although further validation is needed,
Applied Sciences, Winterthur/Switzerland this information is important for future design of clinical trials for therapy
after recurrence.
Background: Although surgical resection remains the optimal treatment for
early-stage NSCLC, up to 50% of patients with stage I and II relapse and die Keywords: NSCLC, prognostic factor, Surgery, post-recurrence
within 5 years after curative resection. Therefore prognostic markers are
important as these patients might benefit from adjuvant therapy. The goal of
this study was to evaluate established PET quantification metrics including:
maximal standard uptake volume (SUVmax), metabolic tumor volume (MTV)
and total lesion glycolysis (TLG) as prognostic markers for early recurrence POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
and overall survival in resected early stage lung cancer. Methods: Between RECURRENCE –
January 2003 and December 2010 182 surgically resected patients with stage
I-II NSCLC who underwent 18 F FDG PET/CT less than one month prior to
surgery have been evaluated. All patients had at least 5 years of follow-up. Cox P1.05-059 FACTORS ASSOCIATED WITH RECURRENCE AND
proportional hazard model was used to determine the association between SURVIVAL IN PATIENTS WITH CURATIVELY RESECTED STAGE IA
variables and survival respectively time to recurrence. For the multivariate ADENOCARCINOMA OF THE LUNG
analysis the following variables have been included: tumor size on CT, age
Masahiko Harada, Hirotoshi Horio
tumor stage, histology, SUVmax, TLG (for TLG42% (threshold at 42% SUVmax)
Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center
and TLG2.5 (cut-off at SUV 2.5) and MTV42% and MTV2.5). To identify high-risk
Komagome Hospital, Tokyo/Japan
patients we used survival trees. Results: 133 patients were included, 71
with adeno carcinoma, 62 with squamous cell carcinoma. TLG2.5 and MTV2.5 Background: Even when meticulously clinically and pathologically studied,
values have been a significant prognostic factor for recurrence (P<0.0001). completely resected stage IA adenocarcinoma of the lung does recur.
Patients with a MTV2.5 above 42 cm3 had a mean recurrence time of 0.8±0.9 However, there are few data regarding the patterns of recurrences and their
years, while patients with MTV2.5 ≤ 42 cm3 recurred within 2.8±1.3 years. risk factors in this population. Therefore, this study characterizes cancer
Using the survival tree models TLG42% has been the first choice variable for recurrence and its risks and assesses recurrence-free survival in patients with
discriminating high risk patients for DOD (dead of disease) independent from curatively resected stage IA adenocarcinoma. Methods: Between January 1990
histological type, whereas MTV2.5 has been the first choice for DOD in adeno and December 2005, a total of 214 patients were given a final diagnosis of
carcinoma patients. Conclusion: TLG and MTV may be useful prognostic pathologic stage IA (UICC-7) adenocarcinoma of the lung. The medical records
variables in stage I-II NSCLC depending on the tumor type. Using a cut-off of these patients were retrospectively reviewed with regard to patient
at 42 cm3 for early stage adenocarcinoma patients a high risk of recurrence characteristics, tumor pathologic findings and follow up status. Survival was
within one year might be identified and adjuvant therapy following surgical analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional
resection could improve outcome for those patients. hazards analysis. Results: The median follow up after curative resection
was 83 months. Cancer recurred in 28 patients (13%). Among them, local
Keywords: prognostic marker, PET-CT, Thoracic Surgery, early stage NSCLC
recurrence occurred in 10 patients (5%), whereas distant recurrence occurred
in18 patients (8%). Recurrence earlier and later than 5 years after surgery was
in 15 patients (7%) and in 13 patients (6%), respectively, with nearly constant
risk. At 5 years after index resection, 175 patients (82%) were alive without
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC evidence of cancer recurrence, 11 patients (8%) had experienced recurrence
RECURRENCE – of cancer but still alive and 11 patients (5%) had died with non-cancer
causes. Recurrence-free 5- and 10-year survival rates were 92.5 and 70.0%,
respectively. Univariate analysis revealed five significant prognostic factors:
P1.05-058 PROGNOSTIC FACTORS OF POST-RECURRENCE gender (p=0.0177); lepidic component (p =0.0007); tumor location (p=0.0099);
SURVIVAL IN RESECTED STAGE I NON-SMALL CELL LUNG CANCER pleural invasion (p=0.0274) and lymphatic or vascular vessel invasion (LVI) (p<
0.0001). Multivariate analysis revealed lepidic component, tumor location,
Yasuaki Kubouchi, Yoshiteru Kidokoro, Takashi Oono, Yohei Yurugi, Makoto and LVI as significant factors. Hazard ratios for recurrence were 0.381 for
Wakahara, Ken Miwa, Kunio Araki, Yuji Taniguchi, Hiroshige Nakamura having lepidic component (95% CI, 0.147-0.979; p= 0.0451), 0.361 for right sided
Department of Surgery, Division of General Thoracic Surgery, Tottori University, tumor (95% CI, 0.188-0.692; p= 0.0022), and 2.785 for having LVI (95% CI, 1.392-
Faculty of Medicine, Tottori/Japan
5.555; p= 0.0038). Conclusion: Surgically “cured” stage IA adenocarcinoma of
Background: Recurrence after surgical resection is a major obstacle in the lung recurs. Our analyses indicate no-lepidic component, tumor location,
the cure and long term survival, and has become the most common cause LVI as an independent indicator for cancer recurrence. Identifying high-risk
of death. However prognostic factors and efficacy of the therapy after patients for recurrence will simplify decision making for postoperative
recurrence remain controversial. We evaluated the prognostic factors treatment strategies.
of post-recurrence survival (PRS) in patients of resected stage I NSCLC. Keywords: recurrence, adenocarcinoma of the lung, lymphovascular invasion,
Methods: Of the 551 patients who underwent a complete resection for p-stage IA
stage I NSCLC between 2005 and 2013, 89 (16.2%) patients who experienced
a postoperative recurrence were selected for this retrospective study.
Case of preoperative therapy and death within 30 days of operation were
excluded. Clinicopathological factors were analysed for PRS by univariate
and multivariate analyses. Univariate and multivariate analyses were
performed by using the Cox proportional hazards model. Results: 89 patients
experienced recurrence during a median follow-up period of 54.0 months. The Miscellaneous –
median recurrence free interval (RFI) was 16.0 months. The 1-year PRS and MONDAY, DECEMBER 5, 2016
3-year PRS were 65.6% and 44.7%, respectively. The pattern of recurrence
was loco-regional in 24(27.0%), and distant in 65(73.0%). The most common
organ sites of recurrence were contralateral lung in 42 patients, the ipsilateral P1.05-060 ADHERENCE TO SURVEILLANCE GUIDELINES IN
thorax in 24, bone in 24, brain in 12, liver in 9. Univariate analysis indicated RESECTED NSCLC: PHYSICIAN COMPLIANCE AND IMPACT ON
that male sex (p=0.035), smoking history (p=0.034), larger tumor size over
OUTCOMES
25mm (p=0.008), stage IB (p=0.044), squamous cell carcinoma (p=0.001),
RFI within 16 months (p=0.011), presence of symptoms (p=0.001), bone Cheryl Ho, Jennifer Siegfried, Karen Remo, Janessa Laskin
metastasis (p=0.001), liver metastasis (p=0.009) and not having received Medical Oncology, BC Cancer Agency, Vancouver/BC/Canada
any treatment (p<0.001) were significant prognostic factors of worse PRS.
Background: Guidelines on resected NSCLC have varying recommendations
Multivariate analysis revealed that larger tumor size over 25mm (p=0.05), RFI
on appropriate post-operative surveillance. There is general consensus that
within 16 months (p=0.05) and no treatment for recurrence (p<0.001) were
patients require follow up q6m with clinic visits or CT scans for the first 2 y.
the independent prognostic factors for poor PRS. The result of multivariate
This study evaluated compliance with surveillance guidelines and the impact
analysis of PRS determined that post-recurrence therapy had a strong impact
on outcomes. Methods: The BC Cancer Agency provides comprehensive cancer
on PRS. Therefore, we further examined PRS in 61 patients who underwent
control for a population of 4.5 million. Inclusion criteria included referred
any post-recurrence therapy. For patients receiving treatment for recurrence,
patients from 2005-2010, resected stage Ib/II NSCLC, minimum 2 y f/u at the
bone metastasis (p=0.042) was a significant predictive factor of worse PRS,
BCCA, no prior lung cancer diagnosis. Retrospective chart review collected
while treatment with EGFR-TKIs (p=0.045) was a good prognostic factor.
baseline parameters, follow up visits, CT imaging, recurrence and death.
Conclusion: This study showed that tumor size, RFI, and post-recurrence
Results: 479 were referred and 263 were eligible. Baseline characteristics
median age 68, male 52%, current/former/never smoker 38/52/10%, stage

Ib/II 51/49%, squamous/non 30%/70%, wedge/lobectomy/pneumonectomy 2 proton beam therapy (PBT) studies with 17 patients and one carbon ion
8/76/16%, adjuvant chemotherapy 46%. Adherence to 4 interventions in 2 beam therapy (CIBT) study with 5 patients were included. Most patients in
y: clinic visits 62%, CT scans 18%, visit and/or CT 67%. Multivariate analysis non-surgical studies were medically inoperable. Treatment-related or 30-day
(MVA) for predictors of guideline adherence demonstrated only stage was post-operative mortality was 2.3%, 15.5%, 8.7%, 5.8% and 0%, respectively,
significant. Recurrence rate was 46% at 2 y with patterns of recurrence and for surgery, SABR, RFA, PBT and CIBT. Treatment-related acute exacerbation
treatment in table 1. Surveillance below vs per/above guidelines; PFS 26.6 m vs of ILD or radiation pneumonitis > grade 3 was 12%, 25%, 25%, 12.5% and
22 m (p=0.54), OS 47 m vs 41.8 m (p=0.27). 20%, respectively. For patients treated with surgery, 5-year overall survival
(OS) was 31.4% to 61.6% (median 54.2%) for patients with ILD and 70.5% to
Follow up visits 88.3% (median 83.0%) for patients without ILD. For medically inoperable
Follow up patients treated with SABR, 2 to 3-year OS was 0% to 53.8% (median 48.8%)
and/or CT scans
visits and/or p for patients with ILD and 54% to 86.7% (median 70.8%) for patients without
per or above
CT scans below value ILD. Studies that included only patients with idiopathic pulmonary fibrosis
guidelines
guidelines n=87 reported higher treatment-related toxicity compared to other studies.
n=176
Conclusion: An elevated level of treatment-related toxicity is observed in
Recurrence within patients treated for ES-NSCLC with co-existing ILD. Medically inoperable
32 (37%) 88 (50%)
2 years patients experienced high levels of treatment-related mortality. For surgery
Method of and SABR, overall survival was worse for patients with ILD compared to those
0.41 without ILD.
detection
Surveillance 18 (56%) 41 (47%) Keywords: interstitial lung disease, Surgery, stereotactic ablative radiation
therapy, non-small cell lung cancer
Patient 14 (44%) 47 (53%)
Distribution of
0.16
recurrence
Second primary 1 (3%) 2 (2%) MISCELLANEOUS –
Locoregional
10 (31%) 14 (16%)
recurrence only
P1.05-062 IS LUNG MICROWAVE THERMOABLATION A VALID
Metastatic 21 (66%) 73 (82%) ALTERNATIVE TO SURGERY IN HIGH RISK PATIENTS? A PROPENSITY
MATCH ANALYSIS
Curative intent
treatment at 5 (16%) 6 (7%) 0.16 Paolo Mendogni1, Davide Tosi1, Alessandro Palleschi1, Lorenzo Rosso1, Ilaria
recurrence Righi1, Matteo Montoli1, Francesco Damarco1, Claudia Bareggi2, Cristina
Marenghi3, Mario Nosotti1
Palliative 1
7/27 (26%) 32/82 (39%) 0.25 Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda
chemotherapy - Ospedale Maggiore Policlinico, Milan/Italy, 2Oncology, Fondazione IRCCS Ca’
Granda - Ospedale Maggiore Policlinico, Milan/Italy, 3 Anesthesiology and Critical
Conclusion: Compliance with follow up recommendations for resected NSCLC Care, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan/Italy
was 67% in our study. Guideline conformity did not increase the rate of
curative intent therapy at recurrence due to metastatic presentation nor did Background: Surgery is considered the best treatment in Stage I non small
it increase the proportion of patients treated with palliative chemotherapy. cell lung cancer. Local non–surgical therapies (radiotherapy, thermoablation)
Better adjuvant treatment and surveillance options need to be developed for are becoming valid alternative to surgery in high risk patients (poor cardiac
resected NSCLC. or pulmonary function, elderly patients). Methods: Patients submitted in
our Department to Microwave thermoablation (MW) were compared with a
Keywords: Surveillance, recurrence, guidelines, Post operative NSCLC cohort of patient submitted to lung lobectomy in the same period of time,
abstracted from our database with a propensity match method. The study
was retrospective on data recorded prospectively. Primary endpoint was
overall survival. Results: From June 2009 to October 2014 in our Department,
36 patients underwent MW for Stage I non-small cell lung cancer (NSCLC)
MISCELLANEOUS – or lung metastasis. From our database were abstracted 41 patients with
MONDAY, DECEMBER 5, 2016 a propensity match method, submitted to lung lobectomy. Two groups
were comparable by age, diagnosis, stage and gender. MW group resulted
elder than Surgery group (75,5 vs 72,2 years; p<0,001). Lesion diameter was
P1.05-061 INCREASED TREATMENT-RELATED TOXICITY IN
greater in MW group (20,9 vs 26,5 cm; p<0,001). Overall survival, analyzed by
PATIENTS WITH EARLY-STAGE NON-SMALL CELL LUNG CANCER actuarial survival curve, was comparable (Logrank test p=0,2). Conclusion: In
AND CO-EXISTING INTERSTITIAL LUNG DISEASE our experience, in a propensity match evaluation, lung MW thermoablation
Hanbo Chen1, Alexander Louie1, Esther Nossent2, Gabe Boldt3, David Palma1, resulted non inferior than lung lobectomy in terms of overall survival. Even
Suresh Senan4 though surgery is still considered the first choice in patients affected by Stage
1
Radiation Oncology, London Health Sciences Centre, London/ON/Canada, 2VU I NSCLC or lung metastasis, lung MW thermoablation is confirmed as a valid
University Medical Center, Amsterdam/Netherlands, 3Library Services, London alternative treatment in high risk patients. Randomized prospective studies
Regional Cancer Program, London/ON/Canada, 4Radiation Oncology, VU University are mandatory.
Medical Center, Amsterdam/Netherlands
Keywords: Microwave; Thermoablation; Lobectomy
Background: Treatment options for early-stage non-small cell lung cancer
(ES-NSCLC) are generally well-tolerated. Minimally-invasive surgical
techniques, stereotactic ablative radiotherapy (SABR) and radiofrequency
ablation (RFA) can all achieve post-treatment mortality of <1% in clinical
trial settings. There has been increasing evidence to suggest that patients POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
with interstitial lung disease (ILD) suffer severe toxicity after treatment for MISCELLANEOUS –
NSCLC. Treatment-related toxicity may result in death and may take the form
of acute exacerbations of existing ILD following surgery or RFA, or severe
radiation pneumonitis following SABR. Methods: We performed a systematic P1.05-063 MULTICENTER OBSERVATIONAL STUDY OF PATIENTS
review of literature in compliance with PRISMA guidelines to investigate WITH RESECTED EARLY-STAGED NSCLC, WHO WERE EXCLUDED
the rate of treatment-related toxicity and mortality following treatment FROM AN ADJUVANT CHEMOTHERAPY TRIAL
for ES-NSCLC. The Medline and EMBASE databases were queried from
Tomoyuki Hishida1, Masahiro Tsuboi1, Kiyotaka Yoh2, Kazuya Takamochi3,
respective dates of inception to January 2016. Treatment modalities included
Hiroyuki Sakurai4, Yasushi Goto5, Takehiro Shukuya6, Yasuo Ohashi7, Hideo
in the search strategy were surgery, SABR, RFA, particle beam therapy
Kunitoh8
and conventionally-fractionated radiotherapy. Results were summarized 1
Thoracic Surgery, National Cancer Center Hospital East, Chiba/Japan, 2Thoracic
with weighted statistics according to the sample size of individual studies.
Oncology, National Cancer Center Hospital East, Chiba/Japan, 3General Thoracic
Results: A total of 3,054 unique records were screened and 282 full texts were
Surgery, Juntendo University School of Medicine, Tokyo/Japan, 4Thoracic Surgery,
reviewed. Forty-nine journal articles were included in the final analysis, with National Cancer Center Hospital, Tokyo/Japan, 5Thoracic Oncology, National Cancer
92% of studies being retrospective in design. Thirty surgical studies with 1716 Center Hospital, Tokyo/Japan, 6Thoracic Oncology, Juntendo University School
patients, 13 SABR studies with 122 patients, 3 RFA studies with 46 patients, of Medicine, Tokyo/Japan, 7Chuo University, Tokyo/Japan, 8 Medical Oncology,
Japanese Red Cross Medical Center, Tokyo/Japan
Background: From Nov. 2008 to Dec. 2013, the Japan Clinical Oncology Group most would obtain a PET/CT to rule out distant metastasis (n=135, 97%)
(JCOG) conducted a randomized phase III trial (JCOG0707), which compared and an MRI to rule out brain metastases (n=76, 55%) but in the absence of
the survival benefit of UFT and S-1 for completely resected pathological (p-) radiographic lymph node involvement most would not stage the mediastinum
stage I (T1>2 cm and T2 in the 6th TNM classification) NSCLC and a total of 963 by bronchoscopy or mediastinoscopy prior to resection (n=90, 65%). Many
patients were enrolled. Recently, there is a growing concern that those who preferred obtaining multiple biopsies of separate lesions (n=139, 63%) and
participated in clinical trials are highly selected and do not represent the “real- genetic testing of these lesions (n=146, 66%) to assess their histologic and
world” population. Hereby, we conducted a multicenter observational study genetic agreement. In the case that surgery was not offered or declined,
of patients excluded from JCOG0707 trial during the study period. Methods: more respondents recommended radiation (n=114, 52%) than those who
We retrospectively collected and analyzed the patients’ backgrounds, tumor did not (n=50, 23%) or were uncertain (56, 26%). Similarly, in the absence of
profiles, post-surgical treatment of the patients who underwent R0 resection surgery or radiotherapy, slightly more respondents recommended systemic
of p-stage I (T1>2cm and T2 in TNM 6th) NSCLC by lobectomy or larger lung chemotherapy (n=83, 38%) than those who did not (n=79, 36%) or those who
resection but were excluded from JCOG0707 from Japanese multi-centers. were uncertain (n=59, 27%). Conclusion: Although most respondents favored
Results: Of the 48 institutions which took part in JCOG0707, 34 (enrolling 917 surgery when feasible for MFLC, many were uncertain as to the optimal
or 95.2% of all JCOG0707 patients) participated in this multicenter study, and approach for this disease. Optimal management of MFLC requires greater
5006 patients were enrolled. Among them, 2617 (52.3%) patients fulfilled evidence from studies which is currently lacking, and current strategies are
the eligibility criteria, but were not enrolled to JCOG0707 mainly due to strongly influenced by specialty bias.
patients’ decline (69.2%), or physicians’ discretion (20.5%). The accrual rate
to JCOG0707 was various by institutions (4.1 to 46.1%), but was 25.9% (917 Keywords: multifocal lung cancer, Surgery, Radiotherapy, chemotherapy
/ [917+2617]) as a whole. Total number of p-stage I and eligible patients at
each institution did not correlate the accrual rate (R2=0.003 and 0.046). In
the remaining 2389 (47.7%) patients, main ineligible reasons included the
existence of active multiple cancer (29.1%), physicians’ decision based on
the patients’ comorbidities (19.4%), delayed recovery from surgery (14.1%), MISCELLANEOUS –
and high age ≥81 years (10.7%). Majority of patients received no adjuvant MONDAY, DECEMBER 5, 2016
chemotherapy (n = 3338, 66.7%). This proportion differed according to
p-T factor (T1: 75.3% vs. T2 : 57.8%, p<0.001) and the JCOG0707 eligibility
P1.05-065 USAGE OF CHEST RADIOGRAPHY OR COMPUTED
(ineligible population: 77.6% vs. eligible population: 56.7%, p<0.001). Standard
UFT and experimental S-1 were given in 1550 (31.0%) and 21 (0.4%) patients,
TOMOGRAPHY IN POST-TREATMENT SURVEILLANCE FOR STAGE I
respectively. Among those who received adjuvant UFT, 971 (62.6%) took UFT AND II NSCLC: INFLUENCE ON SURVIVAL
for one year or longer. Conclusion: Only selected population of candidate Leonie Alberts 1, Renata Karzijn2, Frederik Hofman3, Sherif El Sharouni4,
patients, even if they met the eligibility criteria, were enrolled to JCOG0707 Elisabeth Kastelijn1, Franz Schramel5
adjuvant chemotherapy trial for early-stage NSCLC. The “excluded” patients 1
Pulmonology, St. Antonius Hospital, Nieuwegein/Netherlands, 2 St. Antonius
were mainly treated with observation alone or standard UFT treatment. Hospital, Nieuwegein/Netherlands, 3Department of Cardiothoracic Surgery, St.
Further analysis of this “excluded” population, including long-term survival, Antonius Hospital, Nieuwegein/Netherlands, 4Radiotherapy, University Medical
should be necessary for external validation of the randomized trial results. Center Utrecht, Utrecht/Netherlands, 5Department of Pulmonology, St. Antonius
Hospital, Nieuwegein/Netherlands
Keywords: Early-stage, Surgery, adjuvant chemotherapy, NSCLC
Background: Survivors of stage I and II non-small-cell lung cancer (NSCLC)
have higher risk of developing a recurrence of disease or a second primary
lung cancer compared to the general population. Post-treatment surveillance
(visits and radiological imaging) is needed for early recognition. Although
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC a myriad of international guidelines exist regarding post-treatment
MISCELLANEOUS – surveillance no consensus has derived yet. The aim of this study was to further
establish the appropriate follow-up modality: chest radiography with or
without a computed tomography (CT) scan. Methods: In this retrospective
P1.05-064 GLOBAL PRACTICE PATTERNS OF MULTIFOCAL LUNG study all patients diagnosed with a recurrence of previously treated stage
CANCER I and II NSCLC between 2008 and 2014 at St Antonius Hospital, Nieuwegein
the Netherlands, were included. We categorized patients after treatment in
Aaron Mansfield1, Konstantinos Leventakos1, Tobias Peikert2, David
two imaging modality groups: one group received only chest radiographs (CR
Midthun3, Julian Molina4, Shanda Blackmon5, Francis Nichols5, Yolanda
group) and the other group received ≥ one thoracic CT scan (CT group). The
Garces6, Christopher Hallemeier6, Sarah Kratz1, William Holland7, Charles
overall survival (OS), 1- and 3-yearssurvival and progression free survival (PFS)
Thomas3, John Mullon3, Robert Shen5, Stephen Cassivi5, Randolph Marks1,
were compared between the groups by using the Kaplan-Meier survival, the
Marie Aubry8, Alex Adjei1, Ping Yang9, Mark Allen5, Eric Edell10, Dennis Wigle5
1
log rank-test and the Cox proportional hazard model. Results: 73 patients
Medical Oncology, Mayo Clinic, Rochester/MN/United States of America,
2 were enrolled; 50 patients in the CR group and 23 patients in the CT group. The
Immunology, Mayo Clinic, Rochester/MN/United States of America, 3Pulmonary
and Ccm, Mayo Clinic, Rochester/MN/United States of America, 4 Medical
median overall survival was 22.1 months (interquartile range (IQR) = 14.2-39.2
Oncology, Mayo Clinic, Rochester/United States of America, 5Thoracic Surgery, months) in the CR group compared to 27.2 months (IQR= 18.5-53.2 months)
Mayo Clinic, Rochester/MN/United States of America, 6Radiation Oncology, Mayo in the CT group (p = 0.12). After adjustment for the Eastern Cooperative
Clinic, Rochester/MN/United States of America, 7Thoracic Diseases, Mayo Clinic, Oncology Group (ECOG) performance score and morphology was made, both
Rochester/MN/United States of America, 8Department of Laboratory Medicine and the overall survival (hazard ratio (HR) = 1.43, 95% confidence interval (CI) =
Pathology, Mayo Clinic, Rochester/MN/United States of America, 9Health Sciences 0.76-2.70, p = 0.27) and the progression free survival (HR = 1.16, 95% CI = 0.65
Research Epidemiology, Mayo Clinic, Rochester/MN/United States of America, – 2.07, p = 0.63) were not different in the CR group compared to patients in
10
Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester/MI/United States
the CT group. There was no significant difference in the 1- and 3-yearssurvival
of America
either. The 1-yearssurvival was 80% in the CR group versus 91% in the CT group
Background: Multifocal lung cancer (MFLC) is a clinical scenario that is more (HR = 5.50, 95% CI = 0.52-58.01, p = 0.16) and the 3-yearssurvival was 30%
frequently diagnosed with the increased utilization of computed tomography versus 39% (HR = 1.50, 95% CI = 0.74-3.01, p = 0.29). Conclusion: We showed
of the chest. The management of MFLC is limited by the difficulties in that follow-up with a chest radiography, in patients with earlier diagnosed
accurately staging a patient and understanding whether lesions represent and curative treated stage I and II NSCLC, did not give inferior clinical
separate primaries or metastatic disease. We sought to understand the global outcomes compared to follow-up with a CT scan. Although more investigation
practice patterns of MFLC. Methods: A questionnaire was developed and sent is needed, this study might indicate that there is no need for a CT scan as
to members of the International Association for the Study of Lung Cancer standardized follow-up.
through REDCap electronic data capture tools to assess how a hypothetical
Keywords: NSCLC stage I-II, overall survival, progression free survival,
patient with synchronous MFLC would be evaluated and treated. Responses
surveillance
were compared by specialty using the χ2 test. Results: We received 221
responses from multiple specialists (74 Thoracic Surgeons, 68 Medical
Oncologists, 32 Pulmonologists, 22 Radiation Oncologists and 25 others)
primarily from Europe (n=76) and North America (n=62). Over 87 respondents
reported 20 or more years of experience in the field. Most respondents POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
recommended surgery (n=140, 63%), but many others did not (n=39, 18%) MISCELLANEOUS –
or were uncertain (42, 19%). Surgeons (n=60/74, 81%) were significantly
more likely to recommend surgery than medical oncologists (n=37/68, 54%),
pulmonologists (n=21/32, 66%) or radiation oncologists (n=10/22, 45%; P1.05-066 IMPACT OF MICROPAPILLARY PATTERN IN NODAL
p=0.01). Lobectomy of the primarily involved lobe (n=42, 30%) and various UPSTAGING OF LUNG ADENOCARCINOMA 2CM OR LESS
combinations of segmentectomies (n=48, 34%) were the most commonly
recommended surgical approaches. Of those who recommended surgery, Hirotsugu Yamazaki, Yasuto Kondo, Masahito Naito, Hiroyasu Nakashima,

Yoshio Matsui, Kazu Shiomi, Yukitoshi Satoh determinant for MO consultation. Adjusting for sex, patients aged 41-60yrs (OR
Kitasato University School of Medicine, Sagamiharashi/Japan 2.38, CI:1.25-4.56) and 61-70yrs (OR 2.46, CI:1.35-4.49) were significantly more
likely to have a consultation versus patients >80 yrs. Other characteristics were
Background: Clinical and pathological determinations of lymph node staging not significantly associated with having a consultation. Conclusion: Although
are critical in the treatment of lung cancer. However, upstaging of nodal uptake of guideline-recommended AC is lower than expected (52.1%, CI:48.48-
status frequently is necessitated by postoperative findings. It is now being 55.62), the majority of patients had an opportunity to discuss this treatment
recognized that lung adenocarcinoma (LAC) with tumor cells arranged in a option with a MO. Patients over 80yrs were significantly less likely to have this
micropapillary pattern (MPP) is more malignant than those without such consultation.
pattern. Thus, this study was conducted to evaluate clinicopathologic
features that impact nodal upstaging in patients with small-sized(≤2cm) Keywords: lung cancer, adjuvant chemotherapy, patient decision making
LACs with MPP(LAC-MPP). Methods: We retrospectively reviewed the 182
radically resected lung adenocarcinomas at the Kitasato University Hospital,
Japan, from January 2005 to December 2015. MPP was defined as a small
papillary tumor cell tuft without an obvious fibrovascular core. Tumors with
≥1% of their tumor cells arranged in a MPP were diagnosed as LAC-MPP, MISCELLANEOUS –
while the remainders were diagnosed as conventional LAC. The histological MONDAY, DECEMBER 5, 2016
subtypes and differentiation grade of LAC were determined according to
the 4th WHO classification. The registry date of the patients with LAC and
LAC-MPP were analyzed, and the clinicopathologic profiles and surgical P1.05-068 ELDERLY PATIENTS WITH RESECTED STAGE II
outcomes of the patients were evaluated. Results: One hundred and sixty NONSMALL CELL LUNG CANCER ARE LESS LIKELY TO HAVE A
(88%) of the total 182 were LAC whereas 22(12%) were LAC-MPP. Among the CONSULTATION WITH A MEDICAL ONCOLOGIST
two groups, there is no significant difference in age, sex, smoking habit, Gail Darling 1, Shirley Li2, Ashley Farrelly3, Katharina Forster2, Kelly Wortman2,
preoperative serum CEA level, or surgical procedures. Compared with the Jennifer Stiff3, William Evans4
LAC, the LAC-MPP had worse statuses for lymphatic invasion (p=0.0096), 1
Surgery, Division of Thoracic Surgery, University of Toronto, Toronto/Canada,
pleural invasion (p=0.002), postoperative lymph node metastases (p<0.001) 2
Cancer Care Ontario, Toronto/ON/Canada, 3Cancer Care Ontario, Toronto/Canada,
4
and postoperative recurrence (p=0.002). On the other hand in clinical stages, Oncology (Medical Oncology), McMaster University, Hamilton/ON/Canada
pleural lavage cytology, and postoperative stages, there is not significant
deference statistically. Median follow up time was 48 months. The five-year Background: Adjuvant chemotherapy (AC) is guideline recommended standard
overall survival rates were 92% in LAC group and 85% in LAC-MPP, statistically of care for resected Stage II NSCLC patients in Ontario. Despite evidence of a
not significant deference (p=0.98). Also with regarding to the median significant survival benefit, uptake of AC has been lower than expected and
relapse free survival rates, no significant difference was found between has remained unchanged since 2008 at 50-55%. Factors that may preclude
two groups (p=0.14). Conclusion: The follow-up term of patients was limited use of chemotherapy include comorbid medical conditions, socioeconomic
in this study. But, we concluded that LAC-MPP should be considered as an and demographic factors and the opportunity for consultation with a medical
aggressive disease showing nodal upstage. Although lymph node metastasis oncologist (MO).
and lymphatic infiltration should be usually reported in LAC-MPP patients,
This study evaluated: 1) patient opportunity for a consultation with a MO, and
these are difficult to detect by preoperative imaging tools such as CT and
2) differences between patients who had a consultation and those who did
PET canning. Therefore, MPP could be important factor to determine the
not Methods: Stage II NSCLC adult patients diagnosed between 2010 and 2013
indications for limited resection for LAC patients even if small-sized(≤2cm)
were identified using the Ontario Cancer Registry. Complete surgical resections
LAC- MPP.
and consultation with a MO were identified using multiple administrative
Keywords: upstaging, Adenocarcinoma, micropapillary, small-sized databases. Receipt of guideline-recommended AC within 120 days after
resection, and consultation with MO within 30 days prior and 90 days after
resection were determined. Guideline-recommended AC includes platinum
based regimens, including receipt outside a Regional Cancer Center (RCC).
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC Alternative treatments were defined as non-platinum based chemotherapy
MISCELLANEOUS –
or radiotherapy. Socioeconomic and demographic characteristics were
compared between patients who received a consultation and those who did
not. Characteristics associated with receiving a consultation were assessed
P1.05-067 CONSULTATION WITH MEDICAL ONCOLOGY LESS using univariable analysis and multivariable logistic regression. Results: Of 778
COMMON IN ELDERLY PATIENTS WITH RESECTED STAGE II Stage II resected NSCLC patients who survived at least 120 days, 40.9% (n=318,
NONSMALL CELL LUNG CANCER CI: 37.40–44.42) received guideline-recommended AC, 3.0% (n=23, CI: 1.70-4.40)
received alternative treatment in an RCC, 11.2% (n=87, CI:8.95-13.50) received
Gail Darling 1, Shirley Li1, Ashley Farrelly1, Katharina Forster 1, Kelly Woltman2,
chemotherapy outside of an RCC hospital, and 45.0% (n=350, CI:41.45-48.56)
Jennifer Stiff2, William Evans2
1
of patients did not have systemic treatment after surgery. Overall, 72.9%
Cancer Care Ontario, Toronto/ON/Canada, 2Cancer Care Ontario, Toronto/Canada
(n=567) of patients had a consultation with a MO within 30 days prior or 90
Background: Adjuvant chemotherapy (AC) is guideline recommended standard days after resection. Of 350 patients who did not receive AC, 219 (62.6%) had
of care for resected Stage II NSCLC patients in Ontario. Despite evidence of a a MO consultation. Median time from resection to consultation was 29 days,
significant survival benefit, uptake of AC has been lower than expected and and did not differ between treatment groups (p=0.35). Age was a significant
has remained unchanged since 2008 at 50-55%. Factors that may preclude determinant for MO consultation. Adjusting for sex, patients aged 41-60yrs (OR
use of chemotherapy include comorbid medical conditions, socioeconomic 2.38, CI:1.25-4.56) and 61-70yrs (OR 2.46, CI:1.35-4.49) were significantly more
and demographic factors and the opportunity for consultation with a medical likely to have a consultation versus patients >80 yrs. Other characteristics were
oncologist (MO). This study evaluated: 1) patient opportunity for a consultation not significantly associated with having a consultation. Conclusion: Although
with a MO, and 2) differences between patients who had a consultation and uptake of guideline-recommended AC is lower than expected (52.1%, CI:48.48-
those who did not. Methods: Stage II NSCLC adult patients diagnosed between 55.62), the majority of patients had an opportunity to discuss this treatment
2010 and 2013 were identified using the Ontario Cancer Registry. Complete option with a MO. Patients over 80yrs were significantly less likely to have this
surgical resections and consultation with a MO were identified using multiple consultation.
administrative databases. Receipt of guideline-recommended AC within 120
Keywords: nonsmall cell lung cancer, informed decision making, adjuvant
days after resection, and consultation with MO within 30 days prior and 90 days
chemotherapy, elderly
after resection were determined. Guideline-recommended AC includes platinum
based regimens, including receipt outside a Regional Cancer Center (RCC).
Alternative treatments were defined as non-platinum based chemotherapy
or radiotherapy. Socioeconomic and demographic characteristics were
compared between patients who received a consultation and those who did POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
not. Characteristics associated with receiving a consultation were assessed MISCELLANEOUS –
using univariable analysis and multivariable logistic regression. Results: Of 778
Stage II resected NSCLC patients who survived at least 120 days, 40.9% (n=318,
CI: 37.40–44.42) received guideline-recommended AC, 3.0% (n=23, CI: 1.70-4.40) P1.05-069 STAGE II NSCLC TREATED WITH NON-SURGICAL
received alternative treatment in an RCC, 11.2% (n=87, CI:8.95-13.50) received APPROACHES: A MULTI-INSTITUTION REPORT OF OUTCOMES
chemotherapy outside of an RCC hospital, and 45.0% (n=350, CI:41.45-48.56)
Shaan Dudani1, Xiaofu Zhu2, Daniel Yokom3, Andrew Yamada4, Cheryl Ho4,
of patients did not have systemic treatment after surgery. Overall, 72.9%
Jason Pantarotto5, Natasha Leighl3, Tinghua Zhang6, Paul Wheatley-Price1
(n=567) of patients had a consultation with a MO within 30 days prior or 90 1
days after resection. Of 350 patients who did not receive AC, 219 (62.6%) had Division of Medical Oncology, University of Ottawa, Ottawa/ON/Canada, 2Division
of Medical Oncology, Cross Cancer Institute, Edmonton/AB/Canada, 3Princess
a MO consultation. Median time from resection to consultation was 29 days,
Margaret Cancer Centre, Toronto/ON/Canada, 4Department of Medical Oncology,
and did not differ between treatment groups (p=0.35). Age was a significant
British Columbia Cancer Agency, Vancouver/BC/Canada, 5Division of Radiation a 21-gauge needle is a safe and efficient method for molecular mutational
Oncology, University of Ottawa, Ottawa/ON/Canada, 6Ottawa Hospital Research analysis in patients with NSCLC. It can be used effectively for diagnosis,
Institute, Ottawa/ON/Canada staging and guiding treatment decisions for NCSLC. Adequate samples
for mutational analysis can be obtained and placed in cell block without
Background: Standard management of stage II non-small cell lung cancer
suction. Improving the yield of this technique and comparing the yield with
(NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some
and without suction is important as we start testing for a greater number of
patients do not undergo surgery for various reasons. The optimal non-surgical
mutations.
management of stage II NSCLC is undefined, with a paucity of data to guide
decision making in this setting. We examined outcomes of stage II NSCLC Keywords: NSCLC Mutations, EBUS TBNA, Molecular mutational analysis,
patients who were treated with curative, non-surgical approaches. Methods: Diagnostic yield
We performed a multi-institution review of stage II NSCLC patients treated
non-surgically with curative intent between January 2002 and December 2012,
across three major Canadian academic cancer centres. Data on demographics,
comorbidities, staging, treatment, and outcome were collected. The primary
endpoint was overall survival (OS). Logistic regression and Cox proportional POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
MISCELLANEOUS –
hazard models were used to assess for factors associated with choice of MONDAY, DECEMBER 5, 2016
therapy and OS. Results: 158 patients were included for analysis. Median
age 74 years (range 50-91); 44% female; 94% current/former smokers; 67%
performance status (PS) 0-1. Stage II groupings: T2b-T3 N0 in 55%; N1 in P1.05-071 A REVIEW OF QUALITY OF LIFE MEASURES USED IN LUNG
45%. The commonest reasons for no surgery were inadequate pulmonary CANCER SURGICAL OUTCOMES
reserve (27%) and medical comorbidities (24%). All patients received radical Rowena Yip 1, Emanuela Taioli2, Rebecca Schwartz3, Kunwei Li1, Kathleen
radiotherapy (RT) (median 60 Gy [range 48-75]). 73% received RT alone; 24% Tam4, Yu Maw Htwe5, David Yankelevitz1, Claudia Henschke1
and 3% of patients received concurrent and sequential chemoradiotherapy 1
Radiology, ICAHN School of Medicine, New York City/NY/United States of America,
(CRT), respectively. Of those who received RT only, 39% received conventional 2
Department of Population Health Science and Policy, ICAHN School of Medicine
(1.8-2 Gy/day), 51% received hypofractionated (2.5-4 Gy/day) and 10% received at Mount Sinai, New York/NY/United States of America, 3Occupational Medicine,
stereotactic body RT (≥7.5 Gy/day). In multivariate analyses, CRT was less Epidemiology and Prevention, Hofstra North Shore-Lij School of Medicine, Great
likely in patients ≥70 years old (OR 0.28, 95% CI 0.11-0.70, p=0.006), as well as Neck/NY/United States of America, 4Radiology, ICAHN School of Medicine, New
in those with higher (>5) Charlson comorbidity scores (OR 0.34, 95% CI 0.13- York City/United States of America, 5Kingsbrook Jewish Medical Center, Brooklyn/
0.90, p=0.03) or low (<10x109/L) white blood cell (WBC) counts (OR 0.26, 95% AL/United States of America
CI 0.09-0.73, p=0.01). At time of analysis, 74% have died. Median OS was 22.9
Background: With the increased life expectancy following surgery for early
months (95% CI 17.1-26.6 months). Patients receiving CRT had significantly
stage non-small-cell lung cancer (NSCLC), concern about the quality of life
longer median OS than those receiving RT alone (39.1 vs 20.5 months,
(QoL) of patients after surgery has gained attention. Previous QoL studies
p=0.0019). RT fractionation schedule (p=0.16) and nodal status (p=0.14) did
were limited by small sample size, inclusion of late-stage cancers and non-
not influence survival. After adjusting for possible confounders, treatment
surgical treatments. This review summarized the existing literature on
with CRT was associated with improved survival (HR 0.38, 95% CI 0.21-0.69,
QoL in early stage lung cancer patients who underwent surgical treatment.
p=0.001), while elevated WBC (HR 2.45, 95% CI 1.48-4.04, p=0.0005) and poor
Methods: PubMed and PsycINFO were searched for articles published
PS (ECOG 2-3) (HR 1.87, 95% CI 1.16-3.01, p=0.01) were poor prognostic factors.
between 1995 (year of the last published meta-analysis) and March 21, 2016.
Conclusion: Non-surgical approaches to management of stage II NSCLC are
All English articles reported on quality of life for Stage I NSCLC were included.
varied. Treatment with CRT was associated with significantly longer survival
Data extraction was performed by two independent reviewers using pre-
compared to RT alone, and a randomized trial may be warranted in this
specified criteria. Results: Ten articles from nine studies were identified. Of
population.
the nine studies, four reported on the SF-36, one on the SF-12, one on the
Keywords: Stage II, survival, non-small cell lung cancer, Non-surgical EORTC QLQ-C30, one on POMS-TMD, one on EQ-5D, and one on SGRQ. One
study reported only on pre-surgical QoL, six only on post-surgical QoL and
two studies reported on both pre- and post- surgical QoL. Timing for the
administration of post-surgical QoL survey varied, from time at discharge
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC to up to six years post-surgery. Two studies included only NSCLC patients
MISCELLANEOUS – with COPD. Due to the heterogeneity of these studies, comparison between
studies and traditional meta-analysis were not possible. Conclusion: The
literature on QoL in Stage I NSCLC patients is very sparse. As CT screening
P1.05-070 DIAGNOSTIC YIELD AND EFFICACY OF EBUS TBNA IN for lung cancer becomes more widespread with a consequent shift from late
MOLECULAR TESTING FOR NSCLC MUTATIONS to early stage NSCLC, additional research is needed to explore the impact of
Shashank Nuguru1, Samih Raad1, Edmond Bendaly2, Houssam Oueini1, Khalil different NSCLC surgical approaches on QoL.
Diab1 Keywords: quality of life, early stage lung cancer, Surgery, Non-small cell
1
Iu Health, Indianapolis/IN/United States of America, 2Medical Oncology, Marion
General Hospital, Indianapolis/IN/United States of America
Background: Non-small cell lung cancer (NSCLC) can be further defined at

the molecular level by recurrent driver mutations including ALK, BRAF, EGFR, POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
HER2, KRAS, MEK1, MET, NRAS, PIK3CA, RET, and ROS1. Genetic testing has MISCELLANEOUS –
become a routine part of diagnosis and staging for patients with NSCLC. The MONDAY, DECEMBER 5, 2016
presence of mutations can influence response to targeted therapy; tailoring
therapy accordingly has become standard practice. Methods: Sixty-nine P1.05-072 PREDICTORS AND PATTERNS OF LYMPH NODE
patients referred to Indiana University Hospital with suspected or confirmed
METASTASIS IN SMALL PERIPHERAL NON SMALL CELL LUNG
lung adenocarcinoma underwent EBUS-TBNA of lung masses or lymph nodes
using a 21-gauge OlympusTM needle without suction. Samples were first
CANCER
reviewed by a pathologist, and if suspicious for NSCLC, were sent for different Jun-Tao Lin1, Xue-Ning Yang1, Li-Xu Yan2, Si-Yun Wang 3, Wen-Zhao Zhong1,
types of molecular testing based on the clinical scenario. At least 6 extra Qiang Nie1, Ri-Qiang Liao1, Song Dong1, Ben-Yuan Jiang1, Yi Long Wu1
1
passes were placed in cell block. For Paradigm testing, 10 passes were sent. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong
EGFR and KRAS testing were performed using the FDA approved Thera screen Academy of Medical Science, Guangzhou/China, 2Department of Pathology and
RGQ PCR Kit. Testing for ALK rearrangement was done using fluorescent in Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of
Medical Science, Guangzhou/China, 3Pet Center, Guangdong General Hospital &
situ hybridization. In some cases, testing for these mutations in addition to
Guangdong Academy of Medical Science, Guangzhou/China
ROS1, BRAF, and HER2 was done using the Paradigm Cancer Diagnostics test.
Results: Sixty-nine samples from patients with NSCLC obtained by EBUS- Background: Lobectomy is the standard treatment of early stage non-small
TBNA were sent for molecular testing for EGFR. All samples were sufficient cell lung cancer (NSCLC) and wheather sublobar resection is appropriate for
for analysis (Yield=100%). EGFR mutations were found in 3 patients (4.3%) small peripheral small NSCLC or not is unclear. PET-CT is a powerful imaging
vs. 66 wild-type (95.7%). 60 samples were sent for molecular testing for KRAS modality for the detection of lymph node metastasis with a relatively
(yield = 100%), of which 10 had mutations (16.7%) vs. 50 wild-type (83.3%). 51 low false-negative rate. We identified predictors and patterns to identify
samples were sent for ROS1 testing (0 mutant, 48 wild-type); tissue samples false-negative N(+) disease in PET-CT. Methods: A total of 435 consecutive
were inadequate for testing in 3 patients (yield=94.1%). 64 samples were cN0 peripheral NSCLC underwent curative-intent resections following
sent for ALK testing (3 (4.7%) mutant, 55 (85.9%) wild-type; yield = 90.6%). PET-CT scans from January 2008 to December 2014 in our hospital, we
Ten samples were sent for BRAF testing and two samples were sent for analysed patients’ clinicopathological data retrospectively. 171 patients
HER2 testing, all of which were negative for mutations (yield = 100%). No with tumour size≤2cm were enrolled to identify predictors and patterns
complications were associated with EBUS TBNA. Conclusion: EBUS TBNA with of lymph node metastases by multivariable analysis. The cutoff values,

sensitivity and specificity for the predictors were calculated using a receiver MISCELLANEOUS –
operating characteristic curve. The patterns of lymph node metastases
were also analysed. Results: In total, 9.4% (16/171) PET-CT-diagnosed N0
NSCLC cases were pathologically N1/N2 disease. The preoperative CEA was P1.05-074 FACTORS PREDICTING DISCORDANCE BETWEEN
a unique independent risk factor for lymph node metastasis (OR = 0.914, CLINICAL AND SURGICAL-PATHOLOGIC STAGING IN OPERABLE
95 CI% = 0.85–0.98, P = 0.009). According to ROC curve, we divided the
NON-SMALL CELL LUNG CANCER
patients into two groups by CEA: the N(+) rates in the CEA ≤1.67 and CEA>
1.67 groups were 1.6% (1/64) and 14.0% (15/107), respectively (P =0.007). In Ioannis Koukis1, Dimitra Grapsa1, Periklis Tomos2, Athanasia
16 patients with lymph node metastasis, 7 were N1 disease, and 6 out of 9 N2 Papazafiropoulou3, Anna Karakatsani2, Ilias Kotteas1, Andriani Charpidou1,
diseases were skip N2 disease. 93.5%(15/16) lymph node metastases were Kostas Syrigos 1
1
found in adenocarcinoma and 11 of them were single station metastases. Medical School, University of Athens, Athens/Greece, 2 Attikon University Hospital,
The metastases rates in solid and subsolid lesions were 12.8%(16/125) Athens/Greece, 3Internal Medicine & Diabetology, General Hospital of Piraeus
“tzaneio”, Pireas/Greece
and 0%(0/46)(P=0.007), retrospectively. Solid/mucinous/ micropapillary
predominant adenocarcinoma were associated with LN metastases(31.2% Background: Accurate clinical staging is of the utmost importance for the
vs 7.1%, P=0.01). Conclusion: The preoperative CEA was an independent risk optimal management of patients with non-small cell lung cancer (NSCLC).
factor for lymph node metastases in cN0 NSCLC with T ≤ 2cm. In patients with The aim of this study was to identify factors associated with discordance
CEA>1.67, sublobar resection should be avoided before thorough lymph node between clinical and pathologic staging in patients with operable NSCLC.
sampling that include intrapulmonary lymph node while patients with CEA Methods: The medical records of 85 patients with early-stage NSCLC, who
≤ 1.67 may be candidate for sublobar resection, especially in GGO lesions. In had been submitted to thoracotomy followed by surgical resection of the
patients with solid/mucinous/ micropapillary predominant adenocarcinoma, primary tumor and systematic lymph node dissection, were retrospectively
sublobar resection should be avoided due to high LN metastases rate. reviewed. All patients were staged according to the 7th edition of the TNM
Keywords: non small cell lung cancer, lymph node metastases, sublobar staging system. The presence of postoperative upstaging or downstaging
resection, CEA was correlated with various demographic and clinicopathological factors,
including age, sex, smoking history, tumor histology, tumor size and location.
Results: Discordance between clinical and surgical-pathologic staging
was found in 45/85 cases (52.9%), and the majority of these patients were
upstaged (35/85 cases, 41.2%). Patients with IIB and IB clinical stage had the
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC highest (77.8%) and lowest (48.1%) probability of discordance, respectively.
MISCELLANEOUS – With regard to T stage, disagreement between clinical and surgical-pathologic
T stage was noted in 22/85 patients (25.9%), including 16 upstaged patients
(16/85, 18.8%) and 6 downstaged patients (6/85, 7.1%). Nodal status was
P1.05-073 EVALUATION OF STAGE 1 SUB-SOLID LUNG NODULES altered postoperatively in 39/85 cases (45.9%), including 29 upstaged
USING PET IMAGING patients (29/85, 34.1%) and 10 downstaged patients (10/85, 11.8%). The rate
of unsuspected mediastinal lymph node involvement (pathologic stage N2)
Benjamin Tran1, Daniel Nicastri2, Rowena Yip3, Kunwei Li3, Dongming Xu3,
was 14.1% (12/85 patients), despite negative mediastinoscopy findings. Age
Mary Beth Beasley1, Mary Salvatore3, David Yankelevitz3, Claudia Henschke 4,
was the only statistically significant factor independently associated with
Raja Flores2
1
staging discordance (odds ratio 0.93; 95% confidence interval, 0.87 to 0.99).
ICAHN School of Medicine at Mount Sinai, New York/NY/United States of America,
2 Conclusion: Postoperative upstaging or downstaging was observed in a
Thoracic Surgery, ICAHN School of Medicine at Mount Sinai Hospital, New York/
relatively high percentage of our patient population, and was significantly
United States of America, 3Radiology, ICAHN School of Medicine at Mount Sinai,
New York/NY/United States of America, 4Radiology, ICAHN School of Medicine at and independently correlated with patient’s age. These observations warrant
Mount Sinai, New York/United States of America confirmation in larger prospective series of patients with early-stage NSCLC.
Background: Positron emission tomography (PET) scans are valuable in the Keywords: non-small cell lung cancer., surgical-pathologic staging, clinical
evaluation of lung nodules. Subsolid (SS:<80% solid) lung nodules, however, staging
often have low levels of metabolic activity and rare metastases. The purpose
is to assess PET in the evaluation of SS nodules. Methods: Between 2009-
2015, 892 patients had a chest computed tomography (CT) with a SS finding
and PET within 6 months, with pathology specimen, at our institution. 50
patients had clinical stage IA/B lung cancer and were retrospectively analyzed. MISCELLANEOUS –
CT analysis further classified these subsolid lesions as nonsolid(NS) and MONDAY, DECEMBER 5, 2016
part-solid(PS). Results: 26 patients had NS nodules and 24 PS. Mean maximal
tumor dimension was not statistically significantly different between the
groups (mean±SD; NS- 16.8±6.9; PS- 16.9±6.2). PET positive nodules (SUV>2.5)
P1.05-075 THE CORRELATION BETWEEN THE PROGNOSES
were larger in maximal tumor dimension than PET negative on CT though OF PATIENTS WITH NON-SMALL CELL LUNG CANCER AND
the difference was not statistically significant (mean±SD; PET Neg, n=42- PREOPERATIVE PLATELET- LYMPHOCYTE RATIO
16.1±5.7; PET-pos, n=8- 20.9±8.8). Among the 39 patients in which lymph node Shunta Ishihara, Masanori Shimomura
pathology was obtained, sensitivity and specificity of PET in identifying N1 Department of General Thoracic Surgery, Ayabe City Hospital, Ayabe, Kyoto/Japan
disease was 0% and 92.9%; and 0% and 100% for N2 disease. Recurrence and
overall survival were 0% and 100%, with median follow-up of 34 months. Background: The platelet- lymphocyte ratio (PLR) is a prognostic factor that
correlates immunity or inflammation with tumor invasion. We retrospectively
investigated the correlation between prognosis and preoperative PLR in
patients with non-small cell lung cancer who underwent anatomical lung
resection in our hospital. Methods: We conducted a retrospective study
of 116 patients with primary lung cancer who underwent anatomical lung
resection in our hospital from January 2009 to May 2014. We excluded
patients who underwent previous lung resection or had intraoperative
malignant pleural effusion or positive surgical margins. We analyzed 105
patients (65 with adenocarcinoma, 25 with squamous cell carcinoma, 9 with
large cell carcinoma, and 2 with adenosquamous carcinoma). We constructed
a ROC curve with PLR values calculated preoperative blood analyses and
determined that the threshold was 160. We divided the patients into
high and low PLR groups. We analyzed these two groups with respect to
background, pathological findings, and cancer-specific survival. Additionally,
we investigated factors that correlated with cancer-specific survival with.
Results: The median patient age was 71 years (range, 50-88 years). There were
75 male patients and 25 female patients. The median follow-up duration
was 43 months (range, 0-85 months). Regarding surgical techniques, 101
patients underwent lobectomy, 3 underwent segmentectomy, and 1 patient
underwent sleeve lobectomy. A total of 47, 34, 8, 9, 6, and 1 patients were
Conclusion: The use of PET for the evaluation of SS nodules in stage I lung
diagnosed with pathological stage IA, IB, IIA, IIB, IIIA, and IIIB cancer. The
cancer may have limited value in detecting metastases and affecting current
overall survival rate was 71.3%. When examining background characteristics,
clinical decision making for these patients.
tumor size was larger and T factor was more elevated in the high PLR groups,
Keywords: PET scan, Nodal metastases, early stage NSCLC and pathological stage was more advanced in the high PLR group. N factor
was not significantly different between the two groups. Cancer-specific with median age 63 (40-102). Most of them were ex-smokers (54.4%),
survival was significantly poorer in the high PLR group than in the low group while only 9.5% never smoked cigarettes. Most of them had very good
(p=0.0007). Considering tumor types, patients with adenocarcinoma in performance status at the time of diagnosis (ECOG 0-1 91.9%). 78 (53.1%)
the high PLR group had poorer prognosis compared to the patients with of the patients were diagnosed with adenocarcinoma, 62 (42.2%) with
adenocarcinoma in the low PLR group (p=0.0002), but for squamous cell planocellular carcinoma, 6 (4.1%) with NSCLC-NOS and only 1 (0.7%) with
carcinoma and in the other tumor types, there was no significant difference adenosquamous carcinoma. mOS for all diagnosed lung cancer patients was
(p=0.20 and p=0.86, respectively). Multivariate analysis revealed that PLR was 9 months and for NSCLC 8 months. mOS for IIIA-N2 NSCLC was 14 months.
an independent prognosis factor for the cancer-specific survival. Conclusion: Our patients were treated with chemotherapy in 40.8% of the cases (mOS
In the patients who underwent anatomical resection with lung cancer, PLR 11 months); sequential chemotherapy and irradiation in 25.2% (mOS 17
was correlated with prognosis. months); surgery, sequential chemotherapy and irradiation in 14.3% (mOS
26 months); surgery and adjuvant chemotherapy in 4.1% (mOS 15 months)
Keywords: PLR, NSCLC, lung cancer and neoadjuvant chemotherapy and surgery in 1.4% (mOS 34 months) of
the cases, while only 1.4% of all patients were treated with only surgical
resection (mOS 4 months); (p=0.001). Conclusion: We analyzed the data
collected at our department to assess the difference in outcomes of different
strategies in IIIA – N2 management. The most of our patients were treated
MISCELLANEOUS – with platinum-based doublets only, followed by sequential chemotherapy
MONDAY, DECEMBER 5, 2016 and irradiation as a second most frequent therapy option. Only 21.8% of
the patients were treated with surgery only or surgery combined with other
forms of treatment. Only 1 patient underwent concurrent chemoradiation.
P1.05-076 RISK FACTORS IN PATIENTS WITH PATHOLOGICAL STAGE
The difference in overall survival between different therapy options showed
I NON-SMALL CELL LUNG CANCER highest mOS in patients treated with neoadjuvant chemotherapy and surgery
Yoshimasa Tokunaga, Taku Okamoto, Sung Soo Chang followed by surgery and sequential chemotherapy and irradiation. Sequential
Department of General Thoracic Surgery, Kochi Health Sciences Center, Japan, chemotherapy and irradiation was superior to chemotherapy. The limitation
Kochi/Japan of our study was a small number of patients in this specific subgroup, as well
as small number of patients who underwent concurrent chemoradiation.
Background: Patients with pathological (p-) stage I non-small cell lung cancer
(NSCLC) can have good prognosis with complete resection, whereas some Keywords: N2 disease, therapy regimens, NSCLC
patients die from disease recurrence. The aim of this study was to investigate
the risk factors for p-stage I NSCLC. Methods: We retrospectively reviewed
234 patients with completely resected p-stage I NSCLC from March 2005 to
December 2015. Patients with synchronous or metachronous multiple lung
cancer or malignancies from other organs were excluded. Clinicopathological POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
MISCELLANEOUS –
factors were analyzed, including age, sex, serum carcinoembryonic antigen MONDAY, DECEMBER 5, 2016
(CEA) levels, histology, surgical procedure, tumor size, pleural invasion,
lymphatic invasion, vascular invasion, and histological grade. Univariate and
multivariate analyses of disease-free survival (DFS) and overall survival (OS) P1.05-078 THE RELATIONSHIP BETWEEN IASLC/ATS/ERS GRADING
were performed. Results: The study group included a total 234 patients, with SYSTEM OF ADENOCARCINOMA OF THE LUNG AND QUANTITIVE
119 men and 115 women, ranging in age from 22 to 88 years (mean 68±10.4 PET PARAMETERS
years). The median follow-up period was 50.7 months. The preoperative serum Ülkü Yılmaz 1, Özlem Özmen2, Funda Demirağ3, Tuba Inal Cengiz1, Pınar Akın
CEA level was elevated in 37 patients. Complete resection was performed in Kabalak1, Derya Kızılgöz1, Ibrahim Onur Alıcı4, Göktürk Fındık5
all patients, comprising pneumonectomy in one patient, and bilobectomy 1
Chest Disease, Ankara Atatürk Chest Disease and Thoracic Surgery Training and
in two, lobectomy in 192, segmentectomy in 17, and wedge resection in Research Hospital, Ankara/Turkey, 2Nuclear Medicine, Ankara Atatürk Chest
22. Adenocarcinoma, squamous cell carcinoma, and other histology were Disease and Thoracic Surgery Training and Research Hospital, Ankara/Turkey,
observed in 187, 38 and nine patients, respectively. The maximum tumor 3
Pathology, Ankara Atatürk Chest Disease and Thoracic Surgery Training and
diameter exceeded 30 mm in 63 patients and tumor diameter was 30 mm Research Hospital, Ankara/Turkey, 4 Chest Disease, Izmir Suat Seren Chest Disease
or less in 171 patients. There were 38 patients with pleural invasion, 24 and Thoracic Surgery Training and Research Hospital, Izmir/Turkey, 5Thoracic
patients with lymphatic invasion, and 34 patients with vascular invasion. Surgery, Ankara Atatürk Chest Disease and Thoracic Surgery Training and Research
Multivariate analysis showed that pleural invasion and lymphatic invasion Hospital, Ankara/Turkey
were independent factors for recurrence, whereas older age (>70 years), high
Background: There are differences in terms of survival even in early stage
serum CEA levels, pleural invasion, lymphatic invasion and vascular invasion
adenocarcinomas and subtypes of tumor are the most particular factor. The
were independent factors for poor survival. The 5-year DFS and OS in patients
aim of the study was to investigate the relationship between International
without pleural invasion and without lymphatic invasion were 88.5% and
Association for the Study of Lung Cancer (IASLC)/ American Thoracic
93.5%, respectively, compared with 29.1% and 33.2% in patients with pleural
Society (ATS)/ European Respiratory Society (ERS) grading system of the
invasion and with lymphatic invasion (p < 0.001). Conclusion: Pleural invasion
adenocarcinoma and quantitative PET parameters in terms of survival.
and lymphatic invasion were independent factors for recurrence and poor
Methods: 179 operated adenocarcinoma patients categorized according
survival in p-stage I NSCLC. Adjuvant chemotherapy should be considered for
to grade, histological subtypes (Table 1). All patients underwent complete
patients with lymphatic invasion.
resection and lymph node resection. Invasive adenocarcinoma (MIA) and
Keywords: pathological stage I, non-small cell lung cancer, risk factor adenocarcinoma in situ (AIS) were excluded. PET/CT images were re-evaluated
and MTV, TLG and SUV-max of primary tumors were calculated. Correlations
between quantitative PET parameters and both tumor and overall survival
were analysed. Results: A strong correlation was detected in terms of tumor
size between pathologic tumor size and PET-BT (p<0.001, r=0.816). If the
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC SUV-max of tumor/ lymphadenopathy (LAP) ratio cut-off is taken as <2.5, it
MISCELLANEOUS – is significantly higher to detect metastatic lymph node (p<0.001). SUVmax
value had weak negative correlation with survival (p=0.004 r= - 0,220). 49.6
was determined as cut-off value for TLG and 9.68 cm3 was for MTV. 1, 2, 3 and
P1.05-077 OUTCOME OF N2 DISEASE IN NSCLC - A SINGLE 5 years survival rates were indicated in Table 1 There were significant relation
INSTITUTION EXPERIENCE between survival and SUVmax, tumor size (PET-BT and CTT) and TLG (p<0,05).
In this study over-all survival rates for 1, 2, 3 and 5 years were 88.9%, 77.8%,
Lela Bitar, Fran Seiwerth, Ivona Markelić, Marta Koršić, Sanja Pleština, Branka
76.4% and 66.1%.
Čučević, Suzana Kukulj, Mihovil Roglić, Marko Jakopović, Miroslav Samaržija
Department for Respiratory Diseases Jordanovac, University Hospital Center
Zagreb, Zagreb/Croatia Survival rates 1 year 2 years 3 years 5 years p value
TLG<49.6 88.9 70.4 69 51.6 p=0.0051
Background: There are many different therapy options available for stage
IIIA-N2 NSCLC patients that were set by the NCCN guidelines. That is why TLG>49.6 91.5 87.3 85.9 82.2
we decided to evaluate outcome of different management strategies.
Methods: Medical records of the patients diagnosed with lung cancer MTV<9.68 89.5 72.1 70.8 53.3 p=0.002
in Clinical hospital center Zagreb, Department for respiratory diseases
Jordanovac during the year 2012 and 2013 were retrospectively collected MTV>9.68 89.6 85.1 83.6 79.9
and reviewed. Median overall survival (mOS) was measured and analyzed
Conclusion: Although, there was no correlation between tumor grade and PET
using the Kaplan-Meier and log-rank test. Results: There were 147 patients
parameters, PET/CT is an important imaging modality for a more accurate T
diagnosed with stage IIIA–N2 NSCLC, out of which 105 were male (71.4%),
staging and prediction of lymphatic metastasis and survival. To our opinion

quantitative PET parameters can help to decide on treatment options and it with chemotherapy (1201 days vs 435 days respectively (HR: 3.289, 95% CI:
is possible to avoid unnecessary treatment and to decrease treatment related 1.551-6.997). 10 patients were not treated with TKIs, either because of poor
morbidity rate. performance status (40%), patient’s refusal (30%), rapid disease progression
(20%) or T790M mutation (10%). Conclusion: This study showed that
Keywords: Adenocarcinoma, PET-BT Parameters, New classification incidence of molecular testing improved significantly over the course of the
last years, leading to more effective targeted therapy. Overall survival was
significantly prolonged in patients harboring an EGFR mutation treated with
chemotherapy prior to TKIs, compared to patients without EGFR mutation
treated only with conventional chemotherapy
MISCELLANEOUS –
MONDAY, DECEMBER 5, 2016 Keywords: NSCLC, EGFR, TKI
P1.05-079 LUNG CANCER IN THE ELDERLY: FACTORS AFFECTING

LONG-TERM SURVIVAL FOLLOWING RESECTION
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
Prakash Balakrishnan, Sean Galvin, Barry Mahon, John Riordan, James IMMUNOTHERAPY
Mcgiven ADVANCED GENERAL –
Cardiothoracic Surgery, Wellington Regional Hospital, Wellington/New Zealand
Background: Lung Cancer remains the most common cancer in the world.
P1.06-002 CONTRALATERAL AXILLARY LYMPH NODE METASTASIS
It has progressively become a disease of older people, with the median
age at diagnosis now exceeding 65 years . As population grows older OF A LUNG CANCER: A CASE REPORT
demographically, it poses various distinct treatment & management Omer Giray Intepe, Mehmet Yildirim, Recep Ustaalioglu, Tamer Okay
challenges . Thus, we looked into factors associated with long-term survival Thoracic Surgery, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and
following pulmonary resections for lung cancer in the elderly patients 70 years Research Hospital, Istanbul/Turkey
or older Methods: All medical records for these elderly patients with lung
Background: Primary lung cancer metastasis to axillary lymph node is rare.
cancer who under went pulmonary resections, between years 2000 to 2010,
Routine examination of the axilla is useful way to detect suspicious nodes.
were reviewed . These data was cross-referenced & checked with the operating
Methods: We evaluated retrospectively medical and pathological records of
theatre ORSOS & national mortality data . Results: Patients were stratified
a male patient at our division who had a primary lung cancer with M1b axillary
into various groups . Gender, Median age at diagnosis, patient characteristics,
lymph node metastasis. Results: A 66-year-old male presented with shortness
assocciated medical co-morbidities, Pre-operative lung functions tests,
of breath. His chest x-ray showed a large opacity in the lower one-half of the
extend of pulmonary resections & overall 1, 2 & 5 years survival was calculated
right lung field. Computed tomography (CT) imaging revealed a solid mass in
Conclusion: Stringent & proper selection criterias in elderly patient with lung
the right hemithorax measuring 50x50 mm. Positron emission tomography/
cancer undergoing pulmonary resections will identify groups of patients that
Computed tomography (PET/CT) demonstrated increased fluorodeoxygucose
will benefit from these surgeries . Thus, identifying these elderly sub-groups
uptake (Standard uptake value: 9,9) by the mass. Fiberoptic bronchoscopy
will give new lease of life in survivability following pulmonary resections for
was performed and transbronchial biopsy was consistent with squamous
lung cancer .
cell carcinoma. Mediastinoscopy was performed to evaluate the stage of
Keywords: lung cancer, elderly, survival, NSCLC the tumor and biopsies from 2R, 2L, 4R, 4L, 7. mediastinal lymph nodes
had negative results. Right lower lobectomy was planned and due to
invasion of the right middle lob vein and bronchus, right lower bilobectomy
and mediastinal lymph node dissection were performed. Pathological
evaluation of the tumor and lymph nodes showed that staging of the tumor
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & was T2b N1 (11. lymph node had metastasis, although 2,4,7,9. lymph nodes
were metastasis free). Patient was discharged on post-operative 7. days
CHEMOTHERAPY/TARGETED THERAPY/IMMUNOTHERAPY and received chemotherapy 12 cycles. During follow-up PET/CT revealed
Advanced General – increased FDG uptake by mass in the residual right lung(SUV:9.3) and axillary
MONDAY, DECEMBER 5, 2016 subcentimetric nodule(SUV:11.1). Physical examination of the patient revealed
a palpable nodule in the right axilla. Ultrasound guided needle biopsy was
performed to this nodule but it had negative result. Before performing
P1.06-001 SLUGA R, ROEPMAN P, KUMMER A, VD BOSCH W, VD pulmonary resection, we decided to dissect this lymph node. 30 months
BORNE BEEM, SCHRAMEL FMNH after right lower bilobectomy, axillary lymph node dissection was performed
and frozen section procedure demonstrated squamous cell lung carcinoma
Romina Sluga, Franz Schramel
metastasis to axillary lymph node. Pulmonary resection was cancelled and
Department of Pulmonology, St. Antonius Hospital, Nieuwegein/Netherlands patient was discharged post operatively 3.day and received chemotherapy
again. After 6 month follow-up the patient was dead. Conclusion: Routine
Background: Tyrosine kinase inhibitors (TKIs) for treatment of advanced
physical examination of axilla is recommended even if mediastinal lymph
EGFR mutated adenocarcinoma were shown in many studies to be superior
nodes are metastasis free either at initial presentation or at follow-up of
to chemotherapy in terms of progression-free survival. Since most data
patients. In this case metastatic axillary lymph node was subcentimetric,
is derived from studies on Asian populations, there is a lack of data from
although according to Austin et al. 14 mm or larger axillary lymph nodes are
other ethnicities. In the Netherlands the guidelines recommend that
suggestive of adenopathy. Fishman et al. considered 15mm or larger single
EGFR-mutation analysis should be performed in all patients with stage
axillary lymph node without fatty center as abnormal. Without mediastinal
IIIb and IV adenocarcinoma and a non-small cell lung cancer-not otherwise
lymph nodes metastasis, contralateral axillary lymph node metastasis could
specified(NSCLC- NOS). The aim of this study was to investigate the
be of systemic origin.
compliance to the guidelines in terms of determination of EGFR mutations,
prevalence of EGFR mutations and the outcomes of treatment with the Keywords: axillary lymph node, contralateral, Advanced stage
TKIs in a cohort of European patients with advanced NSCLC harboring an
EGFR mutation. Methods: Data was obtained by retrospective analysis
of the medical records of patients with a stage IIIb and IV non-small cell
lung cancer between 2009 and 2014 in the two top-clinical hospitals in the
Netherlands. Results: The total number of patients included in the study was POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
1022. Molecular diagnostic tests were performed in 57.8% of patients with IMMUNOTHERAPY
ADVANCED GENERAL –
advanced adenocarcinoma or NSCLC-NOS. The prevalence of performing MONDAY, DECEMBER 5, 2016
molecular diagnostic tests improved significantly between 2009 and 2014
(25,2% to 74,4% respectively). Positive EGFR mutation was found in 43
patients (in 9,1% of all molecular diagnostic tests performed). 72,1% of P1.06-003 ANAMORELIN IN CACHECTIC PATIENTS WITH ADVANCED
patients harboring an EGFR mutation were treated with TKIs.A significant NSCLC, A POST-HOC POOLED EFFICACY DATA ANALYSIS OF TWO
overall survival benefit with a mean survival of 763 days was seen in EGFR PHASE 3 TRIALS
positive patients treated with TKIs (with or without prior/subsequent David Currow 1, Jennifer Temel2, Amy Abernethy3, John Friend4, Kenneth
chemotherapy) versus 435 days in patients treated with conventional Fearon5
chemotherapy (hazard ratio (HR): 0.719. 95% confidence interval (CI): 1
Flinders University, Adelaide/SA/Australia, 2Massachusetts General Hospital,
0.587-0.881). A large fraction of the patients with EGFR-mutated tumors Boston/MA/United States of America, 3Flatiron Health, New York/NY/United States
were either initially or after progression treated with chemotherapy. EGFR of America, 4Helsinn Therapeutics (Us), Inc., Iselin/NJ/United States of America,
5
positive patients who were prior to TKI treatment treated with chemotherapy Royal Infirmary, Edinburgh/United Kingdom
had significantly longer survival in comparison to patients treated only
Background: Anorexia-cachexia is a multifactorial syndrome frequently or “Always”). Subjects used the full range of responses (i.e., 0, 1, 2, 3, and 4)
experienced by patients with non-small cell lung cancer (NSCLC). It is and provided answers for all NSCLC-SAQ items. Rasch analyses showed the
characterized by decreased body weight (mainly due to muscle loss) and is items were ordered and the person-to-item distribution was acceptable.
associated with worsen morbidity, poor tolerance of chemotherapy and Factor analysis indicated a single component accounting for 47% of the
reduced survival. The randomized, double-blind ROMANA 1 and ROMANA 2 variance, which supports a unidimensional scale structure and the ability to
phase 3 trials in cachectic NSCLC patients, demonstrated that the ghrelin calculate a total symptom score. Cronbach’s alpha was 0.80. The NSCLC-SAQ
receptor agonist anamorelin was well tolerated, improved body weight, lean total symptom score correlated highly (r=0.87) with the FLSI-17 DRS and was
body mass (LBM), fat mass (FM) and anorexia/cachexia symptoms and able to discriminate levels of overall symptom severity as assessed by the
concerns, with no difference in handgrip strength compared to placebo. Here PGIS (p<0.001). Conclusion: The NSCLC-SAQ has been developed in accordance
we assessed pooled efficacy and numbers needed to treat (NNT) from with the FDA’s PRO Guidance. This study provides quantitative evidence
ROMANA 1 and ROMANA 2 studies. Methods: Stage III/IV NSCLC patients with of adequate item and scale performance. These data will be submitted to
cachexia (≥5% weight loss during prior 6 months or BMI<20 kg/m2) were the FDA to support qualification of the NSCLC-SAQ as a measure to assess a
randomized (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. symptom endpoint for efficacy evaluation and product labeling.
Endpoints included changes in LBM, FM, total body mass (TBM) and in
self-reported anorexia/cachexia symptoms and concerns. We present the Keywords: symptom assessment, NSCLC-SAQ, non-small cell lung cancer
pooled efficacy data from a post-hoc analysis from both trials (anamorelin,
N=552; placebo, N=277); treatment differences, 95% CI, NNT and nominal p
values from baseline to end of study. Results: At the end of study, compared
with placebo, anamorelin-treated patients significantly increased body
composition parameters (LBM, appendicular LBM, FM and TBM), and a greater IMMUNOTHERAPY
proportion of patients showed improvements in these parameters (Table). ADVANCED GENERAL –
The anamorelin group also significantly improved anorexia/cachexia
symptoms and concerns, and compared to placebo, more patients in the
anamorelin arm achieved the minimally important difference of 4 points. P1.06-005 AN INTERNATIONAL COHORT OF PATIENTS WITH SMALL
CELL LUNG CANCER AFTER A NON-SMALL CELL LUNG CARCINOMA
ONCOGENE OR NON-ONCOGENE ADDICTED
Matteo Giaj Levra1, Silvia Novello2, Leonie Ferrer 1, Fausto Barbieri3, Julien
Mazieres4, Virginie Westeel5, Nicolas Girard6, Michel Poudenx7, Jacques Le
Treut8, Maria Rita Migliorino9, Clarisse Audigier Valette10, Anne Madroszyk11,
Charlotte Leduc12, Myriam Locatelli- Sanchez13, Anne Claire Toffart1, Denis
Moro-Sibilot1
1
Michallon University Hospital, Grenoble/France, 2Department of Oncology,
University of Turin, Turin/Italy, 3University Hospital Policlinico of Modena,
Conclusion: Anamorelin has anabolic activity while improving symptom Modena/Italy, 4Toulouse University Hospital, Toulouse/France, 5Centre Hospitalier
burden in cachectic patients with NSCLC. A significantly greater proportion Universitaire, Besançon/France, 6Thoracic Oncology, Hospices Civils de Lyon, Lyon/
France, 7Centre Antoine Lacassagne, Nice/France, 8 Ch Aix En Provence, Aix En
of patients increased lean mass, fat mass and improved anorexia/cachexia
Provence/France, 9Department of Lung Diseases, Azienda Ospedaliera San Camillo -
symptoms and concern score in the anamorelin arm versus the placebo arm,
Forlanini, Roma/Italy, 10 Centre Hospitalier Sainte Musse, Toulon/France, 11Institut
with favorable NNT. Paoli Calmettes, Marseille/France, 12CHU Strasbourg, Strasbourg/France, 13Thoracic
Oncology, Centre Hospitalier Lyon Sud, Lyon/France
Keywords: cachexia, anamorelin, NNT, ROMANA
Background: Phenotypic transformation from Non-small cell lung cancer
(NSCLC) to small cell lung cancer (SCLC) is a resistance mechanism in tyrosine
kinase inhibitors (TKIs) treated EGFR mutant tumors. SCLC is also however
less frequently diagnosed in patients without EGFR mutations treated with
IMMUNOTHERAPY chemotherapy. These transformations are rare and little is known about
ADVANCED GENERAL – the clinical and therapeutic characteristics of these patients. In this study
MONDAY, DECEMBER 5, 2016 we describe and compare the characteristics of SCLC arising from mutant or
non mutant NSCLC. Methods: We performed a multicentric retrospective
P1.06-004 EVALUATING THE NON-SMALL CELL LUNG CANCER collection (27 centers in France and Italy) of cases. Between 2005 and 2015,
patients with stage III or IV NSCLC with a secondary transformation to SCLC
SYMPTOM ASSESSMENT QUESTIONNAIRE (NSCLC-SAQ):
with histological proof were included. Results: Forty seven cases of SCLC
PRELIMINARY RESULTS FROM THE QUANTITATIVE PILOT STUDY
transformation were collected, 34 in EGFR mutant and 13 in non. Most of the
Astra Liepa1, Donald Bushnell2, Thomas Atkinson3, Kendra Debusk4, Kelly patients (n=37, 82%) were stage IV, (n=27, 57%) female and (n=26, 76%) had an
Mccarrier2, Mona Martin2, Stephen Coons5 exon 19 mutation. The last treatment before transformation was a TKI in 23
1
Eli Lilly and Company, Indianapolis/IN/United States of America, 2Health Research (68%) cases in the mutant group and in 3 (23%) patients (erlotinib) in the non-
Associates, Inc, Mountlake Terrace/WA/United States of America, 3Memorial Sloan mutant. Median time to SCLC transformation was 17 [IQR, 11-29] months in
Kettering Cancer Center, New York/NY/United States of America, 4Patient Centered the mutant group and 26 [IQR 23-36] months in the other (p=0.03). Molecular
Outcomes Research, Genentech, South San Francisco/CA/United States of America,
5 analyses were not performed in the non mutant group, 25 (74%) had molecular
Critical Path Institute, Tucson/AZ/United States of America
analyses in the EGFR mutant. A driver mutation was identified in 22/25 (88%)
Background: In collaboration with the US Food and Drug Administration patients: in most of the cases the same as the initial, 1 case of ALK fusion and 1
(FDA), the Patient-Reported Outcome (PRO) Consortium’s NSCLC Working of PI3K mutation. Thirty patients (88%) received at least one line of treatment
Group has developed the 7-item NSCLC-SAQ. Content includes cough, pain (2 after transformation in the mutant group, in all cases a platinum-etoposide
items), shortness of breath, fatigue (2 items), and appetite. A quantitative (P-E) chemotherapy. Median survival from initial diagnosis in the EGFR
pilot study is underway to evaluate the NSCLC-SAQ’s item-level and scale-level mutant group was significantly worse 28 [17-41] months vs 49 [36-118] months
performance. Methods: Eligible subjects with clinically-diagnosed advanced in the non EGFR mutant group (p=0.01). After transformation, the same
NSCLC from US-based clinical sites completed a questionnaire battery tendency was observed with a median survival of 8 [3-12] months for the EGFR
(demographics, NSCLC-SAQ, NCCN/FACT Lung Symptom Index-17 [FLSI-17], mutated patients vs 13 [6-15] months for the non EGFR mutated patients
Patient Global Impression of Severity [PGIS]) using a tablet computer. For (p=0.06). Conclusion: SCLC that occurs in EGFR mutant treated by TKIs is more
this interim analysis, items were evaluated for response distribution, ceiling/ aggressive than classic SCLC, and differs on epidemiological characteristics.
floor effects, missing data, and item-to-item correlations. Exploratory These transformed SCLC are not fully explained and we need to define the
factor and Rasch analyses were examined. Internal consistency reliability molecular characteristics of this cohort, before and after transformation and
was estimated using Cronbach’s coefficient alpha. Construct validity was if funded the whole genome sequencing of the tumors to understand this TKIs
assessed with Pearson correlations between the NSCLC-SAQ and FLSI-17 mechanism of resistant.
Disease-Related Symptom (DRS) subscale. The PGIS was used to assess the
Keywords: Non- small cell lung cancer, Small cell lung cancer transformation
NSCLC-SAQ’s known-groups validity. Results: For this interim analysis, 117
(of the anticipated 150) subjects from nine sites were included. Subjects’
mean age was 64 years old (range 40-85), 55% were female, and 84% were
white (non-Hispanic), ECOG performance status at enrollment was: 0 (33%),
1 (50%), and 2 (17%). NSCLC staging was: Stage IIIB (15%) and IV (85%). A
total of 34% were treatment-naïve, 32% had received first-line treatment
only, and 34% had received second- or third-line treatment. Mean scores for
the 7 items of the NSCLC-SAQ ranged from 0.9 to 2.2 using a response scale
between 0 (“No <symptom> at all” or “Never”) to 4 (“Very Severe <symptom>”

POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ Nacional de Cancerologia of Mexico, with stage IV and oligometastatic
IMMUNOTHERAPY
disease (≤ 5 metastatic lesions). Patients were enrolled to receive, after
MONDAY, DECEMBER 5, 2016 4 cycles of systemic treatment with platinum-doublet chemotherapy or
4 months of tyrosine kinase inhibitors in patients with driver mutations,
local consolidative treatment for the primary lesion and their metastases
P1.06-006 TREATMENT BEYOND PROGRESSION IN PATIENTS WITH with chemoradiotherapy, surgery, radiotherapy, stereotactic radiosurgery
ADVANCED SQUAMOUS NSCLC PARTICIPATING IN THE EXPANDED or radiofrequency ablation based on the decision of the Multidisciplinary
ACCESS PROGRAMME (EAP) Thoracic Committee of the institution. The primary outcome was overall
Frederico Cappuzzo1, Angelo Delmonte2, Serena Capici3, Lucio Crinò4, survival. The study was approved by de Institutional Ethics Committee and
Antonio Fabio Logroscino5, Paolo Sandri6, Lorenzo Livi7, Fabiana Vitiello8, registered in clinical trials NCT02805530. Results: Up to this moment, we
Diego Signorelli9, Luana Calabrò10, Daniele Turci1, Silvia Quadrini11, Paola have evaluated 29 patients with NSCLC and oligometastatic disease. Of
Antonelli12, Sabrina Giusti13, Francesco Di Costanzo14, Francesca Rastelli15, these, 62% males with a median age of 58 years (IQR 52.5-64.5), median CEA
Paolo Marchetti16, Giovanna Finocchiaro17, Enrico Cortesi18, Andrea Ardizzoni19 10.2 (IQR 3.25-55), 59% former or currently smokers (median 37.5 package/
1
Ausl Romagna, Ravenna/Italy, 2Medical Oncology, Istituto Scientifico Romagnolo year), wood-smoke exposure 28%. Overall 90% of the patients presented
Per Lo Studio E La Cura Dei Tumori (IRST) IRCCS, Meldola/Italy, 3Ospedale S. adenocarcinomas, 28% EGFR mutation (50% deletion of exon 19, 38%
Gerardo, Monza/Italy, 4 Azienda Ospedaliera Di Perugia, Perugia/Italy, 5Istituto mutation on exon 21). At diagnosis 93% of the patients had symptoms
Tumori “Giovanni Paolo Ii”, Bari/Italy, 6 Aou Santa Maria Degli Angeli, Pordenone/ mainly cough (48%), dyspnea (30%), neurologic symptoms (26%), weight
Italy, 7Radiation Oncology, Aou Careggi, Firenze/Italy, 8 A.O. Dei Colli-Monaldi- loss (18%) and dysphonia (15%). We evaluated the oligometastatic disease
Cotugno-Cto, Napoli/Italy, 9IRCCS, Istituto Nazionale Dei Tumori, Milano/Italy, status with PET-CT and MRI in 66% of the patients and the remaining with
10
A.O.U. Senese, Siena/Italy, 11 Asl Frosinone-Presidio Ospedaliero Ss Trinità, Sora/
CT scan plus MRI. At diagnosis 66% had one or two metastases, 14% three
Italy, 12Presidio Ospedaliero Di Busto Arsizio, Busto Arsizio/Italy, 13 Asl 8, Arezzo/
to four metastases and 20% five metastases. For metastatic sites CNS was
Italy, 14 Aou Careggi, Firenze/Italy, 15 Asur Marche Area Vasta 4, Fermo/Italy,
16
Azienda Ospedaliera S. Andrea, Roma/Italy, 17Humanitas Cancer Center Milano, the main site of metastases in 52% of patients, 28% contralateral lung, 17%
Rozzano/Italy, 18Policlinico Umberto I, Roma/Italy, 19Medical Oncology, S. Orsola- bone metastases and 7% at suprarenal. For radical treatment to the primary
Malpighi University Hospital, Bologna/Italy tumor, 59% chemoradiotherapy, 21% radiotherapy, 28% surgery and 3%
radiofrequency. For definite treatment for the metastases, 45% received
Background: Response patterns of immunotherapies differ from those seen radiotherapy, 14% chemoradiotherapy and 17% surgery. The mean dose of
with other therapies approved for the treatment of tumors. Due to this radiotherapy received for the control of the primary tumor was 56.3 Gy (SD
reason, immunotherapy protocols generally allow patients (pts) to continue 11.28 Gy) and 29.5 Gy (SD 3.84Gy) for metastases. After multimodal treatment
treatment beyond investigator-assessed radiographic progressive disease 24% had radiologic complete response. The median OS were 18.26 months
(PD) as long as there is ongoing clinical benefit, but to date no data has been (95%CI:10.89-25.64), the median OS for those with and without radiologic
reported regarding treatment beyond PD in routine clinical practice. Here complete response were 28.58 months (95%CI:12.98-44.18) and 14.45 months
we report the analysis about the subgroup of pts treated beyond initial PD (95%CI:10.40-18.51) respectively. Conclusion: Patients with oligometastatic
in the italian cohort of nivolumab EAP for pts with squamous non small cell NSCLC with agressive treatment have a large OS regardless their mutational
lung cancer (Sq-NSCLC). Methods: Nivolumab was available upon physician status.
request for pts aged ≥18 years who had relapsed after a minimum of one
prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 Keywords: oligometastatic NSCLC, Radical treatment
mg/kg was administered intravenously every 2 weeks to a maximum of 24
months. Pts included in the analysis had received ≥ 1 dose of nivolumab and
were monitored for adverse events (AE) using Common Terminology Criteria
for Adverse Events. Patients were allowed to continue treatment beyond
initial PD as long as they met the following criteria: investigator-assessed IMMUNOTHERAPY
clinical benefit, absence of rapid PD, tolerance of program drug, stable ADVANCED GENERAL –
performance status and no delay of an imminent intervention to prevent MONDAY, DECEMBER 5, 2016
serious complications of PD. Results: With a median follow-up of 5.2 months
(range 0-12.9), 363 pts were evaluable for response. Prior to first progression,
P1.06-008 NON-SMALL CELL LUNG CANCER IN OCTOGENARIANS:
the objective response rate (ORR) was 14%, with 1 complete response (CR)
REAL-LIFE CLINICAL PRACTICE; CHARACTERISTICS, THERAPY AND
and 50 (14%) partial responses (PR), and the disease control rate (DCR) was
41%. Sixty-six pts were treated beyond RECIST defined progression, with SURVIVAL
23 pts obtaining a non-conventional benefit, meaning a subsequent tumor Hirsh Koyi1, Gunnar Hillerdal2, Karl Gustav Kölbeck 3, Daniel Brodin3, Eva
reduction or stabilization in tumor lesions. In particular, 17 pts obtained a SD Brandén2
1
and 6 pts obtained a PR. As to July 2016, median overall survival in these pts Dept. of Respiratory Medicine, Gävle Hospital, Gävle/Sweden, 2Dept. of
had not been reached (95% CI: 3.2-4.6) and 6 months and 12 months OS were Respiratory Medicine, Gävle Hopsital, Gävle/Sweden, 3Department of Respiratory
75% and 53%, respectively. The safety profile was consistent to what already Medicine and Allergy, Karolinska University Hospital, Solna, Solna/Sweden
observed in the general population. Conclusion: As already observed in clinical
Background: Globally, more people are surviving to older age; consequently,
trials, these preliminary EAP data seem to confirm that a proportion of pts
an increasing proportion of cancer patients are aged >65 years and many
who continued treatment beyond PD demonstrated sustained reduction
are aged >70 years. Treatment of the elderly with lung cancer has, therefore,
or stabilization of tumor burden, with an acceptable safety profile. Further
become an important issue. We performed a retrospective study of our
investigations are warranted in order to better define and identify pts who
patients to demonstrate how octogenarians with non-small cell lung cancer
can benefit from treatment beyond progression.
(NSCLC) are treated in real-life clinical practice. Methods: A retrospective
Keywords: treatment beyond progression, Nivolumab, squamous NSCLC observational study of all elderly (>80 years) patients with NSCLC referred
to Department of Respiratory Medicine and Allergy, Karolinska Hospital,
Sweden, 2003-2010 and followed until June, 2016. Results: During the period
2662 patients were newly diagnosed with lung cancer. 485 (12.2%) were
80 years or older. 33 (6.8%) hade small cell lung cancer and were excluded,
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ leaving 452 for the study. 216 (47.8%) were male. Mean, median, and range
IMMUNOTHERAPY
age for males were 83.8, 83, and 80-96 years, respectively. These figures for
MONDAY, DECEMBER 5, 2016 females were 83.7, 83, and 86-95. 28 (6.2%) of the population were 90 years
old or older. 77.8% patients were current or former smokers with significant
differences between the genders (p<0.001). There was no difference in
P1.06-007 RADICAL TREATMENT OF SYNCHRONOUS performance status (PS) between the genders (p<0.93), with PS 0-1 in 45%,
OLIGOMETASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) PS2 in 26% and PS3-4 in 29%. 33.9% of patients were diagnosed in stages
Oscar Arrieta1, Rosa Luz Luna Palencia1, Omar Macedo-Pérez1, Feliciano 1-II, 34.1% in stage III and 31.9% in stage IV. Most of the patients, 45.6%, had
Barron1, José Francisco Corona Cruz1, Luis Alberto Chinchilla Trigos1, Monika adenocarcinoma, 18.1% squamous cell carcinoma, while histological diagnosis
Blake Cerda2, Federico Maldonado Magos2 was unavailable in 23.2%. There were significant differences in treatment
1
Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto modalities (p=0.040). Chemotherapy was given in 9.5%, local radiotherapy in
Nacional de Cancerologia, Mexico City/Mexico, 2Departamento de Radiooncología, 17%, stereotactic body radiotherapy (SBRT) in 10.6%, 6.9% underwent surgery
Instituto Nacional de Cancerología, Mexico City/Mexico and 209 (46.2%) were not given any therapy. Second-line chemotherapy
was given in 4% and third-line in 1.5%. Only one patient received fourth line.
Background: Cancer represents a large biological spectrum of disease ranging Median overall survival was 115 days in patients given no therapy and 362
from localized to multisystem involvement with multiple intermediate days in patients given any therapy. Patients who underwent surgery had a
stages. Oligometastatic NSCLC is thought to carry a better overall survival median overall survival of 5,6 years compared to 3,5 years for patients given
(OS) but there are few prospective studies that evaluate it. Methods: SBRT (p=0.0187). There were no significant differences in survival between
Prospective cohort study with NSCLC patients treated at the Instituto genders. Conclusion: Treatment of NSCLC patients 80 years and older with
any modality is feasible with a good PS. Survival is fairly good with surgery or weight loss was >5% and refractory cachexia if survival was <90 days from
SBRT. dietitian review. Results:
Keywords: Therapy, lung cancer, elderly, survival

IMMUNOTHERAPY
P1.06-009 DETERMINING OPTIMAL ARRAY LAYOUTS FOR

DELIVERING TTFIELDS TO THE LUNGS USING COMPUTER
SIMULATIONS
Noa Urman1, Zeev Bomzon1, Uri Weinberg2, Hadas Hershkovich1, Eilon Kirson1,
Yoram Palti1
1
Novocure Ltd., Haifa/Israel, 2Novocure GmbH, Root D/Switzerland
Background: Tumor Treating Fields (TTFields) are low intensity, alternating

310 patients with incurable lung cancer were reviewed by the dietitian. Mean
electric fields in the intermediate frequency range. TTFields disrupt mitosis
age was 68.8 (range 36-89). 42% were female, 58% were male. Mean weight
by interfering with formation of the mitotic spindle. The therapy is FDA
loss was 10%. 76% of patients had lost >5% of usual body weight. Mean
approved for the treatment of glioblastoma (GB). A study to assess the
pre-cancer body mass index (BMI) was 26.9 (kg/m2), mean BMI at referral was
efficacy of TTFields in combination with chemotherapy for the treatment
23.0 (kg/m2). Median survival of non-cachectic and cachectic cohorts were
of mesothelioma is underway, and a pivotal study testing the efficacy of
different (299 vs 188 days respectively, p=0.0078). 24% (73 patients) had
TTFields in NSCLC is planned. TTFields are delivered through two pairs of
refractory cachexia. Conclusion: Our study shows cachexia is very common
transducer arrays applied to the patient’s skin. In-vivo and In-vitro studies
(76%) in lung cancer and affects survival. A quarter of patients had refractory
suggest that treatment efficacy increases with field intensity. Therefore
cachexia. BMI is an insensitive measure of weight loss. Early symptom control
personalizing the array placement to deliver optimal field distributions is
improves survival in lung cancer and this data suggests patients are routinely
important and is a prerequisite when treating GB patients. However, optimal
being referred too late to a dietitian. Cachexia in lung cancer is a significant
array layouts for lung cancer patients have not yet been determined. Here
clinical problem. Could upfront assessment of cachexia improve outcome in
we present a finite element simulations-based study investigating optimal
patients with advanced lung cancer? We propose to investigate this further.
array layouts in male and female anatomic models. Methods: The study was
performed using the Sim4Life software package and the DUKE and ELLA Keywords: cachexia, metastatic, dietitian, nutrition
computational models (ZMT, Zurich, Switzerland). To represent individuals
with a variety of body dimensions, the models were linearly scaled. The
distribution of TTFields within the thorax of these models was calculated
for a set of array layouts. The layouts were ranked with highest scores for
those that conformed well to body contours and delivered uniform high POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
intensity fields to the lungs. Results: Uniform field distributions within the ADVANCED GENERAL –
lungs are obtained when the arrays are axially-aligned with the parenchyma MONDAY, DECEMBER 5, 2016
as much as anatomically possible. Generally, the layouts that received the
highest scores were those in which one pair of arrays delivered an electric field
from the anterolateral to the posterior-contralateral aspect of the patient, P1.06-011 ALTERED BODY COMPOSITION AND FAT LOSS IN
with the second pair inducing the field from the antero-contralateral to the ADVANCED NON-SMALL CELL LUNG CANCER
posterolateral aspect of the patient. However, due to body contours, this Anant Mohan, Rosemary Poulose, Ashraf Ansari, Randeep Guleria, Karan
type of layout does not adhere well to smaller females, potentially hampering Madan, Vijay Hadda, G. Khilnani
the efficient delivery of TTFields. Therefore, for smaller females, a layout in Dept of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical
which one pair of arrays is placed on the lateral and contralateral aspects of Sciences, New Delhi/India
the patients, and a second set of arrays is placed on the anterior and posterior
aspects of the patient is preferred. Conclusion: This study provides important Background: Assessment of body composition, including fat mass and fat%, is
insights into how TTFields distribution in the lungs is influenced by the array a useful measure of nutritional status in cancer and may help guide nutritional
layout. These results should be accounted for when developing guidelines for interventions. However, these abnormalities have not been well documented
transducer array placement on the thorax. in lung cancer. We aimed to study alterations in parameters of body
composition in Non small cell lung cancer (NSCLC). Methods: A retrospective
Keywords: Novel Therapies, Tumor Treating Fields, NSCLC, TTFields chart review was conducted of all newly diagnosed patients with NSCLC. Age
and sex matched healthy controls were recruited prospectively. Disease
staging was done according to the American Joint Committee on Cancer (7th
edition). Performance status was asssessed using the Karnofsky performance
Scale(KPS), and the Eastern Cooperative Oncology Group (ECOG). Details of
IMMUNOTHERAPY
body composition including basal Metabolic Rate (BMR), total body water
ADVANCED GENERAL – (TBW), fat mass, and Fat-free mass (FFM) were calculated by bioelectric
MONDAY, DECEMBER 5, 2016 impedance method using TANITA TBF 300 body composition analyzer. Results:
A total of 256 patients (83.6% males) and 211 controls (81.5% males) were
studied. The mean (SD) age of patients was 54.5(9.0) years, median smoking
P1.06-010 ANALYSIS OF THE INCIDENCE OF CANCER CACHEXIA
index was 598 (range, 0-2500) and mean duration of symptoms was 158.3(91.7)
IN PATIENTS WITH ADVANCED LUNG CANCER AT REFERRAL TO A
days. Median KPS was 80 (range, 40-100). Majority had Stage IV disease
DIETITIAN (54.7%), followed by Stage III (41.4%) and Stage II (3.9%). All measured
Adele Hug 1, Iain Phillips1, Lindsey Allan1, Jeewaka Mendis2, Veni Ezhil1 components of body composition were significantly lower in NSCLC compared
1
St Lukes Cancer Centre, Royal Surrey County Hospital, Guildford/United Kingdom, to controls (Table).Among patients with normal body weight (BMI 18.5 – 25
2
University of Surrey, Surrey Clinical Research Centre, Guildford/United Kingdom kg/m2), the TBW and FFM were significantly lower compared to their healthy
counterparts.
Background: Lung cancer is the second most common cancer diagnosed in
men and women in the UK with a very poor 5 year survival (10%). There is a lack
of robust data on the stage of cachexia in which patients with lung cancer
present. The severity of cachexia can influence overall outcomes and a
patient’s quality of life. Refractory (irreversible) cachexia indicates a poor
prognosis. Methods: We reviewed all patients diagnosed with metastatic
primary lung cancer that were referred to the Macmillan Oncology Dietitians
over a 4 year period at the Royal Surrey County Hospital. Reasons for referral
commonly included: weight loss, glycaemic control in diabetes, decreased oral
intake and food texture modification. We compared self-reported usual body
weight (UBW) to weight at referral. Patients were defined as cachectic if

metastasis (p=0.002). Bone, liver, subcutaneous, and pericardial metastases

showed no such tendencies. Conclusion: There are significant differences in
metastatic organ distributions of central vs. peripheral lung cancers both for
early and late metastases. Central primary tumors are more likely to give rise to
early metastases than peripheral ones. Results of molecular subgroup analyses
will be presented during the Conference.
Keywords: lung adenocarcinoma, primary tumor localization, distant

metastasis, early metastasis

IMMUNOTHERAPY
P1.06-013 PATIENT CHARACTERISTICS AND SURVIVAL: A

REAL-WORLD ANALYSIS OF US VETERANS WITH STAGE IV
ADENOCARCINOMA VS SQUAMOUS NSCLC
Manali Patel1, Monika Parisi2, Manish Patel2, Corey Pelletier2, Charles
Bennett3, Peter Georgantopoulos3
1
Stanford Cancer Center, Menlo Park/CA/United States of America, 2Celgene
Conclusion: NSCLC is associated with significant malnutrition and altered Corporation, Summit/NJ/United States of America, 3Wjb Dorn Va Medical Ctr,
body composition, especially reduction in the percentage of body fat. Columbia/SC/United States of America
Nutritional interventions must, therefore, be tailored accordingly for these
patients. Background: 5-year survival rate in patients with stage IV NSCLC was 1%.
Stage IV adenocarcinoma (ADENO) and squamous (SCC) account for 44% and
Keywords: bioimpedence, lung cancer, body composition 18% of stage IV NSCLC diagnoses, respectively. Patient characteristics and
survival in US veterans with stage IV ADENO vs SCC NSCLC were examined.
Methods: Patients with a unique diagnosis of stage IV NSCLC between
1/1/2010 and 12/31/2015 from the US Veterans Affairs (VA) health system
database were included. Lung cancer diagnoses were confirmed by VA Central
IMMUNOTHERAPY Cancer Registry and Veterans Health Administration National Patient Care
ADVANCED GENERAL – Database. Patients were excluded if they did not have 1 VA visit within 1 year
MONDAY, DECEMBER 5, 2016 before diagnosis. Results: 13,956 patients with stage IV NSCLC were included
(ADENO: n=6525 [47%]; SCC: n=3421 [25%]). Baseline characteristics were
P1.06-012 CENTRAL AND PERIPHERAL LUNG ADENOCARCINOMAS similar for ADENO vs SCC, including age at diagnosis (mean, 68.8 vs 69.2 y),
married at diagnosis (43.9% vs 42.2%), had known Agent Orange exposure
EXHIBIT DIFFERENT TIMING AND PREDILECTION FOR DISTANT
(17.4% vs 16.3%), and the majority were white (60.8% vs 63.8%). For ADENO vs
METASTASIS
SCC, more patients were former smokers (39.5% vs 34.3%), but fewer were
Thomas Klikovits1, Zoltan Lohinai1, Katalin Fabian2, Márton Gyulai3, Andrea current smokers (53.9% vs 61.1%). For ADENO vs SCC, occurrence of brain or
Fodor4, Judit Varga5, Erika Baranya6, Orsolya Pipek7, István Csabai7, Zoltan bone metastases were higher and incidence of chronic obstructive pulmonary
Szallasi8, József Tímár9, Balazs Hegedus1, Balazs Dome10, Judit Moldvay 11 disease or chronic pulmonary disease were lower (Table); age at death (mean,
1
Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria, 69.3 vs 69.7 y) and time from diagnosis to death (TDD; mean, 0.56 vs 0.55 y)
2
Semmelweis University Department of Pulmonology, Budapest/Hungary, 3Conty were similar. More ADENO vs SCC patients received chemotherapy (48.5% vs
Hospital of Pulmonology, Törökbálint/Hungary, 4Pulmonology, University of 44.1%). Mean TDD was longer in patients treated with chemotherapy vs not
Debrecen, Debrecen/Hungary, 5Saint George Hospital of County, Székesfehérvár/
(ADENO: 0.86 vs 0.31 y; SCC: 0.84 vs 0.35
Hungary, 6National Koranyi Institute of Pulmonology, Budapest/Hungary,
7
Department of Physics of Complex Systems, Eötvös Loránd University, Budapest/ y).
Hungary, 8 Children’S Hospital Informatics Program at the Harvard–Massachusetts
Institute of Technology Division of Health Sciences and Technology, Harvard
Medical School, Boston/AL/United States of America, 92nd Department of
Pathology, Budapest/Hungary, 10 Department of Tumor Biology, National Koranyi
Institute of Pulmonology, Budapest/Hungary, 11Tumor Biology, National Koranyi
Institute of Pulmonology, Budapest/Hungary
Background: Although distant metastases are major factors for unfavorable

prognosis in lung adenocarcinoma (ADC), metastatic patterns have not been
widely analyzed in this malignancy. Methods: Clinicopathological data of
1126 ADC patients (541 men, 585 women, mean age: 62.1 ± 9.4 years, 32-88
years) were studied retrospectively, focusing on the localization of primary
tumor and distant metastases. Metastases diagnosed at the time of primary
tumor diagnosis were defined as early metastases. For statistical analyses,
Fisher’s exact test and a chi-squared independence test were performed.
Results: At time of diagnosis, 621 patients had stage IV disease. 435 of them
had a solitary organ metastasis, mainly in the contralateral lung (n=187), in Conclusion: ADENO was more prevalent than SCC in veterans with stage IV
the brain (n=66), or in the bone (n=59). During the follow up period another NSCLC, similar to the overall population; stage IV SCC prevalence was higher
242 patients developed distant metastasis. 39% of all patients had central in the veterans than in the overall population. Mean TDD was longer in
(i.e. endobronchially visible) tumor. In cases with early-, late-, and non- chemotherapy-treated patients regardless of histology.
metastatic disease, the proportions of central tumors were 43%, 35% and 31%,
respectively. Central primary tumors were significantly more likely to give rise Keywords: stage IV, Real-World Analysis, Veterans, NSCLC
to early metastases than peripheral ones (p=0.021). When comparing central
and peripheral lung cancers according to their metastatic sites, in central
tumors lung metastases appeared significantly earlier (p=0.017), while in
peripheral ones bone metastases appeared significantly later (p=0.015). There
were significant differences in the metastatic organ distributions of central vs. POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
peripheral primary tumors for early (p=0.025) and late (p=0.009) metastases. ADVANCED GENERAL –
There was no significant difference in the metastatic organ distributions of MONDAY, DECEMBER 5, 2016
right vs. left lung primaries both for early and late metastases. In right lung
tumors brain metastases appeared later (p=0.047). No significant difference
was observed in the metastatic organ distributions of primary tumors of the
P1.06-014 WHAT FACTORS DETERMINE TREATMENT
upper vs. lower lobes for early (p=0.051), and late (p=0.528) metastases. Early SATISFACTION IN PATIENTS WITH ADVANCED NSCLC RECEIVING
appearance was characteristic for lung, pleural, and adrenal involvement CHEMOTHERAPY?
(p<0.001 in all comparisons), while late development was typical for brain Sabine Visser 1, Mark De Mol2, Nico Van Walree2, Jermo Van Toor 1, Brenda Den
Oudsten3, Bruno Stricker4, Joachim Aerts1 element simulations using realistic computational phantoms were used to
1
Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam/Netherlands, evaluate the field distribution generated by these arrays, and optimize their
2
Amphia Hospital, Breda/Netherlands, 3Tilburg University, Tilburg/Netherlands, design. Results: Novel array designs for delivering TTFields to the lungs were
4
Epidemiology, Erasmus MC, Rotterdam/Netherlands developed. These arrays are not designed as large patches, but comprise sets
of interconnected small patches that adhere to the natural contours of the
Background: In advanced non-small cell lung cancer (NSCLC) treatment patient’s bodies. Simulations showed that these arrays deliver uniform field
decisions regarding palliative chemotherapy are complex due to limited distributions to the lungs. A particularly noteworthy design is a pair of arrays
survival gain and treatment-related toxicities. Insight into determinants of in which one array was shaped as a circular ring placed around the neck and
patients’ treatment satisfaction may impact decision-making and patient care. shoulders, and the second array was shaped as a belt placed on the lower torso.
We determined the relation of patient- and treatment-related variables to This design yielded a highly uniform and intense field directed longitudinally
treatment satisfaction. Methods: In a prospective observational multi-center throughout the torso. Conclusion: The arrays presented in this study deliver
study, patients with stage IIIB or IV NSCLC receiving pemetrexed (PEM)-based high field intensities to the thorax whilst maintaining patient comfort. These
chemotherapy as first- or second-line treatment were enrolled. After four cycles designs could help to improve the outcome of TTFields therapy.
of chemotherapy, patients completed the WHO Quality of Life-BREF (WHOQoL-
BREF), which contains one item measuring overall QoL on a 1-5 scale, and the Keywords: Novel Therapy, TTFields, Tumor Treating Fields
Cancer Therapy Satisfaction Questionnaire (CTSQ). The CTSQ was recently
validated (Cheung et al, Qual Life Res. 2016;25(1):71-80). It consists of 16 items
scored on a 1-5 scale and contains three domains. Only satisfaction with therapy
(SWT) and feelings about side effects (FSE) were used. The domain scores range
between 0-100, with higher scores representing better SWT and more positive POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
FSE. We collected sociodemographic information and ECOG performance ADVANCED GENERAL –
status at baseline. Adverse events (cancer- or therapy-related) during MONDAY, DECEMBER 5, 2016
treatment were weekly registered (CTCAE 3.0). Tumor response measurements
were obtained (RECIST 1.1). Patient- and treatment-related determinants
P1.06-016 PULMONARY TUBERCULOSIS AMONG NEWLY
univariably associated with SWT (p<0.05) were analyzed using multivariable
linear regression (method: Enter). Results: Of the 95 patients receiving four
DIAGNOSED-THERAPY NAIVE ADVANCED NSCLC IN
cycles of chemotherapy, 69 patients completed the CTSQ. The majority of PERSAHABATAN HOSPITAL JAKARTA INDONESIA
these patients had stage IV NSCLC (87.7%) and received PEM-based therapy as Jamal Zaini1, Sita Laksmi Andarini2, Ririen R Ramadhani2, Elisna Syahruddin2,
first-line treatment (92.3%). Treatment resulted in stable disease (SD; 53.8%), Achmad Hudoyo2
partial response (PR; 40.0%) and progressive disease (PD; 6.2%). The mean SWT 1
Pulmonology and Respiratory Medicine/ Persahabatan Hospital, Faculty of
domain score was 79.6±13.1. Univariably, higher patients’ age (p=0.034), tumor Medicine Universitas Indonesia, Jakarta Timur/Indonesia, 2Pulmonology and
response (PR vs. SD or PD, p=0.040), overall QoL (p=0.008) and FSE (p=0.004) Respiratory Medicine/ Persahabatan Hospital, Faculty of Medicine Universitas
were significantly related to SWT. The frequency of (severe) adverse events Indonesia, Jakarta/Indonesia
was not associated with SWT (p=0.546). After including these variables in the
Background: The prevalence of lung cancer increased in the recent years in
multivariable analysis, only age (β=0.44; 95%CI (0.09-0.79)) and FSE (β=0.13;
Indonesia, meanwhile pulmonary tuberculosis (TB) is still a major public
95%CI (0.00-0.26) were independently related to SWT. Conclusion: Importantly,
health problems in this community. Malignancy such as lung cancer increase
higher SWT in elderly supports the opinion that palliative chemotherapy should
the risk of tuberculosis infection and reactivation, therefore evaluation
not be reserved for younger age groups. Although symptomatic adverse events
of tuberculosis among lung cancer patients is needed Methods: Newly
are known key contributors to QoL, the frequency of (severe) adverse events
diagnosed, therapy-naive advanced NSCLC subjects were enrolled from
was not related with SWT. However, in patients with better FSE treatment
a referral respiratory hospital Persahabatan Hospital Jakarta Indonesia
satisfaction was higher. Therefore, patients’ education about and management
between 2014-2015. Active pulmonary tuberculosis were diagnosed by Xpert
of adverse events may have added value in maintaining patients’ well-being
MTB/ RIF from induced sputum and LPA M. TB culture. Latent Tuberculosis
during chemotherapy, ultimately resulting in higher treatment satisfaction.
Infection (LTBI) was determined by Quantiferon-TB Gold-In-Tube (QFT-GIT).
This study is funded by ZonMw, the Netherlands.
Demographic and clinical characteristics were evaluated. Results: Of 50
Keywords: advanced NSCLC, treatment satisfaction, chemotherapy, pemetrexed lung cancer subjects enrolled, 30 (60%) men with mean of age 55 years old
(31- 74 years old). Eighty five percents were adenocarcinoma (42 subjects)
and 15% squamous cell lung cancer. Most of them were at end stage (87%
stage IV and 13%stage IIIB) with WHO performance status (PS) 1 to 3 (20 %
PS 1, 70% PS 2 and 10% PS 3). Comorbidities among this group were COPD
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ (3 ssubjects), diabetes mellitus (2 subjects), hypertension (4 subjects),
IMMUNOTHERAPY congestive heart failure (1 subjects). Active tuberculosis were diagnosed in 2 %
MONDAY, DECEMBER 5, 2016 (1 subject). Based on Quantiferon results, 14 % were positive (7 subjects) and
classified as latent tuberculosis infection (LTBI); 60% (30 subjets) classified
as non-LTBI (negative Quantiferon result) but 12 (24%) indeterminate
P1.06-015 DESIGNING TRANSDUCER ARRAYS FOR THE DELIVERY cases. The characteristics of LTBI patients were 67% men, two third were
OF TTFIELDS WHILST MAXIMIZING PATIENT COMFORT AND FIELD adenocarcinomas, 80% stage IV of lung cancer, 80% having WHO PS 2 and
INTENSITY IN THE THORAX 3, 50% were underweight (body mass index (BMI) < 17.5. Conclusion: Active
Zeev Bomzon1, Hadas Hershkovich1, Uri Weinberg2, Eilon Kirson1, Sholi pulmonary tuberculosis and latent tuberculosis infection is common among
Strauss1 newly diagnosed therapy naive advanced NSCLC in this population. Most of
1
Novocure Ltd., Haifa/Israel, 2Novocure GmbH, Lucerne/Switzerland them are men, adenocarcinoma, PS 2-3, and half of them were underweight.
Background: Tumor Treating Fields (TTFields) are an anti-mitotic therapy that Keywords: advanced NSCLC, active tuberculosis, LTBI
utilizes low intensity electric fields in the intermediate frequency range to
disrupt cell division. A study to test the efficacy of TTFields in combination
with chemotherapy for the treatment of mesothelioma is underway, and a
pivotal study testing the efficacy of TTFields in treating NSCLC is planned. POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
TTFields are delivered via two pairs of transducer arrays placed on the patient’s IMMUNOTHERAPY
skin. The transducer arrays comprise a set of ceramic disks that make electric ADVANCED GENERAL –
contact with the skin through a thin layer of conductive medical gel. The disks
in the arrays currently in use are arranged in an almost rectangular pattern.
One pair of arrays is placed on the posterior and anterior sides of the patient’s P1.06-017 OBSERVATIONAL STUDY ON PROLONGED DISEASE
thorax. The other pair is placed on the lateral and contralateral aspects of the STABILIZATION IN ADVANCED NSCLC EGFR WT/UNKNOWN
patient. This configuration has several limitations: PATIENTS TREATED WITH ERLOTINIB IN SECOND LINE
The array placed on the chest may not adhere well to body curvature, leading to Francesco Grossi1, Agnese Montanino2, Maria Rita Migliorino3, Antonio
sub-optimal electric contact that reduces field intensity in the tumor. Santo4, Michele De Tursi5, Angelo Delmonte6, Fabiana Vitiello7, Manlio
Mencoboni8, Vito D’Alessandro9, Giampiero Romano10, Erika Rijavec1, Andrea
In females and obese individuals, fields generated by arrays placed on the Misino11, Antonio Chella12, Mario Roselli13, Silvio Cavuto14
anterior and posterior have to traverse thick layers of adipose in the breast. 1
Lung Cancer Unit, IRCCS Aou San Martino - Ist, Genova/Italy, 2U.O.C. Oncologia
The high resistivity of these layers damps the intensity of TTFields in the lungs. Medica Toraco-Polmonare, Istituto Nazionale Tumori, Naples/Italy, 3Uosd
Pneumologia Oncologica, San Camillo - Forlanini Hospital, Roma/Italy, 4 Givop
Here we present novel array designs intended to overcome these limitations. (Gruppo Interdisciplinare Veronese Oncologia Polmonare), Azienda Ospedaliera
Methods: Multiple concepts for arrays designed to adhere comfortably to Universitaria Integrata Di Verona, Verona/Italy, 5Dip. Di Scienze Mediche, Orali E
the body, whilst avoiding regions of high adipose were proposed. Finite Biotecnologiche Sezione Di Oncologia Medica, Università G. D’Annunzio, Chieti/

Italy, 6Oncologia Medica – Gruppo Di Patologia Toracica, Istituto Scientifico treatments received included non-platinum based regimens, bevacizumab
Romagnolo Per Lo Studio E La Cura Dei Tumori - IRCCS, Meldola/Italy, 7U.O.S.D. and investigational drugs. The most common second- and third-line treatment
Dh Pneumoncologico, A.O. Dei Colli- Monaldi, Napoli/Italy, 8Struttura Semplice options were docetaxel, erlotinib and gemcitabine. There was limited published
Dipartimentale Oncologia, Villa Scassi, Genova/Italy, 9Sezione Pneumo-
literature on lines of treatment prescribed in the UK whereby only information
Oncologica - Medicina Interna, IRCCS “casa Sollievo Della Sofferenza”, San Giovanni
on second-line prescribed therapies was available. These included docetaxel,
Rotondo/Italy, 10U.O. Oncologia, Presidio Ospedaliero V. Fazzi, Lecce/Italy,
11
Oncologia Medica, IRCCS Oncologico Giovanni Paolo Ii, Bari/Italy, 12Dipartimento erlotinib, and pemetrexed. Based on this data, treatment patterns appear to
Cardiotoracico – Pneumologia 2, A.O. Universitaria Pisana – Ospedale Cisanello, be in-line with recommendations from European and national guidelines of
Pisa/Italy, 13U.O.S.D. Oncologia Medica, Policlinico Universitario Tor Vergata, Roma/ NSCLC treatments with the exception of crizotinib and afatinib, which were not
Italy, 14Direzione Scientifica - Infrastruttura Ricerca E Statistica, Arcispedale Santa approved at the time of the data collection for the majority of studies included
Maria Nuova - IRCCS, Reggio Emilia/Italy in the literature review. Conclusion: Treatment practices in advanced NSCLC
are similar across EU5 countries with slight variations depending on the time
Background: In advanced NSCLC, erlotinib treatment was shown to improve
period assessed and most notably on the approval and availability of novel
survival independently of EGFR status and induce high rates of prolonged
therapies. Overall, treatments reported as part of clinical practices across EU5
stable disease (SD). It has previously been reported that, after second-/third-
countries prior to 2010 are still recommended by both national and European-
line erlotinib, PFS and OS are long-lasting and similar between patients with SD
wide guidelines. Furthermore, there is a paucity of comprehensive treatment
≥8 months and those attaining partial/complete response (PR/CR). The present
patterns information for the UK.
study investigated the clinical value of SD in a real-world setting of advanced
NSCLC. Methods: This Italian multicenter observational study enrolled patients Keywords: treatment patterns, clinical practice, NSCLC, systematic literature
with stage IIIB-IV NSCLC on second-line erlotinib and wild-type/unknown review
EGFR mutational status, with SD, CR or PR per RECIST v1.1 lasting for ≥4 weeks.
Patients were observed from the beginning of erlotinib for approximately 8
months or until death. Primary end-points were the rate and duration of SD
(i.e. time interval from erlotinib start to the last evidence of SD by RECIST)
or CR+PR. Secondary end-points were OS and PFS (i.e. time interval from the POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
erlotininb start to the first evidence of progression), estimated by the Kaplan- ADVANCED GENERAL –
Meier method and calculated by response duration or disease stabilization. MONDAY, DECEMBER 5, 2016
Adverse events occurring during the observation period were also recorded.
Results: At the cut-off date of 30/04/16, 144/172 (83.7%) enrolled patients
were evaluable for response (mean age 69.1 years, 61.8% males). At the start of P1.06-019 THE POSSIBILITY OF THE ADDITIONAL LOCAL THERAPY
erlotinib treatment, 85.4% were non-smokers, 89.6% had an ECOG-PS of 0-1, TO SYSTEMIC CHEMOTHERAPY IN ADVANCED LUNG CANCER CASES
and 84.7% had stage IV NSCLC (83.3% adenocarcinoma and 11.8% squamous WITH MULTIPLE METASTASES
cell carcinoma). Following second-line erlotinib, 82.6% (119/144) of patients Takeshi Honda1, Hirofumi Uehara2, Maika Natsume1, Yoko Fukasawa1,
achieved SD and 17.4% (25/144) PR. Notably, SD was maintained for ≥8 months Takahiko Sakamoto1, Ryo Usui1, Shuji Ota1, Yasuko Ichikawa1, Kiyotaka
in 27% (39/144) of cases. At the end of the observation period, 12 (8.3%) patients Watanabe1, Nobuhiko Seki1
had deceased, none with SD ≥8 months. Median OS had not been reached by 1
Internal Medicine, Teikyo Univ., Tokyo/Japan, 2Thoracic Surgery, Teikyo Univ.,
the entire population. According to SD duration, median OS was 4.3 months if Tokyo/Japan
<2 months, 6.8 if between 2 and 5 months, and not reached if ≥5 months or if
PR. Median PFS was 9.0 months in the entire population, 8.7 among patients Background: In stage IV non-small cell lung cancer (NSCLC) patients with
with SD and 10.8 with PR. According to SD duration, PFS was 1.4 if <2 months, multiple metastases, a various pattern of disease progression is observed,
4.4 months if between 2 and 5 months, 7.5 if between 5 and 8 months and 10.5 including the growth of only primary site, the growth of only pre-existing
if ≥8 months. No unexpected toxicities were observed. Conclusion: In advanced metastatic site, or the appearance of new metastatic site. The aim of our study
NSCLC, second-line erlotinib yielded a high rate of SD, lasting ≥8 months in 27% is to evaluate the detailed recurrence pattern in patients with stage IV NSCLC,
of cases, with PFS similar to PR patients and low mortality rate. and is also to evaluate whether a specific patient’s population exists whose
disease progression is well controlled by the additional local therapy, such as
Keywords: Erlotinib, EGFR wild-type, stable disease, advanced NSCLC surgery or radiotherapy to the primary or pre-existing metastatic site, during
or after the systemic chemotherapy. Methods: NSCLC patients in stage IV
admitted to our hospital from 2012 to 2014 were examined retrospectively.
The recurrence pattern was classified into the following groups; the growth
of primary site, the growth of pre-existing metastatic site, or the appearance
IMMUNOTHERAPY of new metastatic site. Furthermore, progression-free survival (PFS), overall
ADVANCED GENERAL – survival (OS), and new lesion-free survival (NFS) of these groups were examined,
MONDAY, DECEMBER 5, 2016 respectively. Results: Patients treated with chemotherapy for stage IV NSCLC
were 114 cases. The median age was 70 years old, and male was 74 cases. The
P1.06-018 TREATMENT PATTERNS AND CLINICAL PRACTICES OF number of platinum-based combination regimen was 71 cases, monotherapy
was 16 cases, epidermal growth factor receptor tyrosine kinase inhibitor was
ADVANCED (STAGE IV) NON-SMALL CELL LUNG CANCER (NSCLC) IN
25 cases, crizotinib was two cases. In the first-line chemotherapy, median PFS,
EUROPE - A STRUCTURED LITERATURE REVIEW median OS and median NFS in all patients were 172 days, 417 days and 270 days.
Thomas Brodowicz 1, Daniela Niepel2, Emma Booth2, Rohini K Hernandez3, Median PFS, median OS and median NFS in patients for the growth of primary
George Braileanu4, Marie Cawkwell4, Justyna Amelio5 site were 235 days, not reached and not reached. Median PFS, median OS and
1
Clinical Division of Oncology, Medical University Vienna – General Hospital, median NFS in patients for the growth of pre-existing metastatic site were
Austria & Central European Cooperative Oncology Group, Vienna/Austria, 2 Amgen 171 days, 250 days and 205 days. Median PFS, median OS and median NFS in
(Europe) GmbH, Zug/Switzerland, 3 Amgen Inc., Thousand Oaks/CA/United States patients for the appearance of new metastatic site were 149 days, 423 days and
of America, 4 Adelphi Values, Bollington/United Kingdom, 5 Amgen Ltd., Uxbridge/
149 days. Conclusion: The prognosis of the appearance of new metastatic site
United Kingdom
group seems to be worse than the growth of primary site group in the pattern
Background: Non-small cell lung cancer (NSCLC) is associated with high of disease progression in the first-line chemotherapy. And the prognosis of
mortality and a poor five-year survival. Novel therapies in the pipeline hold the growth of pre-existing metastatic site group seems to be worse than the
promise to address these unmet needs and improve prognosis. Furthermore, appearance of new metastatic site group. In the stage IV NSCLC therapy, there
their introduction is expected to bring considerable changes to the European is a possibility that the treatment outcomes will be improved according to well
treatment landscape. The aim of this review is to provide an overview of controlled the pre-existing metastatic site by the additional local therapy.
the current treatment patterns for advanced (stage IV) NSCLC across five
Keywords: local therapy, systemic chemotherapy, NSCLC
European countries (EU5; France, Germany, Italy, Spain and the UK). Methods: A
structured literature search was conducted in electronic databases for studies
published between January 2010 and February 2016 to identify publications
reporting on treatments for stage IV NSCLC in European populations.
Additional literature searches of relevant European conferences and internet- POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
based sources were performed to ensure the most up-to-date evidence and IMMUNOTHERAPY
published clinical guidelines in the EU5 countries were captured. Results: A total MONDAY, DECEMBER 5, 2016
of nine relevant articles (five full-text studies and four conference abstracts) as
well as ten clinical guidelines were eligible for inclusion in the literature review.
All publications identified were observational studies of advanced NSCLC P1.06-020 PREVALENCE OF AUTOIMMUNE DISEASE IN US
treatment patterns in the EU5 with data collected between 2005 and 2014. VETERANS WITH NON-SMALL CELL LUNG CANCER (NSCLC)
The most commonly reported first-line treatments were cisplatin, carboplatin Manali Patel1, Monika Parisi2, Corey Pelletier2, Charles Bennett3, Peter
and pemetrexed, a trend supported by data from individual countries where Georgantopoulos3
platinum-based regimens were the most widely prescribed. Other systemic
1
Stanford Cancer Center, Menlo Park/CA/United States of America, 2Celgene therapy (3L+T). 85% (n=110) of the NSq and 40% (n=17) of the squamous (Sq)
Corporation, Summit/NJ/United States of America, 3Wjb Dorn Va Medical Ctr, patients received at least one Bmx test. 81% (n=105) and 19% (n=25) of NSq
Columbia/SC/United States of America patients, and 40% (n=17) and 24% (n=4) of Sq patients received an EGFR and
ALK test, respectively. EGFR Tyrokinase Inhibitors were most commonly
Background: Immunotherapy has emerged as an effective treatment strategy
used among NSq EGFR mutated patients (n=44) across all lines. 86% (n=38)
in cancer; patients with preexisting autoimmune diseases are often restricted
of the patients used Gefitinib in 1LT and Erlotinib was used in 2LT (n=11 of 30,
from use. The prevalence of autoimmune disease was 12.5% worldwide
37%) and 3LT (n=9 of 15, 60%) patients. All ALK positive patients (n=2) in 1L
(Lerner, Int J of Celiac Disease, 2015) and 24.6% in US patients with lung cancer
received anti-ALK therapy (Crizotinib). Among NSq EGFR/ALK negative or
(LC) (Khan, JAMA Oncol 2016). We report autoimmune disease prevalence in
unknown patients (n=83), 89% (n=74) received platinum combinations, most
veterans with NSCLC in a real-world setting. Methods: Patients with a unique
commonly carboplatin+paclitaxel (n=22, 26.5%). Single agents (n=29, 67%
diagnosis of NSCLC between 1/1/2010 and 12/31/2015 were included.
and n=11, 50%) were commonly used in NSq EGFR/ALK negative or unknown
Diagnoses were confirmed by VA Central Cancer Registry and Veterans Health
patients receiving 2LT (n=43) and 3LT (n=22); most commonly docetaxel
Administration National Patient Care Database. Patients were excluded if
(n=15, 35% & n=5, 23%). Majority of the 1LT patients with Sq histology
they had <1 VA visit within 1 year prior to diagnosis. Baseline autoimmune
(36/43, 84%) received platinum combinations therapy; most commonly
diseases were identified using ICD-9 codes for 36 organ-specific and 7 systemic
carboplatin+paclitaxel (51%). Among 2LT, 67 % (n=20) received a single agent,
autoimmune diseases. Autoimmune disease was defined as having ≥1 claim of
most commonly docetaxel (n=14, 47%). Single agents were commonly used
any type (broad definition) or having ≥1 inpatient claim or ≥2 outpatient
in 73% (n=11) of the patients receiving 3L+T. Overall, the average length of
claims ≥30 days apart (narrow definition). Results: 40,371 patients with
stay, regardless of line of therapy, was 24.6 days per admission. Duration of
NSCLC were included (stage IV adenocarcinoma n=6525, stage IV squamous
treatment was longest for 1LT (mean [SD] 140 [175] days), followed by 2LT (66
cell carcinoma (SCC) n=3421). Almost all patients were male (99.9%).
[129] days) and 3L+T (65 [83] days).Median OS for Japan from start of 1LT & 2LT
Autoimmune disease prevalence was greater per broad vs narrow definition in
was 9.9 and 4.7 months, respectively. Conclusion: NSq patients are frequently
all patients (15.7% vs 13.6%), adenocarcinoma patients (13.4% vs 11.0%), and
tested for Bmx in Japan. Treatment is personalized according to mutation
SCC patients (15.0% vs 12.3%). By broad definition, 13.4% of all patients, 11.7%
status and is in concordance with recommended guidelines.
of patients with stage IV adenocarcinoma, and 13.0% of patients with stage IV
SCC had 1 autoimmune disease; 2.3%, 1.7% and 2.0% had >1 autoimmune Keywords: lung cancer, treatment patterns, HEALTH CARE RESOURCE USE,
disease, respectively. The most common autoimmune diseases in all 3 patient JAPAN
populations were psoriasis, chronic rheumatic heart disease (CRHD),
rheumatoid arthritis (RA), Addison disease, and ulcerative colitis (Table).

IMMUNOTHERAPY
P1.06-022 CLINICAL CHARACTERISTICS OF SURVIVAL OUTLIERS IN

STAGE IV ADENOCARCINOMA LUNG CANCER PATIENTS
Andrea Fung 1, Adrijana D’Silva1, Haocheng Li1, Shannon Otsuka1, D. Gwyn
Bebb2
1
University of Calgary, Calgary/AB/Canada, 2Oncology, TBCC Translational Labs,
University of Calgary, Calgary/AB/Canada
Background: Lung cancer is the leading cause of cancer deaths among men
and women in Canada. Many lung cancer patients are diagnosed at advanced
Conclusion: Prevalence of autoimmune disease was lower in the stages of disease, which is associated with poor survival outcomes. The mean
predominantly male US veterans with NSCLC than the general population survival of stage IV non-small cell lung cancer (NSCLC) patients is typically less
with LC; the prevalence was similar regardless of stage or histology. The most than 12 months; however, there appears to be a small subset of patients with
frequent autoimmune diseases were psoriasis, CRHD, and RA. advanced disease that live substantially longer than the norm. Our study aims
to determine whether certain clinical characteristics correlate with longer
Keywords: NSCLC, real-world setting, Autoimmune, Veterans survival in stage IV NSCLC patients. Methods: Data on 1803 stage IV NSCLC
patients (1291 adenocarcinoma, 512 squamous cell carcinoma) from 1999-2011
were extracted from the Glans Look Lung Cancer database. Adenocarcinoma
data is presented here; squamous cell carcinoma data analysis is ongoing.
Clinical characteristics such as age, gender, ethnicity, smoking history,
IMMUNOTHERAPY histology, molecular testing, metastatic disease, treatments, and
ADVANCED GENERAL – socioeconomic factors were compared between survival outliers and patients
with average survival. Survival outliers were defined as those patients who
lived > 5 years, or greater than 2 standard deviations from mean survival (42.1
P1.06-021 TREATMENT PATTERNS AND HEALTHCARE RESOURCE months). Results: In the survival outlier group, there were 25 patients who
USE FROM A RETROSPECTIVE COHORT OF JAPANESE PATIENTS lived >5 years, and 59 who lived >42.1 months. Survival outliers included a
higher percentage of females, had a smaller smoking history, smaller tumour
WITH ADVANCED NON-SMALL CELL LUNG CANCER
size at diagnosis, received more treatment lines, and had lower metastatic
Terufumi Kato 1, Kiyoshi Mori2, Koichi Minato3, Hideki Katsura4, Kazuko disease burden at diagnosis (P<0.05 in the outlier group with survival >42.1
Taniguchi5, Ashwini Arunachalam6, Smita Kothari6, Xiting Cao6, Hiroshi Isobe7 months). Upon further characterization of metastatic disease, there appears
1
Kanagawa Cardiovascular and Respiratory Center, Kanagawa Cardiovascular and to be survival outliers associated with no liver metastases and less sites
Respiratory Center, Yokohama/Japan, 2Department of Thoracic Diseases, Division of metastases at diagnosis, as well as with stage M1a disease compared to
of Thoracic Oncology, Tsuboi Cancer Center Hospital, Koriyama/Japan, 3Division of
stage M1b. Conclusion: Adenocarcinoma patients with localized and lower
Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma/Japan, 4Division of
Resipratory Medicine, Tokyo Women’s Medical University Yachiyo Medical Center,
metastatic disease burden and no liver metastases at the time of diagnosis
Tokyo Women’s Medical University, Tokyo/Japan, 5Msd K.K., Tokyo/Japan, 6Core, appeared to live longer than their counterparts. Further statistical analysis
Merck & Co, Kenilworth/NJ/United States of America, 7Department of Medical is ongoing to determine the significance of other clinical characteristics with
Oncology, Kkr Sapporo Medical Center, Sapporo/Japan respect to survival. The present study will help us better understand the
importance of various clinical parameters and their association with survival,
Background: The treatment landscape for advanced/metastatic non-small in hopes of improving outcomes for lung cancer patients in the future.
cell lung cancer (NSCLC) has changed with the advent of targeted therapies
and the use of companion diagnostics. Methods: The primary objective Keywords: stage IV adenocarcinoma, Survival Outliers
of this multi-site, retrospective, chart review study was to describe the
treatment patterns, Biomarker (Bmx) testing practices and health care
resource use (HCRU) in patients who initiated first line therapy (1LT) for
newly diagnosed Stage IIIB/IV NSCLC between January 2011 - July 2013 in
Japan. Data were analyzed descriptively. Overall survival (OS) was estimated IMMUNOTHERAPY
using the Kaplan-Meier method. Results: Of the 175 Japanese patients ADVANCED GENERAL –
70% were male, 19% non- smokers, mean age of 68.8 years (SD=7.75), 83% MONDAY, DECEMBER 5, 2016
stage IV and 74 % (n=129) with non-squamous (NSq) histology. 60% (n=105)
received second line therapy (2LT) and 31% (n=55) received third line +
P1.06-023 CLINICOPATHOLOGICAL CHARACTERISTICS OF

AXILLARY LYMPH NODE METASTASIS IN LUNG CANCER computed tomography and brain imaging. Synchronous metastatic sites were
Yue Kong, Ming Chen categorized into 7 areas, and whole-body metastatic scores were calculated
from 1 to 7 by summation of each involved region. We compared the patient,
Zhejiang Cancer Hospital, Hangzhou/China
tumor, and metastatic characteristics according to the histological subtypes,
Background: The morbidity and mortality of lung cancer are rather high. and examined clinical outcomes. Results: The enrolled study cohort comprised
One major metastasis pathway of lung cancer is lymph node metastasis. 81% (n=346) Adenoca patients and 19% (n=81) SQ patients. The median age
The incidence of axillary lymph node metastasis(ALNM) is rare, and little is of the study population was 65 years (range, 30–94 years), and 263 (61.6%)
known about its clinicopathological characteristics. Methods: The clinical patients were male. The most common metastatic sites were thoracic lymph
data of 91 patients with ALNM who were treated in Zhejiang Cancer Hospital nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%)
from January 1, 2007 to December 31, 2013 were retrospectively analyzed. and bone (54.8%). The distribution of patient characteristics revealed that
The relevance of tumor site, local lymph node site and axillary lymph node age 65 years (69.1% vs 50.6%; P=0.003) and male sex (84% vs 56.4%; P<0.001)
site were checked by contingency table. Survival rates were calculated by the were more frequently found in SQ patients. Regarding metastatic features,
Kaplan-Meier method and compared by the log-rank test. Results: Lung cancer bone metastasis (60.4% vs 30.9%; P<0.001), lung to lung/lymphangitic
patients with ALNM were often presented with adenocarcinoma(59.3%, metastasis (63% vs 42%; P=0.001), and brain metastasis (35% vs 16%; P=0.001)
peripheral tumor type(71.4%), pleura invasion with pleural effusion(48.4%) were significantly and more frequently found in Adenoca patients. Patients
or chest wall invasion(52.7%). There was a relationship between tumor withhigh metastatic scores (score 3–6) were more frequently found to have
site(P<0.001), local lymph node site(P<0.001) and axillary lymph node site. The Adenoca (91.6% vs 73.4%; P<0.001). In multivariate prognostic evaluation, sex
median survival time of lung cancer patients with ALNM was 19.02 months, (P=0.001), age (P<0.001), histology (P<0.001), LN status (P=0.032), pleural/
2-year survival rate is 62.64%. Patients detected with ALNM at the initial pericardial metastasis (P=0.003), abdomen/pelvis metastasis (P<0.001),
diagnose had poorer prognosis (p=0.002). axilla/neck metastasis (P=0.006), and treatment factors (P<0.001) remained
independent prognostic factors affecting overall survival. Conclusion: We
observed distinctive patterns of primary metastases and clinical outcomes
according to the histological subtypes in stage IV NSCLC. Future studies need
to disclose the underlying mechanism of these unique metastatic features
and tumor biologies.
Keywords: Adenocarcinoma, Squamous cell carcinoma, Metastases, lung cancer

IMMUNOTHERAPY
P1.06-025 ANALYSIS OF RISK FACTORS FOR DEVELOPMENT OF

SKELETAL-RELATED EVENTS IN WOMEN WITH BONE METASTASES
FROM NSCLC AND BREAST CANCER
Franco Lumachi1, Paolo Ubiali2, Alessandro Del Conte3, Francesco Mazza4,
Stefano Basso2
1
Department of Surgery, Oncology & Gastroenterology, University of Padua, School
of Medicine, Padova/Italy, 2Department of Surgery, General Surgery, S. Maria
Degli Angeli Hospital, Pordenone/Italy, 3Medical Oncology, S. Maria Degli Angeli
Hospital, Pordenone/Italy, 4Department of Medicine, Pneumology Section, S. Maria
Degli Angeli Hospital, Pordenone/Italy
Background: Bone metastasis (BM) are common (up to 50% of cases) in patients
with advanced non-small cell lung cancer (NSCLC) and other malignancies,
including prostate cancer and breast cancer (BC). In patients with BMs, the
onset of skeletal-related events (SREs), such as pathological fracture, malignant
hypercalcemia, or spinal cord compression requiring surgery or radiation
Conclusion: ALNM from lung cancer is rare, it may be involved through direct therapy, seriously affects the quality of life of patients and overall survival. The
chest wall invasion, spread from supraclavicular and mediastinal lymph node purpose of this study was to analyze the risk factors (RFs) for development of
metastasis or systemic origin. Patients detected with ALNM at the initial SREs in women with advanced NSCLC and BC, with the aim of highlighting the
diagnose had poorer prognosis. differences (if any) between the two groups of patients. Methods: The medical
records of 16 women with BMs from NSCLC (Group A) and 15 women with BMs
Keywords: axillary lymph node metastasis, lung cancer, clinicopathological
from luminal-type BC (Group B) were reviewed. The following RFs have been
characteristics, Prognosis
considered: age >65 years, ECOG performance status (PS) <2, the presence
of extra-skeletal metastases (ESM) or hypercalcemia (>2.65 mmol/L), and
number of BMs >1. Odds ratio (OR) estimates and the relative 95% confidence
interval (CI) were calculated. A p-value level <0.05 was considered statistically
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ significant. Results: During follow-up, 5 (33.3%) Group A and 111 (68.7%) Group
IMMUNOTHERAPY B patients developed SREs (OR=4.40, p=0.04), respectively. The results are
reported in the Table. No significant difference (p=NS) was found between
groups in relation to ECOG-PS, ESM or hypercalcemia, and number of BMs. Only
the age >65 years (OR=0.22, p=0.04) represented a weak significant risk factor.
P1.06-024 DISTINCTIVE PATTERNS OF PRIMARY METASTASES
AND CLINICAL OUTCOMES ACCORDING TO THE HISTOLOGICAL Parameter NSCLC BC OR 95% CI p-value
SUBTYPES IN STAGE IV NON-SMALL CELL LUNG CANCER No. of patients 15 16 - - -
Dong Soo Lee 1, Seung Joon Kim2, Yeon Sil Kim3, Jin Hyoung Kang4 0.97-
1 Skeletal-related events 33.3% 68.7% 4.40 0.04
Department of Radiation Oncology, College of Medicine, the Catholic University of 19.85
Korea, Seoul/Korea, Republic of, 2Pulmonary Medicine, Seoul St. Mary’s Hospital,
0.05-
Seoul/Korea, Republic of, 3Radiation Oncology, Seoul St. Mary’s Hospital, Seoul/ Age >65 years 73.3% 37.5% 0.22 0.04
Korea, Republic of, 4 Medical Oncology, Seoul St. Mary’s Hospital, Seoul/Korea, 1.01
Republic of ECOG-Performance status 0.07-
40.0% 18.8% 0.34 0.25
>2 1.76
Background: The purpose of this study was to compare the primary
0.47-
patterns of metastases and clinical outcomes between adenocarcinoma Extra-skeletal metastases 26.7% 43.7% 2.14 0.32
9.70
(Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV
Non-small cell lung cancer (NSCLC). Methods: Between June 2007 and June 0.06-
Malignant hypercalcemia 26.7% 12.5% 0.39 0.39
2013, a total of 427 eligible patients were analyzed. These patients were 2.55
histologically confirmed as Adenoca or SQ and underwent systemic imaging 0.12-
Multiple bone metastases 53.5% 37.5% 0.52 0.38
studies, including 18F-fluorodeoxyglucose positron emission tomography/ 2.20
Conclusion: Women with BMs from NSCLC has a reduced risk for development median age (range), 71 years (55–84); gender male/female, 30/8; pStage at
of SREs compared to those with BC, but elderly (>65 years) patients require operation IA/IB/IIA/IIB/IIIA/IIIB, 9/6/9/8/5/1; histology small cell carcinoma/
a closer surveillance, and a precocious bisphosphonate treatment could be squamous cell carcinoma/adenocarcinoma, 5/12/21. There were no significant
suggested. differences in patient characteristics between each treatment group. The
proportion of patients who experienced disease progression after treatment
Keywords: bone metastases, Skeletal-related events, NSCLC was 75.0% (6/8) in the RT group, 20.0% (2/10) in the CRT group, and 77.8%
(14/18) in the CT group. Progression free survival (PFS) tended to be better in
the CRT group than in the other treatment groups. The differences in median
PFS (months) were; RT vs CRT: 8.0 vs 15.5, HR=0.210 (95%CI 0.042-1.047),
P=0.057; CRT vs CT: 15.5 vs 14.0, HR=0.206 (95%CI 0.047-0.908), P=0.037.
IMMUNOTHERAPY Conclusion: In patients with postoperative local recurrence of lung cancer,
ADVANCED GENERAL – CRT yielded better outcomes than the other treatments in terms of PFS.
Keywords: postoperative, recurrence, relapse, local
P1.06-026 ADENOSQUAMOUS CARCINOMA OF THE LUNG: A SINGLE
INSTITUTION EXPERIENCE IN THE ERA OF MOLECULAR TESTING
Kamal Kishore Mandalapu
Hematology and Oncology, Merit Health Biloxi., Biloxi/MS/United States of America POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
Background: Adenosquamous carcinoma (ADS) lung is rare subtype of non- ADVANCED GENERAL –
small cell lung cancer (NSCLC) that compromises 0.4-4% of all lung cancers and
is thought to carry a worse prognosis than adenocarcinoma (AD) or squamous
cell carcinoma (SC). Epidermal growth factor receptor (EGFR) and Anaplastic P1.06-028 DESCRIPTION OF THE PATIENTS WITH ADVANCED
Lymphoma Kinase (ALK) mutations have been observed in patients (pts) SQUAMOUS NSCLC TREATED IN A SINGLE INSTITUTION
with this rare subtype. In the recent years EGFR tyrosine kinase inhibitors
Irene Torres 1, Joaquín Gimeno1, Isabel Pajares1, Ana Comin1, Jorge Hernando1,
(Gefitinib, Afatinib and Erlotinib) and ALK inhibitors (Critzotinib, Ceritinib)
Pilar Felices1, Ana Nuño1, Esther Millastre1, Ana Viñaras2, Angel Artal Cortes1
have prolonged progression free survival in high-stage adenocarcinomas of
1
the lung. The current NCCN guidelines recommend EGFR and ALK mutation Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza/Spain,
2
Pharmacy, Hospital Universitario Miguel Servet, Zaragoza/Spain
testing in metastatic ADS lung cancer patients. However the frequency of
these mutations as well as outcomes of patients with ADS lung is not known Background: Squamous carcinomas are a distinct subtype of NSCLC. Even if
in this era of targeted therapies Methods: We retrospectively identified all pts it is no longer the most frequent one, still remains a significant percentage
seen in our oncology clinic for ADS during the last 10 years (1/1/2005 - 1/1/2015). of NSCLC patients in our practice. Besides, clinical presentation, associated
Overall survival (OS) was estimated by Kaplan-Meier methods Results: 16 pts comorbidities and available therapies are different for non-squamous
were identified, median age at diagnosis was 71y (52-85y), 63% male, 81% had subtypes. Assessing their characteristics may help to optimize therapy.
a smoking history, 87% had ECOG performance status 0-1. 37% had Stage I, Methods: DAta from patients with a diagnosis of advanced (stage IV
18% had stage II, 18% had stage III and 25% had stage IV disease at diagnosis, patients plus patients with lower stages but not amenable for any local
13% developed metastatic disease after treatment for stage III disease. 75% therapy) squamous NSCLand treated in our Hospital between 2009-15 were
of pts diagnosed with metastatic disease after 2012 were tested for EGFR and reviewed. Results: 209 patients (p) were found. Median age was 69 years
ALK, while none diagnosed prior to 2012 were tested. All pts were negative (40-89). Gender: Male in 89.5%. PS: ECOG 0= 9.1%, 1= 45.9%, 2= 38.3%, 3=
for EGFR and ALK mutations. All pts with Stage I and II received only surgery; 6.7%. By stage, I= 0.5%, II 3.4%, III 27.7%, IV 68.7%. Therapy: 29.1% of p did
pts with stage III got multimodality treatment with chemotherapy, radiation, not receive any systemic therapy and 70.9% receive chemotherapy (CT). CT
and surgery. All the pts with metastatic disease received chemotherapy, included a platinum in 69p (carboplatin 47p, cisplatin 22p) and 61p received
with regimens similar to those for AD or SC of lung. The median OS for pts a non-platinum scheme (gemcitabine-vinorelbine 21p, monotherapy 40 p
with localized disease was 48.3 months (48.0- NA). The median OS for pts (gemcitabine 8p, oral vinorelbine 23p, other 9p). Patients with better PS
with metastatic disease was 5.4 months (2.3-9.2) Conclusion: Our small (p<0.001) and stage less than IV (0.02) were more probable to receive CT and
analysis showed that pts with localized ADS of lung had similar outcomes to also that CT given included platinum. Overall survival (OS) was 6.5 months
those of historical pts with localized AD or SC of the lung. However, pts with (5.4-7.6) for the whole group. For stage IV patients, it was significantly
metastatic ADS of the lung had worse outcomes than historical pts with shorter: 5.4 months (p=0.03). OS for patients not receiving therapy was 2.7m
metastatic AD or SC of the lung even with similar chemotherapy regimens. (vs 7.7m in those treated). Within stage IV OS was shorter for female vs male
Few pts had EGFR and ALK testing, but this is becoming more routine as we (4.2 vs 5.8m), and decreased with poorer performance status: 0, 13.5, 1, 8.2m,
have better targeted therapies if they carry mutation 2, 3.8m, 3, 2.2m. Conclusion: Squamous carcinomas are still the second most
frequent subgroup of NSCLC. They are more frequently male and almost half
Keywords: Targeted Therapies, adenosquamous carcinoma, Anaplastic
of them presented with PS ≥2. Of them, 29% did not even receive CT and out
Lymphoma Kinase (ALK) mutations, Epidermal growth factor receptor (EGFR)
of those treated, only 60% were considered fit to receive a platinum-based
mutations
therapy. OS was generally poor, but it was remarkably low in patients with PS
2 or worse. Median OS in untreated patients was under 3 months.
Keywords: Advanced stage, squamous carcinoma, NSCLC

IMMUNOTHERAPY
IMMUNOTHERAPY
P1.06-027 RETROSPECTIVE STUDY OF TREATMENT FOR MONDAY, DECEMBER 5, 2016
POSTOPERATIVE LOCAL RECURRENCE OF LUNG CANCER
Kenjiro Tsuruoka1, Keiji Miyoshi2, Ninso Matsunaga2, Takahiko Nakamura2,
P1.06-029 EPIDEMIOLOGIC, CLINICAL CHARACTERISTICS AND
Shuhei Yoshida2, Yousuke Tamura2, Masafumi Imanishi2, Soichiro Ikeda2,
Yasuhito Fujisaka2, Isao Goto2 THERAPEUTIC STRATEGY OF ELDERLY NSCLC PATIENTS TREATED
1
Division of Respiratory Medicine and Thoracic Oncology, Osaka Medical College
IN A SINGLE INSTITUTION
Hospital, Osaka/Japan, 2Osaka Medical College Hospital, Osaka/Japan Michael Vaslamatzis1, Elisavet Patila1, Theodoros Tegos1, Nektarios
Alevizopoulos2, Charalambos Zoumblios1, Theodora Kapou1, Charalambos
Background: There is no consensus regarding the standard treatment for Stathopoulos1, Apostolos Laskarakis3, Charalambos Zisis4, Edvin Vasili1
postoperative local recurrence of lung cancer. In order to clarify the impact of 1
Oncology, Evangelismos General Hospital, Athens/Greece, 2Oncology,
differences in treatment on patient survival, we conducted a retrospective Evaggelismos General Hospital, Athens/Greece, 3Oncology, Metropolitan Hospital,
study of treatment outcomes for patients with postoperative local recurrence Athens/Greece, 4Thoracic Surgery, Evangelismos General Hospital, Athens/Greece
of lung cancer. Methods: The subjects of this study were patients who were
diagnosed with postoperative local recurrence of lung cancer and treated at Background: In NSCLC pts 40% are ≥ 70y with poor PS and increased
our hospital from 2008 to 2014. We divided patients according to treatment comorbidities(cbs). The aim of this retrospective study is to present all data in
regimen, and compared patient characteristics and survival. Results: This 208 NSCLC pts stage IIIB and IV admitted in our unit between 1/2007- 3/2016.
study included 38 patients. Among them, 8 received radiation therapy (RT), 10 Methods: Group A(young old):51%,70-75years(y),Group B(old):49%,75-
received chemoradiation therapy (CRT), 18 received chemotherapy (CT), and 87y.Median PS:2(0-3). Histology: Adenocarcinoma(AC) 43%, Squamous
2 received best supportive care. The patient characteristics were as follows: carcinoma(SCC) 31%, Adenosquamous CC 10%, Large CC 5% and Large

Neuroendocrine 11%. Metastasis: Liver 79%, Bones: 72%, Adrenal: 37%, Lung: Our surgical approach suggest the importance of the extend dissection by
35%, Brain: 23% of pts. Cbs included: hypertension, diabetes,heart disease, median sternotomy.
dyslipidemia, COPD, hypothyroidism, osteoporosis, Parkinson and dementia
in 81, 68, 56, 56, 52, 42, 14 and 6% of pts .In Group B had ≥3 comorbidities more Keywords: ND3, median sternotomy, bilateral, extended dissection
often (59% vs 42%), p<0.05).

Group IMMUNOTHERAPY
Symptoms at No of pts Group B ADVANCED GENERAL –
A% N= p
presentation (%) N=208 N = 102 MONDAY, DECEMBER 5, 2016
106
Haemoptysis 163 (78%) 78(74%) 85(83%) 0.05<x<0.1
P1.06-031 A NORTH MALAYSIA PULMONOLOGY CENTER
Cough 69(33%) 35(33%) 34(33%) NS EXPERIENCE IN MANAGEMENT OF ADVANCED NON-SMALL CELL
Dyspnoea 60(29%) 22(21%) 38(37%) x<0.01 LUNG CANCER
Chest discomfort 46(22%) 17(16%) 29(28%) 0.01<x<0.05 Syazatul Syakirin Sirol Aflah1, Razul Md Kassim2, Nafiisah Pathi2
1
Respiratory Department, Hospital Sultanah Bahiyah, Alor Setar Kedah/Malaysia,
Cervical 2
Respiratory Department, Hospital Sultanah Bahiyah, Alor Setar/Malaysia
38(18%) 18(17%) 20(19%) NS
lymphadenopathy
Background: Pulmonologist plays an important role not just in getting
SVCS 27(13%) 12(11%) 15(15%) NS
tissue sampling for diagnosis and molecular testing and staging but also
Pancoast tumors 9(4%) 4(4%) 5(5%) NS administer the treatment when there is no medical oncologist available on
site in some centers in some part of the world. Hence, the treatment needed
Results: Four pts(4.5%) mutated received TKI ± chemo(CT) to be delivered promptly to the patient under the care of pulmonologist.
(Paclitaxel,Carboplatin,Bevacizumab) and are still in PR for 12+, 14+, 14+, 32+, Methods: We retrospectively included patients who undergone palliative
12+ mo respectively. In 40 selected pts (≥ 80y, PS=3, ± brain metastases ± ≥5 chemotherapy and radiotherapy with non-small cell lung cancer histology.
cbs ± weight loss ≥7%) single agent was given. RR in 44% with mPFS 7(3-12) Data were collected from clinical notes and statistical analysis was done
mo, mOS 11(5-16)mo. The rest received 3 cycles least of chemo ± brain RT using SPSS statistic software. The aim of the study is to look at the outcome
+ GCSF support: ORR: 56% in A and 49% in B. mPFS: 9(3+ - 18)mo and mOS of advanced NSCLC patients treated with palliative chemotherapy and
18(3+ - 56+)mo, 17(3+ - 56+) in A and 16 (3+ - 44+) in B. RR was 64% and 34% radiotherapy with the prognostic factors. Results: In total, 86 patients were
for pts PS 0-1 vs 2-3, p<0.001. In 720 cycles (410 and 310 in A and B),toxicity analyzed (56 male, 30 female, median age 59.36 ±12.08 with 53% of them were
grade ≥ III: Febrile neutropenia in 11 vs 19% cycles, p <0.01, Anemia in 23 former and current smoker). Tissue diagnosis were obtained by endobronchial
vs 27%, p=NS, Thrombocytopenia in 25 vs 30%, p=NS, Mucositis in 11 vs biopsy(34%), pleural biopsy (36%), CT guided (26%) and ultrasound guided
15%, p=NS. Conclusion: 1. When indicative CT should be given, without transthoracic biopsy (4%).Majority tissue histology were adenocarcinoma
reduction. 2. Haemoptysis and chest discomfort are common in older pts. 3. (77.9%), squamous cell carcinoma (16.3%) and remaining was non-small
Febrile neutropenia was the main serious side effect. 4. GCSF prophylaxis cell carcinoma. Performance status of patients range from 0 to 2 (based on
is necessary. 5. In selective patients >80y single agent seems beneficial in Eastern Cooperative Oncology Group). Among all adenocarcinoma cases,27
second line . patients with epidermal growth factor receptor(EGFR) positive and 16 patient
received oral tyrosine kinase inhibitor(TKI). The systemic chemotherapy
Keywords: NSCLC, chemotherapy, elderly, ADVANCED,METASTATIC
used were Vinorelbin with Cisplatin/Carboplatin, Premetrexed, Docetaxel
and Bevacizumab. All patients received first line chemotherapy(13 patients
received oral TKI for first line), 24 patients received 2nd line, 6 patients on
3rd line and 3 patients on 4th line chemotherapy. 16 patients undergone
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ concomitant radiotherapy. The median overall survival (OS) of all patients
IMMUNOTHERAPY received chemotherapy was 5.16 months. The median OS were significantly
ADVANCED GENERAL – longer in patients who received 2nd and 3rd line chemotherapy (12.88 month, p
< 0.01 and 20.84 months, p <0.013) than 4th line chemotherapy (20.84 months,
p< 0.89). Former and current smoker patient who undergone chemotherapy is
P1.06-030 EXTENDED LYMPH NODE DISSECTION THROUGH 2.3 times higher risk (HR: 2.30; 95%CI: 1.35, 3.92) to die compare to nonsmoker.
MEDIAN STERNOTOMY IN N3 LEFT NSCLC SURGICAL RESULTS AND Patients who had increase in one unit of number of chemotherapy, will
ANATOMICAL FINDINGS reduce 47% risk to die from advanced non-small cell lung cancer (HR: 0.53;
95%CI: 0.36, 0.76). Patient who undergo radiotherapy treatment is 66%
Shingo Ikeda, Toshiya Yokota, Tatsuya Hoshino, Takashi Sakai
less risk(HR:0.34,95% CI:0.17,0.69) to die compared to those who did not
Surgical Department of Respiratory Center, Mitsui Memorial Hospital, Tokyo/Japan
go for radiotherapy. Conclusion: There were clinical benefits for patients
Background: The role of surgical approach to stage IIIA or IIIB disease surgery received more than first line chemotherapy and radiotherapy, smoking during
has been considered not appropriate. Patients with mediastinal lymph node treatment has negative impact on survival in our cohort of patients.
metastasis have a poor prognosis, especially for N3 (contra lateral lymph
node metastases) diseases, and lung operation is not typically indicated. We
performed bilateral mediastinal lymph node dissection by median sternotomy
to resect lung cancer and dissect the bilateral mediastinal lymph nodes. POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
Methods: An extended surgical approach to bilateral neck and mediastinal IMMUNOTHERAPY
nodal dissection based on the knowledge about the pathways of lymph ADVANCED GENERAL –
drainage,’ systematic neck and bilateral mediastinal nodal dissection through
a median sternotomy,’ beyond the anatomical difficulties would bring some
improvement on the survival of the patients with N3 left NSCLC without any P1.06-032 THE HUMANISTIC BURDEN OF ADVANCED NON-SMALL
preoperative treatments routinely. Results: Patients with p- N3α and N3γ (neck CELL LUNG CANCER PATIENTS IN EUROPE - A REAL WORLD SURVEY
lymph node metastases case) cases have poor prognosis, and lung operation
Gavin Taylor-Stokes1, Robert Wood1, Bill Malcolm2, Michael Lees3, Oana
is not normally indicated. We have performed neck and bilateral mediastinal
Chirita2
lymph node dissection by median sternotomy to resect lung cancer and dissect 1
Adelphi Real World, Bollington/United Kingdom, 2Bristol-Myers Squibb, Uxbridge/
the bilateral mediastinal lymph nodes. We have performed this operation in
United Kingdom, 3Bristol-Myers Squibb, Rueil-Malmaison/France
289 patients with primary left lung cancer excluding small cell carcinoma and
stageIV since 1987. 42 patients had p-N3 lymph node metastases. We will report Background: Previous publications have demonstrated that advanced Non-
the investigation of the prognoses of left NSCLC patients who underwent Small Cell Lung Cancer (aNSCLC) patients have worse HRQoL compared to the
initially our extended neck and bilateral mediastinal dissection, focused on the general population. Few publications have focused on the impact of aNSCLC
patients with N3 disease. According to the macroscopic dissection procedure, on activities of daily living and the humanistic burden incurred by different
dissection of the lymphatics from the lungs to the supraclavicular lymph nodes groups of aNSCLC patients in the real world setting. Methods: Data were taken
was performed by sequential removal of the related organs. We systematically from a multi-center, cross-sectional study of aNSCLC patients conducted in
compared and reviewed the route of lymphatic communications to the neck and France, Germany and Italy. The study consisted of three components: medical
contra lateral side with the anatomical significance of left-to-right lymphatic chart review, patient questionnaire and caregiver questionnaire. Overall,
communications in the bilateral mediastinal lymph nodes. The 5-year survival 683 consulting patients were recruited via treating physicians. Patients’
rate (Kaplan-Meier method), including operative deaths and deaths due to health state was quantified using the EuroQoL-5D (EQ-5D-3L - comprising
unrelated diseases, was 48.8% in p-N3α,35.8% in N3γ. Conclusion: We found of five domains: mobility, self-care, ability to perform usual activities, pain,
various lymphatic metastases pattern such as between neck and mediastinal anxiety and depression) and the burden on HRQoL quantified using the
lymph nodes and around the trachea in terms of clinical and anatomical status. European Organization for Research and Treatment of Cancer Quality of
Life Questionnaire (EORTC QLQ-C30), a 30 item questionnaire yielding five

functional scales, three symptom scales, a global health status/QoL scale, and
six single items. Analysis was stratified by patients’ line of therapy. Statistical
significance was assessed using Mann-Whitney U tests. Results: Patients’
mean (SD) age was 65.2 (9.7), 68.8% were male and 89.0% had stage IV NSCLC.
Over two-thirds (71%) of patients were receiving 1st line advanced therapy,
whilst 29% were receiving later lines of therapy. Regarding histology, 74% of
patients were non-squamous compared to 26% squamous. The mean EQ-5D-3L
index for 2nd line or later patients was significantly lower compared to patients
on 1st line treatment (0.57 vs 0.65; p=0.002). Three domains showed significant
decreases: mobility, self-care and ability to perform usual activities. In terms of
EORTC scores, patients on later lines of treatment experienced a lower overall
global health status (QL2) compared to 1st line patients (43.8 vs 50.7; p<0.001).
Significant differences were also observed in all other EORTC scales except
for diarrhoea. Conclusion: 1st line aNSCLC patients have a diminished health
state in comparison to the general population (EQ-5D scores 0.65 v 0.78). In
addition compared to other cancer sufferers, aNSCLC patients have a worse
QoL (QLQ-C-30 QL2 score 48.8 v 61.5 for stage IIIB/IV cancer patients). The real
world study shows that both health status and QoL significantly worsen with
advancement to later lines of treatment. The results show a high unmet need
for more effective 1st–line treatments to prevent disease progression while
maintaining patient quality of life.
Keywords: NSCLC, Advanced stage, National Cancer Institute, Young age,
Keywords: NSCLC, humanistic burden, quality of life, Real world Response to chemotherapy
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY IMMUNOTHERAPY
ADVANCED GENERAL – ADVANCED GENERAL –
MONDAY, DECEMBER 5, 2016 MONDAY, DECEMBER 5, 2016
P1.06-033 NON-SMALL CELL LUNG CANCER IN YOUNG PATIENTS; P1.06-034 OUTCOMES AFTER PULMONARY METASTASECTOMY FOR
CLINICO-PATHOLOGIC CRITERIA AND PROGNOSTIC FACTORS METASTATIC CANCER
M Rahouma1, Hala Aziz 2, Fatma Abou Elkassem2, Iman Loay3, Galal Ghaly4, Prakash Balakrishnan1, Yousr Al-Sheibani2, Sean Galvin2, Barry Mahon2, John
Mohamed Kamel4, Abdelrahman Abdelrahman4 Riordan2, James Mcgiven2
1
Surgical Oncology, National Cancer Institute, Cairo/NY/Egypt, 2Medical Oncology, 1
Cardiothoracic Department, Wellington Regional Hospital, Wellington/New
National Cancer Institute, Cairo/Egypt, 3Cancer Pathology, National Cancer Zealand, 2Cardiothoracic Surgery, Wellington Hospital, Wellington/New Zealand
Institute, Cairo/Egypt, 4Surgical Oncology, National Cancer Institute, Cairo/Egypt
Background: In most malignant diseases, the ability to constantly
Background: A cancer registry was analyzed to determine the clinicopathologic metastasize remains a truly challenging obstacle in cancer patients.
characteristics and prognosis of non-small cell lung cancer (NSCLC) in patients Historically in the past, any local surgical treatment in patients with systemic
< 45 years old at diagnosis as they were not thoroughly investigated Methods: malignant disease is considered without any prognostic benefit, this has
Among enrolled NSCLC cases attending National Cancer Institute –Cairo (NCI) since evolved with many studies confering huge success rates with excellent
between 2007-2012, we retrospectively reviewed those who were 45 years old prognostic benefits. We hereby report our experience over the last 10 years at
or younger. Data regarding demographics, ECCOG-performance status (PS), Wellington Regional Hospital, Cardiothoracic unit. Methods: A retrospective
histology, grade, stage, chemotherapy type, number of cycles, overall and study was undertaken in series of patients with colorectal, melanoma, breast,
progression free survival (OS, PFS) were obtained. Pearson’s (X2) test, Cox sarcoma & renal metastatic disease undergoing pulmonary metastasectomy,
regression and Kaplan-Meier survival curves were used for statistical analysis. from year 2000 to 2010. These data was identified & stratified into groups
Results: Among 99 NSCLC cases, we identified 22cases ≤ 45years. Lower stages using hospital patient database & ORSOS theatre database with the aid
were more prevalent among young (77.3%) versus old group (54.5%) p=0.05 of Excel spreadsheet. Results: All these patients were operated on either
Median OS in young versus old group was 18 versus 15 months (p=0.773), – unilateral versus bilateral, VATS or thoracotomies with or without lymph
while PFS was 4 versus 6 months respectively (p=0.322) In our subgroup node dssection as well as repeat surgeries. The role of metastatectomy in
analysis(n=22); median age was 42years (30-45years), Nearly three-quarters their treatment options & the prognostic factors with impact on survival
were males, 40.9% were PS >1. The majority of cases in young group were stage discussed. Conclusion: In carefully selected surgical patients, pulmonary
IIIB (77.3.%). Pathology was squamous (40.9%), adenocarcinoma (22.7%), metastasectomy for metastatic diseases confers continual prognostic &
undifferentiated (22.7%) and adenosquamous carcinoma in 4.5% of our cases. survival advantage for these patients.
Median OS and PFS was 18 and 4 months respectively. Significant difference
in OS and PFS was observed among responder versus non responders in Keywords: pulmonary metastasectomy, Metastatic Disease, outcomes
multivariate analysis (Figure) Conclusion: Good response to chemotherapy is
the best way to prolong survival among young NSCLC cases irrespective of PS,
gender, stage or pathology.

IMMUNOTHERAPY
P1.06-035 FREQUENCY AND CLINICAL RELEVANCE OF

EGFR-MUTATIONS AND EML4-ALK-TRANSLOCATIONS IN
OCTAGENARIANS WITH NSCLC
Amanda Tufman1, Simone Reu2, Sandra Hasmann3, Diego Kauffmann-
Guerrero1, Katrin Milger 1, Zulfiya Syunyaeva1, Kathrin Kahnert1, Rudolf Huber 1
1
Respirology and Thoracic Oncology, Comprehensive Pneumology Center, Member
of the German Center for Lung Research Dzl, Ludwig Maximilian University of
Munich, Munich/Germany, 2Institute of Pathology, Ludwig-Maximilians University,
Munich/Germany, 3Ludwig-Maximilians University Munich, Munich/Germany
Background: Novel therapies targeting genetic alterations have improved

response rates and overall survival for some patients with NSCLC;
however, only a minority of caucasian patients with lung cancer benefit
from these treatments. Testing for EGFR mutation and ALK translocation
is recommended for all patients with advanced adenocarcinoma, but
the highest occurance of these driver mutations has been described in

younger patients, females, and those with little or no smoking history. The Conclusion: Local treatment of oligo-recurrence should be considered
frequency of driver mutations in elderly and very elderly patients has not in selected candidates, and use of TKI is reasonable if EGFR mutation is
been described. Methods: We reviewed the charts of all patients over age 70 detected.
treated at our centre in 2015 and assessed the frequency of EGFR and ALK
testing. We report the frequency of EGFR and ALK alterations in patients Keywords: recurrence, Oligometastasis, lung cancer
aged 70-74, 75-79 and >80 years. Results: Out of 179 patients diagnosed at our
centre in 2015, 15 were 80 years or older at the time of first diagnosis and 7 of
15 had non-squamous histology. Among these very elderly patients, 3 patients
were found to have EML4-ALK translocations and 2 patients were found to
have EGFR mutation (1 Del19, 1 L858R). This represents a 71% frequency of IMMUNOTHERAPY
treatable driver mutations in octagenarians with non-squamous NSCLC. ADVANCED GENERAL –
Rates of genetic drivers were somewhat lower, but still clinically relevant,
in non-squamous NSCLC patients aged 70-74 (27.0%) and 75-79 (26.7%).
Conclusion: Very elderly patients (>80 years of age) with non-squamous NSCLC P1.06-037 NON-SMALL CELL LUNG CANCER INVADING THE
were found to have high rates of the driver alterations EGFR mutation and DIAPHRAGM: OUTCOME AND PROGNOSTIC FACTORS
ALK translocation. This is clinically relevant, as this often frail and comorbid
Domenico Galetta, Lorenzo Spaggiari
population may not be suitable for treatment with cytotoxic chemotherapy
and may benefit from first line treatment with a targeted tyrosine kinase Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy
inhibitor. Testing for these genetic alterations should not be restricted to
Background: Diaphragmatic infiltration by non-small cell lung cancer
younger patients. The biology of lung cancer in the very elderly may differ
(NSCLC) is a rare occurrence and surgical results are unclear. We assessed
from that of moderately elderly patients, as the longevity of these patients
our experience with en bloc resection of lung cancer invading the diaphragm
may select for individuals more resistant to, or with little exposure to,
analyzing prognostic factors and long-term outcomes. Methods: We analyzed
environmental carcinogens.
a prospective database of patients with NSCLC infiltrating the diaphragm
Keywords: EGFR, EML4-ALK, elderly, NSCLC who underwent en bloc resection. Univariate and multivariate analysis
was performed to identify prognostic factors. Survival was calculated by
the Kaplan-Meier method. Results: Nineteen patients (14 men, mean age
64 years) were identified. Surgery included nine pneumonectomies, eight
lobectomies, and two segmentectomies. A partial diaphragmatic infiltration
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ was observed in 10 patients (52.6%), and full-depth invasion in nine (47.4%).
IMMUNOTHERAPY Diaphragmatic reconstruction was done primarily in 13 patients (68.4%), and
MONDAY, DECEMBER 5, 2016 by prosthetic material in six (31.6%). Pathological nodal status included nine
N0, four N1, and six N2. Median hospital stay was seven days (range, 4-36
days). Postoperative mortality was 5.2% (1/19). Two patients (10.5%) had
P1.06-036 POST-RECURRENCE SURVIVAL ANALYSIS OF STAGE I major complications (acute respiratory distress syndrome and bleeding), and
NON-SMALL CELL LUNG CANCER: PROGNOSTIC SIGNIFICANCE OF 10 minor complications, arrhythmia in seven (36.8%), and pneumonia in three
LOCAL TREATMENT (15.8%). Five-year survival was 29.8%. Mean survival and disease-free survival
Kanghoon Lee, Hyeong Ryul Kim, Dong Kwan Kim, Yong-Hee Kim, Seung-Il were 30 months (range, 1-164 months) and 20 months (range, 1-83 months),
Park, Se Hoon Choi, Su Kyung Hwang, Jin San Bok, Han Pil Lee, Byung Kwon respectively. Factors adversely affecting survival were diaphragmatic
Chong infiltration (50% superficial vs 0% full-depth infiltration; log-rank test,
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center,
P=0.04), and nodal involvement (43% N0 vs 20% N1-2; log-rank test, P=0.03).
University of Ulsan College of Medicine, Seoul/Korea, Republic of Conclusion: Resection of NSCLC invading the diaphragm is technically feasible
and could be a valid therapeutic option with acceptable morbidity and
Background: The aim of this retrospective study was to review recurrence mortality and long-term survival in highly selected patients.
patterns of stage I non-small cell lung cancer(NSCLC), and to identify
prognostic factors for post-recurrence survival(PRS). Methods: Among 940 Keywords: Surgery, Diaphragm, lung tumor
patients with pathological stage I NSCLC who had undergone curative
resection between 2001 and 2009, total 261 patients who had experienced
recurrence were included in this study. Number of patients with
adenocarcinoma(ADC) were 188, squamous cell carcinoma(SCC) were 62.
Oligo-recurrence was defined as 1-3 loco-regional or distant recurrent lesions IMMUNOTHERAPY
restricted to a single organ. Potentially-curative local treatment(PCLT) ADVANCED GENERAL –
included surgery, stereotactic radiotherapy(SRT), and photodynamic
therapy(PDT). Results: Median follow-up duration was 65 months(range,
4-186 months) and median disease-free interval(DFI) was 23 months(range, P1.06-038 SURVIVAL AND PROGNOSTIC FACTORS OF
2-95 months). Number of patients with oligo-recurrence was 154, and the most OLIGOMETASTATIC NON-SMALL CELL LUNG CARCINOMA: A SINGLE
common sites of oligo-recurrence were lung in 84 patients, followed by brain
CENTER EXPERIENCE
in 18 patients, bronchial stump in 18, and single-station of mediastinal lymph
nodes in 12. Local treatment for recurrent tumor included surgery in 59 Derya Kızılgöz1, Pınar Akın Kabalak1, Ugur Yılmaz 1, Tuba Inal Cengiz1, Metehan
patients, SRT in 50, PDT in 2, and other radiotherapy in 53. Seventy-four Karaca2, Evrim Tunç2, Selim Şakir Erkmen Gülhan3, Kyle Wang4
1
patients received chemotherapy only, and 36 patients took conservative Chest Disease, Ankara Atatürk Chest Disease and Thoracic Surgery Training and
treatment. Among 125 patients who were evaluated for EGFR gene mutation Research Hospital, Ankara/Turkey, 2Radiation Oncology, Ankara Atatürk Chest
Disease and Thoracic Surgery Training and Research Hospital, Ankara/Turkey,
study, positive results was detected in 62 patients, and 31 patients were 3
Thoracic Surgery, Ankara Atatürk Chest Disease and Thoracic Surgery Training
treated with TKI. The 3- and 5-year post-recurrence survival rates were 49.1% and Research Hospital, Ankara/Turkey, 4Radiation Oncology, University of North
and 33.8%, respectively. Age at recurrence, adenocarcinoma cell-type, DFI, TKI Carolina Hospitals, Chapel Hill/NC/United States of America
and PCLT were independent prognostic factors in multivariate analysis.
Background: In patients without targeted mutations platinum-based
chemotherapy is still current treatment method with a median survival
rates of 8-11 months. Patients with single side oligo-metastatic disease
should be consider for curative aggressive therapies for both primary and
metastatic sides for better survival (NCCN 2016). Methods: Totally 19 oligo-
metastatic NSCLC patients was evaluated retrospectively by using hospital
database. All patients had single metastatic side. Results: Among 19 eligible
patents there was male predominance (n= 16, 84.2%). Eight patients had
co-morbidities requiring regular medication. Histopathological, there were
13 (68.4%) adenocarcinoma and 6 (31.6%) non-adenocarcinoma. While brain
was the most common site for metastasis 10 (52.6%), it was followed by
bone (n=6, 31.6%). Treatments for primary tumour side were surgery (n=6,
31.7%), concurrent CRT (n=5, 26.3%) and sequential CRT (n=1, 5.3%). Median
follow-up for whole cases were 59.1 weeks. Median overall survival (OS)
and progression free survival (PFS) were 140 (±33.7) and 76 (±24.2) weeks
respectively. Progressions were observed mostly in 45.4. week. Univariate
cox regression analyses for OS and PFS is indicated in Table 1. Clinical T and
N staging had significant relation with OS (p=0.02 and 0.03 respectively).
There was no relation between bone or brain metastasis and histopathology,

Median OS by Subgroup
gender, clinical T and N staging. Median survival after first progression (SAFP)
was 63 weeks (±SS 29.05). Among study parameters only clinical T staging Patients by
had significant relation with SAFP (p=0.026). Median SFAP was better in Histology, Stage at median OS
n 95% C.I.
patients with progression of primary tumour however median OS was better Diagnosis & Systemic (months)
in patients with progression of distant metastasis (p>0.05). Treatment
NSCLC: Stage I/II
(17.3-36.6) (14-51.6)
Factor OS PFS Systemic Treatment 48 11 37 24.9 25.7 24.9
(16.2-72.9)
No treatment
Hazard Ratio p Hazard Ratio p
NSCLC: Stage III
Age (cut-off=65) 1.034 (0.18-5.1) 0.96 0.4 (0.1-2.2) 0.3 Systemic Treatment 716 24.6 84.0 24.6 (4.5-NA) NA (4.5-NA)
No treatment
Co-morbidity 2.3 (0.54-9.8) 0.24 3.4 (0.8-14) 0.07
NSCLC: Stage IV
Brain Metastasis 0.88 (0.21-3.6) 0.86 1.5 (0.42-5.45) 0.52
Systemic Treatment 33 7 26 3.2 8.7 2.3 (2-4) (4.7-52.4) (1.5-3.5)
Histopathology No treatment
(adeno vs non- 0.22 (0.03-1.4) 0.10 0.67 (0.16-2.8) 0.6
SCLC: Limited Stage
adeno)
Systemic Treatment 651 9.6 14.3 2.0 (2-NA) (8.4-NA) NA
Bone Metastasis 1.78 (0.43-7.31) 0.42 1.7 (0.47-6.6) 0.4 No treatment
pN Staging (n0 SCLC: Extensive
0.12 (0-173) 0.21 0.94 (0.22-4.02) 0.94
and N1-2) Stage (0.2-NA) (1.7-NA)
532 1.7 5.5 0.2
Systemic Treatment (0.2-NA)
cT Staging 2.17 (1-4.7) 0.02 1.11 (0.73-1.81) 0.54
No treatment
cN Staging (n0
2.3 (0.86-6.6) 0.03 1.77 (0.79-3.97) 0.1 Conclusion: Survival was poor in our OTR population compared to historical
and N1-2)
norms in non-transplant patients. A minority of NSCLC patients received
Non-surgical adjuvant or palliative chemotherapy, while most SCLC patients were treated.
curative 1.88 (0.41-8.52) 0.42 1.9 (0.50-7.38) 0.34 Both often had sub-standard dosing. Chemotherapy appeared better
treatment tolerated in early stage disease.
Surgery 0.31 (0.06-1.65) 0.14 0.21 (0.02-1.78) 0.09
Keywords: chemotherapy, transplant, survival, lung cancer
Conclusion: Even oligo-metastatic NSCLC means stage 4 of disease,
curative treatment approaches for both primary and metastasis sides can
increase patients’ prognosis than other stage 4 cases. Similar to the existed
retrospective studies we had OS more than 2 years and PFS more than 1 year.
IMMUNOTHERAPY
Keywords: Oligometastasis, nonsmall cell lung cancer, survival ADVANCED GENERAL –
P1.06-040 HOME-BASED PULMONARY REHABILITATION IN

POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ ADVANCED NON SMALL CELL LUNG CANCER PATIENTS TREATED BY
IMMUNOTHERAPY ORAL TARGETED THERAPY: A FEASIBILITY STUDY
MONDAY, DECEMBER 5, 2016 Caroline Pagniez 1, Cecile Olivier 1, Alexandre Olislagers1, Sophie Peres2, Eric
Wasielewski1, Anne Baranzelli1, Marie-Capucine Willemin1, Xavier Dhalluin1,
Alexis Cortot1, Anne Hoorelbeke2, Arnaud Scherpereel1
P1.06-039 RETROSPECTIVE STUDY OF THE INCIDENCE AND 1
Pulmonary and Thoracic Oncology, Hospital of the University (CHRU) of Lille, Lille/
OUTCOMES FROM LUNG CANCER THAT DEVELOPED FOLLOWING A France, 2 Santelys Association, Loos/France
SOLID ORGAN TRANSPLANT
Kelvin Young 1, Max Marquez2, Jonathan Yeung2, Frances Shepherd1, Shaf Background: Pulmonary rehabilitation (PR) is valuable in the peri-operative
Keshavjee2, Eberhard Renner2, Joseph Kim2, Heather Ross2, Tim Aliev2, setting of non small cell lung cancer (NSCLC) patients, but not established for
Geoffrey Liu3, Natasha Leighl3, Ronald Feld4, Penelope Bradbury1 stage IIIB-IV disease. Previously, we showed that home-based PR is feasible
1
Princess Margaret Cancer Centre, Toronto/ON/Canada, 2Dept of Medical Oncology and may significantly improve quality of life (QoL) and functional status
and Haematology, University Health Network, Toronto/ON/Canada, 3Medical of NSCLC patients treated by chemotherapy (submitted). The goal of this
Oncology, Princess Margaret Cancer Centre, Toronto/ON/Canada, 4Dept of Medical study was to assess the feasibility and value of home-based PR in advanced
Oncology and Haematology, Princess Margaret Cancer Centre, Toronto/ON/Canada NSCLC patients treated by oral targeted therapies. Methods: Advanced
NSCLC patients with oral targeted therapy were recruited in a prospective
Background: Organ transplant recipients (OTR) have an increased risk of study in 2015-2016 in Lille University Hospital, France. After written informed
developing post-transplant malignancies with lung cancer being one of the consent, they benefited from 8 weeks home-based PR including functional
most common. We investigated incidence and outcomes of lung cancer in OTR exercises, psychological and nutrition support, therapeutic education.
managed at the University Health Network. Methods: The study population, Exclusion criteria were cardiovascular contraindication to PR, symptomatic
patient characteristics, treatments and outcomes were summarized from brain metastasis, bone metastasis with high fracture risk, or severe cognitive
solid OTR databases, our cancer registry and patient charts from January disorder. Main endpoints were adherence, inclusion rate, and cause of refusal.
1, 1980 to December 31, 2015. Univariate Kaplan-Meyer curves estimated Secondary endpoints were PR benefits assessed by QoL scales (EORTC QLQ
overall survival (OS) by histology, stage and chemotherapy. Results: Amongst C 30, FACT-L, HAD); functional capacity: 6min walk test, 6 min stepper test,
7994 OTR (heart [N=765], lung [n=1668], liver [n=238], kidney [n=3273]), 123 spirometry, respiratory muscle strength; and global condition: nutrition,
developed lung cancer (1.54%) of which (55) 44.7% occurred in lung OTR; 108 treatment tolerance. This study was approved by local Ethical Committee
(1.35%) patients had sufficient data for subsequent analyses. Median age: Results: Among 36 screened patients, the adhesion rate was 55.6% with
62 years (29 - 85); male: 66%; smoking status at time of transplant - former/ 20 patients joining the study. Other patients refused mostly because (a) of
current/never/unknown: 62%/10%/15%/8%. Histologies included non-small “lack of interest for PR and they don’t want to be disturbed” (40% of cases),
cell lung cancer (NSCLC): 81%; small cell lung cancer (SCLC): 10%; neuro- or (b) they considered “their physical activity already sufficient” (12%), or (c)
endocrine tumours: 9%. NSCLC: Adjuvant chemotherapy, after it became “family constraints” (12%). Only 15 patients (41.6%) started PR (3 early deaths,
standard of care (SOC), was given to 16% of eligible NSCLC patients. At 1 exclusion for intraventricular thrombosis, 1 consent withdrawal). No serious
recurrence, 28% received chemotherapy while 28% received a TKI. In patients adverse event was reported but only grade 1 asthenia or musculoskeletal
initially presenting with stage IV NSCLC, 18% received chemotherapy and pain. Significant increases of FACT-L score from 84.7 to 100.2 (p=0.02) and 6
3% received a TKI. SCLC: For limited and extensive stage SCLC patients, 83% min stepper test from 140 to 195.7 steps (p=0.01) were found after PR, and
and 60% received SOC chemotherapy, respectively. All: Where chemotherapy preservation of patients’ autonomy reflected by stability of 6WT data. Most
dosing was known (n=23), 42% of patients received initial dose reductions. For of other parameters exhibited a positive but not significant trend, likely due
early stage patients, 22% required dose reduction and 11% had chemotherapy to the limited number of participants. Conclusion: Home-based PR is feasible
discontinuation due to toxicity. For stage IV patients, 42% required dose and well-tolerated in patients with advanced NSCLC treated by oral targeted
reductions and 50% required discontinuations. therapies. Significant improvements were obtained with PR based on 6ST
and QoL FACT-L data. Moreover, PR was highly appreciated by patients, their
relatives, and all medical teams raising our will to be able to propose PR to

all our stage III-IV NSCLC patients. Currently, this study is still ongoing and Background: Medication related osteonecrosis of the jaws (MRONJ) is an
multicentric, aiming at recruiting 50 extra patients. increasing problem globally, which may lead to loss of teeth and jaw bone
and has a significant impact on qualtity of life. MRONJ is known since 2003,
Keywords: NSCLC, pulmonary rehabilitation, Targeted therapy, supportive reported after antiresorptive treatment with bisphosphonate, and since 2010
care also from Denosumab for skeletal metastases from breast cancer, prostate
cancer and multiple myeloma, Recently, MRONJ has also been related to
chemotherapy, including Tyrosine Kinase Inhibitors for lung cancer, kidney
cancer and gastrointestinal cancer without skeletal metastases. The onset
of MRONJ is often precipitated by of one of the above medication types in
IMMUNOTHERAPY combination with a tooth extraction. Therefore it is recommended that all
ADVANCED GENERAL – patients have a dental screening and relevant dental treatment before the
start of medication with antiresorptives (bisphosphobnates/denosumab) or
Tyrosine Kinase Inhibitors The purpose of this pstudy is to raise awareness
P1.06-041 OVERALL SURVIVAL AND INTERMEDIATE OUTCOMES that MRONJ can be prevented and that MRONJ also occurs among patients
AMONG SCANDINAVIAN NON-SMALL CELL LUNG CANCER receiving chemotherapy without bisphosphonates or denosumab. Methods:
Rigshospitalet established the Copenhagen ONJ Cohort of consecutive
PATIENTS: THE SCAN-LEAF STUDY
patients with MRONJ since 2004, and have performed systematic prospective
Simon Ekman1, Jens Benn Sørensen2, Julia Rockberg 3, Martin Sandelin4, data collection since 2010. Results: Among 247 patients enrolled in the
Melinda Daumont5, Patrik Sobocki3, Peter Klint6, Han-Yao Huang7, Jenny Copenhagen ONJ Cohort 163 had cancer and received treatment with
Svärd3, Oana Chirita8, Leif Jørgensen3, Maria Planck 9 bishosphonates in 109 cases and denosumab in 54 cases. In addition, since
1
Oncology, Karolinska University Hospital, Stockholm/Sweden, 2Rigshospitalet 2013 we have received 7 patients with MRONJ from Tyrosine Kinase inhibitors.
Blegdamsvej, København Ø/Denmark, 3Rwes, Ims Health Sweden/pygargus In 85 out of 163 cancer patients (52%) the onset of MRONJ was related to
Ab, Solna/Sweden, 4Dept. of Medical Sciences, Respiratory Medicine, Uppsala
tooth extraction. Conclusion: More than 50% of the MRONJ cases could
University, Uppsala/Sweden, 5Bristol-Myers Squibb, Rueil-Malmaison/France,
6
Bristol-Myers Squibb, Solna/Sweden, 7Bristol-Myers Squibb, Pennington/NJ/
potentially be avoided.If all patients had dental examination and had repaired
United States of America, 8Bristol-Myers Squibb, Uxbridge/United Kingdom, or extracted bad teeth before start of antiresorptive medication, Thus all
9
Oncology and Pathology, Lund University, Lund/Sweden cancer patients should have dental examination before start of medical
treatment.
Background: The past decade has seen several advances in the field of non-
small cell lung cancer (NSCLC), with improved tools for tumor characterization Keywords: Chemotheraphy Jaw necrosis Prevention of jaw necrosis
as well as novel targeted and immune therapies. It is important to understand
the current treatment landscape including treatment outcomes, in order to
maximize patient benefits from these advances. SCAN-LEAF is a Scandinavian
retrospective cohort study with prospective annual data cuts, providing
a unique opportunity for insights into real-world clinical NSCLC practice IMMUNOTHERAPY
over more than a decade. It includes clinical practice patterns of tissue ADVANCED GENERAL –
biopsy, pathological diagnosis and tumor biomarker status testing, and MONDAY, DECEMBER 5, 2016
their relationship to treatment choices and outcomes. Here, we present
intermediate and survival outcomes by disease stage and histology subtype, P1.06-043 A STUDY TO SELECT RATIONAL THERAPEUTICS IN
and factors associated with survival. Methods: SCAN-LEAF consists of a
SUBJECTS WITH ADVANCED MALIGNANCIES (WINTHER) - THE
registry-based cohort including all diagnosed NSCLC patients in Denmark,
SHEBA EXPERIENCE IN LUNG CANCER PATIENTS
Norway and Sweden (Cohort 1), and a Swedish sub-cohort (Cohort 2)
supplemented with data from electronic medical records (EMRs). Based Amir Onn1, Jair Bar2, Tal Sela1, Aliza Ackerstein1, Sharon Halperin1, Goni Hout-
on the first data collection including data from NSCLC patients diagnosed Siloni1, Sivan Lieberman3, Hovav Nechushatan4, Raanan Berger2
1
2005-2013, overall survival (OS; Cohort 1 & 2) and progression-free survival Pulmonary Medicine, Sheba Medical Center, Ramat Gan/Israel, 2Oncology, Chaim
(PFS; Cohort 2) will be estimated using Kaplan-Meier analysis and reported as Sheba Medical Center, Ramat Gan/Israel, 3Imaging, Sheba Medical Center, Ramat
cumulative incidences (with 95% CI) by disease stage at diagnosis, histological Gan/Israel, 4 Medical Oncology, Hadassah Medical Center, Jerusalem/Israel
subtype, biomarker status, presence of metastases, age and gender. Response
Background: Patient-tailored therapy based on tumor genomics is a promising
rates (Cohort 2) will be described by treatment line in addition to stage and
tool in cancer therapy. However, in current practice it is limited to 30-40% of
histology subtype. Association of stage with survival (Cohort 1 & 2) and
the patients whose tumor harbor actionable DNA mutations or amplifications
treatment response (Cohort 2) will be analyzed by Cox regression with time
Methods: : WINTHER is an open label non-randomized clinical trial developed
to event (death or response) as outcome variable and disease stage category
by the WIN consortium to provide a rational personalized therapeutic choice
at diagnosis, follow-up time, and therapy line as stratification variables.
to all (100 %) enrolled patients, irrespective of the type of genomic events.
In addition, the relationship between OS and intermediate outcomes, as
The study includes patients with metastatic cancer who progressed on at
well as predictors of OS (e.g. smoking and biomarker status, lesion location,
least one line of therapy. Matched tumor and normal tissue biopsies are
metastasis at diagnosis), will be explored by Cox regression (Cohort 2).
collected from each patient and analyzed by next-generation-sequencing for
Results: Intermediate and survival outcomes for Scandinavian NSCLC patients
known oncogenic driver aberrations (Foundation Medicine) or by functional
diagnosed between 2005 and 2013, as well as any association between overall
genomics utilizing a prediction model of efficacy developed at Ben Gurion
survival and factors such as patient characteristics and treatment patterns,
University. Based on these results study leaders from all centers make therapy
will be presented. Conclusion: The SCAN-LEAF study, expected to include
decisions. The study aim is to compare progression free survival rates between
>115,000 Scandinavian NSCLC patients and >2,000 sub-cohort patients
the previous treatment line and the study drug/s. Patient accrual began in
diagnosed between 2005 and 2018 during the full duration of the study, will
2013 in four international cancer centers. The following is a description of
give valuable insights into current care, changing treatment patterns and
the experience at Sheba Medical Center., specifically focusing on a large sub-
patient outcomes in a real-world setting. A better understanding of factors
population of lung cancer patients. Results: Fifty six patients were screened
associated with survival and intermediate outcomes among NSCLC patients
and biopsied for the study. The majority of patients were diagnosed with lung
will inform clinical decision-making.
cancers (52%), with a diverse representation of other malignancies including
Keywords: Progression-free survival, epidemiology, non-small cell lung cancer, breast (16%), renal (9%), colon (9%), sarcoma, bladder and head and neck.
survival Successful biopsies yielding sufficient material for genomic analyses were
achieved in 35 subjects (63%). Lung biopsy success rates were 75% and 60%
respectively for normal and tumor specimens. To date, 11 lung cancer patients
were treated with a variety of chemotherapy (1) or biologic agents (11) based
on study recommendations while 3 have yet to progress on previous therapy.
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ Targeted genomic alterations included EGFR (3), RET (2), KRAS (2), ALK (1),
IMMUNOTHERAPY ErbB2 (1), ErbB3 (1), BRAF (1). We observed a clinical benefit rate (CBR) of 55%
MONDAY, DECEMBER 5, 2016 (6/11) with 1 subject achieving compete response (CR), 2 partial responses
(PR) and 3 stable disease (SD). Subjects recruited during the second year of
the study, compared to the first year had a reduced biopsy failure rate, were
P1.06-042 THE IMPORTANCE OF MEDICATION RELATED more likely to receive treatment and achieved an increased clinical benefit.
OSTEONECROSIS OF THE JAWS (MRONJ) Conclusion: The proposed strategy for tumor genomic analysis based on the
Mark Krasnik 1, Hoda Mahedi2, Morten Schiodt3 comparison of matched tumor and normal biopsies is acceptable and feasible.
1
Rigshospitalet, Copenhagen Ø/Denmark, 2Department of Oral & Maxillofacial The experience of the multidisciplinary team is an important contributor to
Surgery, Rigshospitalet, Copemhagen/Denmark, 3Department of Oral & the program’s success.
Maxillofacial Surgery, Rigshospitalet, Copenhagen/Denmark
Keywords: lung cancer, personalized medicine, Multidisciplinary team
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ malignancy diagnosis. We think that a prognosis is improved.
IMMUNOTHERAPY
Keywords: synchronous, multiple neoplasm, metachronous
P1.06-044 COSTS OF ADVERSE EVENTS (AE) ASSOCIATED WITH

CANCER THERAPIES IN NON-SMALL CELL LUNG CANCER (NSCLC) IN
FRANCE POSTER SESSION 1 - P1.06: ADVANCED NSCLC &
Christos Chouaid1, Delphine Loirat2, Chloé Godard3, Emilie Clay4, Aurélie CHEMOTHERAPY/TARGETED THERAPY/IMMUNOTHERAPY
Millier4, Laurie Lévy-Bachelot3, Eric Angevin5 Advanced Elderly –
1
Centre Hospitalier Intercommunal Créteil, Créteil/France, 2Curie Institute, Paris/ MONDAY, DECEMBER 5, 2016
France, 3Msd, Courbevoie/France, 4 Creativ-Ceutical, Paris/France, 5Départment
Innovations Thérapeutiques Et Essais Précoces (Ditep), Gustave Roussy, Villejuif
Cedex/France
P1.06-046 CAN WE BETTER MANAGE ADVANCED NSCLC IN THE
Background: AE associated with existing and future treatments in NSCLC ELDERLY WITH THE NEW THERAPEUTIC AGENTS? PRELIMINARY
are frequent and should be accounted for in health economic models. In ANALYSIS OF A REAL-LIFE MULTICENTER STUDY
addition to utility decrements, appropriate costing of AE management is
Tindara Franchina1, Silvia Novello2, Alessandro Russo1, Martina Gianetta2,
needed. In the case of NSCLC which affects 45 200 patients per year in France,
Enrica Capelletto2, Domenico Galetta3, Annamaria Catino3, Maria Rita
published data are scarce and not always complete. It was therefore thought
Migliorino4, Serena Ricciardi4, Floriana Morgillo5, Carminia Maria Della Corte5,
of importance to assess resource use and costs associated with AEs. Methods:
Danilo Rocco6, Hector Soto Parra7, Antonio Russo8, Francesca Ambrosio9,
When looking at the grade 3 or 4 AEs appearing for at least 1% of patients
Veronica Franchina1, Vincenzo Adamo1
in the clinical trials for erlotinib (TITAN, LUX-LUNG 8), ramucirumab plus
1
docetaxel (REVEL), docetaxel and pembrolizumab (KEYNOTE 010), a list of Department of Human Pathology, University of Messina and Medical Oncology
Unit, A.O. Papardo, Messina/Italy, 2Department of Oncology, University of Turin,
20 grade 3 and 4 AE was identified as relevant for Health Economic analysis.
Turin/Italy, 3Medical Oncology Unit, Clinical Cancer Centre “Giovanni Paolo Ii”,
Among them, 7 did not have cost data available in the literature. Three
Bari/Italy, 4Uosd Pneumologia Oncologica, San Camillo - Forlanini Hospital, Roma/
French oncology experts were consulted. A questionnaire was sent before Italy, 5Oncologia Medica, Dipartimento Medico-Chirurgico Di Internistica Clinica E
the meeting with the experts, asking for, according to the grade, insight on Sperimentale “F. Magrassi E A. Lanzara”, Seconda Università Degli Studi Di Napoli,
resource use (hospitalisation, follow-up visits, diagnosis exams, treatments). Napoli/Italy, 6 Aorn Ospedale Dei Colli, Plesso Monaldi, Napoli/Italy, 7Department
Results were discussed during the meeting in order to reach a consensus. of Medical Oncology, A.O.U. Policlinico-Vittorio Emanuele, Catania/Italy,
8
Direct medical cost per AE, expressed in 2016 Euros, was then calculated Department of Surgical, Oncological and Oral Sciences, University of Palermo,
from a national health insurance perspective based on public and private Palermo/Italy, 9Uosc Oncologia, Aorn Cardarelli, Napoli/Italy
weighted tariffs and 2014 PMSI database. Results: The mean AE cost was €206
Background: Systemic treatment of NSCLC has profoundly changed over
for thrombocytopenia, €263 for ocular toxic effect, €2,332 for arthralgia,
the past years with novel therapeutic strategies recently implemented
€3,282 for venous thromboembolism, €3,732 for pulmonary bleeding,
in clinical practice. Benefit of these novel agents in elderly patients (pts)
€5,176 for dehydration, €5,751 for pneumonia, infiltration or pneumonitis.
is uncertain, given the paucity of prospective data in this population.
Hospitalization costs corresponded to 46% to 100% of total AE cost. These
Moreover, elderly pts are often undertreated, due to comorbidities and
AE costs were consistent with the costs of other grade ¾ AEs previously
toxicity concerns. Therefore, we aimed to evaluate the access, safety and
published for NSCLC therapies. Conclusion: Among seven grade 3 and 4 AEs
outcome with novel therapeutic agents in pts ≥ 70 years (yrs). Methods: We
seen, four appear to have an important economic impact, with a management
planned an observational study to retrospectively evaluate consecutive
cost of at least €3,000 per event.
elderly patients (≥ 70 yrs) with metastatic NSCLC treated at 9 Italian Centers
Keywords: cost, adverse events, Health Economics, NSCLC between January 2014 and December 2015. Data collected include clinical
and pathological characteristics, treatment types, safety and outcome
report. Results: 220 patients with stage IV NSCLC were included in this
preliminary analysis (53% IVa, 47% IVb). Median age was 74,5 (range 70-85)
and 69% were male. 15% of pts aged 80 years or older. ECOG PS was 0, 1, 2 in
POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ 37%, 51% and 12% of pts, respectively. According to comprehensive geriatric
IMMUNOTHERAPY assessment, 59% of pts were fit, 28% vulnerable and 13% frail. Histology was
MONDAY, DECEMBER 5, 2016 23% squamous cell carcinoma, 72% non-squamous cell carcinoma and 5%
NOS. EGFR mutation was diagnosed in 24% of cases; 1,4% and 1% of pts had
ALK and ROS-1 translocations, respectively. 90% of pts received a systemic
P1.06-045 MULTIPLE NEOPLASMS CONSIST OF LUNG CANCER AND therapy: 48% a platinum doublet chemotherapy (CHT), 27% a mono-CHT,
HEMATOLOGICAL MALIGNANCIES 25% an EGFR tyrosine kinase inhibitor (TKI). Only 1% of pts were treated with
Kazuhiko Natori1, Daisuke Nagase2, Susumu Ishihara3, Yurika Mitsui3, Akiko antiangiogenic drugs. Immunotherapy (IT) was administered in 16% of all
Sakai2, Yasunobu Kuraishi2, Haruka Izumi2 treated pts. 7% of pts received only BSC. Second- and third-line treatment
1
Division of Hematology & Oncology, Toho University Medical Center Oomori were given to 44% and 8% of pts, respectively. 51% of pts who received second
Hospital, Oota City/Japan, 2Division of Hematology and Oncology, Department of line treatment and 60% of pts treated with a third line therapy had a novel
Medicine, Toho University Medical Center Oomori Hospital, Oota City/Japan, 3Toho therapeutic agent (II line TKI 20%, IT 31%; III line TKI 33%, IT 27%). 31% of
University Medical Center Oomori Hospital, Oota City/Japan pts were included in clinical trials. A dose reduction was reported in 41% of
therapies and the discontinuation rate was 9%. Survival data are not mature
Background: The lung cancer is a cancer of the most in Japan and first place at this time. Conclusion: Our data, albeit preliminary, suggest an evolution
in cause of death. Lung cancer (LC)is still poor prognosis disease that cure in the management of NSCLC in the elderly. The interesting activity and the
only in early clinical stage. We report that we reviewed 55 cases of multiple good safety profile encourage the use of novel agents also in this setting of
neoplasms with lung cancer and the hematological malignancies. Methods: NSCLC. Adequate selection of elderly pts and personalized approach are still
We intended for multiple neoplasms 339 cases including hematological matters of debate. Use of adapted schedule and dose reduction could warrant
malignancy. We reviewed 55 multiple neoplasms including the lung cancer. a good compromise between safety and efficacy.
All patients were followed up until death or untile August 2016. Survival
was measured from the diagnosis of multiple cancer to time of death or last Keywords: elderly, Advanced non small cell lung cancer, Targeted therapy,
contact. Definition of the multiple neoplasms in compliance with Warren & Immunotherapy
Gates. Also we determined the synchronous type and metachronous type in
accordance with the definition of Moertel, so within less than 6 months was
synchronous type, more than 6 months was metachronous type. Results: All
cases are 55 cases, consist of male 44 cases, female 11 cases, type of multiple POSTER SESSION 1 - P1.06: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
neoplasms, synchronous type 14 cases, metachronous type 41 cases. Number ADVANCED ELDERLY –
of multiple neoplasms, double neoplasms 38 cases, triple neoplasms 14 cases, MONDAY, DECEMBER 5, 2016
quadple neoplasms 3 cases. The median age was 71years (range,47-86years)
The counterpart of malignancies, MHL 26 cases, MDS 7 cases, AML 7 cases, HL
P1.06-047 MANAGEMENT OF PATIENTS AGED OVER 70 YEARS WITH
2 cases, MG 1 case, CLL 2 cases, CML 2 case, ALL 1 case, MGUS 3 cases. In double
neoplasms, the median age of first diagnosis, 69years, the second cancer were NEWLY DIAGNOSED LUNG CANCER
71years, About interval between lung cancer and hematological malignancies, Haider Abbas 1, Mariam Jafri2, Adenike Williams1, Megan Jones1, Joyce
lung cancer precedence case was 40M, hematological malignancy precedence Thompson1
1
case was 54M. The median overall survival was 24M. Conclusion: Diagnosis Medical Oncology, Birmingham Heartlands Hospital, Birmingham/United
of LC within 5 years were 26 cases out of 41 cases. The important point is that Kingdom, 2Medical Oncology, Queen Elizabeth Hospital, Birmingham/United
5 years are required for careful observation at the time of hematological Kingdom

Background: Lung cancer is an important cause of mortality and morbidity PFS was 21.9 (95% CI: 11.7, 29.3) weeks, and OS was 7.1 (95% CI: 4.8, 14.7)
worldwide. It is the third most common cancer in the UK. Due to an increase in months. The most common treatment-related adverse events (AEs) of any
life expectancy there is an increase in the proportion of patients greater than grade were diarrhea (66.7%), nausea (55.6%), fatigue (38.9%), and vomiting
70 years being diagnosed with lung cancer. We looked at the management (27.8%). Neutropenia occurred in 2 cases, both grade 2, without neutropenic
of patients diagnosed with newly diagnosed lung cancer over a period of fever. The most common AEs ≥grade 3 were lymphopenia, hyponatremia
12 months in a large UK Teaching hospital. The main aim of this study was and muscular weakness (2 cases each, all grade 3). Conclusion: Etirinotecan
to compare the outcome of various treatment options offered to elderly pegol has shown promising activity with acceptable toxicity profile in
patients diagnosed with lung cancer. Methods: All individuals diagnosed treatment of chemotherapy-sensitive patients with relapsed SCLC. Accrual of
with lung cancer discussed at specialist thoracic multidisciplinary meeting chemotherapy-resistant patients is expected to be completed soon.
aged over 70 between September 2014 and September 2015 were identified
and retrospectively reviewed. Demographic data, histology, treatment and Keywords: chemotherapy, Etirinotecan, NKTR-102, small cell lung cancer
survival were evaluated Results: 123 patients were included in the study,
37% were between 70-74yrs, 39% were between 75-79yrs and 48% were >=
80yrs. The commonest histology was adenocarcinoma which constituted
36.2% followed by squamous cell about 19.3%. Majority of patients were
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
referred from hospital (57%), about 30% were referred from A&E and 12% DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
were referred from GP. In terms of treatment; 52% received best supportive MONDAY, DECEMBER 5, 2016
care (BSC), 30% surgery and 17% chemotherapy. Common reasons for patients
receiving BSC were: poor performance status (65%), and co-morbidities (21%).
P1.07-002 G1T28, A CYCLIN DEPENDENT KINASE 4/6 INHIBITOR,
Patients who had chemotherapy had improved survival compared to BSC;
5 v.s. 10 months. Node positivity was poor prognostic sign; median survival
IN COMBINATION WITH TOPOTECAN FOR PREVIOUSLY TREATED
for N0, N1, N2 and N3 were 17, 10, 5 and 3 months respectively Conclusion: SMALL CELL LUNG CANCER: PRELIMINARY RESULTS
Treating elderly patients with lung cancer is challenging because at the time of Lowell Hart 1, Patrick Roberts2, Renata Ferrarotto3, Rodolfo Bordoni4, Paul
diagnosis the tumor is often advanced and furthermore elderly patients often Conkling5, Tejas Patil6, Caio Max Rocha Lima7, Taofeek Owonikoko8, Steven
suffer with multiple comorbidites which makes treatment more difficult. In Schuster9, Robert Jotte10, Robert Hoyer 11, Katie Stabler2, Karen Makhuli2, Raid
our cohort, patients who received active oncological treatment had improved Aljumaily12, William Edenfield13, Alexander Spira14, Rajesh Malik2, Geoffrey
overall survival. Majority of the patients didnt receive active oncological Shapiro15
treatment due to poor perfomance status or co morbidites and hence not 1
Florida Cancer Specialists, Fort Myers/FL/United States of America, 2G1
fit for treatment. Our data suggests that age should not be considered as a Therapeutics, Research Triangle Park/NC/United States of America, 33University
limiting factor for chemotherapy and there is a need for prospective studies to of Texas M.D. Anderson Cancer Center, Houston/TX/United States of America,
4
further evaluate active oncological management of older patients, since with Georgia Cancer Specialists, Marietta/United States of America, 5Virginia Oncology
Associates, Norfolk/United States of America, 6Department of Internal Medicine,
careful selection this group can benefit from active treatment.
University of Colorado, Aurora/United States of America, 7Gibbs Cancer Center
Keywords: lung cancer, elderly, chemotherapy, Best supportive care and Research Institute, Spartanburg/SC/United States of America, 8Hematology/
Medical Oncology, Emory University, Atlanta/GA/United States of America,
9
University of Colorado Health, Fort Collins/CO/United States of America, 10 Rocky
Mountain Cancer Centers, Denver/CO/United States of America, 11University of
Colorado Health, Colorado Springs/CO/United States of America, 12University of
Oklahoma Health Sciences Center, Oklahoma City/OK/United States of America,
13
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE Ghs Cancer Institute, Greenville/SC/United States of America, 14Virginia Cancer
Specialists, Fairfax/VA/United States of America, 15Dana-Farber Cancer Institute,
TUMORS Boston/MA/United States of America
Drug Treatment Alone and in Combination with
Radiotherapy – Background: Chemotherapy-induced bone marrow and immune system
toxicity causes significant acute and long-term consequences. G1T28 is a
MONDAY, DECEMBER 5, 2016 potent and selective CDK4/6 inhibitor (CDK4/6i) in development to reduce
chemotherapy-induced myelosuppression and preserve immune system
function in small cell lung cancer (SCLC) patients. Hematopoietic stem
P1.07-001 A PHASE II STUDY OF ETIRINOTECAN PEGOL (NKTR-102), and progenitor cells (HSPC) are dependent upon CDK4/6 for proliferation,
A TOPOISOMERASE-L LNHIBITOR POLYMER CONJUGATE, IN SMALL and preclinical models demonstrated that transient G1T28-induced G1 cell
CELL LUNG CANCER cycle arrest renders them resistant to chemotherapy cytotoxicity, allowing
Hongbin Chen1, Grace Dy1, Adrienne Groman1, William Brady1, Saad Jamshed2, faster hematopoietic recovery, preservation of long-term stem cell and
Peter Bushunow2, Noelle Brunsing1, Alex Adjei3 immune system function, and enhancement of chemotherapy anti-tumor
1
Medicine, Roswell Park Cancer Institute, Buffalo/NY/United States of America,
activity. Methods: Objectives of this ongoing multicenter Phase 1b/2a
2
Rochester General Hospital, Rochester/NY/United States of America, 3Medical study are to assess the dose limiting toxicities (DLTs), safety, hematological
Oncology, Mayo Clinic, Rochester/MN/United States of America profile, PK, and anti-tumor activity of G1T28 in combination with topotecan
(NCT02514447). The study consists of a limited open-label, dose-finding
Background: Small cell lung cancer (SCLC) has poor prognosis and systemic portion (Part 1; up to 40 patients), and an openlabel, single-arm expansion
chemotherapy is the standard treatment. Irinotecan is a topoisomerase-I portion (Part 2; 28 patients). Eligible patients had histologically/cytologically
inhibitor that has been used in treating SCLC. Etirinotecan pegol (NKTR- confirmed SCLC, adequate organ function, ECOG performance status 0-2, 1-2
102) is a polyethylene glycol conjugate of irinotecan. It is a next generation prior lines of chemotherapy, and no symptomatic brain metastases. G1T28,
topoisomerase-I inhibitor uniquely designed for prolonged tumor cell at a starting dose of 200 mg/m2 (derived from the Phase 1a healthy volunteer
exposure by using the polymer conjugate technology. This is a single arm study and expected to maintain HSPC G1 arrest beyond topotecan exposure),
phase II study to evaluate single agent etirinotecan pegol in patients was administered IV prior to IV topotecan on days 1-5 every 21-days. Results:
with relapsed SCLC (NCT01876446). Methods: A total of 38 patients 21 patients (median age 68, 5 females, 20 white and 1 African-American)
who have received only one prior systemic therapy for SCLC are being have been enrolled across 5 cohorts. DLTs due to Grade 3/4 myelotoxicity
accrued over 3 years. There are 2 patient cohorts: those progressing on occurred in the first two cohorts and were associated with supra-therapeutic
first-line chemotherapy <3 months after completion of treatment (Group topotecan exposures due to decreased topotecan clearance by G1T28.
A: chemotherapy-resistant, N=20) and those progressing on first-line Reducing the topotecan dose achieved exposures in the therapeutic range
chemotherapy ≥3 months after completion of treatment (Group B: and was well tolerated. No episodes of febrile neutropenia or bleeding have
chemotherapy-sensitive, N=18). Etirinotecan pegol was administered at 145 occurred to date. For the 17 evaluable patients, there were 5 PR, 8 SD, and
mg/m2 IV once every 3 weeks. Cycles were repeated every 21 days until disease 4 PD. In the 6 platinum refractory patients there were 1 PR, 3 SD, and 2 PD.
progression, unacceptable toxicity, or withdrawal from study. The primary Conclusion: G1T28, a novel CDK4/6i, combined with topotecan for previously
endpoint is the 18-week progression free survival (PFS) rate. The secondary treated SCLC patients has been well tolerated, without any episodes of febrile
endpoints are objective response rate (ORR), duration of response (DOR), neutropenia or bleeding. There are encouraging early signs of anti-tumor
overall survival (OS) and toxicity. A single-stage design is used to assess activity, with a response rate of 29% overall (36%, 4/11 in sensitive and 17%,
the primary endpoint separately for each patient group. Results: Accrual 1/6 in refractory) and a clinical benefit rate (CR+PR+SD) of 76% overall (82%,
of Group A is ongoing. Group B has completed targeted enrollment of 18 9/11 in sensitive and 67%, 4/6 in refractory). This novel approach, allowing the
patients and the results are presented here. Median age was 61.6 (50-76.5) administration of chemotherapy with preservation of hematopoietic function
years, with 50% male. Prior chemotherapy included cisplatin/etoposide and cellular immunity, could potentially improve treatment outcomes of
(41.2%) and carboplatin/etoposide (58.8%). Patients received a median of 6 patients with CDK4/6-independent tumors. Updated data will be presented.
(1-30) cycles of etirinotecan pegol, with dose reduction in 22.2%. PFS rate at
week 18 was 72.2% (13/18, 95% Confidence Interval (CI): 47-90%). ORR was Keywords: small cell lung cancer, CDK4/6, immune system, G1T28
44.5% (8/18), including one complete response. Another one-third (6/18) of
patients had stable disease. Median DOR was 4 (1.4-14.5) months. Median
while first line patients are randomized to receive either HA-irinotecan/

POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS carboplatin or irinotecan/carboplatin. The response was measured by CT/PET
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY – at baseline, after 1 cycle and every 2 cycles subsequently. Baseline tumour
samples were stained for CD44s (standard) and CD44v6 (variant 6). Blood
samples for circulating tumour cells (CTCs) were also obtained at the baseline
P1.07-003 A PHASE II STUDY EVALUATING THE COMBINATION and before each treatment cycle till progression of disease. Results: Forty (40)
OF EVEROLIMUS WITH CARBOPLATIN/PACLITAXEL AS 1ST LINE patients, median age 66 (range 39-83) were enrolled treated on this study.
Seven (7) patients either died or progressed before the first evaluation scan.
TREATMENT IN PATIENTS WITH ADVANCED LCNEC
Of 34 evaluable patients, the overall response rate was 50%, with 4 (12%)
Christian Grohé 1, Walburga Engel-Riedel2, Cornelia Kropf-Sanchen3, Von complete and 13 (38%) partial responses. Four patients (12%) achieved stable
Pawel Joachim4, Sylvia Gütz5, Jens Kollmeier6, Wilfried Eberhardt7, Petros disease while 7 patients (20%) progressed during the treatment. There was
Christopoulos8, Inko Nimmrich9, Christian Sieder9, Volker Baum9, Monika no PFS difference in the two first line treatment arms (median 28 weeks in
Serke10, Michael Thomas8 experimental vs 42 week in standard arm) (P = 0.892 HR=0.93, 95% CI 0.36-
1
Evangelische Lungenklinik, Berlin/Germany, 2Lungenklinik Köln-Merheim, Kliniken 2042). Median PFS was 14.4 weeks in the second line cohort. The toxicity
Der Stadt Köln, Köln/Germany, 3University Hospital Ulm, Ulm/Germany, 4Klinik Für profile was similar to standard irinotecan, with the incidence of grade III/
Pneumologie, Asklepios Fachklinik München-Gauting, Gauting/Germany, 5Kliniken IV diarrhea seen in the experimental arm of 11% compared with 25% in the
Für Pneumologie Und Kardiologie, Diakonissenkrankenhaus Leipzig, Leipzig/
standard arm. Biomarker data was available in case of 24 patients, which
Germany, 6Lungenklinik Heckeshorn, Helios Klinikum Emil Von Behring, Berlin/
Germany, 7Department of Medical Oncology, University Hospital Essen, Essen/ suggested that there was no difference in response rates or survival according
Germany, 8Translational Lung Research Centre Heidelberg, Member of the German to baseline CD44s or CD44v6 expression. A possible correlation between the
Centre for Lung Research, Thoraxklinik Heidelberg, Heidelberg/Germany, 9Business number of CTCs and tumour response and relapse was noticed. Conclusion:
Unit Oncology, Novartis Pharma GmbH, Nuremberg/Germany, 10 Lungenklinik HA-irinotecan is well tolerated and has shown activity in the treatment of
Hemer, Hemer/Germany extensive stage small cell lung cancer. However, no improvement in efficacy
was seen in CD44s+ or CD44v6+ SCLC treated with HA-irinotecan. Further
Background: Approximately 3% of all lung cancers are made up of large cell
strategies to combine HA with other chemotherapeutic agents may be
neuroendocrine carcinoma of the lung (LCNEC). These tumors in general
warranted.
have a bad prognosis and currently there are only very limited treatment
options, including platinum derivatives and etoposide. The PI3/AKT/mTOR Keywords: Hyaluronic acid, small cell lung cancer, CD44, irinotecan
pathway is known to be dysregulated in neuroendocrine tumors (NETs). Since
the mTOR inhibitor RAD001 (everolimus) already has proven effectiveness
in different types of NETs, we tested whether everolimus might be also an
effective treatment option in advanced LCNEC patients. Methods: In this
multi-center, open-label, phase II study, everolimus was combined with POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
platin-based chemotherapy in patients with histologically confirmed stage IV MONDAY, DECEMBER 5, 2016
LCNEC according to WHO criteria. Further inclusion criteria were measurable
disease according to RECIST 1.1 and adequate bone marrow, renal, and liver
function. Main exclusion criteria were symptomatic CNS metastases and P1.07-005 A RETROSPECTIVE STUDY OF SEQUENTIAL
prior treatment for advanced LCNEC. Enrolled patients received everolimus CHEMORADIOTHERAPY FOR LD-SCLC PATIENTS IN WHOM
once a day in combination with 4 cycles of carboplatin and paclitaxel, CONCURRENT THERAPY IS NOT INDICATED
followed by daily everolimus maintenance therapy. The primary objective Sayaka Ohara1, Shintaro Kanda2, Keiko Goto3, Hideaki Shiraishi2, Hitomi
was to evaluate the efficacy by assessing the proportion of progression-free Okuma3, Kota Itahashi2, Yasushi Goto2, Hidehito Horinouchi2, Yutaka
patients after three months of treatment. Results: Ten German trial sites Fujiwara4, Hiroshi Nokihara2, Yoshinori Ito3, Noboru Yamamoto2, Kazuhiro
enrolled altogether 49 patients (mean age: 62 ± 9 years; 71% men). The primary Usui1, Yuichiro Ohe3
endpoint (proportion of pts progression-free at month 3) was achieved by 1
Division of Respirology, NTT Medical Center Tokyo, Tokyo/Japan, 2Department of
24 patients (49%), assessed by an independent central imaging reviewer. Thoracic Oncology, National Cancer Center Hospital, Tokyo/Japan, 3National Cancer
Further efficacy evaluation showed an overall response rate (ORR) until Center Hospital, Tokyo/Japan, 4Thoracic Oncology, National Cancer Center Hospital,
month 3 of 45%, a disease control rate (DCR) until month 3 of 73.5%, a median Tokyo/Japan
progression-free survival (PFS) of 4.3 months, and a median overall survival
(OS) of 9.8 months. At least one toxicity occurred in 86% of all enrolled Background: The standard treatment for limited-disease small-cell lung
patients with grade 3/4 toxicities in 51%. Most frequent toxicities were cancer (LD-SCLC) is a combination of cisplatin-doublet chemotherapy and
diarrhea, fatigue, anemia, and neutropenia. Conclusion: The results show that concurrent thoracic radiotherapy. However, sequential radiotherapy, rather
a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor than concurrent radiotherapy, is selected for some cases because of concerns
everolimus is an alternative treatment option for LCNEC patients. When regarding the irradiation field, patient age, comorbidities, or performance
comparing to other trials, the effectiveness is comparable to a treatment status. Nevertheless, the efficacy of sequential chemoradiotherapy in
regimen of cisplatin and etoposide. patients in whom concurrent chemoradiotherapy is contraindicated is not
well known. Methods: We retrospectively analyzed 286 patients with LD-SCLC
Keywords: LCNEC, Neuroendocrine tumor, Everolimus at the National Cancer Center Hospital and the NTT Medical Center in Japan
between 2000 and 2014. We then compared the clinical characteristics and
treatment outcomes of patients undergoing sequential radiotherapy with
those undergoing concurrent radiotherapy. Results: One hundred and eighty-
three patients received concurrent chemoradiotherapy and 30 received
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY – sequential chemoradiotherapy. The median age of the patients was 64 years
MONDAY, DECEMBER 5, 2016 (range, 18-81 years) for the concurrent group and 71.5 years (50-83 years) for
the sequential group. The concurrent group contained 43 women (23%), while
the sequential group contained 9 women (30%). The major reasons for the
P1.07-004 UPDATED ANALYSIS OF PHASE II STUDY OF HA- selection of sequential radiotherapy were patient age (13 patients), a large
IRINOTECAN, A CD44-TARGETING FORMULATION OF HYALURONIC irradiation field (8 patients), and comorbidities (5 patients). In the sequential
ACID AND IRINOTECAN, IN SMALL CELL LUNG CANCER group, 23 (77%) received conventional radiotherapy, whereas 7 (23%) received
Muhammad Alamgeer 1, Peter Briggs1, Ben Markman1, Peter Midolo1, Neil accelerated hyperfractionated radiotherapy. The median overall survival
Watkins2, Beena Kumar3, Vinod Ganju1 period was 34.5 months for the concurrent group and 27.6 months for the
1
Medical Oncology, Monash Cancer Centre, East Bentleigh/Australia, 2The Kinghorn sequential group (P = 0.39). The 2-, 3-, and 5-year survival rates were 71%, 50%,
Cancer Centre, Garvan Institute of Medical Research, Darlinghurst/NSW/Australia, and 40% for the concurrent group and 56%, 56%, and 35% for the sequential
3
Anatomical Pathology, Monash Medical Centre, Clayton/Australia group. Recurrence was seen in 149 patients (81%) in the concurrent group and
19 patients (63%) in the sequential group. Conclusion: We obtained treatment
Background: Preclinical studies in small cell lung cancer cell (SCLC) have outcomes for patients who could not receive concurrent radiotherapy but
shown that hyaluronic acid (HA) can be effectively used to deliver irinotecan could complete sequential radiotherapy that were comparable with the
and selectively decrease CD44 expressing (stem cell-like) tumour cells. The outcomes for those who received concurrent radiotherapy. For patients
current “proof of principle” study was aimed to replicate these findings by in whom concurrent chemoradiotherapy is not indicated, sequential
investigating the effect on clinical outcome according to CD44 expression. chemoradiotherapy should be considered.
Final efficacy and bio-marker data on the study is presented. Methods:
Patients with ESLC, having measurable disease, suitable for safe biopsy and Keywords: sequential chemoradiotherapy, LD-SCLC
able to give informed consent were screened for this study. First 5 patients
were treated with HA-irinotecan (150mg/m2) and carboplatin (AUC 5), every
3 weeks to evaluate safety data. Subsequent patients were stratified as first
line or second line. All second line patients receive open label HA-irinotecan,

POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS was distant (include pulmonary metastasis and malignant pleural effusion)
in 17, locoregional in 11, lymph node metastasis out of the radiation field in
2 and both distant and locoregional in 3. In the locoregional progression
patients, 6 developed mediastinal lymph node progression in their clinical
P1.07-006 PRECLINICAL SUPPORT FOR EVALUATION OF courses. Finally, 5 in 33 progressive patients had locoregional progression
IRINOTECAN LIPOSOME INJECTION (NAL-IRI, MM-398) IN SMALL without mediastinal lymph node progression, and were thought possible
CELL LUNG CANCER candidates for salvage surgery. Conclusion: Most of the patients experienced
distant metastasis and/or mediastinal lymph node progression. About 15%
Shannon Leonard, Helen Lee, Stephan Klinz, Nancy Paz, Jonathan Fitzgerald,
of patients who presented with apparently localized disease at the primary
Bart Hendriks
pulmonary site after chemoradiation might become possible candidates for
Merrimack Pharmaceuticals, Inc., Cambridge/MA/United States of America
salvage surgery.
Background: Nal-IRI (irinotecan liposome injection, MM-398, ONIVYDE®),
Keywords: salvage surgery, limited stage, SCLC
in combination with 5-fluorouracil and leucovorin, is currently approved by
the FDA for treatment of patients with advanced pancreatic cancer who
have progressed on gemcitabine-based therapies. Nal-IRI is designed for
extended circulation relative to non-liposomal irinotecan and to exploit leaky
tumor vasculature for enhanced drug delivery to tumors. Following tumor POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
deposition, nal-IRI is taken up by phagocytic cells followed by irinotecan DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
release and conversion to its active metabolite SN-38 in the tumors.
Sustained inhibition of topoisomerase 1 (TOP1) by extended SN-38 delivery is
hypothesized to enable superior anti-tumor activity compared to traditional P1.07-008 LOMUSTINE ENDOXAN VP16 AS SECOND OR FURTHER
TOP1 inhibitors. Topotecan, a TOP1 inhibitor, is currently a standard of care LINE FOR RECURRENT OR PROGRESSIVE BRAIN METASTASES
for second-line treatment of small cell lung cancer (SCLC). Here, we evaluate
FROM SCLC
nal-IRI compared to topotecan in preclinical models of SCLC. Methods: Anti-
tumor activity of nal-IRI as a monotherapy was evaluated in DMS-53 and Charles Naltet1, Audrey Dugué1, Catherine Dubos1, Pascal Dô 1, Serge Danhier 1,
NCI-H1048 xenograft models. Cells were implanted subcutaneously into right Delphine Lerouge1, Christos Chouaid2, Radj Gervais1
1
flanks of NOD-SCID mice; treatments were initiated when tumors had reached Baclesse, Caen/France, 2Chic, Créteil/France
approximately 280 mm3. Nal-IRI was dosed at 16 mg/kg salt, q1w, which is
Background: Up to fifty percent of patients with small-cell lung cancer
equivalent to a proposed clinical dose of 90 mg/m2 free base, q2w. Topotecan
(SCLC) will experience brain metastases (BM) during the whole course of
was dosed at 0.83 mg/kg/week, Day 1-2 every 7 days, which approximates a
their disease. The oral regimen Lomustine Cyclophosphamide Etoposide
clinical dose intensity of 1.5 mg/m2 (Day 1-5 every 21 days). Tumor metabolite
(LCE) has been tested in SCLC as second line treatment and was shown to
levels were compared in mice treated with nal-IRI or non-liposomal irinotecan
be equivalent to the intravenous regimen Cyclophosphamide Adriamycin
at 24 hours post-injection, using previously established high performance
Vincristine (Gervais R et al. Clin Lung Cancer 2015;16:100-5). This retrospective
liquid chromatography methods. Results: Carboxylesterase activity and
study evaluates the cerebral response rate (CRR) of this oral chemotherapy
sensitivity to SN-38 in mouse SCLC models were comparable to those
on brain metastases (BM) from SCLC relapsing after platinum-based
measured in tumor types where either nal-IRI or irinotecan HCl has proven
chemotherapy. Methods: Patients with disease progression after one or
to be efficacious clinically (e.g. pancreatic cancer, colorectal cancer). Nal-IRI
more prior chemotherapy regimens for SCLC were included if they had at
delivered irinotecan to SCLC tumors to a similar or greater extent than other
least one measurable BM according to RECIST 1.1, with PS<2. Patients with
tumor types including pancreatic tumors. The tumor irinotecan and SN-38
symptomatic BM were eligible. They were excluded if they had received
levels of nal-IRI (16 mg/kg salt) were 12 to 57-fold and 5 to 20-fold higher than
previous whole brain irradiation before LCE or were receiving concomitant
non-liposomal irinotecan (30 mg/kg salt), respectively. Nal-IRI demonstrated
brain irradiation. Patients received the chemotherapy according to modalities
anti-tumor activity in both xenograft models of SCLC at clinically relevant
described in the GFPC-0501 study (1). The doses were determined by a
dose levels, and resulted in complete or partial responses after 4 cycles in
therapeutic risk level: lomustine, 80 to 120 mg on day 1, cyclophosphamide 100
NCI-H1048 or DMS-53 models, respectively, compared with topotecan which
mg/d, and etoposide 75 mg/d, for 6 to 14 days, every 28 days, until progression
had limited tumor growth control. Conclusion: This study demonstrated
or major toxicity. Primary prophylactic granulocyte colony-stimulating
that nal-IRI is more active than topotecan at clinically relevant doses in
factor was recommended. The primary objective was the cerebral response
SCLC preclinical models, and thus support further clinical development of
rate (CRR) using RECIST 1.1 .Secondary objectives included the extra-cerebral
nal-IRI versus topotecan in patients with SCLC that have progressed on prior
response rate (ECRR), the overall survival and the safety. Results: From 2008
platinum-based therapy.
to 2014 in Baclesse comprehensive cancer center, 24 patients fulfilled the
Keywords: small cell lung cancer treatment, irinotecan liposome, MM-398, inclusion criteria. The median age was 57.5 years (interquartile range [IR]
topoisomerase 1 inhibitor 51.5–64.5). CCR was 50% while ECRR was 26% (NS, p=0.135). Interestingly, 8 of
the 9 patients with neurological symptoms had symptomatic improvement.
Previous treatment (chemotherapy and/or radiotherapy) for BM did not
appear to have any effect on CRR (p=1.000). The hematologic toxicities
were the most common side effects with neutropenia (grade ¾ : 26%) and
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS thrombocytopenia (grade ¾ : 21%). Median overall survival was 6.3 months.
Conclusion: In our study, Lomustine Cyclophosphamide Endoxan has a high
activity on BM from SCLC, with a comparable extra cerebral response rate
than others regimen currently used in second line setting. It has a manageable
P1.07-007 CLINICAL OUTCOMES OF PATIENTS WITH LS- toxicity profile and the oral route allows patients with a short expectancy
SCLC TREATED WITH CHEMORADIOTHERAPY. CAN WE FIND of life to benefit from a home-delivered treatment. We suggest that this
CANDIDATES FOR SALVAGE SURGERY? combination should be tested in a prospective study.
Junichi Shimizu1, Yuko Oya1, Kosuke Tanaka1, Chiaki Kondo1, Hiromi Furuta1, Keywords: brain metastases, small cell lung cancer, Second Line, Lomustine
Tatsuya Yoshida1, Yoshitsugu Horio1, Yukinori Sakao2, Yasushi Yatabe3, Toyoaki
Hida1
1
Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya/Japan, 2Thoracic
Surgery, Aichi Cancer Center Hospital, Nagoya/Japan, 3Pathology and Molecular
Diagnostics, Aichi Cancer Center Hospital, Nagoya/Japan POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
Background: Although small cell lung cancer (SCLC) is generally considered a MONDAY, DECEMBER 5, 2016
systemic disease even in patients with limited stage (LS). Selected recurrent
LS-SCLC patients after chemoradiation treatment have been reported long
P1.07-009 OUTCOMES OF PATIENTS WITH RELAPSED SMALL-CELL
survival with receiving salvage surgery. Purpose of this study was to find
LUNG CANCER TREATED WITH PACLITAXEL PLUS GEMCITABINE. 10
candidates for salvage surgery. Methods: We retrospectively reviewed the
charts of 43 consecutive patients who were treated with chemoradiotherapy YEAR-ANALYSIS
for LS-SCLC at our hospital from January 2011 to December 2015 to search for Ana Laura Ortega Granados 1, Natalia Luque Caro1, Juan Francisco Marín
the patients with locoregional progression without mediastinal lymph node Pozo2, Nuria Cárdenas Quesada1, Francisco José García Verdejo1, David
involvement. Results: Of the 43 patients, the median age was 69 (38-83), 91% Fernández Garay1, Capilla De La Torre Cabrera1, María Ruiz Sanjuan1, Mónica
were male and all of them had ECOG PS 0 or 1. Clinical stage: IIA (12%), IIIA Fernández Navarro1, Carmen Rosa Garrido3, Miguel Ángel Moreno Jiménez1,
(53%), IIIB (35%). 35 (81%) received hyperfractionated RT (45Gy/30fr/3w). Pedro Sánchez Rovira1
1
Objective response rate was 95%. One patient died of pneumonia. The median Oncología Médica, Complejo Hospitalario de Jaén, Jaén/Spain, 2Farmacia
survival time was 1584 days and the median progression free survival was 280 Hospitalaria, Complejo Hospitalario de Jaén, Jaén/Spain, 3Fibao, Complejo
days. 33 (77%) demonstrated disease progression. The first progression site Hospitalario de Jaén, Jaén/Spain
Background: We conducted a retrospective study to investigate the outcome POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
and prognostic factors of patients with relapsed SCLC who receive second or MONDAY, DECEMBER 5, 2016
third line chemotherapy with paclitaxel plus gemcitabine, a regimen that is
used in our institution since a phase II trial in 2001. We reviewed the medical
records of patients with SCLC who received paclitaxel plus gemcitabine P1.07-011 EXTENSIVE-STAGE SMALL CELL LUNG CANCER IN A
in a ten-years period, since 2005 from 2015. Overall survival (OS) from the 13-YEAR-OLD MALE PATIENT TREATED WITH BEVACIZUMAB
initiation of this regimen was evaluated, plus characteristics of these FOLLOWED BY HIGH-DOSE CHEMOTHERAPY
patients. Methods: Patients diagnosed of SCLC were selected from our lung
Michihiro Yano, Miwa Hebiguchi, Koya Kodama
cancer database, and compared with our Pharmacy Department database. We
Pediatrics, Akita University Hospital, Akita/Japan
selected all patients with relapsed SCLC that received therapy with paclitaxel
plus gemcitabine (PG) at any moment of the disease. Results: The median age Background: Small cell lung cancer (SCLC) is exceedingly rare in children.
of the cohort was 58 years (43–81 years). There were 69 males (83.2%) and Methods: We herein report a pediatric case of extensive-stage SCLC in
14 females (16.8%). 72 patients (86.7%) had a previous history of smoking. a patient who was treated with intensive chemotherapy and high-dose
ECOG PS at relapse was 0 in 3 (3.6%), 1 in 70 (84.3%), and 2 in 10 (12.1%) chemotherapy (HDC). Results: A 13-year-old male patient was admitted
patients. Fifty patients (60.2%) had extensive disease at baseline diagnosis, to our department with a three-month history of cough. Thoracic CT and
and the remaining 33 (38.8%) had limited disease. All patients were exposed MRI showed two large masses, one was a 5.8 × 4.3 × 3.9 cm primary tumor
previously to etoposide and platinum. The platinum used was cisplatin in 52 that was located close to the right middle lobe bronchus; the other was a
patients (60.3%) and carboplatin in 30 patients (38.7%). Previous radiation subcarinal lymph node. Systemic PET-CT revealed multiple bone metastases.
at local tumor site was received by 38 patients (45.8%). The response was A serological analysis revealed high levels of pro-GRP (4,075 pg/mL [normal, ≤
evaluated in 78 patients. The response post2 months of PG was complete 81 pg/mL]) and NSE (52.3 ng/mL [normal, ≤ 16.3 ng/mL]). The patient’s plasma
response in 2 patients (2.5%), partial response in 29 (37.1%), stable disease level of VEGF was 259 pg/mL (normal, ≤ 115 pg/mL). We diagnosed the patient
in 24 (30.7%), and progressive disease in 23 patients (30.6%). The median with SCLC based on the results of the histopathological examination of
number of cycles of PG received was 8 (2-28) cycles. Toxicity related cessation endoscopically-obtained biopsy specimens that were obtained from part of
of treatment was required in 12 patients (14.4%). The reason for stoppage the tumor that was partially exposed on the bronchial wall. Treatment was
was Grade 3–4 toxicities in 8 patients (9.6%) and deterioration in PS in 4 initiated with cisplatin and irinotecan (PI). After four courses of PI therapy
patients (4.8%) The median PFS was 148 days (95% CI: 30–173.5 days) while followed by two courses of PI plus etoposide (PIE) therapy, there was a
the median OS was 172 days (95% CI: 60–485 days). Conclusion: Paclitaxel plus reduction in the tumor volume and a remarkable decrease in the patient’s
gemcitabine it is a well tolerated regimen in relapsed SCLC in the schedule we biomarker levels. Thereafter, we administered three courses of chemotherapy
usually use (every 2 weeks). Unless this study is retrospective, we believe that consisting of bevacizumab, cisplatin and etoposide. Furthermore, HDC
this combination can be used nowadays in these patients, if there is no clinical with autologous peripheral blood stem cell rescue and prophylactic cranial
trial available. irradiation were performed. Early recurrence appeared one month after
the completion of the series of initial treatments. He died ten months after
Keywords: SCLC, chemotherapy, second line
the relapse. Conclusion: The long-term prognosis of adult SCLC patients is
generally poor, even if desirable initial treatment responses are obtained. In
order to improve their prognosis, new trials with other anti-cancer agents
should be performed. Bevacizumab, an anti-VEGF monoclonal antibody that
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS is effective against non-SCLC, is an intriguing candidate molecular target drug
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY – that should be evaluated for SCLC. Because the value of VEGF in the present
patient’s plasma was high, we were of the opinion that the administration
of bevacizumab after effective chemotherapy with PI and PIE might have
P1.07-010 INFLUENCE OF CREATININE CLEARANCE ON SURVIVAL represented an intensive treatment that had the potential to improve his
PARAMETERS IN SMALL CELL LUNG CANCER TREATED WITH prognosis. Because intensive chemotherapy has been observed to be highly
tolerable in adolescence and young adults, we expected HDC to have a greater
CISPLATIN-BASED CHEMOTHERAPY REGIMEN
effect on the patient’s disease. However, the intensified therapy strategy
Sedat Gözel1, Ahmet Sumbul1, Ali Murat Sedef 1, Ayberk Besen1, Huseyin had no impact on the patient’s disease and the results were similar to those
Mertsoylu1, Celal Batmaci2, Fatih Kose 3 observed in elderly patients with extensive-stage SCLC.
1
Baskent University, Adana/Turkey, 2Hakkari Devlet Hastanesi, Hakkari/Turkey,
3
Medical Oncology, Baskent University, Adana/Turkey Keywords: SCLC, high-dose chemotherapy, bevacizumab, adolescence and
young adult
Background: Extensive stage Small Cell Lung Cancer (ES-SCLC) remains
incurable with the current management strategies. Despite huge effort,
only the small increment in overall survival has been achieved over the past
2 decades. Cisplatin-based combination chemotherapy regimen remain
standard and provide high response rate with significant improvement in POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
survival parameters compared to non-platin based regimen. Cisplatin dose DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
was calculated by multiplying body surface area(BSA) and 60-100 according
to chemotherapy protocol. Main excretion route for the cisplatin is kidney
and the drug is contraindicated for the patients with creatinine clearance P1.07-012 EFFICACY OF IMMUNE CHECKPOINT INHIBITORS IN
(CClr) below the 60 mL/min. In other words, decrease in CClr provide higher LARGE CELL NEUROENDOCRINE LUNG CANCER: RESULTS FROM A
concentration of cisplatin and may increase therapeutic effect. Therefore, FRENCH RETROSPECTIVE COHORT
with this study, we try to explore whether creatinine clearance has significant
Matteo Giaj Levra1, Julien Mazieres2, Clarisse Audigier Valette3, Olivier
effect on survival parameters or not for the ES-SCLC patients. Methods: A
Molinier4, David Planchard5, Violaine Frappat6, Leonie Ferrer 1, Anne Claire
total 53 patients, 47 (88.7%) male and 6 (11.3%) female, were included. Mean
Toffart1, Denis Moro-Sibilot1
age was 58 years-old (range 42-73). All patients were at good performance 1
scale with normal renal function (CClr>60mL/min) treated with cisplatin Michallon Hospital - University Hospital, Grenoble/France, 2Toulouse University
Hospital, Toulouse/France, 3Centre Hospitalier Sainte Musse, Toulon/France,
(60-100 mg/m2/3wk)-etoposide (100 mg/m2/3wk) with. Mean cisplatin dose 4
Pneumology, Centre Hospitalier Du Mans, Le Mans/France, 5Medical Oncology,
per cycle were 121 mg/3wks and 66 mg/m2/3wks. Objective response rate Gustave Roussy, Villejuif/France, 6Pneumology, Centre Hospitalier de Chambery,
was 71.7%. During follow-up period 41 patients (77.4%) were death. Mean Chambery/France
body surface area(BSA), CClr accounted by formula of MDRD and Cockcroft
gault were 1.8 kg/m2, 116.6 and 118.2 mL/min. The statistical analysis failed Background: Nivolumab and pembrolizumab, two programmed death
to show significant correlation between cisplatin dose and BSA; between (PD)-1 immune-checkpoint–inhibitor antibodies, demonstrated superiority
cisplatin dose and MDRD and Cockcroft gault with spearman’s correlation test versus standard chemotherapy in second- third line in both squamous and
(r: 0.258, n:53, p: 0.58; r: -0.211, n:53, p: 0.129; r: 0.048, n:53, p: 0.73). Median non-squamous lung cancer. Large cell neuroendocrine lung cancer (LCNEC)
overall survival(OS) was 14 months (12.1-15.9, 95%CI). Statistical analysis is a rare tumour often treated as a small cell lung cancer, but there is not
failed to show significant effect of CClr (>120 mL/min vs <120 mL/min) on OS a standard of care after a first line progression. Aim of the study was to
(p: 0.260). Results: In this study specifically included ES-SCLC patients with assess clinical efficacy of PD-1 inhibitors in these patients. Methods: We
excellent performance score with healthy renal function but failed to show retrospectively reviewed all consecutive LCNEC stage IIIB- IV patients treated
significant effect of CClr on OS. Conclusion: In conclusion, calculation of with nivolumab or pembrolizumab after platinum-based first line therapy
cisplatin dose according to the method including CClr like the area under the between July 2014 and November 2015 in six French centres. Patients were
curve(AUC) may not provide better survival rate in ES-SCLC. followed until June 2016. The drugs were given in an early access program or a
clinical trial. Results: The analysis included 10 patients with advanced stage
Keywords: creatinine clearance, small cell lung cancer, survival disease. Eight patients (80%) had a stage IV disease with a median age of 59
[interquartile range (IQR) 55-62] years. The majority were males (n=9; 90%),
with good performance status (0-1; 9/90%) and 50% were treated in third line

or further. Three patients presented brain metastases. In 5 cases a molecular small cell lung cancer (SCLC), empiric use of chemotherapy is common in this
test was done, finding in one case (20%) a KRAS mutation. Patients received setting in the absence of supporting prospective data. In order to assess the
a first line treatment with platinum and etoposide in 8 cases (80%) with a potential benefit and predictors of chemotherapy use beyond the second
disease control rate of 50%. Nine patients received nivolumab and the PD-L1 line setting in SCLC, we analyzed the SEER-MEDICARE database. Methods:
status was never performed, while the patient treated with pembrolizumab We employed data of SCLC patients diagnosed between 1985 and 2005.
expressed PD-L1. Patients received a median number of 16 [IQR, 13-18] cycles, Univariate (UVA) association of line of chemotherapies with covariates was
6 showed a partial response (60%), 1 a stable disease (10%). Median PFS was examined with Wilcoxon rank-sum test, chi-square or Fisher’s exact test.
57 [24-57] weeks. Most of the patients stopped treatment due to disease Multivariable (MVA) logistic regression analysis for line of therapy was
progression (n=4; 80%), only one for a pulmonary interstitial pneumonia. conducted using the following covariates: year of diagnosis, age, gender,
Conclusion: Our findings suggest that the use of immune-checkpoint– race, Medicare status, urban/rural location, and radiation. Survival functions
inhibitors in LCNEC could be explored in a larger cohort of patients. This were estimated by the Kaplan-Meier method and the log-rank test was used
treatment could be considered in the scenario of a disease with limited to assess for difference in overall survival (OS) stratified by line of therapy.
therapeutic strategy. UVA and MVA survival analyses were carried out using the Cox proportional
hazards model. To further balance confounders between patients receiving
Keywords: Immune checkpoint inhibitors, large cell neuroendocrine different lines of therapy, propensity scores were estimated using a MVA
carcinoma logistic regression model to predict the receipt of 3rd line chemotherapy
based on relevant covariates. Propensity score analysis was further
conducted by including the estimated propensity score as a covariate in a
Cox proportional hazards model. All analyses were done using SAS 9.3 with
two-sided tests and a significant level of 0.05. Results: There were 47,351
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY – patients with SCLC of which 23,535 (49.7 %) received chemotherapy and
MONDAY, DECEMBER 5, 2016 10,887 (23%) received platinum-based chemotherapy. Of the platinum-
treated patients, 1424 (13.1%) received additional salvage therapy of either
topotecan alone (n=801) or topotecan and additional treatments as 3rd line
P1.07-013 TREATMENT RELATED SIDE EFFECTS OF ORAL
and beyond (n=623). The median OS was 11, 13, 15 and 17 months respectively
TOPOTECAN IN SMALL CELL LUNG CANCER for patients treated with one, two, three or > 3 lines of chemotherapy
Filip Popovic, Marko Jakopovic, Miroslav Samarzija, Branka Čučević, Suzana respectively. Propensity score analysis showed additional lines of therapy
Kukulj, Mihovil Roglić, Sanja Pleština beyond the second line was associated with a reduced risk of death (HR: 0.786;
Department for Respiratory Diseases “Jordanovac”, University Hospital Center, 0.729 - 0.847, p<0.001 and 0.617; 0.564 - 0.675; p<0.001 for 3rd line and > 3 lines
Zagreb/Croatia of therapy respectively). Age (p=0.043) and year of diagnosis (P<0.001) were
significantly associated with treatment beyond 2nd line topotecan on MVA
Background: Lung cancer is the most common tumor in men and the second
analysis. Conclusion: Salvage chemotherapy is not commonly used following
most common tumor in woman according to the latest data available from
failure of platinum containing chemotherapy in SCLC patients. However,
the Croatian National Cancer Registry. Approximately 20% of all lung cancers
chemotherapy beyond the second line was associated with an incremental
are categorized as small cell lung cancer (SCLC). Topotecan is recommended
survival benefit in US MEDICARE-eligible SCLC patients.
as second-line chemotherapy in treatment of SCLC. Topotecan can be
administrated orally with the same effectiveness as parenteral. Methods: The Keywords: SCLC, chemotherapy, third line, survival
aim of this study was to determine toxicity of oral topotecan in second line
of chemotherapy and to establish the frequency of drug related admissions.
Results: A total of 177 courses of therapy were administered to the 64
patients, 17 woman and 47 men, with SCLC patients ranging from 42 to 77
years with the mean age of 59.3. All the patients were treated in University POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
Hospital Centre Zagreb from January 2012 to October 2015. Included patients MONDAY, DECEMBER 5, 2016
had ECOG performance status of 0 or 1. Topotecan was administrated every 21
day, at the dose of 2.3 mg/m2 /day, during 5 days. Average number of courses
received was 2.8. Of all included patients 17 of them (26.5%) were admitted P1.07-015 STOMP: A UK NATIONAL CANCER RESEARCH NETWORK
to hospital because of adverse events related to topotecan administration. RANDOMISED, DOUBLE BLIND, MULTICENTRE PHASE II TRIAL OF
The majority of patient hospitalizations (11 patients, 16.9%) was due to OLAPARIB AS MAINTENANCE THERAPY IN SCLC
febrile neutropenia. Other reasons for hospitalization were severe diarrhea Penella Woll1, Piers Gaunt2, Nicola Steele3, Samreen Ahmed4, Clive Mulatero5,
in 4 patients (6.2%), pneumonia in 1 patient (1.5%) and severe electrolyte Riyaz Shah6, Sarah Danson1, Elizabeth Hodgkinson7, Karen James2, Ben
imbalance in 1 patient (1.5%). Of 17 admissions to hospital 10 (58.9%) of Watkins2, Peter Fletcher2, Lucinda Billingham2
them were after application of first chemotherapy cycle, 3 (17.6%) after 1
University of Sheffield, Sheffield/United Kingdom, 2Cancer Research Uk Clinical
second cycle and 4 (23.5%) after third cycle. Quantitative hematologic Trials Unit, University of Birmingham, Birmingham/United Kingdom, 3Beatson
toxicities were assessed using the National Cancer Institute Common Toxicity West of Scotland Cancer Centre, Glasgow/United Kingdom, 4University Hospitals
Criteria. Anemia grade 3 or 4 occurred in 13 patients (20.3%). Grade 3 or 4 of Leicester, Leicester/United Kingdom, 5St James’ University Hospital, Leeds/
thrombocytpenia occurred in 7 patients (10.9%). Grade 3 or 4 neutropenia United Kingdom, 6Maidstone Hospital, Maidstone/United Kingdom, 7Weston Park
occurred in 16 patients (25%). Of other, non-hematologic adverse effects Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield/United
the most serious was grade 3 or 4 diarrhea that occurred in 5 patients (7.8%). Kingdom
Conclusion: although admission of oral topotecan is well tolerated it is related
Background: STOMP (ISRCTN 73164486, CRUK/10/037, EudraCT 2010-
with high rate of hospitalizations due to myelotoxicity and gastrointestinal
021165-76) is a randomised, double-blind, placebo-controlled phase II trial
toxicity during therapy.
to evaluate activity and safety of the PARP inhibitor olaparib (AstraZeneca)
Keywords: SCLC, topotecan, side effects as maintenance treatment for patients with chemo-responsive small cell
lung cancer (SCLC). Two schedules of olaparib oral tablets were investigated:
300mg twice daily (bd) or 200mg three times daily (tds). Methods: Eligible
patients had pathologically confirmed SCLC with response to first line
chemotherapy or chemo-radiotherapy. Patients were stratified by metastasis-
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS status and prior radiotherapy and randomised in a 2:2:1:1 ratio to: olaparib
MONDAY, DECEMBER 5, 2016 tds, olaparib bd, placebo tds or placebo bd. Placebo arms were pooled for
analyses. Primary outcome was progression-free survival (PFS). There is 80%
power to detect a difference of 3 months in PFS (from 4.8 months) between
P1.07-014 IMPACT OF CHEMOTHERAPY FOR SMALL CELL LUNG treatments based on a one-sided 5% significance level. Key secondary
CANCER IN THE THIRD LINE AND BEYOND, A SEER-MEDICARE outcome measures were overall survival (OS), adverse events (AEs) and quality
ANALYSIS of life. Results: Between November 2013 and December 2015, 220 UK patients
were randomised. Arms were well balanced for stratification factors of prior
Sungjin Kim1, Camille Ragin2, Zhengjia Chen1, Madhusmita Behera1, Rathi
radiotherapy (89% Yes) and metastasis status (66% M1) as well as sex (46%
Pillai1, Conor Steuer 1, Chandra Belani3, Fadlo Khuri1, Suresh Ramalingam4,
M) and age (median=64, range 42-89). Median follow-up for 31 event-free
Taofeek Owonikoko5
1 patients was 14 months (range 0–24). Median PFS was 2.6 (90%CI 1.8, 3.7), 3.6
Emory University, Atlanta/United States of America, 2Fox Chase Cancer Center,
(90%CI 3.1, 6.0) and 3.6 (90%CI 3.1, 4.7) months in the placebo, olaparib bd and
Philadelphia/PA/United States of America, 3Penn State Hershey Cancer Institute,
Hershey/PA/United States of America, 4Winship Cancer Institute, Emory University, tds arms, respectively. There was no significant difference in PFS between
Atlanta/GA/United States of America, 5Medical Oncology, Emory University olaparib and placebo for either the bd (Cox-Adjusted HR 0.87; 90% CI 0.64,
Winship Cancer Institute, Atlanta/United States of America 1.18; stratified logrank p=0.29) or the tds arm (0.89; 90% CI 0.67, 1.20; p=0.43).
Median OS was 8.9 (90%CI 7.0, 11.9), 9.9 (90%CI 7.6, 12.9) and 9.0 (90%CI 6.6,
Background: While there is no approved third line chemotherapy option for 11.8) months in the placebo, olaparib bd and tds arms, respectively. There was
no significant difference in OS between olaparib and placebo for either the bd POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
LOCAL TREATMENT –
(Cox-Adjusted HR 0.97; 90% CI 0.69, 1.37; stratified logrank p=0.73) or the tds MONDAY, DECEMBER 5, 2016
arm (1.05; 90% CI 0.76, 1.46; p=0.73). The most common AEs on olaparib were
fatigue, nausea, anaemia, vomiting and anorexia. 68 patients discontinued
treatment citing AEs (17 placebo, 26 olaparib bd, 25 olaparib tds). Conclusion: P1.07-017 INDICATIONS FOR ADJUVANT MEDIASTINAL RADIATION
There is no evidence that either the bd or tds regimen for olaparib improves IN SURGICALLY RESECTED SMALL CELL LUNG CANCER
PFS or OS in an unselected population. The AE profile for olaparib in SCLC is Elliot Wakeam1, Meredith Giuliani2, Natasha Leighl3, Tom Varghese Jr4,
similar to that observed in other studies. Samuel Finlayson5, Gail Darling1
1
Keywords: maintenance, SCLC, PARP, olaparib Division of Thoracic Surgery, University of Toronto, Toronto/ON/Canada,
2
Radiation Oncology, University of Toronto, Toronto/ON/Canada, 3Medical
Oncology, University of Toronto, Toronto/ON/Canada, 4Division of Thoracic Surgery,
University of Utah, Salt Lake City/United States of America, 5Surgery, University of
Utah, Salt Lake City/UT/United States of America
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE Background: Adjuvant mediastinal radiation (AMR) is an adjunctive therapy for
patients with surgically resected small cell lung cancer (SCLC). However, little
TUMORS
data guides its use. We sought to examine whether there was a survival benefit
Local Treatment – associated with AMR for resected SCLC patients and to define sub-populations
MONDAY, DECEMBER 5, 2016 who should be selected for AMR. Methods: Patients undergoing resection
(lobectomy, pneumonectomy and sublobar resection) for SCLC were identified
in the National Cancer Database, 2004 – 2013. Kaplan-Meier survival curves
P1.07-016 TRENDS, PRACTICE PATTERNS AND UNDERUSE OF and Cox proportional hazards were used to evaluate the impact of receipt of
SURGERY IN THE TREATMENT OF EARLY STAGE SMALL CELL LUNG AMR on survival. Hazard ratios were adjusted for patient comorbidity and
CANCER demographic information, as well as tumor stage, grade, histology, margin
status and receipt of adjuvant chemotherapy. Results: 3,113 patients were
Elliot Wakeam1, Tom Varghese Jr2, Natasha Leighl3, Meredith Giuliani4,
identified. Those receiving AMR were younger, more likely to have greater
Samuel Finlayson5, Gail Darling6
1
pathologic T- and N- stage, more likely to undergo sublobar resection and
University of Toronto, Toronto/ON/Canada, 2University of Utah, Salt Lake City/ have a positive margin. Kaplan-Meier curves showed better median survival
United States of America, 3Medical Oncology, University of Toronto, Toronto/
for patients with N1-3 disease who received AMR. After adjustment, Cox
ON/Canada, 4Radiation Oncology, University of Toronto, Toronto/ON/Canada,
5
University of Utah, Salt Lake City/UT/United States of America, 6Division of models showed lower risk of death for N1, N2/3 and sublobar resection with
Thoracic Surgery, University of Toronto, Toronto/Canada AMR (HR0.79 CI0.65 – 0.96, p=0.02; HR 0.60 CI0.48 – 0.75, p<0.0001). In the
overall cohort, AMR was not associated with better survival in node-negative
Background: Current National Comprehensive Cancer Network guidelines patients. AMR was, however, associated with improved survival for patients
recommend pathologic mediastinal staging and surgical resection for all receiving sublobar resection (HR0.72 CI0.58 – 0.92, p=0.006).
patients with clinically node negative T1 and T2 small cell lung cancer (SCLC),
but the extent to which surgery is used for early stage SCLC is unknown.Our
obejctive was to assess trends and practice patterns in the use of surgery for
SCLC. Methods: Clinical stage T1 or T2N0M0 SCLC cases were identified in the
National Cancer Database (NCDB), 2004 – 2013. Demographics and clinical
characteristics of patients undergoing resection were analyzed. Hierarchical
logistic regression was used to identify individual and hospital-level predictors
of receipt of surgical therapy. Trends in the rates of surgical resection for
eligible patients were analyzed over the study period. Results: 9,740 patients
were identified with a diagnosis of clinical T1 or T2 N0M0 SCLC. Of these, 2,210
underwent surgery (22.7%), with 1,421 (64.3%) of these patients undergoing
lobectomy, 739 (33.4%) sublobar resections and 50 (2.3%) pneumonectomies.
After adjustment for clinical, demographic and facility characteristics,
Medicaid patients were less likely to receive surgery (OR0.65 95% CI 0.48 –
0.89, p=0.006), as were those with T2 tumors (OR0.25 CI0.22 – 0.29, p<0.0001).
Academic facilities were more likely to resect eligible patients (OR 1.90 CI1.45 –
2.49, p<0.0001). Between 2004 and 2013, rates of resection more than doubled
from 9.1% to 21.7%. Overall, 68.7% of patients were not offered surgery despite
having no identifiable contraindication. In patients not receiving surgery, only
7% underwent pathologic mediastinal staging.
Conclusion: Although rates of resection are increasing, surgery is rarely used

nationally in the treatment of potentially eligible SCLC patients. About two
thirds of potentially eligible patients fail to undergo potentially curative
surgery. Further study is required to address the lack of concordance between
guidelines and practice.
Keywords: small cell lung cancer, Health Services Research, quality

improvement

Conclusion: AMR has significant benefit for node-positive patients after

resection for SCLC, especially those with pN2 or pN3. Patients undergoing
sublobar resection may benefit from AMR.
Keywords: adjuvant mediastinal radiation, small cell lung cancer

LOCAL TREATMENT –
P1.07-018 INCIDENCE OF BRAIN RECURRENCE AND SURVIVAL

OUTCOMES IN HIGH-GRADE NEUROENDOCRINE CARCINOMAS OF
THE LUNG: IMPLICATIONS FOR CLINICAL PRACTICE
Giannis Mountzios 1, Biagio Ricciuti2, Rita Chiari2, Marina Baretti3, Lorenzo
Falcinelli4, Diana Giannarelli5, Angelo Sidoni6, Lucio Crinò2, Guido Bellezza6,
Alberto Rebonato7, Piero Ferolla2, Luca Toschi3, Giulio Metro2
1
Medical Oncology, University of Athens School of Medicine, Athens/Greece,
2
Medical Oncology, Santa Maria Della Misericordia Hospital, Azienda Ospedaliera
Di Perugia, Perugia, Italy, Perugia/Italy, 3Division of Oncology and Hematology,
Humanitas Clinical and Research Center, Rozzano, Milan/Italy, 4Radiotherapy Unit,
Santa Maria Della Misericordia Hospital, Azienda Ospedaliera Di Perugia, Perugia/
Italy, 5Biostatistics & Data Management Core, Regina Elena Cancer Institute, Rome/
Italy, 6Department of Experimental Medicine, Pathological Anatomy and Histology
Unit, University of Perugia, Perugia/Italy, 7Department of Diagnostic Imaging,
University of Perugia, Perugia/Italy
Background: Among patients with advanced high-grade neuroendocrine

carcinoma (HGNEC) of the lung, the optimal therapeutic management is much
less established for large cell neuroendocrine carcinomas (LCNECs) than for
small cell lung cancers (SCLCs). We evaluated the survival outcomes and
incidence of brain recurrence of advanced LCNECs, and compared them with
those of a population of SCLCs matched by stage. Methods: Forty-eight
unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV
Conclusion: Patients with advanced LCNECs are at high risk for brain
HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy
recurrence. Unresected stage III LCNECs treated with platinum-etoposide
of platinum-etoposide chemotherapy with or without thoracic radiotherapy
with or without TRT bear a dismal prognosis, when compared indirectly with
(TRT) and/or prophylactic cranial irradiation (PCI) was investigated. Results:
SCLC counterparts. Randomized trials should evaluate whether PCI could
Overall response was significantly lower for LCNECs compared with SCLCs for
improve survival of advanced LCNECs.
both stage III (43.8% vs 90.6% respectively, P=0.004) and stage IV (43.3% vs
64.5%, respectively, P=0.04). Similarly, an inferior outcome was observed in Keywords: small cell lung cancer, prophylactic cranial irradiation,
terms of progression-free survival (PFS), and overall survival (OS) for LCNECs Neuroendocrine tumors, Large Cell Neuroendocrine tumours
compared with SCLCs, which, however, reached significance only for stage III
disease (median: 5.6 vs 8.9 months, P=0.06 and 10.4 vs 17.6 months, P=0.03 for
PFS and OS, respectively), (Figure 1). Histologic subtype (LCNEC vs SCLC) was
an independent prognosticator in multivariate analysis. In the lack of PCI,
LCNECs showed a high cumulative incidence of brain metastases, as 58% and POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
LOCAL TREATMENT –
48% of still living stage III and IV patients, respectively, developed brain MONDAY, DECEMBER 5, 2016
metastases at 18 mo
P1.07-019 LARGE CELL NEUROENDOCRINE CARCINOMA OF THE

LUNG: PROGNOSTIC FACTORS OF SURVIVAL AND RECURRENCE
AFTER R0 SURGICAL RESECTION
Maria Cattoni1, Eric Vallieres1, Lisa Brown2, Amir Sarkeshik2, Stefano
Margaritora3, Alessandra Siciliani3, Pier Luigi Filosso4, Francesco Guerrera4,
Andrea Imperatori5, Nicola Rotolo5, Farhood Farjah6, Grace Wandell6,
Kimberly Costas7, Catherine Mann1, Michal Hubka8, Stephen Kaplan8,
Alexander Farivar 1, Ralph Aye1, Brian Louie1
1
Thoracic Surgery, Swedish Cancer Institute, Seattle/WA/United States of America,
2
General Thoracic Surgery, UC Davis Medical Center, Sacramento/CA/United States
of America, 3Thoracic Surgery, Catholic University “sacred Heart”, Rome/Italy,
4
Thoracic Surgery, San Giovanni Battista Hospital, Torino/Italy, 5Thoracic Surgery,
University of Insubria-Ospedale Di Circolo, Varese/Italy, 6Cardiothoracic Surgery,
University of Washington Medical Center, Seattle/WA/United States of America,
7
Thoracic Surgery, Providence Regional Medical Center, Everett/WA/United States
of America, 8Virginia Mason Hospital & Seattle Medical Center, Seattle/WA/United
States of America
Background: Large cell neuroendocrine carcinomas (LCNEC) represent

approximately 3% of all lung cancers. Due to this rarity, little knowledge
exists about their outcome, prognosis or optimal treatment strategy. The
objective of this study is to evaluate the outcomes of patients undergoing
lung resection for LCNEC to identify the factors affecting survival and
recurrence to help refine the optimal treatment strategy. Methods: We
retrospectively reviewed 116 patients who underwent lung resection at 8
centers between 2000-2015. We excluded 18 patients: pNX(3), stage IV(5),
R1-2(10). Univariate and multivariate analysis were performed to identify
factors influencing disease-specific survival, overall survival and recurrence.
The variables included age, gender, smoking habit, previous malignancy, ECOG
performance status, symptoms at diagnosis, extent of resection, extent of
lymphadenectomy, tumor location, tumor size, pT, pleura invasion, pN, pStage
and neo/adjuvant treatments. Kaplan-Meier, Cox regression and ROC curve
were used. Results: A total of 98 patients (M/F:60/38) were analyzed with
a median age of 66 years (IQR=58-72). Prior to resection, 11 (11%) received
induction therapy. Resections included pneumonectomy (8), bilobectomy prospective studies are warranted to optimize multimodal approach and
(3), lobectomy (76) and sublobar (11) with an associated lymph node sampling selection of patients.
(N=52, 55%) and lymphadenectomy (N=43, 45%). Adjuvant therapy was
delivered in 28 (30%). Pathologic stages were I (N=40, 41%), II (N=33, 34%) Keywords: PDL-1, small cell lung cancer, Surgery, multi modality treatment
and IIIA (N=25, 25%). Median follow-up was 62 (IQR=19-120) months. The
5-year disease-specific and overall survival rates were 51.6% and 42.7%.
On univariate analysis, pT was associated with disease-specific and overall
survival (p=0.011, p=0.028). Similarly pT was also associated on multivariate
analysis with disease-specific and overall survival (p=0.044, p=0.034). LOCAL TREATMENT –
The recurrence rate was 55% (2% local, 10% regional, 32% systemic, 11% MONDAY, DECEMBER 5, 2016
not-specified). The median disease-free interval was 16 (IQR=6-80) months.
Local-regional recurrence wasn’t associated with any factor on univariate
P1.07-021 IMPACT ON SURVIVAL OF HIGH DOSE CONSOLIDATIVE
analysis. Systemic recurrence was correlated with tumor size (p=0.002),
pT (p=0.003) and pStage (p=0.024) on univariate analysis. Tumor size was
THORACIC RADIOTHERAPY IN EXTENSIVE STAGE SMALL CELL
an independent prognostic factor of systemic recurrence on multivariate LUNG CANCER
analysis (p=0.001) with a threshold value of 3 cm (AUC=0.712). The 5-year Josep Jové, Anabel Mañes, Yolanda Luis, Geovanna Perez, Rosa Ballester,
disease-free survival for systemic recurrence in tumors < 3 cm or >3 cm was Beatriz Gutierrez, Victoria Tuset, Monica Caro, Alex Melero, Jaume Molero,
75.4% and 37.8% (p=0.001). The 5-year disease-specific survival was 56.7% and Isabel Planas, Ernest Luguera, Ana Alvarez, Salva Villà, Antonio Arellano
47.3% (p=0.088). Conclusion: Treatment of LCNEC with predominately surgical Radiation Oncology, Institut Catala Oncologia, Badalona/Spain
resection results in a respectable 5-year survival. However, a high proportion
of systemic recurrence occurs. Tumors >3 cm have a higher rate of systemic Background: Consolidative thoracic radiotherapy for metastatic small cell
recurrence and lower rate of survival suggesting that adjuvant chemotherapy lung cancer patients who have responded to chemotherapy is controversial.
may be indicated for completely resected LCNEC >3 cm. Some publications suggest improved local control which could influence
survival. Slotman et al. have recently published a randomized study that
Keywords: large cell neuroendocrine carcinoma, prognostic factors of survival, showed that thoracic radiotherapy improves long term survival for patients
lung surgery, prognostic factors of recurrence with extensive stage small cell lung cancer (ES-SCLC) who have responded
to chemotherapy. Slotman also demonstrated in 2007 that prophylactic
cranial irradiation in metastatic small-cell lung cancer with response to initial
chemotherapy, reduces the incidence of symptomatic brain metastases
and prolongs disease-free and overall survival. Methods: In our Radiation
LOCAL TREATMENT – Oncology Department we have reviewed those patients with ES-SCLC
MONDAY, DECEMBER 5, 2016 (disseminated disease excluding brain metastases) who have achieved
an objective response after chemotherapy, received prophylactic cranial
irradiation and, after that, some of them treated with consolidative thoracic
P1.07-020 SURGICAL RESECTED SMALL CELL LUNG CANCERS radiotherapy (CRT). Between 1995 and 2015 we have treated 68 patients, 59
(SCLCS): A MONOCENTRIC RETROSPECTIVE ANALYSIS men and 9 women (median age 63 years, range 42-79), with the characteristics
Laura Bonanno 1, Elisabetta Di Liso1, Marco Schiavon2, Alberto Pavan1, Mara mentioned above. Prophylactic cranial irradiation was administered at
Mantiero1, Dario Gregori3, Giovanni Comacchio2, Matteo Fassan4, Ilaria Attili1, median doses of 24 Gy (range 24-36 Gy). Thoracic radiotherapy consolidation
Nazarena Nannini3, Fiorella Calabrese3, Giuseppe Natale2, Giulia Pasello1, was delivered to 23 patients (33.8 %), with a median total dose of 46 Gy (range
Massimo Rugge4, Federico Rea2, Pierfranco Conte5 20-54 Gy). We compared this group with the 45 patients (66.2%) who did not
1
Medical Oncology, Istituto Oncologico Veneto, Padova/Italy, 2Thoracic Surgery, receive CRT. Results: Among those patients treated with CRT, 17 patients
Department of Cardiothoracic and Vascular Sciences, Università Degli Studi Di (74%) had residual disease after chemotherapy, 4 patients (17.4%) had chest
Padova, Padova/Italy, 3Department of Cardiothoracic and Vascular Sciences, progression and 2 patients (8.7%) achieved complete response. No grade
Università Degli Studi Di Padova, Padova/Italy, 4Department of Medicine, Surgical 3 toxicity has been reported. Median overall survival (OS) is 18 months in
Pathology and Cytopathology Unit, Università Degli Studi Di Padova, Padova/Italy, patients who received CRT, compared to 10 months in those patients who
5
Department of Surgery, Oncology and Gastroenterology, Università Degli Studi Di
have not CRT. OS after one year was 78.3% in the group of patients with CRT
Padova, Padova/Italy
and 41.3% when CRT was not performed. OS after two years was 34.8% with
Background: Standard treatment for stage I-III SCLCs is chemoradiotherapy CRT and 6.9% without CRT. Conclusion: We have found a benefit (p=0.002)
followed by prophylactic cranial irradiation, with 5-year survival rate of in the group of patients who received CRT, compared with patients who did
about 20%. Recent retrospective analyses reported benefit from surgery not, obtaining significant differences in median survival and overall survival,
followed by adjuvant platinum-based chemotherapy but no randomized trials taking into account that a bias selection could have affected the results. In
confirmed these results. Methods: A series of 365 SCLCs treated from 1996 comparison with Slotman study, we have found an improved survival with
to 2015 has been retrospectively evaluated. Among 141 evaluable patients, higher doses of CRT, without additional severe toxicity.
61 underwent radical-intent surgery and 21 underwent chemoradiotherapy.
Keywords: thoracic radiotherapy, Consolidative radiotherapy, extensive small
Clinical, radiological and pathological data were reviewed and related with
cell lung cancer
outcome. Mitotic count, necrosis, TP53, Bcl-2 and PD-L1 immunohistochemical
expression were analyzed. Results: Median follow-up was 42 months.
Among resected patients, 46 (75%) were male and median age was 68 (95%
CI: 46.9-83.4) years. Seven patients (11%) underwent pneumonectomy, 43
(71%) received chemotherapy before (20%) or after (51%) surgery. Adjuvant POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
radiotherapy was administered in 19 (31%) cases. Pathological review of LOCAL TREATMENT –
resected SCLCs was performed. Median mitotic count was 59/10 hpf and
extensive necrosis was found in 80% of samples. P53 (>30%), Bcl-2 (H-index
>150) and PD-L1 (>5%) expression was reported in 58%, 58% and 62% of P1.07-022 THE ROLE OF SURGERY IN COMBINATION TREATMENT OF
samples respectively. None of these factors significantly affected survival. A PATIENTS WITH SMALL CELL LUNG CANCER
significant correlation between necrosis and mitosis (p 0.00002), and pN2 and
Bcl-2 (p 0.03) was found. Median overall survival (OS) and relapse-free survival Aleksei Aksarin1, Michail Ter-Ovanesov2, Sergei Kopeika1, Aleksei Mordovskiy3
1
(RFS) were 62.3 (95% CI: 32.4-82.1) and 12.8 (95% CI: 6.57-47.27) months, Surgut District Clinical Hospital, Surgut/Russian Federation, 2Oncology and
respectively. Mortality of surgery was 0%, morbidity was 23%. Surgical Haematology, Rudn University, Moscow/Russian Federation, 3Oncology, Surgut
District Clinical Hospital, Surgut/Russian Federation
margins were found positive in 8 (13%) cases. Median OS for pN0-1 patients
was 65.7 (95% CI: 44.5-108) months versus 30.3 (95%CI: 12-NA) months for Background: Small cell lung cancer (SCLC) as the most aggressive tumor
patients with pN2 disease (p 0.04). Multivariate analysis confirmed pN2 deserves a special attention. The aim of this research was to define the
stage (p 0.04) and surgical margins (p 0.03) as significant prognostic factors. place of surgery of patients with SCLC in order to improve the results of
Among non-resected patients, the median age was 69.4 (95% CI: 54.7-84) treatment. Methods: Clinical material for research consists of 46 patients
years. Median OS and RFS were 13.4 (95% CI: 7-26.9) and 7 (95% CI: 5.9-19) in stage IA-IIIA with SCLC, which were radically operated in Ugra (region
months. To confirm our results, we compared outcome of patients with pN2 Russia) between 1999 and 2013. Among patients predominate males 38
disease according to surgical resection. Median OS of surgically resected (82,6%), versus females – eight (17,4%). Results: All patients underwent
SCLCs was 30.3 (95% CI: 7.03-36.9), while it was 14.7 (95% CI: 12-NA) months radical operations R0. All resection types were included (pneumonectomy,
among patients treated with chemoradiotherapy, but the comparison was bilobectomy, and lobectomy). By 32 patients (69,6%) systematic nodal
not statistically significant. Conclusion: Radical-intent surgery was feasible dissection (SND) was carried out, by 5 (10,9%) - mediastinal lymph node
and associated with considerable long-term survival. Mediastinal nodal sampling (MLS) and by 9 patients mediastinal node dissection was not carried
involvement and non-radical surgery were the main elements able to affect out. By SCLC combination treatment was used more often – 32 (69,6%). By
OS. The expression of PDL1 was not prognostic in stage I-III SCLCs. Further that only in 8 cases additional adjuvant of thoracic radiotherapy was used.

In 14 cases only surgical resection was used (30,4%). 5-year overall survival Yue Kong1, Honglian Ma1, Zhongxin Liao3, Jianhua Zhang4, Lauren Averett
(OS) rate was 47,1%. Median survival rate was 58 months. Five-year OS rate Byers5, Don Lynn Gibbons5, Bonnie S. Glisson6, Ignacio Wistuba6, John
by surgery combined with adjuvant chemotherapy was 52,1%, as compared Heymach6, Daniel Richard Gomez6, Andrew Futreal6, Ming Chen1
to only surgical treatment – 35,6%. At I stage satisfactory results were 1
Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital,
achieved: 5-year OS rate was 69% (p<0,05), – that corresponds with results Hangzhou/China, 2Department of Thoracic/head and Neck Medical Oncology, The
of treatment of patients with non-small cell lung cancer with similar stage University of Texas MD Anderson Cancer Center, Houston, Hx/TX/United States of
of process. Median survival rate was not achieved. At II stage 5-year OS rate America, 3Department of Radiation Oncology, The University of Texas MD Anderson
was 31%. Median survival rate was 46 months. At III stage unsatisfactory Cancer Center, Houston, Hx/TX/United States of America, 4Department of Genomic
results were obtained. 5-year OS rate was 21%. Median survival rate was Medicine, The University of Texas MD Anderson Cancer Center, Houston, Hx/United
States of America, 5The University of Texas MD Anderson Cancer Center, Houston,
only 11 months. Conclusion: SCLC at I and II stages is the indication to radical
Hx/TX/United States of America, 6The University of Texas MD Anderson Cancer
treatment, mandatory including surgical resection with SND and adjuvant Center, Houston, Hx/United States of America
chemotherapy. The main method of treatment at III stage is chemotherapy or
chemoradiotherapy. Background: EGFR mutations in SCLC were first reported in cases of lung
adenocarcinoma which transformed to SCLC after TKI treatment and such
mutation was speculated to be a TKI resistance mechanism. Recently case
reports and high throughput sequencing in a small number of samples
suggested that EGFR mutations do exist in de novo SCLC. But the genetic
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE and clinical characteristics have not been studied in large number of samples.
TUMORS This study aims to conduct a large scale survey of the EGFR mutations among
Chinese SCLC patients, and to analyze the genetic and clinical characteristics
Molecular Changes – of such mutations. Methods: Mutation status in exon 18-21 of EGFR was
MONDAY, DECEMBER 5, 2016 assessed by dideoxy-sequencing in 565 SCLC tumors treated in Zhejiang
Cancer Hospital, Hangzhou, China from 2009 to 2014 and correlated with
clinical parameters. Chi-square test were used to show the correlation of clinic
P1.07-023 NGS MAY DISCRIMINATE EXTREME LONG-TERM VERSUS variables with EGFR mutation. Survival analysis was performed using the
SHORT-TERM SURVIVAL IN PATIENTS WITH STAGE IV SMALL-CELL Kaplan-Meier method. Results: 40 instances of EGFR mutation are detected
LUNG CANCER (SCLC) in 565 clinical samples. The mutation rate is 7.1%. Besides classic mutations
E19 deletion (n=3) and E21 L858R(n=3), the rest of the mutations detected
Zoltan Lohinai1, Balazs Dome2, Glen Weiss3
1
are atypical including E18 (G719D/S, G696R, S695N/D, N700D, I715F, L688F,
Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria,
2 P694L), E19(K757N, A755V, V742I, E736K, N756Y, E749K, P753L, A755T), E20
Department of Tumor Biology, National Koranyi Institute of Pulmonology,
(T790M, H773R, S768R/N, R776H/C, G796D, D807N, R803W/Q, Y813C, G810S,
Budapest/Hungary, 3Western Regional Medical Center, Ctca, Goodyear/AZ/United
States of America A763T, G779D, Q791R, C781Y, N771S), E21(L858V, G874R, K867E). Among the
EGFR mutation positive patients, 27.5% (11/40) are non-smokers, higher than
Background: Molecular underpinnings that may prognosticate survival the EGFR negative group (16.4%, 86/525). But it is not statistically significant
and could increase our understanding of tumor progression are far less (p=0.129). And EGFR mutation is not correlated with sex (female vs male),
understood processes in highly aggressive malignancies such as SCLC. We age (≥65y vs <65y) or clinical stages (limited stage vs extensive stage). After
aimed to describe the clinocopathological characteristics and biomarker matching the treatment history of the EGFR mutation positive and negative
profiling of short versus long-term SCLC survivors using the latest, most patients (excluding patients who were not treated ,only treated by traditional
clinically actionable genomic and immunohistochemical (IHC) alterations. Chinese medicine or one cycle chemotherapy or biological therapy, treatment
Methods: Consecutive 876 metastatic SCLC patients receiving standard of unkown ), univariate analysis shows that the EGFR mutation positive patients
care therapy were evaluated between 2000 and 2013 at the National Koranyi have better overall survival than the EGFR negative group, with medium OS of
Institute of Pulmonology. Long-term (LT) (overall survival (OS) > 24 months) 24.433m±4.864m vs 14.00m±0.838m respectively (p=0.018). COX regression
and short-term (ST) survivors (OS range 2-9 weeks) with histologically analysis suggests that limited stage (HR=2.610), <65 years (HR=1.476) and
confirmed stage IV SCLC were included in this retrospective analysis. DNA EGFR mutation (HR=0.587, p=0. 0.039) were independently predictive of
and RNA were isolated from FFPE tissues. A comprehensive next-generation better OS. Conclusion: Among the de novo SCLC patients diagnosed, there
sequencing test (NGS) was performed to analyze gene mutations, copy exists a group harboring EGFR mutations, most of which are non-classic
number variations (CNV), mRNA expression, and protein expression by IHC mutations. After matching the treatment history of patients, analysis reveals
(PCDx, Paradigm). Multiplex sequencing analysis had coverage >5,000x. that EGFR mutations are predictive of better OS.
We then evaluated the associations amongst these various biomarkers
and clinicopathological characteristics. Results: Four LT and 11 ST were Keywords: EGFR mutation, Small cell lung cancer (SCLC), Genetic
identified for NGS. There were five mutually exclusive gene mutations, heterogeneity, Prognostic impact
previously not described in SCLC (EP300: c.650A>G p.N217S; c.4561G>A
p.E152K; ERBB4: c.949G>A p.E317K; BRCA1: c.4981G>A p.E1661N; and EGFR
(ERBB1): c.2225T>C p.V742A). Mismatch repair (MMR) deficiency, CNV and
PD-L1 in tumor-infiltrating lymphocytes (TIL)/tumor cells were not found
in any of the samples. TOP1 was highly elevated in both groups, supporting MOLECULAR CHANGES –
campothecins as effective drugs in SCLC. Certain mRNA genes appeared to MONDAY, DECEMBER 5, 2016
be linked in a similar or overlapping pathway. HENT1 (SLC29A1) with 50-79%
protein concordance and survivin (BIRC5) mRNAs were high in most of the ST
P1.07-025 MIR-495 PROMOTES CHEMORESISTANCE OF SCLC
vs. LT. All LT survivors, but none of the ST survivors, received consolidation
thoracic radiation therapy (RT) along with standard of care chemotherapy.
THROUGH EPITHELIAL-MESENCHYMAL TRANSITION VIA ETK/BMX
SSTR2 mRNA expressions were higher in LT survivors (vs. ST survivors) Linlang Guo 1, Ting Wei2, Weiliang Zhu2, Shun Fang2, Jian Zhang2
1
treated with first-line platinum-etoposide. Molecular testing revealed that Pathology, Zhujiang Hospital, Southern Medical University, Guangzhu/China,
2
ST survivors treated with cyclophosphamide, epirubicin, and vincristine Zhujiang Hospital, Southern Medical University, Guangzhou/China
were not predicted to be sensitive to doxorubicin or epirubicin. LT survivors
Background: MiR-495 is firstly found in the brain tissues and it can regulate
proved to be sensitive to irinotecan/topotecan and lanreotide/octreotide but
neuronal plasticity by affecting the expression of brain-derived neurotropic
not to platinum (BRCA1 and/or survivin mRNA was not present). Conclusion:
factor. Studies have shown that the function of miR-495 is still controversial
Consolidation RT and certain linked pathways may discriminate between LT
in different types of cancer. For example, it serves as a tumor suppressor
and ST survivors in SCLC. NGS profiling of extreme survivors may improve
in MLL-rearranged leukemia, while functions as an oncogenic miRNA in
classification of SCLC and possibly identify clinically-relevant new targets.
breast cancer. However, whether the miR-495 serves as a tumor suppressor
Keywords: extreme survival, new targets, NGS profiling, stage IV small-cell or an oncogene in SCLC has not been reported. Methods: In this study, we
lung cancer (SCLC). investigated whether miR-495 regulates chemoresistance of SCLC through
epithelial-mesenchymal transition (EMT) via Epithelial and endothelial
tyrosine kinase (Etk/BMX) using two drug resistant cell lines. The expression
of miR-495 and Etk/BMX in SCLC patients were examined in 86 SCLC tissues
and 60 normal lung tissues by qRT-PCR and Immunohistochemical staining.
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS Results: Loss- and gain-of-function experiments showed miR-495 regulated
MOLECULAR CHANGES –
MONDAY, DECEMBER 5, 2016 cells proliferation, tumor growth and drug resistance. MiR-495 suppression
or Etk/BMX elevation in SCLC specimens correlated with poor pathologic
stage and survival time. The expression of Etk/BMX was one of the directly
P1.07-024 EGFR MUTATIONS IN SMALL CELL LUNG CANCER (SCLC): targeted genes of miR-495. Ectopic expression of Etk/BMX obviously
GENETIC HETEROGENEITY AND PROGNOSTIC IMPACT rescued miR-495 elevation induced inhibition of drug resistance. Etk/BMX
Huarong Tang 1, Jianjun Zhang2, Xiao Hu1, Yujin Xu1, Baiqiang Dong1, Jin Wang1, over-expression led to higher EMT mesenchymal factors (Zeb-2, Twist, Vim)
and lower epithelial molecule β-catenin, while suppression of Etk/BMX was and TC (n=7) were included, EMT gene expression was quantified with a
opposite. Knockdown of Zeb-2 and Twist inhibited the chemoresistance of quantitative real-time (RT)- PCR carried out on StepOnePlus™ Real-Time
cells. Conclusion: Our study revealed that miR-495 promoted chemoresistance PCR System (Applied Biosystems), with RT2 Profiler PCR Array System for
of SCLC through epithelial-mesenchymal transition via Etk/BMX. MiR-495 re- EMT (Qiagen, Dusseldorf, Germany). Associations of the gene signature and
expression or Etk/BMX depletion is a promising strategy for interfering with clinicopathological features, as well as prognostic factors were evaluated.
chemoresistance in SCLC. Results: A 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB,
SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3 and VIM) that was related to EMT
Keywords: Etk/BMX, small cell lung cancer, chemoresistance, miR-495 was up-regulated in tumor-tissue from all NELC patients, mainly in those with
high-grade NELC. An increased expression of DSP, TCF3 and TGFβ3 was found
in SCLC compared to AC, TC and LCNEC, and associated with lymph nodes
metastasis with statistical significance respectively for DSP (p=0.03 and
MOLECULAR CHANGES – 0.02), TCF3 (p=0.02) and marginal significance for TCF3 and TGFβ3 (p=0.08 and
MONDAY, DECEMBER 5, 2016 p=0.08). TCF3 was also associated with tobacco history (p=0.04). A significant
correlation was found between enolase and IL1RN (p=0.03), chromogranin and
TGFβ2 (p=0.04), synaptophysin and TGFβ1 and TGFβ2 respectively (p=0.04
P1.07-026 ACTIVIN A IS ASSOCIATED WITH POOR PROGNOSIS AND
and p=0.02). Conclusion: The EMT analysis identified genes involved in cell
PROMOTES METASTATIC GROWTH IN SMALL CELL LUNG CANCER proliferation, motility, invasion and metastasis of NELC. We further inferred
Anita Rozsas 1, Elisabeth Lang2, Mir Hoda1, Thomas Klikovits1, Ildiko Kovacs3, DSP, TCF3 and TGFβ3 as target against lung cancer metastasis and invasion,
Szilvia Torok 3, Balazs Hegedus4, Walter Berger2, Walter Klepetko1, Michael thus arising as promising therapeutic agent.
Grusch2, Balazs Dome1, Viktoria Laszlo1
1
Division of Thoracic Surgery, Medical University Vienna, Vienna/Austria, Keywords: Gene signature, EMT, Neuroendocrine carcinomas, lung cancer
2
Department of Medicine I, Institute of Cancer Research, Medical University of
Vienna, Vienna/Austria, 3National Institute of TB and Pulmonology, Budapest/
Hungary, 4Ruhrlandklinik University Hospital, University of Duisburg-Essen, Essen/
Germany
Background: Small cell lung cancer (SCLC) is a devastating malignancy MOLECULAR CHANGES –
characterized by resistance to therapy and poor clinical outcome. Therefore,
identification of novel therapeutic strategies and non-invasive biomarkers
that facilitate early detection and predict prognosis is urgently needed. P1.07-028 DUAL ROLE OF THE FOCAL ADHESION KINASE IN SMALL-
Expression of the growth factor activin A (ActA), a member of the TGF beta CELL LUNG CANCER
superfamily, is deregulated in a number of malignancies. However, to date
Frank Aboubakar Nana1, Marylène Lecocq2, Maha Ladjemi2, Bruno Detry2,
there is no data on the role of ActA in SCLC. Methods: In a cohort of SCLC
Sebastien Dupasquier2, Pierre Massion3, Yves Sibille2, Yves Sibille4, Charles
patients (n=79) and in sex- and age-matched controls (n=66), plasma levels
Pilette2, Charles Pilette5, Sebahat Ocak1, Sebahat Ocak4
of ActA were measured by ELISA. The diagnostic value of plasma ActA was
1
evaluated by ROC curve analysis. The mRNA and protein expression levels of Institut de Recherche Expérimentale Et Clinique (Irec), Pôle de Pneumologie, Orl
Et Dermatologie, Université Catholique de Louvain, Bruxelles/Belgium, 2Institut
ActA were analyzed in SCLC cell lines by qRT-PCR and by ELISA, respectively,
de Recherche Expérimentale Et Clinique, Université Catholique de Louvain,
and one of the cell lines with low baseline ActA expression was transfected
Bruxelles/Belgium, 3Division of Allergy, Pulmonary and Critical Care Medicine,
with ActA and a control vector. The effect of ActA overexpression on the in Vanderbilt-Ingram Cancer Center, Nashville/TN/United States of America, 4Division
vivo growth of SCLC cells was investigated in an orthotopic xenograft model. of Pneumology, CHU UCL Namur (Godinne Site), Yvoir/Belgium, 5Division of
Results: Increased plasma ActA levels were found in patients with SCLC (vs. Pneumology, Cliniques Universitaires St-Luc, Bruxelles/Belgium
controls) and ActA levels were elevated in a TNM stage-dependent manner.
Moreover, high ActA levels were associated with significantly shorter overall Background: Small cell-lung cancer (SCLC) is a devastating illness with
survival and multivariate analysis revealed that plasma ActA concentration five-year overall survival as low as 5%. The molecular steps leading to SCLC
is an independent negative prognostic factor in this patient cohort. With development and progression are still poorly understood and this has
an area under the curve of 0.81 (95% CI: 0.74-0-0.88), circulating ActA was translated into the absence of targeted therapies. Focal Adhesion Kinase
identified as a useful biomarker for the diagnosis of SCLC. Expression of ActA (FAK) is a non-receptor tyrosine kinase which regulates integrin and growth
in SCLC cell lines was detected in vitro. Furthermore, ActA overexpression factor signaling pathways involved in cell proliferation, survival, migration,
increased the metastatic capacity of SCLC cells in our xenograft model. and invasion. FAK is overexpressed and/or activated in many cancers,
Conclusion: Our findings suggest that the measurement of circulating ActA including SCLC. We hypothesized that FAK overexpression/activation in
can support the diagnosis and staging of SCLC and, moreover, that it can help SCLC contributes to its aggressive behavior and that FAK may represent
to predict the clinical outcome. We also conclude that ActA has a role in the a therapeutic target in SCLC. Methods: Two SCLC cell lines growing in
aggressive behavior of this tumor type and that its potential therapeutic suspension (NCI-H82, NCI-H146), and adherent SCLC cell lines (NCI-H196,
relevance needs to be further investigated. NCI-H446) were treated with PF-228. NCI-H446 and H82 cells were stably
transfected with FAK shRNA and/or FRNK using lentivirus vector. Cell
Keywords: small cell lung cancer, activin A, prognosis, metastasis proliferation was evaluated by WST-1 assay; cell cycle by flow cytometry with
propidium iodide and bromodeoxyuridine; apoptosis by caspase 3 staining
in flow cytometry and by cleaved PARPp85 Western blotting (WB); motility
by wound healing assay; and invasion by Boyden chambers. FAK expression/
activity was evaluated by WB. Results: While PF-228 did not modify total
FAK expression, it decreased FAK phosphorylation (Y397). Inhibition of FAK
MONDAY, DECEMBER 5, 2016 activity by PF-228 decreased cell proliferation, DNA synthesis, induced cell
cycle arrest in G2/M phases, and increased apoptosis in dose-dependently.
PF-228 also decreased motility in the adherent H196-H446 cells. To confirm
P1.07-027 13-GENE SIGNATURE OF EMT REVEALS IMPACT ON the specificity of the antitumoral effects of PF-228, we stably transfected
INVASION AND METASTASIS OF NEUROENDOCRINE CARCINOMAS SCLC cells with FAK shRNA and FRNK and then analyzed the phenotypic
OF THE LUNG: A PRELIMINARY STUDY changes induced by these approaches. Knockdown of total FAK protein by
Tabatha Prieto 1, Vanessa De Sá2, Eloisa Olivieri2, Eduardo Da Silva3, Rui Reis3, transfection of FAK shRNA inhibited FAK activity, but did not have any effect
Dirce Carraro2, Vera Capelozzi1 on cell proliferation, DNA synthesis, and cell cycle. However, reintroduction of
1
Pathology, Faculdade de Medicina Da Usp, São Paulo/Brazil, 2Pathology, Ac FRNK in cells stably transfected with FAK shRNA inhibited cell proliferation
Camargo Cancer Center, São Paulo/Brazil, 3Molecular Oncology Research, Barretos and DNA synthesis. Expression of FRNK decreased cell proliferation and
Cancer Hospital, Barretos/Brazil DNA synthesis in SCLC cells. Conclusion: Inhibition of FAK activity by PF-
228 in SCLC cell lines demonstrates that FAK activity is required for cell
Background: Metastasis are responsible for the death of 90% of patients proliferation, cycle progression, survival, and motility, suggesting that FAK
with lung cancer, indicating the need to know the multiple signaling inhibition may represent a suitable therapeutic target for SCLC. Inhibition of
pathways involved. Neuroendocrine lung carcinomas (NELC) encompass FAK by a genomic approach suggests that FAK has a dual role in SCLC biology,
a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and namely (i) a pro-tumoral effect related to the kinase domain, which induces
atypical carcinoid (AC), to the high-grade large cell neuroendocrine carcinoma downstream signals (ii) an anti-tumoral effect mediated by the non-kinase
(LCNEC) and the small cell lung carcinoma (SCLC). Low-grade NELC are C-terminal domain (FRNK domain), which keeps inactive other pro-tumoral
indolent, while high-grade NELC invade and metastasize rapidly. Biomarkers effectors
of NELC aggressiveness remain to be determined. Epithelial to mesenchymal
transition (EMT) genes profile emerge promise as indicator of invasion and Keywords: Targeted therapy, FAK, SCLC
metastasis. Our aim was to evaluate: (1) EMT gene expression in NELC; (2)
its relationship with the histologic subtypes and (3) its impact on behavior
of the tumors. Methods: Patients with SCLC (n = 10), LCNEC (n=5), AC (n=2)

POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS outcome (p <0.01). Conclusion: Different expression of EMT gene signature in
endocrine and non-endocrine lung carcinomas, its relationship with histologic
types, advanced stage, lymph node metastasis and death suggest a possible
role of these markers in this malignancy, but more importantly provide a
P1.07-029 IN VITRO EFFECTS OF PEGYLATED ARGINASE IN SMALL potential biomolecular marker to predict outcome. The correlation between
CELL LUNG CANCER NELC, ADc, SqCC and specific EMT genes involved in cell proliferation and
Shi Xu1, Sze Kwan Lam1, Paul Ning Man Cheng2, James Chung Man Ho1 motility provides a possible role of these genes on the development and
1 aggressiveness in these tumors. Moreover, the specific genes expressed
The University of Hong Kong, Hong Kong/Hong Kong Prc, 2Bio-Cancer Treatment
International Limited, Hong Kong/Hong Kong Prc only in NELC emerges as promise biomarker of behavior. Further studies are
needed to validate EMT gene expression to predict prognosis and tumoral
Background: Small cell lung cancer (SCLC) accounts for 15% of all lung cancer aggressiveness.
cases. SCLC is notoriously difficult to treat with high relapse rate and the
current standard treatment remains chemotherapy. Arginine is an important Keywords: Neuroendocrine carcinomas, metastasis, lung cancer, EMT
amino acid in normal human cells that can be replenished through urea cycle,
but some tumors are arginine-auxotrophic due to deficient argininosuccinate
synthetase (ASS1) and/or ornithine transcarbamylase (OTC). BCT-100 is a
pegylated arginase, which converts arginine to citrulline, has demonstrated POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
anticancer activity in human melanoma, hepatocellular carcinoma and acute MOLECULAR CHANGES –
myeloid leukemia. We aim to determine the in vitro effects of BCT-100 in SCLC. MONDAY, DECEMBER 5, 2016
Methods: A panel of 7 SCLC cell lines was obtained from ATCC. Cell viability
was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
P1.07-031 CLINICAL EVALUATION OF FOLATE RECEPTOR-POSITIVE
bromide (MTT) assay and protein expression by Western blot. Knockdown
CIRCULATING TUMOR CELLS DETECTION IN PATIENTS WITH SMALL
of OTC was performed using siRNA. Flow cytometry was applied to detect
mitochondrial membrane depolarization (MMD). Results: The IC50 values CELL LUNG CANCER
of BCT-100 in H69, DMS79, H187, H209, H526, H841 and SW1271 cells were Chunxia Su1, Jing Zhao1, Xuefei Li1, Tao Jiang2, Chao Zhao1, Wenchen Zhao1,
462.9±112.2, >1000, 24.9±6.4, 8.6±0.8, 10.1±0.7, >1000 and 49.2±7.4 mU/mL Shengxiang Ren1, Caicun Zhou2
1
respectively. Overexpression of ASS1 in H69 and DMS79 cells, and OTC in Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai/
H841 cells were associated with resistance to BCT-100. Knocking down of OTC China, 2Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji
increased sensitivity of BCT-100 in H841 cells partially via apoptosis. H526 cells University School of Medicine, Shanghai/China
(BCT-100-sensitive) was selected for mechanistic study. MMD was observed
Background: Small cell lung cancer (SCLC) is distinguished by extremely
in BCT-100 treatment accompanied by cytochrome c and SMAC release from
high numbers of circulating tumor cells (CTCs) in comparison to other
mitochondria to cytosol. N-acetylcysteine (NAC) could significantly reverse
malignancies, however, the role of CTCs in evaluating chemotherapy effect
apoptosis induced by BCT-100. Besides, cyclin A2, cyclin B1 and CDK7 were
of SCLC is to be further clarified. The purpose of this study was to investigate
downregulated in a time-dependent manner. The protein expression of p-AKT
the predictive and prognostic role of folate receptor–positive CTCs in
and p-mTOR was increased after exposure while RAS/RAF/ERK cell signaling
unresectable SCLC. Methods: In this single-center prospective study, blood
pathway was inhibited with BCT-100 treatment. Conclusion: SCLC cell lines
samples for folate receptor–positive CTCs analysis were obtained from 80
with low ASS1 and OTC expression were sensitive to arginine depletion with
patients with chemotherapy-naive unresectable SCLC at baseline, after two
BCT-100, mediated through oxidative stress, cell cycle arrest and apoptotic
cycles of chemotherapy, and on disease progression. All patients received
pathway.
chemotherapy with EC or EP regimen for at least two cycles. CTCs number
Keywords: small cell lung cancer, apoptosis, Pegylated arginase BCT-100, at baseline, after chemotherapy and changes with chemotherapy were
oxidative stress evaluated as predictive factors for chemotherapy effect, along with clinical
characteristics. Results: Of all 80 patients, CTCs was detected at baseline
as positive (CTCs>8.7 FU/3mL) in 67 patients, with the percentage of 83.8%,
which was not associated with age, sex, smoking status or disease stage. In
72 evaluable patients, the disease control rate was 83.9% (52/62) and 50%
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS (5/10) in CTCs positive and negative patients respectively (P=0.004). In CTCs
positive patients, those harboring low levels of folate receptor (8.7<CTCs<14,
n=29) were associated with longer PFS (275 days, 95%CI:82-468) than those
with high expression levels (CTCs ≥14, n=38)(PFS: 210days, 95%CI:159-261;
P1.07-030 GENE SIGNATURE OF EMT IN NEUROENDOCRINE LUNG P=0.0458). Reduction in CTCs number after two cycles of chemotherapy
CARCINOMA: A COMPARATIVE ANALYSIS WITH ADENOCARCINOMA was associated with partial response (P=0.049) but not with stable disease
AND SQUAMOUS CELL CARCINOMA (P=0.47). The results of a multivariate analysis showed that the baseline
CTCs level was an independent prognostic factor for survival time (HR=2.19;
Tabatha Prieto 1, Vanessa De Sá2, Eloisa Olivieri2, Eduardo Da Silva3, Rui Reis3,
P=0.024). Conclusion: CTCs number at baseline could be used as a useful
Dirce Carraro2, Vera Capelozzi1
1 prognostic biomarker for SCLC. Reduction in CTCs number with chemotherapy
Pathology, Faculdade de Medicina Da Usp, São Paulo/Brazil, 2Pathology, Ac
could predict better chemotherapy effect of SCLC.
Camargo Cancer Center, São Paulo/Brazil, 3Molecular Oncology Research, Barretos
Cancer Hospital, Barretos/Brazil
Keywords: Circulating tumor cells, Folate receptor, small cell lung cancer,
Background: Recurrence and metastasis are responsible for 90% of the chemotherapy
death of patients with lung cancer. Adenocarcinomas (ADc) primarily invade
blood vessels with distant metastasis, whereas squamous cell carcinoma
(SqCC) involves the mediastinal lymph nodes. Neuroendocrine carcinomas
of low-grade (typical and atypical carcinoid) are indolent, while high-grade POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
NE carcinoma (large cell NE and small cell carcinomas) metastasize rapidly. MOLECULAR CHANGES –
Biomarkers of invasiveness in lung carcinomas still cannot be definitely MONDAY, DECEMBER 5, 2016
determined. Epithelial to mesenchymal transition (EMT) genes profile emerge
promise as indicator of invasion and metastasis. Our aim was to compare EMT
P1.07-032 MOST COMMON GENOMIC ALTERATIONS IN SCLC
gene expression in NELC, ADc and SqCC and its impact on behavior of these
tumors. Methods: EMT gene expression was quantified with a quantitative Ioana Bonta1, Rabih Bechara2, Christopher Parks3, Daniel Miller4, Dacian
real-time (RT)- PCR carried out on StepOnePlus™ Real-Time PCR System Bonta5, Patricia Thompson 6
1
(Applied Biosystems) with RT2 Profiler PCR Array System for EMT (Qiagen, Hematology Oncology, Cancer Treatment Centers of America, Newnan/GA/United
Dusseldorf, Germany). Results: Younger patients expressed higher amount of States of America, 2Cancer Treatment Centers of America, Newnan/GA/United
States of America, 3Center for Advanced Oncology - Thoracic, Cancer Treatment
AHNAK, IL1RN, MSN, TCF3 and VIM than older (p<0.05), whereas SNAI3 and
Centers of America, Newnan/United States of America, 4Thoracic Surgery, Wellstarr
TGFβ2 were more expressed in smokers (p<0.05). ADc and SqCC presented Health Network, Marietta/GA/United States of America, 5Radiology/imaging,
significant higher expression of COL3A1, DSP and MSN in tumor compared to Emory University, Atlanta/United States of America, 6Thoracic Oncology, Cancer
normal tissue (p<0.05). 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, Treatment Centers of America, Newnan/GA/United States of America
PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3 and VIM) was up-regulated
in tumor-tissue from all NELC patients. In ADc and NELC, AHNAK, IL1RN, TCF3 Background: Lung cancer is the leading cause of cancer death in US. The
and VIM was significantly different (p<0.05). ADc and SqCC compared with American Cancer Society’s estimates for lung cancer in the United States for
high-grade NELC also presented differences in COL3A1 (p<0.01). Interestingly, 2016 are: approx 224,390 new cases of lung cancer and approx 158,080 deaths.
only NELC expressed PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3. Approximately 10-15% of lung cancers are classified as small cell (SCLC). These
Advanced tumors, usually with metastasis, showed higher expression of cancers portend a poor prognosis. Genomic sequencing of non-small cell lung
AHNAK, DSP, IL1RN, MSN and VIM (p<0.05), as well as association with poor cancer led to developing of new therapeutic modalities, i.e. targeted therapy
with superior results to conventional cytotoxic chemotherapy. At this time, cannot induce enough ADCC activity. Delivery of a cytotoxic agent DM1 to the
there is no approved targeted therapy for SCLC. In order to develop targeted inside of cells via HER2-mediated internalization is expected and crucial to
therapies we need to identify and characterize molecular targets exert antitumor effect in such ADCC-lacking SCLC cells.
(alterations). This study aims to report our experience with genomic
sequencing of SCLC Methods: We performed a retrospective analysis of a
dataset of 54 cases of SCLC, who underwent genomic sequencing. Patients
were treated at 5 tertiary referral centers, between October 2012 and June
2016. The recorded data included: age at diagnosis, date of the genomic
sequencing, genomic alteration (affected genes and the type of molecular
alteration identified). For genomic profiling we used a platform commercially
available (FoundationOne). Results: We obtained 54 samples from 54
patients. Age range is 42 to 75 years, mean 60 and median 61 years old. All
cases had a histologic diagnosis of SCLC. The genomic analysis found 88
affected genes with 230 alterations. The most common affected genes: Tp53
alteration, 45 cases (83%) and Rb1 33 cases (61%). There were an average of 4.3
mutations per patient; with a median of 4 mutations per patient, with a
minimum of 0 and a maximum of 13.
Keywords: HER2, trastuzumab emtansine, SCLC, T-DM1

P1.07-034 SOMATOSTATIN RECEPTORS EXPRESSION IN SMALL

CELL LUNG CANCER PATIENTS
Conclusion: Sustained investigations and sequencing of larger numbers of
Efimia Boutsikou1, George Gerasimou2, Dionisios Spyratos1, Ellada
SCLC are aiming to identify potential actionable mutations in these tumors.
Eleptheriadou1, Anna Gotzamani2, Konstantinos Zarogoulidis 1
The ultimate goal is to determine new therapies and optimal treatment
1
strategy based on the genomic profile. Pulmonary Department, G.Papanikolaou Hospital, Aristotle University of
Thessaloniki, Thessaloniki/Greece, 2 2nd Clinical Laboratory of Nuclear Medicine,
Keywords: small cell, genomic alteration Ahepa Hospital, Thessaloniki/Greece
Background: Somatostatin receptors have been described on the membrane

of neoplastic cells and their expression has also been demonstrated on
small cell lung cancer (SCLC). In this study we examined if the expression of
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS somatostatin receptors at the time of disease progression correlated with
MOLECULAR CHANGES – survival and time to progression (TTP) of SCLC patients. Methods: 10 patients
with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy
at diagnosis and disease progression. Scintigraphic examinations were
P1.07-033 TRASTUZUMAB EMTANSINE (T-DM1) SUPPRESSES performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with
THE GROWTH OF HER2-POSITIVE SMALL-CELL LUNG CANCER IN whole-body scintigraphy and planar scintigraphy of the thorax as well as the
SPECT technique .The scintigraphic results were expressed in comparison with
PRECLINICAL MODELS
soft tissue intake (normal prices <1.5). Results: 111In-OCT was positive in all
Osamu Morimura1, Toshiyuki Minami2, Takashi Kijima1, Shohei Koyama3, 10 SCLC patients at the time of diagnosis and progression of the disease. No
Tomoyuki Otsuka1, Yuhei Kinehara1, Akio Osa1, Masayoshi Higashiguchi1, statistical correlation was found between somatostatin receptors expression
Kotaro Miyake1, Izumi Nagatomo1, Haruhiko Hirata1, Kota Iwahori1, Takayuki at the progression- mainly subtype 2( SSTR 2)- and survival (p=0.43), nor
Takimoto2, Yoshito Takeda1, Hiroshi Kida1, Atsushi Kumanogoh1 TTP(p=0.25) .Also the difference in somatostatin receptors expression during
1
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka diagnosis and progression had no statistical correlation with survival and TTP.
University Graduate School of Medicine, Suita/Japan, 2Department of Oncology Conclusion: The clinical utility of receptor status characterization obtained
Center, Osaka University School of Medicine, Suita/Japan, 3Department of
with 111In-OCT scintigraphy is rather confined. Our study shows that 111In-
Immunopathology, Immunology Frontier Research Center, Osaka University, Suita/
OCT scintigraphy, although is a reliable, non-invasive technique to detect
Japan
primary SLCL and its locoregional or distant metastases, cannot be used as a
Background: To overcome chemoresistance is indispensable to bring about prognostic or predictive factor in SCLC patients.
better prognosis in small-cell lung cancer (SCLC). We have reported that
Keywords: somatostatin receptors, small cell lung cancer
HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance.
Moreover, HER2-upregulated cisplatin- or etoposide-resistant SCLC cells
were sensitive to trastuzumab-mediated antibody-dependent cell-mediated
cytotoxicity (ADCC). However, irinotecan-resistant SCLC cells, e.g. SBC-3/SN-
38, were refractory to trastuzumab despite high HER2 expression. To address POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
this issue, we studied the antitumor efficacy of trastuzumab emtansine MOLECULAR CHANGES –
(T-DM1) on trastuzumab-resistant HER2-positive SCLC. Methods: SBC-3/ MONDAY, DECEMBER 5, 2016
SN-38 (HER2-positive) or OS2RA (HER2-negative) SCLC cells were inoculated
subcutaneously in the flank of six-week-old male nude mice. Tumor size was P1.07-035 CIRCULATING CELL-FREE TUMOR DNA (CFDNA) TESTING
measured with a caliper two or three times per week. When tumor volume
IN SMALL CELL LUNG CANCER
reached about 150-200 mm3, mice were randomly assigned to three treatment
groups. Each group was treated with intravenous injection of T-DM1 15 mg/ Daniel Morgensztern1, Siddhartha Devarakonda2, Ashiq Masood2, Saiama
kg, intraperitoneal injection of trastuzumab 30 mg/kg, or saline as control. To Waqar3, Alicia Carmack2, Kimberly Banks4, Richard Lanman4, Ramaswamy
confirm the HER2-specific delivery of T-DM1, in vivo imaging was performed. Govindan3
1
Namely, several tumor-bearing mice were intravenously administered with Washington University School of Medicine in St. Louis, St. Louis/MO/United States
fluorescence-labeled T-DM1. Fluorescence images of mice were captured of America, 2Washington University School of Medicine, St. Louis/MO/United
States of America, 3Medical Oncology, Washington University School of Medicine,
with IVIS® Lumina II system (PerkinElmer). Results: Treatment with T-DM1
St. Louis/MO/United States of America, 4 Guardant Health, Redwood City/CA/
significantly suppressed the growth of SBC-3/SN-38 xenografts compared United States of America
with trastuzumab and saline groups. Histological analysis revealed that T-DM1
remarkably induced apoptosis and inhibited proliferation. Fluorescence- Background: The diagnosis of small cell lung cancer (SCLC) is often made using
labeled T-DM1 definitely accumulated to the xenografts in a HER2-selective fine needle aspiration or small biopsy of tumor specimens that are typically
fashion. Conclusion: T-DM1 treatment could be an attractive therapeutic insufficient for next generation sequencing (NGS) analysis. Guardant360
option in trastuzumab-resistant HER2-positive SCLC where trastuzumab (G360), a blood-based liquid biopsy that analyzes circulating free tumor

DNA, may allow the detection of potentially targetable gene abnormalities Advanced LCNEC patients are at high risk for brain metastases, therefore,
without the need for repeated tissue biopsies. Methods: Peripheral blood routine brain imaging surveillance during follow-up may be beneficial. The
samples from patients with SCLC were collected in two 10 mL tubes. Cell-free chemotherapeutic responsiveness of LCNEC patients was intermediate
DNA was extracted and analyzed by digital sequencing for the detection of between that of NSCLC and SCLC patients. Future prospective, multicenter,
single nucleotide variants (SNVs), small Insertions and Deletions (INDELs), clinical trials are needed to determine the best chemotherapy regimen for
Copy Number Alterations (CNAs), and gene fusions. The Tumor Alterations these rare tumors.
Relevant for Genomics-Driven Therapy (TARGET) curated database (http://
www.broadinstitute.org/cancer/cga/target) was queried for potentially Keywords: lung cancer, chemotherapy, Prognosis, large cell neuroendocrine
actionable alterations. Results: 240 samples from 227 de-identified patients carcinoma
were collected between June 2014 and June 2016. 7 patients had more than
one sample analyzed. During this time period, the number of genes in the
panel increased from 54 (10 samples) to 68 (87 samples) and finally to 70
(143 samples). The median time from sample collection to reporting was 13
days (range 8-28 days). Alterations in at least one gene were found in 222 PATHOLOGY –
(92.5%) of samples and 210 (92.5%) patients. SNVs in TP53 and RB1 were MONDAY, DECEMBER 5, 2016
seen in 72.4% (152/210) and 25.7% (35/136) of patients with detectable
alterations respectively. The most common potentially actionable alterations
P1.07-037 CLINICOPATHOLOGICAL SIGNIFICANCE OF CANCER
were amplifications of FGFR1 (11.8%) and ERBB2 (7.1%). MYC amplification,
which was not considered an actionable alteration by TARGET but has been
STEM-LIKE CELL MARKERS IN HIGH-GRADE NEUROENDOCRINE
associated with sensitivity to Aurora kinase inhibitors in pre-clinical studies, CARCINOMA OF THE LUNG
was observed in 15.8% of patients. Eight patients had EGFR activating Masahiro Morise 1, Tomoyuki Hishida2, Akiko Takahashi3, Junji Yoshida2,
mutations (exon 21 L858R mutation or exon 19 deletion), of which 2 patients Yuichiro Ohe4, Kanji Nagai2, Genichiro Ishii5
also had EGFR T790M mutation, likely representing transformation from 1
Department of Respiratory Medicine, Nagoya University Graduate School of
NSCLC following targeted therapy with EGFR Tyrosine kinase inhibitors. Medicine, Nagoya/Japan, 2Thoracic Surgery, National Cancer Center Hospital East,
KIF5B-ALK and AFAP1-RET fusions were seen in 1 patient each. Conclusion: Kashiwa/Japan, 3Department of Respirology, Nippon Medical School, Tokyo/Japan,
4
G360 is a rapid non-invasive NGS platform which may be particularly useful in Thoracic Oncology, National Cancer Center Hospital, Tokyo/Japan, 5Division of
Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer
patients with advanced stage SCLC where tissue samples may be suboptimal
Center Hospital East, Kashiwa/Japan
for NGS. Due to the limited treatment options in this patient population, the
detection of potentially actionable genes through G360 may provide valuable Background: Over the past decade, cancer stem cells or cancer stem-
information to guide treatment decisions. like cells (CSLCs) have been identified in various tumors. However, few
studies have examined the significance of CSLC marker expression in
Keywords: small cell lung cancer, cfDNA
high-grade neuroendocrine carcinoma (HGNEC). This study aimed to
evaluate the clinicopathological significance of CSLC markers in high-grade
neuroendocrine carcinoma (HGNEC) of the lung, including small cell lung
carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Methods:
We retrospectively studied patients who underwent surgical resection
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE of SCLC (n = 60) and LCNEC (n = 45) to analyze their clinicopathological
TUMORS profiles and the immunohistochemical expression of putative CSLC markers
Pathology – (Caveolin, Notch, CD44, CD166, SOX2, ALDH1, and Musashi1). Staining
MONDAY, DECEMBER 5, 2016 scores for these markers in tumor cells were calculated by multiplying the
percentage of positive tumor cells per lesion by the staining intensity level
(0, 1, and 2); a score of ≥ 10 represented positive expression. Results: There
was a difference between SCLC and LCNEC with respect to both SOX2 (55
P1.07-036 LARGE CELL NEUROENDOCRINE CARCINOMA OF THE
vs. 27 %, p = 0.003) and CD166 (27 vs. 47 %, p = 0.034) expression. ALDH1
LUNG: THE MAYO CLINIC EXPERIENCE expression was equally observed in SCLC and LCNEC (67 vs. 73 %, p = 0.46), and
Kunlatida Maneenil1, Ming Liu2, Alex Adjei3, Julian Molina3, Ping Yang2 patients with ALDH1-positive HGNEC had significantly worse recurrence-free
1
Oncology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine, survival (RFS) and overall survival (OS) rates than those with ALDH1-negative
Rangsit University, Bangkok/Thailand, 2Health Sciences Research, Mayo Clinic, HGNEC (5-year RFS: 39 vs. 67 %, p = 0.009; 5-year OS: 50 vs. 79 %, p = 0.021).
Rochester/MN/United States of America, 3Medical Oncology, Mayo Clinic, A multivariate analysis revealed that positive ALDH1 expression was an
Rochester/MN/United States of America independent unfavorable prognostic factor with respect to both RFS and
OS. Conclusion: The differences in the expression profiles of CSLC markers
Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a
might reflect morphological differences between SCLC and LCNEC. Positive
relatively uncommon, high-grade neuroendocrine tumor sharing several
ALDH1 expression in lung HGNEC was associated with an unfavorable patient
features with small-cell lung carcinoma (SCLC). LCNEC is considered
prognosis, which suggested that ALDH1-positive tumor cells might be future
aggressive, and the optimal treatment strategy and chemotherapy regimen
therapeutic targets for the treatment of lung HGNEC.
remain undefined. Methods: We retrospectively evaluated a LCNEC patient
cohort established from 1997 to 2015 at Mayo Clinic (Minnesota). A diagnosis Keywords: small cell lung carcinoma, large cell neuroendocrine carcinoma,
of LCNEC was made when all WHO classification criteria were present High grade neuroendocrine carcinoma, Cancer Stem Cells
in the tumor section examined. Clinical characteristics, treatment and
outcomes were analyzed. Available radiology assessment was evaluated by
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Results:
The study included 55 LCNEC patients. Median age at diagnosis was 63 years
(range: 38-88); two thirds were men; and majority were smokers (94%). POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
Clinical staging was I, II, III or IV in 52.8%, 9.1%, 14.5%, and 23.6% of cases, PATHOLOGY –
respectively. Forty-six percent of stage IV patients presented with brain
metastases at time of diagnosis (n=6/13) and 18% (n=7/38) developed brain
recurrence in the follow up period. Thirty-nine (71%) patients had surgery P1.07-038 TYPICAL MORPHOLOGICAL FEATURES REVEALED
and 9 (16%) patients received adjuvant platinum-based chemotherapy. UNFAVORABLE SURVIVAL BENEFITS IN HIGH-GRADE
Sixty-five percent of patients with complete resection experienced disease NEUROENDOCRINE CARCINOMAS
recurrence with 80% recurring within 2 years of resection. Treatment data for
Hao-Ran Zhai1, Jia-Tao Zhang1, Li-Xu Yan2, Chao Zhang 3, Jian Su4, Song Dong4,
first-line palliative chemotherapy were available on 23 patients: 10 received
Qiang Nie4, Ri-Qiang Liao4, Ben-Yuan Jiang4, Xue-Ning Yang4, Yi Long Wu4,
platinum/etoposide and 13 received other regimens. In 19 patients with
Wen-Zhao Zhong4
available imaging; the overall response rate was 52.6% (95% CI, 31.7-72.7) and 1
there was no difference in ORR between platinum/etoposide (ORR=55.6%) Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong
Academy of Medical Sciences; Southern Medical University., Guangzhou/China,
or platinum plus other agents (paclitaxel or pemetrexed; ORR=55.6%). The 2
Department of Pathology, Guangdong General Hospital, Guangdong Academy
median survival time was 26.3 months (95%CI; 18.6-33.9); the 1-, 2-, 3- and of Medical Sciences, Guangzhou/China, 3South China University of Technology,
5-year overall survival rates (OS) were 75%, 53%, 36%, and 30%, respectively. Guangzhou/China, 4 Guangdong Lung Cancer Institute, Guangdong General
Patients who received platinum/etoposide demonstrated longer median Hospital, Guangdong Academy of Medical Sciences, Guangzhou/China
time to progression (TTP), and median OS than those who received ‘other’
regimens (14.7 months vs. 7.1 months; p value 0.07, and 28.2 months vs. 21.1 Background: The 2015 WHO classification of lung cancer has proposed an
months; p value 0.22, respectively); the differences did not reach conventional revision about high-grade neuroendocrine carcinomas(HGNEC).
statistical significance, likely due to the small sample size. Rigorous Neuroendocrine(NE) markers are necessary for differentiations in cases lacing
pathologic confirmation and genomic analysis are ongoing. Conclusion: LCNEC in typically morphological features, but their roles in survival benefits remain
is associated with a poor prognosis and high recurrence rates after surgery. unclear. Methods: A total of 700 consecutive patients diagnosed with pNET
were re-diagnosed during 2008 to 2015 and 632 were HGNECs. NE markers, Conclusion: The number of positive NE markers were necessary for precise
such as Syn(synaptophysin), CgA(chromogranin A) and CD56, were stained by diagnoses but not significant for survival benefits. Typical morphological
immunohistochemistry(IHC) if morphological features were not enough for features of NE tumor cells were unfavorable factors for OS. Further studies
diagnoses. Results: Four were excluded due to clinical identification of are imperative to identify its crucial role in HGNEC patients.
transformation from adenocarcinomas to SCLC. Nine HGNECs were previously
diagnosed with AC. TTF1 stained 77.4%(459/593) HGNEC patients, of which Keywords: High grade neuroendocrine carcinoma, Neuroendocrine markers,
50.6% in LCNEC, 80.9% in SCLC and 62.5% in poorly differentiated Synaptophysin, Chromogranin A
HGNEC(P<0.001). Syn staining(94.1%, 571/607) were not statistically
significant in three groups(89.1% vs. 94.6% vs. 100.0%, respectively; P=0.30).
The same situation was in CgA(52.6%, 319/607), with a frequency of positive
staining as 46.9%, 53.6% and 25.0%(P=0.26), respectively in three diagnoses.
The number of positive NE markers were generally balanced(P=0.62). Cases
with zero to three positive NE markers indicated marginal significant
differences of overall survival(OS)(P=0.05). Meanwhile, no differences of mOS
existed in positive and negative staining of Syn(14.7 vs. 32.53 mons, P=0.14) or
CgA(14.6 vs. 15.9 mons, P=0.82); but patients with typical morphological
features for diagnose and thus without IHC staining Syn or CgA (mOS,
9.13mons) bore significantly poorest OS benefits than those with
positive(Syn, HR=2.71, 95%CI=1.24-5.86, P=0.01; CgA, HR=2.72, 95%CI=1.25-
5.92, P=0.01) or negative(Syn, HR=3.44, 95%CI=1.39-8.52, P<0.01; CgA,
HR=2.76, 95%CI=1.26-6.05, P=0.01) staining. The same condition occurred
especially in I to IIIa patients(P<0.01).

POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS regarding age, gender, PS, disease extent (LD vs stage IV), neutrophil count
PATHOLOGY –
and weight loss. No statistically significant difference was observed between
CE and IVE groups according to main evaluation criteria: best response rate
(60% vs 59%, p=0.88), progression-free survival (median 5.1 vs 5.3 months;
P1.07-039 INSULINOMA-ASSOCIATED 1 (INSM1) p=1) and overall survival times with medians of 9.6 months and 10 months and
IMMUNOHISTOCHEMICAL EXPRESSION IN LUNG 2-year rates of 5 % and 9 % (p=0.16), respectively.
NEUROENDOCRINE TUMORS
The following variables were statistically significantly associated with
Rie Sakakibara1, Kentaro Inamura1, Hironori Ninomiya1, Yasuyuki survival in univariate analysis: age (continuous evaluation) (HR=1.02,
Shigematsu1, Tomoyo Kakita1, Daisuke Noma2, Yoshifumi Hirata2, Yosuke p=0.002), gender (male as reference) (HR=0.69, p=0.008), PS (PS ≤ 70 as
Matsuura2, Masayuki Nakao2, Mingyon Mun2, Makoto Nishio2, Sakae reference) (HR=0.60, p=0.0001), weight loss (≤5% as reference) (HR=1.28,
Okumura2, Yuichi Ishikawa1 p=0.05) and neutrophil count (≤7500/mm3 as reference) (HR=1.46, p=0.003).
1
The Cancer Institute, Tokyo/Japan, 2The Cancer Institute Hospital, Tokyo/Japan In addition, variables with a p-value < 0.2 in univariate analysis were also
included in the multivariate analysis: disease extent (LD as reference)
Background: Insulinoma-associated 1 (INSM1) is a transcription factor,
(HR=1.38, p=0.10), WBC count (≤10000/mm3 as reference) (HR=1.23, p=0.08)
and expressed during early embryonal development. In vitro and in vivo,
and treatment arm (CE as reference) (HR=0.84, p=0.16).
INSM1 has been reported to regulate the neuroendocrine differentiation
pathway represented by achaete-scute complex homolog-like1 (ASCL1) and Two variables retained their statistical significance in multivariate analysis:
neuroendocrine molecules (CGA, SYP, CD56) in lung cancer. We examined gender (HR=0.69, 95% CI 049-0.97; p=0.03) and PS (HR=0.53, 95% CI 0.49-0.97;
association between INSM1 protein expression and clinicopathological p<0.0001). Conclusion: Adding CDDP to VP16 failed improving survival in ED
characteristics in lung neuroendocrine tumors. Methods: Using 139 SCLC. In this population, gender and performance status confirmed their
consecutive surgically resected cases of lung neuroendocrine tumor prognostic value for survival.
(78 small cell lung carcinomas [SCLCs], 42 large cell neuroendocrine
carcinomas [LCNECs], and 19 carcinoids), we evaluated INSM1 and ASCL1 Keywords: Prognostic factors, chemotherapy, small cell lung cancer
immunohistochemical expression, and examined the association of INSM1
and ASCL1 expression with clinicopathological features. Results: For the 78
SCLCs, male/female ratio was 3.9:1, age ranged 46-84 with a median of 67
years, average cumulative smoking was 50.6 (pack-years), and 60/78 (77%)
were positive for any one of neuroendocrine molecules. For the 42 LCNECs, PROGNOSTIC FACTORS –
male/female ratio was 5:1, age ranged 42-84 years with a median of 70, and MONDAY, DECEMBER 5, 2016
average smoking was 47.9. For the 19 carcinoids, male/female ratio was
0.73:1, age ranged 38-85 years with a median of 67, and average smoking
was 21.9. All of SCLCs positive for neuroendocrine molecules (n=60) were P1.07-041 VALIDATION OF PROGNOSTIC SCORES IN SMALL CELL
positive for INSM1 (60/60) and 72% positive for ASCL1 (43/60). In the SCLCs LUNG CANCER
negative for all neuroendocrine molecules (n=18), 72% were positive for INSM1 Raphael Hagmann, Alfred Zippelius, Sacha Rothschild
(13/18) and all of them were negative for ASCL1 (0/18). For LCNECs, 57% were Medical Oncology, University Hospital Basel, Basel/Switzerland
positive for INSM1 (24/42) and 50% were positive for ASCL1 (21/42). All of the
carcinoids were positive for INSM1 (19/19) and 53% of them were positive Background: Treatment decisions in small-cell lung cancer (SCLC) are made
for ASCL1 (10/19). Taken together, INSM1 and ASCL1 were detectable in lung based on the extent of the disease. However, the outcome differs among
neuroendocrine tumors by immunohistochemistry in 83% (116/139) and 53% patients at the same stage. A simple tool to predict outcome in SCLC patients
(74/139), respectively. Conclusion: Our study suggests INSM1 is a sensitive and would be helpful for decision-making. In recent years, several prognostic
useful neuroendocrine marker, even for SCLC without apparent expression of scores have been proposed. However, most of them have never been validated
neuroendocrine markers. in independent patient population. Methods: From January 2000 to December
2010, 92 SCLC patients were treated at our institution. Data acquisition
Keywords: Insulinoma-associated 1 (INSM1), lung cancer, Neuroendocrine from consecutive patients was done through patients’ medical records, and
tumors blood results recorded at the time of diagnosis. Univariate and multiple cox
regression analyses of survival were performed to assess the prognostic
value of relevant clinical and laboratory factors for SCLC. Furthermore, we
investigated the relationship between seven published prognostic scores for
SCLC and overall survival (OS). Results: We recently published clinical data
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE of our study population (Hagmann R. J Cancer 2015). In a univariate analysis,
TUMORS we evaluated 29 parameters. Staging (p<0.001), number of metastastic
sites (p<0.001), liver metastasis (p<0.001), bone metastasis (p<0.001),
Prognostic Factors –
adrenal gland metastasis (p=0.028) and response to initial therapy (p<0.001)
MONDAY, DECEMBER 5, 2016 were significantly related to OS. From the established laboratory markers
hypoalbuminemia (<35 g/l; p=0.044), hyponatraemia (<131 mmol/l; p=0.041),
and elevated alkaline phosphatase (AP) (≥ 129 U/l; p<0.001) significantly
P1.07-040 PROGNOSTIC FACTORS IN EXTENSIVE DISEASE predicted OS. Multivariate analysis confirmed staging (HR 2.7; p=0.022)
(ED) SMALL CELL LUNG CANCER (SCLC): AN ELCWP PHASE III and elevated AP (HR 3.3; p=0.004) as independent prognostic factors. The
RANDOMISED TRIAL Manchester Score incorporating LDH, tumor stage, serum sodium, Karnofsky
performance status, AP and serum bicarbonate (Cerny T. Int J Cancer 1987) was
Thierry Berghmans 1, Jean-Jacques Lafitte2, Anne-Pascale Meert1, Arnaud
the only published scoring system significantly associated with OS. Patients
Scherpereel2, Marianne Paesmans3, Nathalie Leclercq1, Jean-Paul Sculier 1
1 in good, intermediate and poor prognosis groups had a median OS of 12.9,
Intensive Care and Thoracic Oncology, Institut Jules Bordet, Brussels/Belgium,
2 6.6 and 5.8 months, respectively (p=0.008). Conclusion: We confirmed the
Pneumology, Hôpital Albert Calmette, Lille/France, 3Data Centre, Institut Jules
Bordet, Brussels/Belgium prognostic role of the Manchester Score in an independent patient population
whereas the reliability of more complex and recent scoring systems could not
Background: Main prognostic factors for survival in SCLC patients are be validated. We therefore recommend using simple clinical and laboratory
performance status, disease extent, age or gender, as previously reported factors instead of complex scores to estimate prognosis of SCLC patients.
by the European Lung Cancer Working Party (ELCWP) (Paesmans et al, Eur
Respir J 2011). Based on a previous meta-analysis (Mascaux et al, Lung Cancer Keywords: prognostic score, outcome, small cell lung cancer, Manchester
2000) showing a survival advantage for regimens including cisplatin (CDDP) Score
or etoposide (VP16), the ELCWP designed a phase III trial to determine
if addition of CDDP to VP16 would improve survival in comparison with
VP16 combination without CDDP in a population of ED SCLC. The aim
of this work was to search for prognostic factors for survival. Methods:
Untreated patients with ED (limited (LD) not amenable to radiotherapy or PROGNOSTIC FACTORS –
stage IV disease) SCLC, Karnofsky performance status (PS) ≥60, adequate MONDAY, DECEMBER 5, 2016
haematological, hepatic, renal and cardiac functions, were centrally
randomised to receive either CDDP-VP16 (CE) or ifosfamide-VP16-epirubicin
P1.07-042 NEUTROPHIL-LYMPHOCYTE AND PLATELET-
(IVE). According to statistical considerations, 315 deaths had to occur before
analysis. Univariate and multivariate tests were performed for prognostic
LYMPHOCYTE RATIOS PREDICT PROGNOSIS IN EARLY-STAGE
factors analyses. Results: 346 eligible patients were randomised (176 in RESECTED SMALL-CELL LUNG CANCER PATIENTS
CE and 170 in IVE arms) between 2000 and 2013. At the time of analysis, Virag Hollosi1, Judit Moldvay2, Matyas Bendek2, Gyula Ostoros3, Balazs
329 deaths occurred. No statistically significant imbalance was observed Hegedus4, Balazs Dome4, Glen Weiss5, Zoltan Lohinai2
1
Department Iv., National Koranyi Institute of Pulmonology, Budapest/Hungary, developed DM. The most common metastases were seen in brain, liver and
2
Tumor Biology, National Koranyi Institute of Pulmonology, Budapest/Hungary, bone respectively. 2 and 5 years OS and DFS were 45.3%-20.6% and 32.2%-
3
Viii, National Koranyi Institute of Pulmonology, Budapest/Hungary, 4Division of 17.1% retrospectively. On univariate analysis, OS was significantly better in
Thoracic Surgery, Medical University Vienna, Vienna/Austria, 5Western Regional the patients with T1, N0-1 tumors and clinical stage I-II than the others and
Medical Center, Cancer Treatment Centers of America, Goodyear/AZ/United States patients who did not developed brain and DM and thoracic radiotherapy
of America
dose >60Gy(p<0.05). DFS was superior in patients with N0-1 tumor, stage I-II
Background: Surgical resection is rarely possible in small-cell lung cancer disease, who received PCI and thoracic radiotherapy dose >60Gy(p<0.05). On
(SCLC), a highly aggressive malignancy with limited treatment options. multivariate analysis, PCI was found to be an independent factor affecting
However, although in the past decades, for selected early-stage cases, a DFS (p=0.042). DM, thoracic radiotherapy dose were significant prognostic
curative intent surgery is often performed, there is no biomarker to help factors for OS (p=0.048, <0.0001 respectively). 64 patients developed brain
the selection of patients eligible for surgery. Because previous studies - metastases with a median 16 months(6-113months). Brain metastases were
predominantly from East Asia - showed that high neutrophil to lymphocyte find to be significantly less in the patients with N0, stage I-II disease and who
ratio (NLR) and platelet-lymphocyte ratio (PLR) correlate with poor prognosis were treated by PCI. Conclusion: Limited disease definition includes wide
in several types of tumors including SCLC, the aim of our study was to spectrum of patients, therefore TNM staging should be useful in order to
investigate the prognostic value of NLR and PLR in Caucasian patients with predict the prognosis of the patients. In our series, DFS and OS was superior
resected SCLC. Methods: Consecutive patients with histologically confirmed for the patients with T1 and N0-NI tumors than the others . Besides, the
and surgically resected SCLC evaluated between 2000 and 2013 at the patients with T1 and N0 tumors developed fewer brain metastases, therefore
National Koranyi Institute of Pulmonology were analyzed in this retrospective PCI might be omitted for some of the patients with early staged tumor.
analysis. Patients were divided into “high” and “low” groups according to
Keywords: limited stage, SCLC, TNM staging
their NLR and PLR at diagnosis. The cut-off NLR and PLR values were 3 and
110, respectively. Next, we evaluated the associations of preoperative NLR or
PLR with vascular involvement, tumor necrosis, peritumoral inflammation,
tumor grade, clinicopathological characteristics (including age, gender, stage)
and overall survival (OS) in univariate and multivariate analyses. Results:
There were a total of 65 patients (39 men and 26 women) with a median age POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE
of 57.7 years (range, 40-79). The pathological stages were 1, 2 and 3A in 23, 23 TUMORS
and 14 cases by AJCC 7th edition (in five patients no pTNM was available). PLR SCLC/Neuroendocrine Tumors in General –
was high (HPLR) in 41 (63%) and low (LPNR) in 24 (37%) patients. NLR was MONDAY, DECEMBER 5, 2016
high (HNLR) in 35 (66%) and low (LLNR) in 17 (33%) patients. PLR significantly
correlated with pathologic lymph node status (p<0.001) and NLR (p=0.007).
HPLR was associated with shorter OS (vs. LPLR, HR, 2.2; 95% CI, 1.13–4.29;
p=0.02). There was a non-significant trend towards longer OS in patients with
P1.07-044 EDUCATIONAL LEVEL AND MANAGEMENT IN SMALL-
LNLR (vs. HNLR, p=0.078). There were no significant associations between CELL LUNG CANCER (SCLC): A POPULATION-BASED STUDY
NLR or PLR and age, gender, stage, vascular involvement, tumor necrosis, Salomon Tendler 1, Marit Holmqvist2, Gunnar Wagenius3, Rolf Lewensohn1,
peritumoral inflammation and tumor grade. Conclusion: This is the first study Kristina Viktorsson4, Luigi De Petris1
1
in Caucasian patients with resected SCLC which shows that LPLR (<110) before Oncology, Karolinska University Hospital, Solna/Sweden, 2 Akademiska Sjukhuset,
surgical resection may be a favorable prognostic factor for longer OS. We also Uppsala/Sweden, 3Karolinska University Hospital, Solna/Sweden, 4 Oncology-
conclude that preoperative HPLR may predict lymph node involvement. PLR Pathology, Karolinska Institutet, Stockholm/Sweden
but not NLR may help in selecting patients for surgery in the future. Further
Background: In a previous study we reported that educational level is a
prospective studies are needed to confirm these observations.
prognostic factor in SCLC, with females and LD patients with a higher
Keywords: platelet-lymphocyte ratio, early-stage resected small-cell lung education having a longer survival. In this study we examined possible
cancer (SCLC), neutrophil-lymphocyte ratio, prognostic factor associations between educational level, lead times and treatment strategies
in the same cohort. Methods: The study was based on information in LcBaSe,
a lung cancer research database generated by record linkages between the
Swedish National Lung Cancer Register and several other population-based
registers. Educational level was categorized according to number of years
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS of schooling;low(≤ 9 years), middle (10-12 years), high (≥13 years). Stage was
PROGNOSTIC FACTORS –
MONDAY, DECEMBER 5, 2016 classified as limited disease (LD) and extensive disease (ED). Lead times were
defined as A) from first radiological sign of a tumor to definite diagnosis and
B) from date of referral from primary care to diagnosis. Treatment groups were
P1.07-043 PATTERNS OF FAILURE AND THE PROGNOSTIC FACTORS divided as; chemotherapy (CT), CT+Radiation Therapy (CT+RT), Palliative RT
OF THE PATIENTS WITH LD SCLC ACCORDING TO THE TNM STAGING; or no oncological therapy. Results: The study population encompassed 4278
TOG-TROD STUDY patients with a SCLC diagnosis between 2002-2011. Median age was 69 years.
988 (23.1 %) patients were diagnosed with LD (low E: 22.9 %, middle E: 23.6%,
Şefika Arzu Ergen1, H Fazilet DinçbaŞ1, Evrim Metcalfe2, Serap Akyurek 3,
high E: 26.7 %) and 3187 (74.5 %) with ED (low E: 74.8, middle E: 74.0 %, high
Güler YavaŞ4, Şükran Ülger5, Beyza Şirin Özdemir6, Birsen Yücel7, Didem
E: 73.3%) .One fifth of patients had a poor performance score (PS 3-4). The
Çolpan Öksüz1, Mustafa Şenocak8, Hakan Bozcuk9
1 median lead time A was 14 days (IQR 5-32 days) and for lead time B 9 days (IQR
Radiation Oncology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul/
3-21 days). There were no differences in lead times between the educational
Turkey, 2Radiation Oncology, Eskisehir Osmangazi University Medical Faculty,
Eskisehir/Turkey, 3Radiation Oncology, Ankara University, Medical Faculty, Ankara/ groups. The proportion of patients receiving CT+RT was approximately 80 % in
Turkey, 4Radiation Oncology, Selçuk University Medical Faculty, Konya/Turkey, LD (Low E: 78.5% Middle E: 79.2% High E: 82.4 %) and 5 % in ED (Low E: 4.2%,
5
Radiation Oncology, Gazi University, Medical Faculty, Ankara/Turkey, 6Radiation Middle E: 5.3% High E: 6.8%). The percentage of patients receiving CT was 18
Oncology, Akdeniz University, Medical Faculty, Antalya/Turkey, 7Radiation % in LD (Low E: 19.7% Middle E: 18.7 % High E: 15.3%) and 82 % in ED (Low E:
Oncology, Cumhuriyet University, Medical Faculty, Sivas/Turkey, 8Biostatistics, 81.2 %, Middle E: 83.9 % High E: 81.4 %). Conclusion: There were no significant
Istanbul University, Cerrahpasa Medical Faculty, Istanbul/Turkey, 9Medical differences between educational groups in lead times or management. We
Oncology, Akdeniz University, Medical Faculty, Antalya/Turkey
conclude that the prognostic impact of educational status in Swedish SCLC
Background: The prognostic factors and patterns of relapse were patients does not appear to reflect inequalities in access to the healthcare.
retrospectively analyzed according to the TNM staging in Turkish patients Keywords: SCLC, Epidemiology, Educationl level, Managment
with limited SCLC on behalf of Turkish Oncology Group(TOG)-Turkish
Radiation Oncology Association(TROD). Methods: The data of 266 patients
with limited disease SCLC from 13 multiple oncology centers who have at
least 1 year follow-up were analyzed. The patients were restaged according
to TNM staging by means of their initial thorax-CT or PET-CT . Brain MRI was POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
performed for all of the patients before treatment. Median age was 59(21-86) SCLC/NEUROENDOCRINE TUMORS IN GENERAL –
years old and 85% of the patients were male. PET-CT was used in 62.4 % of
the patients for staging. Concomitant chemoradiotherapy with Cisplatinum-
Etoposide was given in 38.3% of the patients. Median thoracic radiotherapy P1.07-045 CHARACTERISTICS OF EXCEPTIONAL LONG TERM
dose was 56Gy(30-66.8Gy). PCI was performed to the 180 patients (67.7%), SURVIVORS IN EXTENSIVE STAGE SMALL CELL LUNG CANCER
The effect of age, gender,clinical stage, T, N stage and prophylactic cranial
Kunlatida Maneenil1, Julian Molina2, Jun She3, Ruchi Gupta4, Marie Aubry5,
irradiation(PCI) on OS and DFS rates were analyzed in both univariate and
Eunhee Yi5, Ping Yang4
multivariate analysis with Log-rank and cox regression tests. Results: Median 1
Oncology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine,
follow-up was 19 months(6-113 ) for the patients who are alive. Thirty-six
Rangsit University, Bangkok/Thailand, 2Medical Oncology, Mayo Clinic, Rochester/
percent of the patients had LR and approximately half of the patients MN/United States of America, 3Pulmonary Medicine, Zhongshan Hospital, Fudan

University, Shanghai/China, 4Health Sciences Research, Mayo Clinic, Rochester/ uninsured patients not receiving recommended treatment or no treatment
MN/United States of America, 5Department of Laboratory Medicine and Pathology, was 1.7 (95% CI 1.543-1.932) in LS-SCLC and 1.9 (95% CI 1.751-2.060) in ES-SCLC
Mayo Clinic, Rochester/MN/United States of America patients. Both LS-SCLC and ES-SCLC patients aged 65-74 years had 1.5 (95% CI
for LS-SCLC: 1.402-1.587; 95% CI for ES-SCLC: 1.454-1.613) times higher odds of
Background: Small cell lung cancer (SCLC) remains a frustrating disease to all
not receiving recommended treatment or no treatment, compared to younger
parties involved. Most patients present with extensive stage disease (ED),
patients. In both groups, patients who received recommended treatment had
with a median survival of 8 to 13 months (Expected). The aim of this study
better survival than those who did not receive recommended treatment or
is to present data on survivors who lived beyond 3 years after a diagnosis
any treatment (median survival time of 18.4 vs. 6 months in LS-SCLC; 8.3 vs.
of ED-SCLC (Exceptional) in order to uncover favorable factors for better
1.2 months in ES-SCLC). Conclusion: This study demonstrated an increase in
patient management and clinical outcomes. Methods: We retrospectively
the uptake of recommended treatment in LS-SCLC, but relatively no change in
evaluated the SCLC patient cohort diagnosed and followed from 1997 to
ES-SCLC. Reasons for not receiving recommended treatment warrant further
2015 at Mayo Clinic (Minnesota), and searched for Exceptional survivors
investigation. The survival benefit among patients with recommended
with matched Expected survivors who had passed away within 12 months of
treatment highlights the need to alleviate any system-based barriers that
diagnosis on age and year of diagnosis. Patient characteristics, treatments,
may impact more patients receiving recommended treatment.
and outcomes were compared between the two groups. Results: To date, we
identified 36 Exceptional and 144 Expected ED-SCLC patients. Women and Keywords: small cell lung cancer, survival, treatment provision
an Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) 0-1
were higher in Exceptional than in Expected group (61.8% vs 36.1%, p<0.01;
97.2% vs 77.6%, p<0.01; respectively). Smoking history, comorbidities (COPD,
prior cancers or paraneoplastic syndrome), and T or N stage did not differ
significantly. The top two metastatic sites in Exceptional group were brain POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
SCLC/NEUROENDOCRINE TUMORS IN GENERAL –
(26.7%) and distant lymph nodes (20.0%), and in Expected were liver (28.3%) MONDAY, DECEMBER 5, 2016
and bone (22.5%). Use of chemotherapy and the mean cycle number were
higher in the Exceptional than the Expected group (100.0% vs 80.0%, p<0.01;
5.0 vs 3.6, p<0.01; respectively), with the main regimen being platinum/ P1.07-047 REFUSAL OF CHEMORADIOTHERAPY AND
etoposide. However, carboplatin was used more frequently than cisplatin in CHEMOTHERAPY AMONG SCLC PATIENTS: ANALYSIS OF US
Expected group (all patients, p=0.02; ECOG 0-1 patients, p=0.05). The overall NATIONAL FACILITY-BASED DATA
response rate of chemotherapy was significantly higher in exceptional group Poppy Deviany1, Km Islam1, Apar Ganti2
(91.4% vs 56.7%, p<0.01). Thoracic radiotherapy and prophylactic cranial 1
Epidemiology, University of Nebraska Medical Center, Omaha/NE/United States of
irradiation (PCI) in Exceptional were also higher than in Expected group America, 2Internal Medicine, Division of Oncology-Hematology, Veteran’S Affairs
(58.3% vs 17.4%; p<0.01, 19.4% vs 6.9%; p=0.03). Multivariate analysis is Nebraska-Western Iowa Health Care System, University of Nebraska Medical
underway. In Exceptional group, median overall survival was 5.4 years (95% CI Center, Omaha/NE/United States of America
3.7-6.8); 9 (25%) patients were still alive. Twelve (33%) patients had disease
recurrence or progression with the median progression free survival 1.2 (95% Background: Less than 7% of small cell lung cancer (SCLC) patients survive
CI 0.7-2.0) years. The most common recurrent site was brain. Three patients five years after diagnosis. Although receipt of recommended treatment is
had secondary malignancy, 2 being a non-small cell lung cancer. Conclusion: a key to survival, factors associated with treatment refusal have not been
Although the chance of curing ED-SCLC is small, long-term survival can be well studied in SCLC. Our study examined factors associated with treatment
achieved. This study supports the importance of good performance status refusal by SCLC patients and effect of refusal on survival. Methods: We
and the achievement of a response to cisplatin-based chemotherapy on analyzed data of 114,004 SCLC patients diagnosed between 2003 and 2012
long-term survival. Addition of thoracic radiotherapy and PCI are beneficial in from the National Cancer Data Base. Analyses were conducted separately
prolong life of ED-SCLC patients. for refusal of chemoradiotherapy among limited stage (LS) and refusal of
chemotherapy among extensive stage (ES) patients. We used multivariable
Keywords: small cell lung cancer, long term survival, extensive stage, logistic regression to investigate factors associated with treatment refusal
treatment and calculated median survival using Kaplan-Meier method. Results: There
was a female preponderance among LS (56%), whereas 52% of ES patients
were male (p <.001). Majority of the LS patients received chemoradiotherapy
(67%), and ES patients received chemotherapy only (44%) as their first-
course treatment. Refusal of chemoradiotherapy among LS patients
SCLC/NEUROENDOCRINE TUMORS IN GENERAL – was 2%, and refusal of chemotherapy among ES patients was 5%. On
MONDAY, DECEMBER 5, 2016 multivariable analysis, patient diagnosed at age >70 years were more likely
to refuse treatment compared to those age 50-70 years; the adjusted odds
ratio (AOR) was 3.39 (95% CI: 2.68-4.28) for refusal of chemoradiotherapy
P1.07-046 UPTAKE OF RECOMMENDED TREATMENT IN SMALL among LS patients and 2.54 (95% CI: 2.28-2.84) for refusal of chemotherapy
CELL LUNG CANCER: TREND OVER THE LAST 15 YEARS AND RISK among ES patients. Females were more likely to refuse recommended
FACTORS treatment than males, the AOR was 1.34 (95% CI: 1.09-1.65) for refusal of
Trisari Anggondowati1, Km Islam2, Apar Ganti3 chemoradiotherapy and 1.29 (95% CI: 1.17-1.42) for refusal of chemotherapy.
1
Epidemiology, University of Nebraska Medical Center, Omaha/NE/United States Compared to those with private insurance, uninsured patients were more
of America, 2Epidemiology, University of Nebraska Medical Center, Omaha/United likely to refuse chemoradiotherapy (AOR= 2.70, 95% CI: 1.49-4.91) and
States of America, 3Internal Medicine, Veteran’S Affairs Nebraska-Western Iowa chemotherapy (AOR=2.26, 95% CI: 1.76-2.91). Patients with comorbid
Health Care System, University of Nebraska Medical Center, Omaha/NE/United conditions were more likely to refuse recommended treatment compared to
States of America those without comorbidity; the AOR was 1.66 (95% CI: 1.33-2.07) for refusal of
chemoradiotherapy and 1.37 (95% CI: 1.23-1.53) for refusal of chemotherapy.
Background: Despite the dismal outcomes of small-cell lung cancer (SCLC),
Median survival of LS patients who received and refused chemoradiotherapy
the fact that SCLC patients are generally responsive to treatment emphasizes
was 18 and 3 months respectively (p <.001). Among ES patients, median
the importance of adherence to recommended treatment. This study
survival was 8 months for those who received chemotherapy and 1 month
analyzed the trend in treatment provision in SCLC over the last 15 years and
for those who refused (p <.001). Conclusion: Although treatment refusal was
its associated factors. Methods: A total of 207,375 adult patients diagnosed
uncommon, older age at diagnosis, female, uninsured status, and comorbid
with SCLC between 1998 and 2012 in the United States were identified from
conditions were associated with higher treatment refusal. These factors
the National Cancer Data Base. In this study, recommended treatment
should be specially addressed in patient-provider communication and patient-
was defined as surgery and/or chemoradiation for the limited stage (LS-
education. Interventions targeting these issues will increase acceptance of
SCLC), regardless of sequence; and chemotherapy for the extensive stage
recommended treatment and ultimately will improve patient outcomes.
(ES-SCLC). We excluded patients who did not receive treatment due to a
contraindication. Logistic regression was used to analyze the risk of not Keywords: factors associated, small cell lung cancer, survival, treatment
receiving recommended treatment, adjusted for socio-demographics, facility refusal
type, and clinical factors. Kaplan-Meier estimator was used to estimate
patients’ survival. Results: Between 1998 and 2012, the proportion of patients
receiving recommended treatment increased among LS-SCLC patients (63%
to 73.4%), but was unchanged in ES-SCLC (75.7% to 76.6%). Nevertheless, a
significant proportion of patients did not receive recommended treatments. POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
Older age, low income, use of non-private insurance or no insurance, higher SCLC/NEUROENDOCRINE TUMORS IN GENERAL –
comorbidity score, and diagnosis and/or treatment at a community cancer
program were independent predictors of inadequate treatment for both
LS-SCLC and ES-SCLC, while Black race was a predictor only in LS-SCLC. For P1.07-048 CLINICAL IMPACT OF THE RELATIONSHIP BETWEEN
instance, compared to patients with private insurance, the odd ratios of POST-PROGRESSION SURVIVAL AND OVERALL SURVIVAL IN
EXTENSIVE DISEASE SMALL CELL LUNG CANCER PATIENTS appropriate patients can prevent cerebral metastases, improve PFS and
Hisao Imai1, Keita Mori2, Nodoka Watase3, Sakae Fujimoto1, Kyoichi Kaira4, ultimately OS. The time to initiation of chemotherapy may also have a
Masanobu Yamada5, Koichi Minato1 significant impact on outcomes.
1
Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma/ Keywords: limited stage, small cell lung cancer, cancer treatment, Survival
Japan, 2Clinical Research Support Center, Shizuoka Cancer Center, Shizuoka/
outcomes
Japan, 3Division of Pharmacy, Gunma Prefectural Cancer Center, Gunma/Japan,
4
Department of Oncology Clinical Development, Gunma University Graduate
School of Medicine, Gunma/Japan, 5Department of Medicine and Molecular
Science, Gunma University Graduate School of Medicine, Gunma/Japan
Background: The effects of first-line chemotherapy on overall survival (OS) POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
might be confounded by subsequent therapies in patients with small-cell MONDAY, DECEMBER 5, 2016
lung cancer (SCLC). Therefore, by using individual-level data, we aimed to
determine the relationships between progression-free survival (PFS) or
post-progression survival (PPS) and OS after first-line chemotherapies in P1.07-050 PATTERNS OF RELAPSE IN SMALL CELL LUNG CANCER
patients with extensive disease SCLC (ED-SCLC) treated with carboplatin (SCLC): A RETROSPECTIVE ANALYSIS OF OUTCOMES FROM A
plus etoposide. Methods: Between July 1998 and December 2014, we analyzed SINGLE CANADIAN CENTER
63 cases of patients with ED-SCLC who were treated with carboplatin and Abdulaziz Al Farsi1, Anand Swaminath2, Peter Ellis2
etoposide as first-line chemotherapy. The relationships of PFS and PPS with 1
Medical Oncology, Juravinski Cancer Center, Hamilton/Canada, 2Oncology,
OS were analyzed at the individual level. Results: Spearman rank correlation McMaster University, Hamilton/Canada
analysis and linear regression analysis showed that PPS was strongly
correlated with OS (r = 0.90, p < 0.05, R2 = 0.71) and PFS was moderately Background: We conducted a retrospective review of small cell lung cancer
correlated with OS (r = 0.72, p < 0.05, R2 = 0.62). Type of relapse (refractory/ patients (SCLC) to explore patterns of relapse and utility of Prophylactic
sensitive) and the number of regimens administered after disease progression Cranial Irradiation (PCI). Methods: A retrospective chart review was carried
after the first-line chemotherapy were both significantly associated with on patients diagnosed with SCLC from January 1st 2011 until December 31st
PPS (p < 0.05). Conclusion: PPS has a stronger relationship with OS than 2014 and treated at Juravinski Cancer Center. The primary outcome was to
does PFS in ED-SCLC patients who have received first-line chemotherapy. In determine pattern of first relapse. Secondary outcomes were physician
addition, type of relapse (refractory/sensitive) after first-line treatment and assessed response rate, overall survival (OS), utilization of PCI, time to
the number of additional regimens after first-line treatment are significant systemic relapse (TTR) and time to central nervous system (CNS) relapse.
independent prognostic factors for PPS. These results suggest that Results: A total of 275 patients were identified, of whom 46 (16.7%) received
treatments administered after first-line chemotherapy affect the OS of ED- no chemotherapy (median OS 2.2 months (m)) and were not included in
SCLC patients treated with carboplatin plus etoposide. further analyses. The median age of 229 treated patients was 66 (SD 9.3)
yrs. There were 115 men, 114 women, 84 (37%) had limited stage (LS) and 145
Keywords: overall survival, post-progression survival, Progression-free (63%) extensive stage (ES) disease, performance status (PS) was 0-1 in 133
survival, extensive disease small cell lung cancer (58%), PS2 in 66 (28%) and PS3-4 in 32 (13%). Brain metastases were present
in 36 (16%) patients at diagnosis. Almost all patients received cisplatin (53%)
or carboplatin (43%) plus etoposide chemotherapy. Most patients received
4 (23%), or more (52%) cycles of chemotherapy. Physician assessed RR was
68% (PR 61%, CR 7%) and 16% of patients progressed during first-line therapy.
SCLC/NEUROENDOCRINE TUMORS IN GENERAL – Thoracic radiation (TRT) was given to 112 (49%) of patients (LS 87%, ES 27%).
MONDAY, DECEMBER 5, 2016 Patients with brain metastases at diagnosis, or progressing during first-
line chemotherapy were not considered eligible for PCI. Among 156 eligible
patients, 80 (51%) received PCI (LS 64%, ES 39%). Forty-one patients (26.3%)
P1.07-049 LIMITED STAGE SMALL CELL LUNG CANCER: PATTERNS
declined PCI. The median overall survival for all patients was 11.1m (LS 21.7m,
OF CARE AND OUTCOMES OF A SINGLE INSTITUTION OVER 15
ES 8.9m). Relapse occurred in 167 (73%) of patients: CNS alone 8.7%, CNS
YEARS plus systemic relapse (13.1%), thoracic (28%), extra-thoracic (9%), thoracic/
Eunji Hwang 1, Janet Williams1, Rebecca Venchiarutti1, Craig Lewis2, Wenchang extra-thoracic (14%). Median time to any relapse was 9.2m (LS 14.3m, ES 7.5m),
Wong1 while median time to CNS relapse was 6.9m (PCI given 6.2m, PCI not given
1
Radiation Oncology, Prince of Wales Hospital, Randwick/NSW/Australia, 2Medical 4.4m). Among 50 patients with CNS relapse, 16 received PCI (LS 9, ES 7) and
Oncology, Prince of Wales Hospital, Randwick/NSW/Australia 34 did not (LS 8, ES 26). Among 64 patients with thoracic relapse, 31 received
TRT (LS 19, ES 12) and 33 did not (LS 5, ES 28). Conclusion: Only 50% of eligible
Background: The past two decades have seen an increase in survival of SCLC patients receive PCI. CNS relapse occurs frequently and more commonly
patients with limited stage small cell lung cancer (SCLC). This retrospective in patients who do not receive PCI. Implementation of PCI in routine clinical
audit analysed patterns of care, toxicity and survival for all patients with practice appears to influence patterns of recurrence.
limited stage SCLC diagnosed and treated at Prince of Wales hospital over
15 years. Our results were compared with the literature to assess this single Keywords: relapse, Patterns, SCLC
institution’s performance and outcomes, and explore what factors may most
be influencing these results. Methods: We identified 120 patients diagnosed
with SCLC at Prince of Wales Hospital between 2000 and 2014 from the
departmental electronic patient information system (Mosaiq). Eligibility
criteria were: age >18 years, histopathologically confirmed diagnosis of POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
SCLC, limited stage according to the two-stage Veterans’ Affairs Lung Study MONDAY, DECEMBER 5, 2016
Group staging criteria (2016), and treatment with either curative or palliative
intent. Median progression free survival (PFS), cancer specific survival (CSS)
and overall survival (OS) were estimated using the Kaplan-Meier method P1.07-051 INCIDENCE AND CLINICAL CHARACTERISTICS OF
and log-rank test (IBM SPSS version 23.0). Results: Thirty-two patients PULMONARY LARGE-CELL NEUROENDOCRINE CARCINOMA: AN
fulfilled the eligibility criteria. The median age of patients was 66.5 years; 19 OVERVIEW OF OUR OWN DATA
(59%) patients were female and 50% had an Eastern Cooperative Oncology Gordana Drpa, Kaltrina Krasnic, Marina Serdarevic, Filip Popovic, Bernard
Group (ECOG) score of 0. Median PFS, CSS and OS were 12.6, 22.1 and 18.0 Budimir, Suzana Kukulj
months respectively, comparable with published literature. Ten patients
Department of Mediastinal Tumours, Clinic for Respiratory Diseases “jordanovac”,
(31%) received prophylactic cranial irradiation (PCI) as a component of their University Hospital Centre Zagreb, Zagreb/Croatia
therapy. Of the 10 patients who received PCI, none had brain recurrence,
while 36.4% of the non-PCI group developed brain metastases. Patients Background: Pulmonary neuroendocrine tumors are a heterogenous group of
receiving PCI demonstrated a trend toward improved PFS compared to neoplasms. They are clasified into four histological types: typical carcinoid,
patients not receiving PCI (18.3 months versus 10.5 months, p=0.057). This atypical carcinoid, small-cell lung cancer (SCLC) and large-cell neuroendocrine
trend was also seen in OS in this group (25.4 months versus 15.5 months, carcinoma (LCNEC). They represent about 20% of all lung cancers. The most
p=0.072). The median time from date of diagnosis to start of chemotherapy frequent one is small-cell lung cancer with incidence about 15%. In contrast,
was 21 days, and there was correlation between time to chemotherapy and large-cell neuroendocrine carcinoma is an orphan disease with estimated
OS (p=0.037) and PFS (p=0.045). Twenty-six of the 32 patients underwent a incidence between 2.1% and 3.5%. Because of many diagnostic difficulties,
combination of chemotherapy and radiotherapy. Seventeen patients (65%) LCNEC is considered to be of a higher frequency. It is lung neuroendocrine
received concurrent chemoradiotherapy, and 9 (35%) received sequential tumor, but it is also a type of non small-cell lung cancer (NSCLC). So its
chemoradiotherapy, with no significant difference in survival or toxicity features overlap with both of these groups. However, the clinical behavior
between these two regimens. Conclusion: Survival outcomes from this of LCNEC is very similar to SCLC and so new term high-grade neuroendocrine
single institution are comparable with current literature. The use of PCI in carcinoma (HGNEC) is in use. Methods: We retrospectively analysed

patients diagnosed with cancer at our department between January 1, 2012 POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
and December 31, 2014, with special focus on pulmonary neuroendocrine MONDAY, DECEMBER 5, 2016
tumors. We examined incidence of different histologic types of pulmonary
neuroendocrine tumors and sorted out patients with diagnosis of large-
cell neuroendocrine carcinoma. We also analysed clinical characteristics of P1.07-053 APATINIB FOR CHEMOTHERAPY-REFRACTORY
patients with LCNEC. Results: During the three-years period 1242 pulmonary EXTENSIVE STAGE SCLC: RESULTS FROM A SINGLE-CENTER
patients were admitted to our department. Among them there were 726 RETROSPECTIVE STUDY
newely diagnosed cancer patients. Various types of lung cancer were found
Wei Hong, Hui Li, Xiangyu Jin, Xun Shi
in 652 patients. There were 104 patients with pulmonary neuroendocrine
Zhejiang Cancer Hospital, Hangzhou/China
tumors, what makes about 16%. Thirteen of them (2%) were „pure“ LCNEC,
16 (2,5%) mixed LCNEC with small-cell component, 68 SCLC (10%), 4 Background: It has no standard treatment strategy for patients with
atypical carcinoid, 2 typical carcinoid and 1 typical carcinoid in patient with extensive stage small cell lung cancer (SCLC) who experienced progression
adenocarcinoma. Generally in our patients high-grade neuroendocrine tumors with three or more lines of chemotherapy. Apatinib, a new tyrosine kinase
make about 15%, and low-grade neuroendocrine tumors (carcinoides) make inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2),
only 1% of all lung cancers. Most patients diagnosed with LCNEC were men has been shown confirming antitumor activity and manageable toxicities in
over 50 years, heavy smokers, which is consistent with published data, but breast and gastric cancers. Until now, couples of clinical trials investigating
one patient was a 40-year-old woman. Conclusion: Pulmonary neuroendocrine the efficacy of apatinib on non-small cell lung cancer are ongoing. However,
tumors are group of neoplasms classified into four categories based on the effects of apatinib on small cell lung cancer are still unclear. We
their patohistology. Three of them (carcinoides and LCNEC) are rare tumors. retrospectively assessed the efficacy and safety of apatinib in patients with
LCNEC is type of neuroendocrine tumor with most diagnostic and therapeutic extensive-stage small cell lung cancers after the failure of second or third-line
difficulties. Clinical features of our patients are similar to previously chemotherapy. Methods: The study group comprised 13 patients who received
published, while incidence is slightly lower. oral apatinib, at a dose of 500 mg daily, for progression after the failure of
second or third-line chemotherapy for extensive-stage small cell lung cancer.
Keywords: LCNEC, lung cancer, Neuroendocrine tumors
Treatment was continued until disease progression. For the patients who had
grade 3 or 4 toxicities, the dose of apatinib was decreased to 250mg daily. The
patients stopped the treatment if they still had the unacceptable toxicity
after dose downregulation. We analyzed safety and response (RECIST 1.1) for
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS the available patients monthly. Results: Between Aug 30, 2015 and May 1,
SCLC/NEUROENDOCRINE TUMORS IN GENERAL – 2016, 13 patients were enrolled. In 13 patients, there were 11 patients available
for efficacy and safety evaluation. 5/11 (45.5%) patients experienced dose
reduction during treatment. Followed up to July 20, 2016, the median during
P1.07-052 PULMONARY NEUROENDOCRINE TUMORS: SINGLE time of afatinib treatment was 2.8 months (95% confidence interval (CI),
INSTITUTION EXPERIENCE IN BRAZIL 1.67-5.04). According to RECIST criteria, the disease control rate was 81.8%,
9/11 (partial response 18.2%, 2/11 and stable disease 63.6%, 7/11). The most
Renata Rosenthal1, Maria Teresa Tsukazan2, Álvaro Vigo2, Flávio Cabral1,
frequent treatment-related adverse events were secondary hypertension
Arthur Vieira1, Gabriel Schwarcke1, Jayme Rios1, José Antonio Pinto1, Vinícius
(45.5%, 5/11), oral mucositis (27.3%, 3/11), hand-foot syndrome (27.3%, 3/11)
Duval Da Silva1
1
and fatigue (27.3%, 3/11). Main grade 3 or 4 toxicities were hypertension
Hospital São Lucas Da Pucrs Porto, Porto Alegre/Brazil, 2Universidade Federal Do (27.3%, 3/11), oral mucositis (9.1%, 1/11) and fatigue (9.1%, 1/11). Conclusion:
Rio Grande Do Sul - Ufrgs, Porto Alegre/Brazil
Apatinib exhibits modest activity and acceptable toxicity for the heavily
Background: The primary lung neuroendocrine tumors (NET) are uncommon. pretreated patients with extensive-stage small cell lung cancer.
They have a wide spectrum of clinical behavior, currently being classified into
Keywords: SCLC, Apatinib
four types: tumor typical carcinoid (low grade malignancy), atypical carcinoid
(intermediate malignancy grade), neuroendocrine large cells carcinoma and
small cells. Neuroendocrine lung tumors represent a large and heterogenic
group with different management and survival rates. Little information
regarding neuroendocrine tumors is available for Latin American countries. POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
Methods: Retrospective service database review of patients with NET treated SCLC/NEUROENDOCRINE TUMORS IN GENERAL –
at Hospital São Lucas in Porto Alegre, Brazil between 1991-2015. Inclusion
criteria were age 18 or older with histologically or immunochemistry
confirmed neuroendocrine tumor. For analysis purposes we divided between, P1.07-054 SECOND PRIMARY SMALL CELL CARCINOMA OF LUNG IN
typical carcinoid, atypical carcinoid and poorly differentiated (large and small PREVIOUSLY TREATED CARCINOMA BREAST
cells). Results: From January of 1991 to December of 2015, of 946 lung cancer
Prasanta Mohapatra1, Pritinanda Mishra2, Manoj Panigrahi1, Gourahari
resections 49 patients with NET were resected. Most the patients were
Pradhan1, Sourin Bhuniya1, Susama Patra2, Madhabananda Kar3
female (57,1%), mean age 55 years (28- 84 years). Typical carcinoid represented 1
63,3% of patients, followed by atypical carcinoid (22,4%) and poorly Pulmonary Medicine, All India Institute of Medical Sciences, Bhubaneswar/India,
2
Pathology, All India Institute of Medical Sciences, Bhubaneswar/India, 3Surgical
differentiated neuroendocrine tumors (14,3%). Mean age was 51,4 for typical
Oncology, All India Institute of Medical Sciences, Bhubaneswar/India
carcinoid, 56 for atypical carcinoid and 63 for undifferentiated NET.
Lobectomy was the surgical approach for 85,7%, pneumonectomy was Background: Breast cancer is the major cause of cancer among women
required for 4,1% and segmentectomy for 10,2% of patients. Minimally worldwide. Some of the patients are treated with surgery followed by
invasive (VATS) was done in 4,1%. adjuvant chemotherapy and radiation therapy. It is presumed that the
radiation of surrounding tissues during breast radiotherapy may cause
cancer in other areas of body. Methods: A 40 year old woman presented with
chest pain and breathing difficulties for four months. She was diagnosed
as infiltrating duct cell carcinoma of right breast and undergone modified
radical mastectomy. Her 1 of 20 lymph nodes showed tumour metastases
with perinodal extension. Triple marker (oestrogen receptor, progesterone
receptor, her 2 neu receptor) was negative. She was given four cycles of CEF
regimen cyclophosphamide,epirubicin,5-FU) and four cycles of paclitaxel.
Conclusion: According to the European Consensus, pulmonary carcinoids She had also received 25 fraction of radiotherapy completed over one year
account for 1–2% of all invasive lung malignancies. We found 85,7% of our lung before. There was no other co-morbid conditions, family history was not
resections were carcinoids and a higher mean age 51,4 for patients with significant. She had average body built and nutrition. On general examination
typical and 56 for atypical carcinoids compared to the literature. mild pallor was only positive finding, no peripheral lymphadenopathy or
clubbing. Contrast enhanced computed tomogram of chest revealed bilateral
Keywords: Pulmonary Neuroendocrine tumors, Carcinoids, large cells
lung nodular infiltrates more predominantly in left lower lobe, mediastinal
carcinoma, Small cells
lymphadenopathy with left lower lobe collapse. Ultrasound abdomen
detected no significant abnormality. Bronchoscopy showed multiple nodules
present over carina, infiltration in right lower lobe segmental opening,
left main bronchus lumen narrowed due to diffuse infiltrative growth. The
endobrochial biopsies were taken from this area. Results: Endobronchial
biopsy revealed tumour cells were strongly and diffusely positive for
synaptophysin and negative for chromogranin and TTF1 . The diagnosis of
small cell carcinoma lung was made. MRI of brain showed ring enhancing
lesions in right cerebellar hemisphere suggestive of metastases. Staging
of the tumour came to T4N2M1a according to 8th edition of IASLC TNM LODDS it is possible to discriminate patients with regard to lung cancer stage
classification for lung cancer. Her performance status improved to ECOG 2. more effectively compared to pN and LNR classification, and it is also a better
She was given cisplatin and etoposide in addition to brain radiation therapy. classification system. Therefore, a new system of lung cancer classification
Conclusion: The second primary malignancy refers to a different type of based on LODDS should be considered.
cancer in a person who has survived an earlier cancer. There are series of non-
small cell lung cancer (NSCLC) reported as second primary after breast cancer.
To our knowledge, this is the first case presented as small cell lung cancer as
second malignancies in lung in a fully treated breast cancer patient. This may
be related risk of second malignancies associated with radiotherapy exposure POSTER SESSION 1 - P1.08: SURGERY
RISK ASSESSMENT & PROGNOSTIC FACTORS –
to lung applied for breast cancer or due to adjuvant treatment as in this case. MONDAY, DECEMBER 5, 2016
Keywords: Second primary SCLC lung breast cancer

P1.08-002 THE PROGNOSTIC SIGNIFICANCE OF PLEURAL LAVAGE
CYTOLOGY BEFORE AND AFTER LUNG RESECTION
Yohei Yurugi, Yoshiteru Kidokoro, Takashi Ono, Yasuaki Kubouchi, Makoto
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS Wakahara, Ken Miwa, Kunio Araki, Yuji Taniguchi, Hiroshige Nakamura
SCLC/NEUROENDOCRINE TUMORS IN GENERAL – General Thoracic Surgery, Tottori University, Yonago/Japan
Background: The status of intraoperative pleural lavage cytology (PLC) has
been reported to be a predictive factor of recurrence in resected non-small
P1.07-055 INTRODUCING THE US NATIONAL CANCER INSTITUTE’S
cell lung cancer (NSCLC). However, prognostic significance of PLC remains
SMALL CELL LUNG CANCER CONSORTIUM unclear and it has not been included in the TNM classification. Furthermore,
Peter Ujhazy, Eva Szabo, Suzanne Forry the appropriate timing to perform PLC, before lung resection (pre-PLC) or
National Cancer Institute, Rockville/MD/United States of America after lung resection (post-PLC), is not evident. Methods: Of 627 consecutive
patients with NSCLC who underwent complete resection (segmentectomy
Background: Small cell lung cancer (SCLC) remains a major clinical challenge, or more) in Tottori University Hospital from January 2004 to December 2013,
however recent discoveries and early positive signals in clinical trials are 615 patients who were performed both pre-PLC and post-PLC were enrolled
promising more optimistic outcomes for patients with this disease. The in present study. Patients were divided into four groups, negative pre-PLC /
United States National Cancer Institute (NCI) launched in December 2015 negative post-PLC (Group A), positive pre-PLC / negative post-PLC (Group B),
a series of solicitations for grant applications with the goal to establish a negative pre-PLC / positive post-PLC (Group C), and positive pre-PLC / positive
SCLC consortium. The Consortium will address five strategic priority areas post-PLC (Group D). Then differences in recurrence free survival (RFS) and
established by an international group of experts and the NCI. These areas disease specific survival (DSS) among each groups were analyzed by log-rank
are: 1. Better research tools for the Study of SCLC, 2. Comprehensive genomic test. Moreover, PLC status as a prognostic factor for RFS and DSS were
profiling of SCLC, 3. New diagnostic and prevention approaches for SCLC, 4. analyzed using univariate and multivariate Cox regression models. Results:
Therapeutic development efforts, and 5. Mechanisms underlying both high There were 573 patients in Group A, 11 in Group B, 14 in Group C, and 17 in
rate of initial response and rapid emergence of drug and radiation resistance. Group D, respectively. Survival analysis revealed significant differences in not
The initiative for early detection and prevention of SCLC is now open for only RFS but also DSS between Group A and Group B (log-rank test, p<0.001),
potential applicants through 2017 (PAR-16-51); applications for therapy and Group A and Group C (p<0.001), Group A and Group D (p<0.001), respectively.
mechanism of resistance projects can be submitted through 2018 (PAR-16-49). However, there was no significant differences among Group B, C, and D
Methods: Section not applicable Results: (Note: The first round of application (p=0.861). Multivariate analysis identified advanced age (75≤), male sex, larger
was reviewed right before the IASLC abstract submission deadline, funding tumour size (3cm<), lymphnode metastasis, lymphatic invasion, and positive
decisions will be made in early November 2016, so by the time of the November PLC status (Hazard Ratio: 3.735, 95% confidence interval: 2.312 to 6.063,
11 deadline for the poster submission we will be able to include the first funded p<0.001) as statistically independent prognostic factors for DSS. Conclusion:
projects in the consortium in the abstract and in the poster.) Conclusion: In conclusion, positivity of both pre-PLC and post-PLC were significant worse
Section not applicable prognostic factor for DSS of patients with completely resected NSCLC.
Therefore, surgeons should consider performing PLC both before and after
Keywords: Therapy, Early Detection, small cell lung cancer, drug resistance
lung resection to estimate patients’ prognosis correctly. Moreover, further
accumulation of knowledge about PLC are needed to reflect PLC status in the
TNM classification.
Keywords: lung cancer, pleural lavage cytology, prognostic factor

POSTER SESSION 1 - P1.08: SURGERY
Risk Assessment & Prognostic Factors –
P1.08-001 LOG ODDS AS A NOVEL PROGNOSTIC INDICATOR
SUPERIOR TO THE NUMBER-BASED AND RATIO-BASED CATEGORY
FOR NON-SMALL CELL LUNG CANCER P1.08-003 SURVIVAL OF LUNG CANCER PATIENTS WAS DEPENDED
Dariusz Dziedzic, Piotr Rudzinski, Tadeusz Orlowski ON TUMOR CHARACTERISTICS, BLOOD CELL CIRCUIT, CELL RATIO
Thoracic Surgery, National Institute of Chest Diseases, Warsaw, Poland, Warsaw/ FACTORS, HEMOSTASIS SYSTEM
Poland Oleg Kshivets
Surgery, Saint-Petersburg Clinic, Saint-Petersburg/Russian Federation
Background: The paper aimed to compare the efficacy of log odds (LODDS)
compared to a classification based on the number of positive lymph Background: This study aimed to determine homeostasis and tumor factors
nodes (pN) and lymph node ratio (LNR). Methods: Material was collected for 5-year survival (5YS) of non-small cell lung cancer (LC) patients (LCP)
retrospectively from an online survey-based database of the Polish Lung (T1-4N0-2M0) after complete en block (R0) lobectomies/pneumonectomies
Cancer Group and included a group of 17369 patients who received radical (LP). Methods: We analyzed data of 676 consecutive LCP (age=57.5±8.3
surgical treatment (R0) due to lung cancer. The follow-up period was between years; tumor size=4.4±2.4 cm) radically operated and monitored in 1985-2016
11.4 and 66.0 months (median 30.1 months). Results: In the whole group the (m=585, f=91; lobectomies=431, pneumonectomies=245, mediastinal lymph
median survival for N0, N1 and N2 was 76.1, 41.7 and 24.2 months, respectively. node dissection=676; combined LP with resection of trachea, carina, atrium,
The median survival for individual LODDS categories (-6,-4], (-4,-3], (-3,-2], aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=188;
(-2,-1], (-1,0], (0,1] and (1,2] was 76.5, 76.3, 71.7, 45.4, 25.0, 19.1 and 17.7 months, only surgery-S=532, adjuvant chemoimmunoradiotherapy-AT=144: CAV/
respectively. The median survival for LNR in individual categories (0), (0,0.25], gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=239,
(0.25,05], (0.5,075] and (0.75,1.0] was 75.6, 40.3, 24.1, 18.8 and 16.4 months, T2=249, T3=131, T4=57; N0=428, N1=130, N2=118, M0=676; G1=168, G2=202,
respectively. When comparing LODDS and LNR significant heterogeneity G3=306; squamous=381, adenocarcinoma=249, large cell=46; early LC=134,
can be seen that is especially visible in categories (0), (0,0.25] LNR, where 4 invasive LC=542. Multivariate Cox modeling, clustering, SEPATH, Monte
LODDS categories were distinguished. A multi-variant analysis demonstrated Carlo, bootstrap and neural networks computing were used to determine
that each LODDS category is an independent prognostic factor: (-4,-3] (HR = any significant dependence. Results: Overall life span (LS) was 2109.1±1692.4
0.982; 95% CI 0.867-1.112; P = 0.775), (-3,-2] (HR = 1.114; 95% CI 0.984-1.262; P = days (median=1936 days) and cumulative 5-year survival (5YS) reached 69.7%,
0.089), (-2,-1] (HR = 1.241; 95% CI 1.080-1.425; P = 0.002), (-1,0] (HR = 1.617; 95% 10 years – 61.4%, 20 years – 42.9%. 419 LCP lived more than 5 years without
CI 1.385-1.887; P < 0.0001), (0,1] (HR = 1.918; 95% CI 1.579-2.329; P < 0.0001) cancer, 111 – 10 years, 14 – 20 years. 195 LCP died because of LC (LS=560±372.1
and (1,2] (HR = 2.016; 95% CI 1.579-2.573; P < 0.0001). Conclusion: Based on days). AT significantly improved 5YS (64.4% vs. 34.1%) (P=0.00002 by log-rank

test) only for LCP with N1-2. Cox modeling displayed that 5YS significantly POSTER SESSION 1 - P1.08: SURGERY
depended on: phase transition (PT) early-invasive LC in terms of synergetics, MONDAY, DECEMBER 5, 2016
PT N0-N12, histology, G, blood cell circuit, cell ratio factors (ratio between
blood cells subpopulations and cancer cells-CC), prothrombin index, heparin
tolerance, recalcification time, glucose, AT (P=0.000-0.041). Neural networks, P1.08-005 STRATIFICATION OF PSTAGE I LUNG ADENOCARCINOMA
genetic algorithm selection and bootstrap simulation revealed relationships BY THE SCORING SYSTEM BASED ON PROGNOSTIC FACTORS
between 5YS and PT N0-N12 (rank=1), PT early-invasive LC (rank=2), Naoya Kawakita, Hiroaki Toba, Toru Sawada, Mitsuhiro Tsuboi, Koichiro
eosinophils/CC (3), prothrombin index (4), thrombocytes/CC (5), glucose (6), Kajiura, Yukikiyo Kawakami, Mitsuteru Yoshiada, Hiromitsu Takizawa, Kazuya
lymphocytes/CC (7), erythrocytes/CC (8), healthy cells/CC (9), segmented Kondo, Akira Tangoku
neutrophils/CC (10), stick neutrophils/CC (11), monocytes/CC (12), leucocytes/
Department of Thoracic and Endocrine Surgery and Oncology, Institute of Health
CC (13). Correct prediction of 5YS was 100% by neural networks computing Biosciences, the University of Tokushima Graduate School, Tokushima/Japan
(error=0.000; area under ROC curve=1.0). Conclusion: 5YS of LCP after radical
procedures significantly depended on: tumor characteristics, blood cell Background: In Stage I lung cancer, tumor size and PL factors are only
circuit, cell ratio factors, hemostasis system and AT. reflected by the TNM staging system. However, other clinicopathological
factors have the potential to influence recurrence and prognosis, especially
in pStage I lung adenocarcinoma. This study aimed to evaluate prognostic
factors, and to thereby stratify pStage I lung adenocarcinoma patients.
Methods: A total of 203 patients who underwent curative resection for
Stage I invasive adenocarcinoma, from 2006 to 2013, were retrospectively
MONDAY, DECEMBER 5, 2016 reviewed. 18F-Fluorodeoxyglucose positron emission tomography/computed
tomography (FDG-PET/CT) was performed in 194 patients and the maximum
standardized uptake value (SUVmax) of the tumor was calculated. Invasive
P1.08-004 PREDICTION OF SURGICAL OUTCOME BY MODELING adenocarcinoma was classified into 3 predominant subtypes (lepidic,
BASED ON RISK FACTORS OF MORBIDITY FOLLOWING PULMONARY papillary and others) according to the IASLC/ATS/ERS classification. The
RESECTION FOR LUNG CANCER IN THE ELDERLY associations between various clinicopathological factors and recurrence were
Yuzhao Wang, Nan Wu, Jingfeng Chen, Qingfeng Zheng, Shi Yan, Shaolei Li, evaluated, and disease-free survival (DFS) was analyzed. Results: Twenty-
Yinan Liu, Yue Yang eight patients had recurrent disease during the follow-up period (mean;
Department of Thoracic Surgery Ii, Peking University Cancer Hospital & Institute, 59.3±25 months). Univariable analysis showed male gender, smoking history
Beijing/China >20 pack-years, BMI≤20, CEA>5ng/ml, T classification, tumor size>20mm,
predominant histologic subtype (lepidic, papillary, others), pleural invasion,
Background: Surgical treatment for elderly patients with lung cancer presents vascular invasion, and SUVmax>3.0 to be significantly associated with
more challenges compared with general population. The aim of the study worse DFS. On multivariable analysis, tumor size>20mm (P=0.006), papillary
was to predict surgical outcome following pulmonary resection in the elderly predominant (P=0.023), other predominant (P=0.008), and SUVmax>3.0
with lung cancer by developing a clinical model. Methods: Clinical records (P=0.008) were extracted as independent prognostic factors associated with
of 525 patients aged over 70 years who underwent pulmonary resection worse DFS. Predictive variables were scored as follows; tumor size>20mm
for lung cancer in a single center were reviewed. Patients were divided into (1 point), papillary predominant (1 point), other predominant (2 points) and
three ordered categories of surgical outcome according to the Clavien–Dindo SUVmax >3.0 (1 point). Patients were classified into 3 risk groups (low-risk;
classification. Using a development cohort of 401 patients, an ordinal logistic 0-2, intermediate-risk; 3, high-risk; 4) according to their aggregate scores.
regression was performed to develop a prediction model for surgical outcome. The 5-year DFS rate was 91% in the low-risk group, 55% in the intermediate
The model was internally validated by bootstrap method and externally group and 36% in the high-risk group. The 5-year DFS rates during the same
validated by another cohort of 124 patients. Two previous models were period in our institute were 88% in pStage IA, 69.5% in pStage IB, 53% in
tested as benchmarks of our model. Results: The model was developed based pStage II, and 38% in pStage IIIA patients. Therefore, the DFS rate in the
on five risk factors of morbidity: ASA classification (p<0.001), pulmonary intermediate-risk group was comparable to that of pStage II, and the DFS rate
disease (p=0.001), tumor size (p=0.011), tumor location (p=0.015) and surgical in the high-risk group was comparable to that of pStage IIIA. Conclusion: In
approach (p=0.036). C-statistics of the model was similar to bootstrapping Stage I lung adenocarcinoma, tumor size, SUVmax and histologic subtypes
one. Hosmer-Lemeshow test showed a good goodness-of-fit. In external were suggested to be prognostic factors. This scoring system may predict
validation the performance of our model was superior to the two previous the groups, such as patients with pStage II and IIIA, requiring platinum based
models. post-operative chemotherapy.
Keywords: Adenocarcinoma, Prognostic factors, Surgery

P1.08-006 PROGNOSTIC IMPACT OF INCOMPLETELY LOBULATED

FISSURES IN NON-SMALL-CELL LUNG CANCER
Junichi Okamoto 1, Hirotoshi Kubokura1, Jitsuo Usuda2
1
Thracic Surgery, Nippon Medical School Musashikosugi Hospital, Kawasaki/Japan,
2
Thoracic Surgery, Nippon Medical School, Tokyo/Japan
Background: The division of the incompletely lobulated fissures is often

performed during the surgical resection of non-small-cell lung cancer (NSCLC).
However, the influence of lobulation on tumor recurrence was unclear in
these patients. Therefore, we assessed the prognostic impact of lobulation
in patients with NSCLC. Methods: A retrospective study of patients with
Prediction Performance of the Present and Previous Models
NSCLC who underwent lobectomy and bi-lobectomy was conducted between
Models c-statistic (95%CI) Hosmer-Lemeshow test April 2008 and May 2016. Patients who underwent division of the interlobar
fissure using stapling devices were compared with those who did not undergo
The present model 0.75 (0.69-0.80) 0.674
division of the interlobar fissure. Results: A total of 126 patients with NSCLC
After bootstrapping 0.75 (0.68-0.80) 0.671 (from p-stage IA to IIIA) who underwent surgery with (n = 103) or without
(n = 23) division of the interlobar fissure were included in this analysis. No
External validation 0.70 (0.64-0.75) 0.382
significant between-group differences were observed with respect to most
Kates M, et al (2009) 0.63 (0.57-0.69) 0.115 variables, except for operation side (p = 0.0483), operation time (p = 0.0469),
and post-operative lung comorbidity (p = 0.0031).Survival analysis revealed
Poullis M, et al
0.61 (0.54-0.67) 0.091 a significant between-group difference in disease-specific survival (DSS; p
(2013)
= 0.0340); however, no significant differences were observed with respect
Conclusion: Our model displayed an acceptable ability to predict surgical to disease-free survival (p = 0.1372) and overall survival (p = 0.0666).Cox
outcome in elderly patients undergoing pulmonary resection for lung cancer. regression univariate analysis revealed a significant association between DSS
and the number of staplers used to divide the interlobar fissure (p = 0.0486).
Keywords: morbidity, lung cancer, Surgery, elderly Conclusion: In this study, the extent and status of the incompletely lobulated
fissures was a significant risk factor for DSS in patients with resected NSCLC. characteristic curve revealed a dROM cut-off value of 327 during the
operation. Patients with a dROM value of 327 or less showed significantly
Keywords: Surgery, NSCLC, lobulation, Prognosis superior 3-year survival as compared to those with a greater value (87.5%
vs. 20.0%, p<0.001). Conclusion: Surgical stress caused an increase in dROM
during the postoperative course. The dROM value obtained during the
operation was correlated with long-term survival of patients after undergoing
resection for lung cancer.
P1.08-007 THE SIGNIFICANT IMPROVEMENT OF LUNG FUNCTION POSTER SESSION 1 - P1.08: SURGERY
AFTER PREOPERATIVE REHABILITATION IN PATIENTS WITH RISK ASSESSMENT & PROGNOSTIC FACTORS –
THORACIC TUMORS AND ABNORMAL SPIROMETRY
Oliwia Glogowska1, Sebastian Szmit2, Maciej Glogowski1
1
Lung and Thoracic Tumors Dept., The Maria Sklodowska-Curie Memorial Cancer P1.08-009 DOES BODY MASS INDEX (BMI) AFFECT OUTCOMES
Centre & Institute of Oncology, Warsaw/Poland, 2Department of Pulmonary POST LUNG RESECTION SURGERY?
Circulation and Thromboembolic Diseases, The Medical Centre of Postgraduate Eilidh Logan1, Sanjeet Avtaar Singh1, Tomoyo Fujiwara2, Kirsty Graham1, Alan
Education, European Health Centre Otwock, Otwock/Poland Kirk1, Michael Klimatsidas3
1
Background: The evaluation of degree of improvement of exercise Thoracic Surgery, Golden Jubilee National Hospital, Clydebank/United Kingdom,
2
Clinical Nutrition, NHS Golden Jubilee National Hospital, Clydebank/United
tolerance and rest lung function parameters after preoperative pulmonary
Kingdom, 3Golden Jubilee National Hospital, Clydebank/United Kingdom
rehabilitation in patients with thoracic tumors and baseline borderline
abnormal spirometry results. Methods: Clinical inclusion criteria were: Background: Increased BMI increases the surgical risk, atelectasis and
diagnosis of thoracic tumors and reduced values of FEV1 and FVC predicting postoperative complications in patients considered obese (BMI≥30). Several
postoperative complications. published studies have shown a protective effect of increased BMI. The
introduction of Enhanced Recovery Programmes (ERP) in surgical units has
We observed 29 patients (16 women, 13 men) in mean age of 68 (range 57-68)
greatly benefited obese patients in other surgical specialties but its impact in
years. Spirometry, six minute walking test distance (6MWT) and maximum
patients undergoing thoracic surgery is uncertain. We looked at the outcomes
metabolic equivalent during exercise on treadmill (MET) were chosen for
of patients at our unit since its implementation. Methods: A retrospective
evaluation of lung function and physical performance during rehabilitation.
cohort study was performed on all patients undergoing first time lobectomies
The tests were performed twice during screening phase to eliminate the
for primary lung cancer between January 2015-June 2016. Patients with
factors of learning, and were repeated after first and second week of
BMI<18 were excluded from the study. Student’s T-test, Mann-Whitney-U Test
rehabilitation. Pulmonary rehabilitation included two weeks of training on
and Chi-Squared analysis was used for statistical analysis of demographics
the treadmill with individually selected speed, physiotherapy exercises and
and outcomes. Results:
breathing training with using of Triflo. Results: The significant differences
were observed after pulmonary rehabilitation: 1). FEV 1 (L): 1.41 vs 1.58
(p=0.000027) 2). FEV1 (%N): 60.49 vs 71.49 (p=0.000021) 3). FVC (L): 2.34 vs
2.64 (p=0. 000520) 4). FVC (%N): 79 vs 95 (p=0.000269) 5). 6MWT Distance
(m): 350 vs 400 (p=0.000007) 6). MET: 2.66 vs 2.905 (p=0.000007) Conclusion:
A two-week pulmonary rehabilitation leads to significantly improvement
of lung function and physical performance in patients with thoracic tumors
and borderline abnormal spirometry results which may provide significantly
better outcome of patients in short- and longtime follow-up.
Keywords: pulmonary rehabilitation, Surgery, lung function test

P1.08-008 IMPACT OF PERIOPERATIVE REDOX BALANCE ON LONG-

TERM OUTCOME IN PATIENTS UNDERGOING LUNG RESECTION
Osamu Araki, Takashi Inoue, Yoko Karube, Sumiko Maeda, Satoru Kobayashi,
Masayuki Chida
General Thoracic Surgery, Dokkyo Medical University, Shimotsuga/Japan
Preoperatively, the FEV1 and DLCO were both significantly higher in patients
Background: Surgical stress provokes a cytokine storm and systemic with BMI≥30. There were no statistically significant postoperative
inflammatory response syndrome, and can also affect redox balance during differences between the two groups. Conclusion: Patients with a BMI≥30 can
the postoperative course. However, whether inflammatory status, especially do just as well as patients with BMI<30 in an ERP for patients with lung cancer
redox balance, during the perioperative period has effects on long-term undergoing lobectomy.
outcome following surgery for lung cancer remains unclear. The aim of this
Keywords: BMI, lobectomy, Obesity, NSCLC
study was to determine whether redox balance during the perioperative
period is associated with long-term survival of patients after undergoing lung
resection. Methods: Consecutive patients who underwent an anatomical
lung resection greater than a segmentectomy for non-small cell lung cancer
from January to June 2013 at our institution were investigated. The Ethical POSTER SESSION 1 - P1.08: SURGERY
Committee of Dokkyo Medical University Hospital approved this study RISK ASSESSMENT & PROGNOSTIC FACTORS –
(#24043) and all participating patients provided informed consent. Serum MONDAY, DECEMBER 5, 2016
was collected during the operation, and on post-operative day (POD) 3 and
7, and the levels of reactive oxygen metabolites (d-ROM) and biological P1.08-010 OCTOGENARIANS PERFORM EQUALLY TO YOUNGER
antioxidant potential (BAP) were measured using FREE carpe diem (Wismerll).
PATIENTS IN LUNG CANCER SURGERY
We analyzed overall survival, relapse, and cause of death. Results: Twenty-
two patients (males 18, females; 69±7 years old) were enrolled, of whom Florian Kocher 1, Caecilia Ng2, Herbert Maier2, Magdalena Sacher2, Gregor
12 underwent open surgery and 6 VATS. Histology findings showed 12 Laimer2, Michael Fiegl1, Paolo Lucciarini2, Thomas Schmid2, Florian Augustin2
1
adenocarcinomas, 6 squamous cell carcinomas, and 4 others. Comorbidities in Department of Hematology and Oncology, Medical University Innsbruck,
the patients were chronic obstructive pulmonary disease in 8 and idiopathic Innsbruck/Austria, 2Department of Visceral, Transplant and Thoracic Surgery,
Medical University Innsbruck, Innsbruck/Austria
pulmonary fibrosis in 5. d-ROM values on POD 3 and 7 were significantly
increased as compared to those obtained during the operation (perioperative Background: Due to prolonged life expectancy, more patients aged 80
288±65, POD 3 439±49, POD 7 479±49; p<0.001), whereas BAP did not change years or older will be diagnosed with lung cancer and eventually undergo
after surgery. Overall survival was 71.4% after 3 years. A receiver operating anatomic lung resection. This study was performed to evaluate outcome in

surgically treated octogenarians compared to younger patients. Methods: or over have been increasing in the aging society, which are accounted for
The institutional database of all consecutive patients treated between 2009 approximately 10% in Japan. Due to the prolonged life expectancy in the
and 2015 was analysed. The age cut-off was set at 80 years. Perioperative elderly, it is inevitable to assess the feasibility of pulmonary resection for
and follow-up data were compared between the two groups. Results: A total lung cancer especially in patients over 85 years in age. Methods: From 1995
of 453 patients were treated by a VATS approach at our center for proven to 2015, we underwent 3,099 pulmonary resections for lung cancers in our
NSCLC. 28 (6.2%) patients were aged 80 or older. There was no difference in department. Among them, 213 (6.8%) were aged 80 years or older. They were
gender distribution, clinical T stage, preoperative FEV1/FVC and preoperative divided into 2 groups based on the age, i.e., “Over80” who were aged from 80
haemoglobin values. Clinical N stage was higher in the octogenarians to 84 and “Over85” who were aged 85 or elder. Clinicopathological factors
(p=0.049). Median operative time was 175 minutes in the younger patients were analyzed between these two groups, using the t-test or the Chi-squared
compared to 156 minutes in the octogenarians (p=0.104). Neither tumor test. Survivals were calculated by Kaplan-Meier estimation methods. Results:
diameter nor distribution of tumor histology showed any significant Of the cases, 174 (84%) showed Over80 and 39 (18%) showed Over85. The
difference between the two groups. Postoperative haemoglobin values as proportions for male, comorbidity rate, c-stage I disease in the Over85 group
a surrogate parameter for intraoperative complications were comparable were not significantly different than those of the Over80 group (age; 20 (51%)
between the groups. Median hospital stay was 10 days in both groups vs. 105 (60%), p=0.189: comorbidity; 36 (92%) vs. 154 (89%), p=0.489: c-stage I;
(p=0.634). There was no in-hospital mortality in the octogenarians. Disease 36 (92%) vs. 143 (82%), p=0.119). The surgical candidates of the octogenarian
free (72.1 vs. 58.4 months, p=0.673) and overall survival (81.7 vs. 83.8 months, included 167 (78%) radiological pure-solid lung cancer, however, there was
p=0.456) did not show any significant difference between octogenarians and not significant difference between the 2 groups (28 (72%) vs. 139 (80%),
younger patients. p=0.267). Lobectomy was equally performed in 28 (72%) on the Over85 and
126 (72%) of the Over80 (p=0.938), respectively. Perioperative morbidities
were observed in 104 (48%) of the patients, though, significant difference
was not found between the two study arms (84 (48%) vs. 20 (51%), p=0.734)
and the 30-day mortality rates was observed just one patient for the Over80
group. The 5-year overall survival was 51.1% in the Over80 group, 62.6% in
the Over85 group (p=0.275), respectively. Conclusion: In the octogenarians,
a patient with radiological pure-solid lung cancer was more common as a
surgical candidate for the definitive local management. Although proper
patient selection and meticulous perioperative management were mandatory
for surgical resection of the very elderly, our results support the finding that
radical surgical intervention could be feasible even for the patients with high
age over 85 years.
Keywords: Pulmonary resections for lung cancer in patients aged 80 years or

over

P1.08-012 CHARACTERIZING TIME TO CARE FOR LUNG CANCER

SURGICAL PATIENTS
Breanne Cadham1, Janine Olsen2, Rasika Rajapakshe2, Michael Humer 3
1
BC Cancer Agency, Kelowna/Canada, 2BC Cancer Agency, Kelowna/BC/Canada,
3
Kelowna Thoracic Surgical Group, Kelowna/BC/Canada
Background: The Kelowna Thoracic Surgical Group (KTSG), centered in

Kelowna, British Columbia (BC), Canada provides care to a geographic area of
807,538 km2. This is 85% of the province of BC and approximately 9 times the
size of Austria. A significant portion of this population consists of remote and
rural communities. Ensuring equal and prompt access to lung cancer diagnosis
and treatment regardless of proximity to treatment center is important not
only because of the time sensitivity of care, but also because of the overall
healthcare burden of this highly prevalent and often lethal malignancy.
Methods: A retrospective chart review was performed on all patients seen
by the KTSG who came to definitive surgical treatment in Kelowna for a
diagnosed or suspected lung cancer between January 2010 and December
2015. Dates were collected at three time-points along the care pathway:
Referral, Consult, and Surgical Treatment. We calculated times from referral
to consult (RC), consult to treatment (CT), and overall referral to treatment
(RT). Demographic information was collected for each of the patients and
the distances patients’ lived from the Surgical Centre were determined. The
Conclusion: Lung resection can safely be performed in selected octogenarians study has received approval from both University of British Columbia – BC
with acceptable morbidity and low mortality rates. In our experience it is even Cancer Agency and Interior Health Authority research ethics boards. Results:
as safe as in younger patients. Our data adds evidence that in such patients There were 902 patients in the cohort; 446 local patients who lived within a
potentially curative treatment should not be withheld. radius of 100 km or less from Kelowna and 456 distant patients who resided
Keywords: octogenarians, VATS further than 100 km from the city. For the entire group, the median RT was
50.5 days comprised of RC = 6 days, and CT = 42 days. For the local patient
group, the median RT was 49 (Interquartile Range (IQR) = 33.75 to 69) days
compared to a median of 52.5 (IQR = 36 to 52.5) days for the distant patients.
The extreme overlap in the IQR shows no significant clinical difference in time
POSTER SESSION 1 - P1.08: SURGERY to care between the local and distant patients. Conclusion: Time from referral
RISK ASSESSMENT & PROGNOSTIC FACTORS – to treatment for patients with suspected or confirmed lung cancer seen by
the IHTSG is similar for both local and distant patients. The equitable times
to care with the IHTSG suggests that the current model of patient-doctor
P1.08-011 FEASIBILITY OF SURGICAL RESECTION FOR LUNG communication provides a growing opportunity to mitigate the impact of
CANCER PATIENTS AGED OVER 85 YEARS distance on access to care.
Takehiro Ouchi, Aritoshi Hattori, Takeshi Takeshi Matsunaga, Kazuya Keywords: Health Equity, Thoracic Surgery, Time to Care
Takamochi, Shiaki Oh, Kenji Suzuki
General Thoracic Surgery, Juntendo University, Tokyo/Japan
Background: Pulmonary resections for lung cancer in patients aged 80 years
POSTER SESSION 1 - P1.08: SURGERY in 15 (11.2%) asymptomatic patients. Table 1 – Correlation between type of
recurrence and presence of symptoms.
Local recurrence Distant recurrence

P1.08-013 PREOPERATIVE MANAGEMENTS FOR PULMONARY
COMPLICATIONS USING INHALATIONS IN LUNG CANCER PATIENTS CT (Asymptomatic) 9 (90%) 2 (25%)
WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE CT (Symptomatic) 1 (10%) 6 (75%)
Kyoshiro Takegahara, Jitsuo Usuda
Total 10 (100%) 8 (100%)
Thoracic Surgery, Nippon Medical School Hospital, Tokyo/Japan
p = 0.09 Conclusion: Routine chest-CT detected most cases of local recurrence
Background: Chronic obstructive pulmonary disease (COPD) is related
and second primary lung cancers in asymptomatic patients after curative
to the prognosis of patients with lung cancer, and one of risk factors of
resection of non-small cell lung cancer. Clinical examination and chest CT
respiratory complications after surgical resections. This study aimed to
should be recommended for follow up after complete surgical resection.
investigate whether perioperative inhalations of long-acting beta-agonists
(LABAs) or long-acting muscarinic antagonists (LAMAs) would decrease the Keywords: lung cancer, Surgery, Chest CT, follow up
postoperative complications in lung cancer patients with COPD. Methods: We
retrospectively analyzed 108 patients with COPD who underwent pulmonary
resections for primary lung cancer at our hospital between January 2013 and
January 2016, in order to determine the association between the incidence
of postoperative complications (e.g., prolonged air leakage and pneumonia) POSTER SESSION 1 - P1.08: SURGERY
and the use of LABAs or LAMAs. Results: Among 108 patients with COPD RISK ASSESSMENT & PROGNOSTIC FACTORS –
patients, there were 86 men and 22 women, with a mean age of 69.3 years
(range, 46–84). The mean Brinkman index was 1172.1(range, 50-3480). The
mean FEV1.0/FVC was 61.4%(range, 26.8%-69.9%). The surgical procedures P1.08-015 SURGERY OF STAGE I NON-SMALL CELL LUNG CANCER IN
were partial resection in 11 patients, pulmonary segmentectomy in 3 PATIENTS AGED 80 YEARS OR OLDER
patients, lobectomy in 92 patients, and pneumonectomy in 2 patients. The
Osamu Kawamata
histological types showed adenocarcinoma in 53 patients, squamous cell
Surgery, Onomichi Municipal Hospital, Onomichi/Japan
carcinoma in 38 patients, adenosquamous carcinoma in 5 patients, large cell
neuroendocrine carcinoma in 3 patients, large cell carcinoma in 4 patients, Background: Non-small cell lung cancer (NSCLC) is a typical disease of the
small cell carcinoma in one patient, and pleomorphic carcinoma in 4 patients. elderly patients, and is becoming increasingly. Surgical resection is standard
There were 29 postoperative complications in COPD (26.9%), prolonged air treatment for early-stage NSCLC. We evaluate the efficacy of lobectomy
leak (more than 7 days) 14 cases, pneumonia 9 cases, arrhythmia 2 cases, versus segmentectomy for stage I non- small cell lung cancer in elderly
chylothorax 2 cases, wound infection 2 cases. The frequency of postoperative patients 80 years or older. Methods: 54 cases with stage I of 82 patients aged
pulmonary complications such as prolonged air leakage and pneumonia, was 80 years or older who underwent surgery for non-small cell lung cancer at our
significant higher in COPD (23 cases, 21.3%) than in non COPD (15 cases,6.7%). hospital between 2004 and 2013 were studied. The patients’ medical records
Inhaled bronchodilators such as LAMA or LABA were prescribed to 34 cases in were reviewed with type of operation, histological diagnosis, postoperative
COPD, not to 74 cases. The pulmonary complications were significant lower morbidity, postoperative mortality and survival results. Results: There were
in LAMA or LABA users (3 cases, 8.8%) than in no users (20 cases, 27.0%). 33 men and 21 women. The average ages were 83.4 years (range, 80-90 years).
Conclusion: For lung cancer patients with COPD, preoperative management Adenocarcinoma was identified in 45 patients and squamous cell carcinoma
using the inhalants with LABA or LAMA, and smoking cessation can reduce was identified 9 patients. Lobectomy was performed in 25 patients for stage
the frequency of the postoperative pulmonary complications after surgical IA (n=10) and IB (n=15), segmentectomy was performed in 18 patients for
lung resection. The inhalants with LAMA or LABA may be adapted for the stage IA (n=15) and IB (n=3) and wedge resection was performed in 11 patients
management of not only perioperative care but also long-term survival of for stage IA (n=10) and IB (n=1). Mean follow-up was 53 months. 4 cases of 54
COPD patients after surgery. patients died for lung cancer and 8 cases died for other causes within 5 years
after lung resection. Overall survival rate at 5 years in all patients was 70.6%.
Keywords: Chronic obstructive pulmonary disease, lung cancer, Long-acting
One case of 25 patients who underwent lobectomy died for lung cancer (IA
beta-agonist, Long-acting muscarinic antagonist
n=1, IB n=0). 3 cases died for other causes (IA n=1, IB n=2). Two cases of 18
patients who underwent segmentectomy died for lung cancer (IA n=0, IB n=2),
3 cases died for other causes (IA n=2, IB n=1). Overall survival rate at 5 years
for lovectomy vs segmentectomy was 74.5% vs 68.1% (IA; 67.5% vs 86.7%, IB;
POSTER SESSION 1 - P1.08: SURGERY 77.0% vs 0%). Morbidity rate in all patients was 22.2% (lobectomy; 20.0% vs
RISK ASSESSMENT & PROGNOSTIC FACTORS – segmentectomy; 27.8%), atrial fibrillation 5 patients (3 vs 2), heart failure 1
patient (0 vs 1), prolonged air leakage 3 patients (1 vs 2), atelectasis 2 patients
(0 vs 2), delirium 1 patient (1 vs 0). Mortality rate was 0% in both groups.
P1.08-014 USEFULNESS OF CHEST CT IN FOLLOW-UP OF PATIENTS Conclusion: The lobectomy and segmentectomy were equal results in elderly
WITH COMPLETELY RESECTED LUNG CANCER patients 80 years or older for stage IA NSCLC. These data further support the
use of lobectomy for resection of stage IB tumors.
Jefferson Gross 1, Juliana Morelato2, Marcos Guimarães2, Fabio Haddad2, João
Paulo Medici2, Marcus Baranauskas2, Helio Carneiro2, Maria Luiza Medeiros2 Keywords: 80 years or older, Early-stage NSCLC, segmentectomy
1
Thoracic Suregry, Ac Camargo Cancer Center, Sao Paulo/Brazil, 2 Ac Camargo Cancer
Center, Sao Paulo/Brazil
Background: There is no consensus about the best method to follow up

patients after complete resection of lung cancer. This study was performed POSTER SESSION 1 - P1.08: SURGERY
to identify how often follow-up chest-CT detected recurrence or a RISK ASSESSMENT & PROGNOSTIC FACTORS –
second primary lung cancer in asymptomatic patients. Methods: This is a
retrospective study. Patients with diagnosis of non-small cell lung cancer
submitted to complete surgical resection were included. They were followed- P1.08-016 BMI IN PATIENTS WITH OPERATED LUNG CANCER IN
up with regular visits to the clinic and chest CTs. The visits to the clinic were COMPARISON WITH THE SCOTTISH HEALTH SURVEY 2014. IS
every three months in the first two years, semiannually up to the fifth
THERE A DEMOCRACY IN BMI?
year, and annually thereafter. Patients were classified in symptomatic and
asymptomatic according to the presence of clinical manifestations at each Tomoyo Fujiwara1, Sanjeet Avtaar Singh2, Alan Kirk2, Michael Klimatsidas2
1
visit. Results: From 2003 to 2013, 134 patients were included. Median age Clinical Nutrition, Golden Jubilee National Hospital, Clydebank/United Kingdom,
2
was 63.5 years. Seventy three (54.5%) were male. Current or former-smokers Golden Jubilee National Hospital, Clydebank/United Kingdom
were 70.1% of the patients. Adenocarcinoma was the most common histologic
Background: Lung cancer has the most common cancer related mortality
type, observed in 82 (61.2%) of the patients. Lobectomy/bilobectomy was
in Scotland¹. Malnutrition is common in these patients and may affect
performed in 99 (73.8%), segmentectomy in 31 (23.1%), and pneumonectomy
survival². However many patients with operable lung cancer are overweight³.
in 4 (3%). Pathological stage was: IA(53%), IB(10.2%), IIA(11.7%), IIB(6,6%),
We looked at lung cancer resection rates at our unit and compared it to the
IIIA(13.3%), IIIB(3.1%), and IV (2.1%). Forty six (44.3%) patients were submitted
Scottish Health Survey (SHS) 2014. Methods: A retrospective cohort study of
to adjuvant treatment. Median follow-up was 30.2 months. Recurrence was
all patients undergoing lobectomy and pneumonectomy for pathologically
detected in 18 (13.4%) patients, being local (including mediastinal) in 10 (7.4%),
proven primary lung cancer from April 2012 to May 2016. Results: 5833
and distant in 8 (5.9%). Local recurrences were mainly detected by chest CT in
patients have been operated in our centre during the period, 1882 had
asymptomatic patients. Distant recurrence was detected mostly by clinical
anatomical lung resections and 979 of these were eligible to enter our study.
symptoms (Table 1). Second primary lung cancers were found by chest CT

Mean age of male patients was 68±9.5 years and female patients was 66.7 ±9.0 recurrence between two groups was not significantly different. The patients
years. The median length of stay for males and females were 8 (Q1=6, Q3=12) who underwent lobe-specific LND did not show superior survival (p=0.598)
and 7 (Q1=6, Q3=10) days respectively. The Chi squared test for trend for males It was same in the patient who underwent adequate LND mentioned in AJCC
showed X²(1) =0.07, 2p=0.8, females showed X²(1) =0.00, 2p=1.0. There was no guidelines (p=0.714). The difference in risk of recurrence was not presented
statistical difference for both males and females BMI distribution between in stratified analysis by stage. Conclusion: In early stage lung cancer, the
the SHS and our cohort. possibility of hidden LN metastasis is very low. Therefore, limited LN
dissection such as LN sampling based on the result of intraoperative frozen
BMI males females section diagnosis can be acceptable in surgery for early stage NSCLC.
<18.5kg/m² 8 15 Keywords: early stage NSCLC, LN dissection
18.5-24.9kg/m 2 106 155
25-29.9kg/m2 146 135
30-39.9kg/m 2 90 123 POSTER SESSION 1 - P1.08: SURGERY

>40kg/m2 1 13 MONDAY, DECEMBER 5, 2016
total *BMI not recorded (missing data) 351 89 441 98

P1.08-018 POSITIVE N STAGE IS A RISK FACTOR FOR SURVIVAL
IN FIVE-YEAR DISEASE FREE SURVIVORS WITH COMPLETELY
RESECTED NON-SMALL CELL LUNG CANCER
Jin Gu Lee, Seokkee Lee, Chang Young Lee, Dae Joon Kim, Kyung Young Chung
Yonsei University College of Medicine, Seoul/Korea, Republic of
Background: Lung cancer has a poor prognosis and it has a small number of
long term survival patients compared to other cancers. Therefore, there is
a limitation in evaluating survival beyond 5 years after surgical treatment.
The purpose of this study is to analyze risk factors of survival and late
recurrence in these patients after 5 years disease free period. Methods: This
is a retrospective analysis of patients who had at least 5 years disease free
survival after surgical treatment for NSCLC at a single institute between
January 1998 and December 2007. We excluded patients who received
neo-adjuvant therapy, incomplete resection, or advanced stage (stage IIIb
and IV). Results: 463 (41.1%) out of 1126 patients were enrolled. 318 patients
(68.7%) were male, and their mean age was 61.3 ± 9.7 years (range, 21.3 – 82.2).
Pathologic N0 (337 patents, 72.8 %) and stage I (263 patents, 56.8 %) were
dominant stage. Late recurrence occurred in 5.4 % (25 patients) after 5 years
Conclusion: Our study reveal that the rate of resection in our cohort
of surgery. In multivariate analysis, male, age (≤ 60 years), node positive, and
was similar to the SHS. Further studies will be required to look into the
late recurrence were independent risk factors for overall survival, while the
relationship between surgical outcomes and BMI.
node positive was the only independent risk factor for disease free survival on
Keywords: Surgery, BMI, lung cancer multivariate analysis (HR, 2.609; p=0.017; CI, 1.190 – 5.719).
Table. Multivariate analysis of Overall Survival & Disease Free Survival

Variables HR p 95% CI
RISK ASSESSMENT & PROGNOSTIC FACTORS – Overall Survival
Sex
P1.08-017 DOES MEDIASTINAL LYMPH NODE DISSECTION AFFECT Female 1

PROGNOSIS OF EARLY STAGE NSCLC?
Male 2.243 0.003 1.323-3.801
Hye-Seon Kim, Won Sang Chung, Hyuck Kim
Department of Thoracic and Cardiovascular Surgery, Hanyang University Seoul Age
Hospital, Seoul/Korea, Republic of
age < 60 1
Background: Adequate staging is important in treatment of non-small cell
lung cancer (NSCLC). Owing to innovation of imaging tools, the preoperative 60 ≤ age <70 2.647 <0.001 1.593-4.398
clinical staging is accurate while surgical staging is still a golden standard. For
70 ≤ age 4.607 <0.001 2.605-8.149
complete resection of NSCLC, a systematic nodal dissection is recommended
in all cases. However, for peripheral T1 tumor, a more selective nodal p-N stage
dissection depending on the lobar location of the primary tumor (lobe-specific
systematic nodal dissection) is acceptable. In this study, we try to evaluate N0 1
more selective lymph node sampling is acceptable in early stage NSCLC; stage
N1+N2 1.809 0.003 1.231-2.660
IA and IB. Methods:
Recurrence
Stage IA (n=86) Stage IB (n=44)
No 1
Lobe-Specific LN Dissection vs LN Sampling
Yes 5.377 <0.001 3.316-8.719
Lobe-Specific LN Dissection 30 17
Disease free survival
LN Sampling 56 27
Adequate LN Dissection vs LN Sampling p-N stage
Adequate LN Dissection 32 17 N0 1
LN Sampling 54 27 N1+N2 2.609 0.017 1.190-5.719
From January 2011 to December 2015, 186 patients underwent surgical Conclusion: This study confirmed that late recurrence occurred in patients
treatment at out center. Among them 130 patients were stage IA and IB. with no recurrence for 5 years after surgical resection, and it had a negative
We retrospectively reviewed medical records and classified patients into effect on overall survival beyond 5 years after operation. Furthermore, N
two groups by lymph node dissection (LND) method. When we perform LN positive (N1 or N2) was an independent risk factor for both overall survival and
smapling, the intraoperative frozen section diagnosis for dissected LNs is disease free survival. Therefore, careful follow-up is needed for the detection
routine procedure in our center. Survival analysis to evaluate effect of LND of late recurrence even in patients with five years disease free survival, and
on cancer recurrence was performed. Results: In survival analysis, the risk of especially for node-positive patients. More studies are needed to clarify this
point.
Keywords: long term survivor with 5 years disease free, late recurrence risk
factor, positive N stage, non-small cell lung cancer

P1.08-019 RISK FACTORS AND SURVIVAL OF OCCULT N2 LYMPH

NODE METASTASIS IN NSCLC PATIENTS WITH CLINICAL N0-1
DIAGNOSED BY PREOPERATIVE PET-CT
Ks Park 1, Ch Bae1, Eb Lee2
1
Dcmc, Daegu/Korea, Republic of, 2Kyungpook National University Medical Center,
Daegu/Korea, Republic of
Background: Accurate staging of NSCLC for N2 lymph node metastasis is

crucial for prognosis and optimal therapy. Suggestion of occult mediastinal
lymph node metastasis could help physicians for decision making of staging
and management. This study was aimed to know risk factors and survival
for occult N2 lymph node metastasis in NSCLC patients with clinical N0 and
N1 diagnosed by preoperative PET-CT. Methods: This study was evaluated
NSCLC patients with clinical N0-1 who underwent R0 lung resection with
complete lymphadenectomy. Clinicopathological factors such as tumor
size, tumor location, tumor laterality, histology, and FDG uptake were
analyzed to delineate risk factors. Overall survival was analyzed. Results:
Between November 2005 to December 2014, the incidence of N2 lymph node
metastasis was 13.3%(22 patients of 166). The risk factors for pN2 were
central located tumor(p<0.001), larger tumor size on CT(p=0.038), and high
SUV on PET(p=0.001). Patients having risk factor of central tumor had shorter
survival, significantly(p<0.001). Conclusion: The central located tumor, larger
tumor size on CT, and high SUV of primary tumor were predictable factors for
N2 lymph node metastasis in clinical N0-1 NSCLC. Therefore, these factors
may help determined whether to enforce cN0-1 patients to do mediastinal
staging selectively.
Keywords: NSCLC, occult N2 LN metastasis

P1.08-020 THE EFFECT OF TWO INTERVENTIONS ON ATTAINMENT

OF SURGICAL QUALITY MEASURES IN RESECTED NON-SMALL CELL
LUNG CANCER (NSCLC)
Nicholas Faris 1, Meredith Ray2, Matthew Smeltzer2, Carrie Fehnel1, Cheryl
Houston-Harris1, Paul Levy3, Chris Mutrie4, Brad Wolf5, Lawrence Deese6,
Lynn Wiggins7, Vishal Sachdev8, Sam Signore4, Edward Robbins4, Raymond
Osarogiagbon1
1
Thoracic Oncology Research Group, Multidisciplinary Thoracic Oncology
Program, Baptist Cancer Center, Memphis/TN/United States of America, 2 School
of Public Health, University of Memphis, Memphis/TN/United States of America,
3
Cardiothoracic Surgery, Nea Baptist, Jonesboro/AR/United States of America,
4
Cardiothoracic Surgery, Baptist Memorial Hospital, Memphis/TN/United States of
America, 5Cardiothoracic Surgery, Baptist Memorial Hospital, Desoto/MS/United
States of America, 6Cardiothoracic Surgery, Baptist Memorial Hospital, Oxford/MS/
United States of America, 7Cardiothoracic Surgery, St. Bernard’s Regional Medical
Center, Jonesboro/AR/United States of America, 8North Mississippi Medical Center,
Tupelo/MS/United States of America
Background: Better pathologic staging improves early-stage NSCLC survival.

We sought to measure the impact of complementary surgery (lymph node
specimen collection kit) and pathology (a novel gross dissection method)
interventions on attainment of guideline-recommended surgical staging Conclusion: The combined effect of two interventions to improve pathologic
quality. Methods: We analyzed curative-intent resections from 2004-2016 lymph node examination has a greater effect on attainment of a range of
from 4 contiguous Dartmouth Hospital Referral Regions in 3 US states. surgical quality parameters than either intervention alone.
Preoperatively-treated patients were excluded. Patients were categorized
into groups based on whether a lymph node specimen collection kit was used Keywords: quality improvement, non-small cell lung cancer, intervention
during surgical resection, and whether a novel, anatomically-sound gross study, Surgical resection
dissection method was used to retrieve intrapulmonary lymph nodes.
Chi-squared tests were used to examine differences in demographic and
disease characteristics and surgical quality parameters across
implementation groups. Results: Of 2,094 patients, 1,492 received neither
intervention; 152 received only the pathology intervention; 161 received only RISK ASSESSMENT & PROGNOSTIC FACTORS –
the surgery intervention; 289 had both (Table 1). Attainment of surgical MONDAY, DECEMBER 5, 2016
quality guidelines significantly increased in ascending order of the pathology,
kit, and combined interventions (Table 2).
P1.08-021 PREDICTORS OF POST-OPERATIVE MORTALITY IN NON-

SMALL CELL LUNG CANCER (NSCLC) IN A HIGH MORTALITY REGION POSTER SESSION 1 - P1.08: SURGERY
OF THE US MONDAY, DECEMBER 5, 2016
Matthew Smeltzer 1, Yu-Sheng Lee1, Edward Robbins2, Nicholas Faris3, Chris
Mutrie3, Meredith Ray1, Sam Signore2, Carrie Fehnel3, Cheryl Houston-Harris2,
P1.08-022 RISK STRATIFICATION MODEL TO PREDICT SURVIVAL
Meghan Meadows1, Raymond Osarogiagbon2
1 FOLLOWING SURGICAL RESECTION FOR LUNG CANCER USING
Epidemiology and Biostatistics, University of Memphis School of Public Health,
Memphis/TN/United States of America, 2Multidisciplinary Thoracic Oncology PATHOLOGICAL VARIABLES
Program, Baptist Cancer Center, Memphis/TN/United States of America, 3Thoracic Timothy Edwards, Charlene Tennyson, Haval Balata, Phil Foden, Anshuman
Oncology Research Group, Multidisciplinary Thoracic Oncology Program, Baptist Chaturvedi, Rajesh Shah, Philip Crosbie, Richard Booton, Matthew Evison
Cancer Center, Memphis/TN/United States of America
University Hospitals of South Manchester, Manchester/United Kingdom
Background: Surgical resection is recommended for most patients with
Background: The risk of lung cancer recurrence remains a significant problem
early-stage NSCLC. High postoperative mortality risk diminishes the benefit
following curative-intent treatment. Novel methods of calculating this risk
of curative-intent surgery. We examined factors associated with mortality
may have potential benefits in defining adjuvant strategies and stratifying
within 120 days of curative-intent resection in a population-based cohort.
the intensity of surveillance programs. The aim of this study was to identify
Methods: We examined all NSCLC patients with curative-intent resections
factors at surgical resection of NSCLC that influenced survival in attempt to
from 2009-2016 in all 11 hospitals in 4 US Dartmouth Referral Regions. We
develop a probability model to predict mortality. Methods: Pathological
evaluated patient demographics, disease characteristics, pre-operative
variables were recorded from 1311 patients undergoing surgical resection for
evaluation, treatment, and perioperative complications to identify risk
NSCLC from 2011 to 2014 at a tertiary UK lung cancer centre. Pathological
factors for 30-, 60-, 90-, and 120-day mortality using logistic regression
variables analysed included T-stage, N-stage, adequacy of intra-operative
models. Results: The 2,258 patients’ median age was 67, 48% were female;
lymph node sampling, pleural invasion, lymphovascular invasion,
78% were White, 21% Black. The 30-, 60-, 90-, and 120-day post-operative
extracapsular spread, histological sub-typing, extent of surgery, grade of
mortality rates were 4%, 6%, 8%, and 9%. After adjusting for all other
differentiation and R status (residual disease). Survival data was obtained
factors, American Society of Anesthesiologists score (ASA) (p=0.0405), prior
from national death registries and logistic regression was used to develop a
lung cancer (p=0.0406), and Charlson comorbidity score (p=0.0163) were
probability model to predict mortality. Results: Table 1. Pathological
associated with 30-day mortality. Adjusted models for 120-day mortality
predictors of survival 1 year post surgery for NSCLC
indicate associations with age (p=0.0001), tumor size (p=0.0012), intra-
operative blood loss (p=0.0150), hospital (p=0.0065), ASA (p=0.0035), prior
lung cancer (p=0.0466), and Charlson score (p=0.0064) (Table 1). Patients
>75 years old had 1.5 times the odds of 120-day mortality compared with
those <49. A Charlson score >=3 (vs. 0) conferred 2.7 times the odds of 120-day
mortality. On average, each 1 cm increase in tumor size increased the odds
of 120-day mortality by 12%. Patients with all three risk factors (age >75,
Charlson score >=3, tumor >4cm) had 26.5% 120-day mortality. Although
17.5% of pneumonectomy patients died within 120 days, extent or duration of
surgery were not significant after adjusting for other factors.
30-Day 120-Day
N (total=2258)
Mortality Mortality
% %
Age
< 49 101 3 7.9
50-64 730 2.6 4.3
65-74 937 4.7 9.9
75+ 490 6.1 13.1
p=0.1954 p=0.0001
Tumor Size(mean) 2258 3.6 3.9

p=0.1834 p=0.0012
Surgery Type
Lobectomy/Wedge 1696 3.5 7.8
Pneumonectomy 143 9.1 17.5
Bilobectomy 126 6.4 11.9
Segmentectomy/Wedge 293 5.5 7.9
p=0.4359 p=0.6029
Previous Lung Cancer
No 2166 4 8.3
Yes 92 10.9 17.4
p=0.0406 p=0.0466
Charlson Comorbidity
0 455 1.8 4.2
1-2 1132 3.8 8.2
≥3 671 6.7 12.5
Using the probabilities from the logistic regression model to predict one year
p=0.0163 p=0.0064 mortality gives an AUC of 0.741. If a probability of 0.144 is used to predict
Blood loss(surgical) whether a patient will die within one year of surgery, sensitivity is 70.0%
0-500cc 2048 4 7.8 (119/170), specificity is 67.3% (625/929), PPV is 28.1% (119/423) and NPV
501-1000cc 136 6.6 16.9 is 92.5% (625/676). Conclusion: Survival post-curative intent surgery for
>1000cc 74 8.1 18.9 NSCLC is based on multiple pathological factors as described above. Further
analysis of these factors will be performed in the future to determine a risk
p=0.4842 p=0.015
stratification model to predict patients with low versus high risk mortality
Conclusion: Age, ASA, Charlson score, and tumor size are important risk post surgery. Whilst indications for adjuvant therapy are well documented,
factors for post-operative mortality. Inter-hospital disparity suggests an the optimal surveillance regime is not as clear. Given the heterogenous group
opportunity for institution-level corrective interventions. Patients with the of patients receiving surgery for NSCLC, a predictive model may be useful in
combination of age >75, Charlson score >=3, and advanced T-category had a determining optimal surveillance strategies.
high rate of post-operative mortality.
Keywords: non small cell lung cancer, survival, Surgical resection
Keywords: Surgical resection, Early-stage NSCLC, Post-operative Mortality

MONDAY, DECEMBER 5, 2016 Epidemiologic Studies in Surgery for NSCLC –
P1.08-023 ANALYSIS OF PROGNOSTIC FACTORS AND LONG-TERM
RESULTS OF PRIMARY PULMONARY PLEOMORPHIC CARCINOMA
P1.08-025 LONG-TERM SURVIVAL OF LUNG CANCER IN CHILE
Domenico Galetta, Alessandro Borri, Roberto Gasparri, Francesco Petrella,
Lorenzo Spaggiari Ruben Valenzuela, Claudio Suárez, Mauricio Fica, Francisco Suárez, Rodrigo
Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy
Aparicio, Virginia Linacre, José Lobos, Rodrigo Villarroel
Thoracic Surgery, Clínica Santa María, Santiago/Chile
Background: Pulmonary pleomorphic carcinoma (PPC) is a rare neoplasm and
factors affecting survival after pulmonary resection, as well as its clinical Background: Lung cancer is the leading cause of cancer death worldwide. The
and pathologic characteristics, are still unknown. For a better understanding long-term survival is an important outcome of oncologic therapies. In early
we reviewed our large experience with these patients. Methods: Records stages permits to evaluate the quality of surgical oncology services,
of patients 134 patients (108 men, median age: 65 years) with diagnosis of meanwhile in advanced stages the quality of the multidisciplinary teams.
PPC operated on between January 1999 and May 2015 were retrospectively Screening programs and early diagnosis are the most efficient way to achieve
analyzed from a prospective database; survival was calculated by using increase in overall survival. The results of Clínica Santa Maria in Lung Cancer
Kaplan-Meier method. Results: 86 patients (64.1%) were smokers. Median patients are presented. Methods: All patients diagnosed with Non-small Lung
tumor size was 4.8 cm (range, 0.6 to 23 cm). Initial histological diagnosis Cancer, treated by the team of Thoracic Surgery in our private hospital, during
was NSCLC in 88 cases, adenocarcinoma in 21, pleomorphic tumor in 13, the period January 2011 to July 2016 were entered prospectively, consecutively
and no diagnosis in 12. 62 patients (46.0%) received a platinum based and daily to a web database. Demographic, clinical and pathological data, as
induction chemotherapy. Surgery included lobectomy in 87 patients well as monitoring all events were recorded. All our patients underwent to an
(65%), pneumonectomy in 27 (20.1%), wedge resection in 12 (8.9%), and exhaustive staging process. Statistical descriptive analysis of clinical and
segmentectomy in 8 (6%). Four patients (3%) had an incomplete resection. demographic variables and 5 year overall survival are shown. Results: 313
Postoperative staging included 45 stage I (33.6%), 47 stage II (35.1%), and 42 patients were included, median age of 65 years old (32-89), 48,6% female.
stage III (31.3%). 64 patients (47.7%) received adjuvant treatment. Five-year Adenocarcinoma was the most frequent histology (78,9%). Stage I 48,6%,
overall survival and disease-free survival were 36.6% and 35.7%, respectively Stage II 9,27%, Stage III 14,8%, and Stage IV 26,5%. The median follow-up time
(median, 28 and 18 months, respectively). Recurrences occurred in 76 patients was 50 months (1-289) with a mean survival time of 99 months. Overall 5-year
(56.7%) most of them at distant sites (47/76 [61.8%]). Factors associated with survival was 63,7% (95%CI, 57-69%), and by stages: Stage I 91,4% (95%CI,
increased survival included no smoke habit (p=.02), no induction therapy 84,9-95,2%), Stage II 63,7% (95%CI, 39,5-80,3%), Stage III 44,3% (95%CI,
(p=.04), right side disease (p=.01); pathological stage I (p=.001), no metastatic 26,4-60,8%) and Stage IV 19,1% (95%CI, 10,1-30,3%). Adenocarcinomas was
lymph nodes (p=.001), and adjuvant treatment (p=.003). At multivariate 64% (95%CI, 56,6-70,5%).
analysis, pN0, pstage I, and adjuvant treatment were independent prognostic
factors (p=.002, 95%CI: 1.54-6.43; p=.003, 95%CI: 1.23-7.32, p=.001, 95%CI:
1.26-4.72, respectively). Conclusion: PPC are aggressive tumors usually
presented as a large lesion in males. Preoperative diagnosis remains difficult.
Prognosis is poor, and distant recurrence rate is high. Long-term survival can
be achieved in early stage disease and by an appropriate adjuvant therapy.
Keywords: lung tumor, Pleomorphic carcinoma

P1.08-024 SURGICAL OUTCOMES AND PROGNOSTIC FACTORS IN

THE TREATMENT OF ADENOSQUAMOUS CARCINOMA OF THE LUNG
Lorenzo Spaggiari
Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy Conclusion: The epidemiological profile of our patients is similar to those
published in most of the World Series. The diagnosis in early stages is high,
Background: Adenosquamous carcinoma (ASC) of the lung is a rare pulmonary further up than most publications, however, lower than those shown by
disease with poor prognosis. We evaluated the prognostic factors and Asamura, who reported 58,6%. We believe that the overall survival of this
outcome of this tumour. Methods: Records of patients undergoing pulmonary series results are superior to most international publications, due to the high
resection for ASC between 1998 through 2015 were reviewed using a percentage of patients in early stages, exhaustive staging and adequate
prospective database. 124 patients (91 men, median age, 67 years) with multidisciplinary treatment.
ASC were operated on. Results: Surgical procedures included 3 exploratory
thoracotomies, 6 bilobectomies, 76 lobectomies, 19 pneumonectomies, 12 Keywords: Surgery, lung cancer, survival, non-small cell lung cancer
wedges resections, and 8 segmentectomies. 38 patients (30.6%) received
induction therapy (IT). 30-day mortality rate was 4.0% (n=5). Morbidity
occurred in 29 (23.4%) patients; six patients (4.8%) had major complications:
2 bronchopleural fistulae, 3 haemothoraces, and 1 chylothorax. 23 patients
(18.6%) had early minor complications: 14 (11.2%) atrial fibrillation, and 9 EPIDEMIOLOGIC STUDIES IN SURGERY FOR NSCLC –
(7.2%) pulmonary (5 prolonged air leaks, 2 atelectasis and 2 subcutaneous MONDAY, DECEMBER 5, 2016
emphysema). Overall 5-year survival rate and disease-free survival was
27.4% and 36.0%, respectively. 47 (37.9%) patients relapsed: 14 had brain
P1.08-026 LUNG CANCER - EARLY AND LATE OUTCOMES OF
metastases, 10 bone, 8 lung, and 15 at other sites. Patients <65 years (p=0.01),
with early pathological stage (p=0.0001), without nodal involvement SURGICAL PATIENTS OF A NEW DISTRICT HOSPITAL
(p=0.001) had the best prognosis. At multivariate analysis, age <65 years Paulo Calvinho 1, Jorge Santos1, Claudia Matos2, Margarida Felizardo2, Sofia
(p=0.009 [95% CI 2.53-8.29]), early pathological stage (p=0.04 [95% CI Furtado2
1
1.66-7.88]), and no nodal involvement (p=0.03 [95% CI 2.01-6.42]) influenced Cardiothoracic Surgery, Hospital de Santa Marta, Lisboa/Portugal, 2Pneumology,
survival. Conclusion: ASCs are uncommon and extremely aggressive tumours. Hospital Beatriz Angelo, Loures/Portugal
Young patients (<65 years) with early stage tumour and no nodal involvement
have the best prognosis. Background: To compare surgical patient outcomes of a new district hospital
with the expected results described in the literature. Methods: From
Keywords: lung tumor, Surgery March 2012 to December 2015, 288 lung cancer patients were treated in our
hospital, of which 58 were operated on. All patients were discussed at a
multidisciplinary team. The mean age at diagnosis was 64.6+9.2y yrs, being
69% males. At the time of diagnosis, 45 had history of smoking, 28 filled the
criteria of COPD, 2 had history of tuberculosis, 2 had type 2 diabetes, 37 had
history of cardiovascular disease, 8 had history of other cancer and 3 had

chronic renal disease. As for tumour types, the majority was adenocarcinoma
(34), followed by squamous cell (18), carcinoid tumour (3), SCLC (1),
adenosquamous (1) and poorly differentiated lung cancer (1). One patient had
2 synchronous tumours and two patients developed a new type of tumour
during follow-up. As for staging, the majority of patients were in clinical stage
IA (20) and the rest distributed as follows: IB - 13 pts, IIA - 4 pts, IIB - 4 pts,
IIIA - 10 pts, IIIB - 1 pt and IV - 6 pts. At the time of pathological staging 1 was
up-staged and 1 down-staged. In stage IV patients, 4 surgeries were performed
with paliative intent and 2 with curative intent. In 17.2% patients was given
neo-adjuvant chemotherapy, and 44.8% received adjvant chemotherapy.
We performed 64 surgeries (41 lobectomies with lymphadenectomy (11
VATS); 6 bilobectomies; 3 pneumectomies; 6 wedge resections; 1 exploratory
thoracotomy and 3 mediastinoscopies. Results: There was no perioperative
mortality. Eight patients had major complications (6 - post-operative
pneumonia). The mean follow-up time was 21+11 months with an overall
mortality of 15.5%. Stage related mortality: for stages IA and IB the overall
survival was 100% with mean follow-up time of 23 months, in stage IIA the
overall survival was 83.4% with mean follow-up time of 28 months, in stage
IIB the overall survival was 75% with mean follow-up time of 24 months, in
stage IIIA the overall survival was 70% with mean follow-up time of 20 months
and in stage IV the overall survival was 33.3% with mean follow-up time of 18
months. Conclusion: These outcomes overlap those reported in recent data
from the literature. Although our Hospital is a low/medium volume centre for
Lung Cancer we show with these data that with a dedicated multidisciplinary
team it is possible to replicate the international results.
Keywords: Surgery, outcomes, new hospital

EPIDEMIOLOGIC STUDIES IN SURGERY FOR NSCLC –
P1.08-027 EVOLUTION OF SURVIVAL IN A REGIONAL POPULATION-

BASED US LUNG CANCER RESECTION COHORT
Raymond Osarogiagbon1, Nicholas Faris1, Matthew Smeltzer2, Meredith
Ray2, Carrie Fehnel1, Cheryl Houston-Harris1, Paul Levy3, Chris Mutrie4, Brad
Wolf5, Lawrence Deese6, Lynn Wiggins7, Vishal Sachdev8, Sam Signore4,
Edward Robbins4
1
Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis/TN/
United States of America, 2Epidemiology and Biostatistics, University of Memphis
School of Public Health, Memphis/TN/United States of America, 3Cardiothoracic
Surgery, Nea Baptist, Jonesboro/AR/United States of America, 4 Cardiothoracic
Surgery, Baptist Memorial Hospital, Memphis/TN/United States of America,
5
Cardiothoracic Surgery, Baptist Memorial Hospital, Desoto/MS/United States of
America, 6Cardiothoracic Surgery, Baptist Memorial Hospital, Oxford/MS/United
States of America, 7Cardiothoracic Surgery, St. Bernard’s Regional Medical Center,
Jonesboro/AR/United States of America, 8North Mississippi Medical Center, Tupelo/
MS/United States of America
Background: Quality variances in surgical resection and pathology

examination practice translate into survival disparity in patients with early
stage lung cancer after curative-intent resection. We evaluated the survival
patients from two eras in a US regional cohort. Methods: All curative-intent
lung cancer resections in 11 US hospitals in 4 contiguous Dartmouth Hospital
Referral Regions were analyzed for stage-stratified survival before and after
an ongoing regional quality improvement campaign started in 2009. Overall
and stage-stratified survival of patients with surgery in the 2004-2009 Conclusion: Survival has improved since introduction of a regional quality
(pre-era) v 2010-2015 (post-era) were compared using the log-rank test and Cox improvement campaign in a high lung cancer mortality region of the US.
proportional hazards models. Results: Of the total cohort of 3246 patients,
Keywords: Lung cancer survival, non-small cell lung cancer, Surgical resection,
40.6% were in the earlier era, 59.4% in the later era. Demographic
quality improvement
characteristics were similar between cohorts (Table 1). Preoperative PET/CT,
brain MRI scans, bronchoscopy, and adjuvant therapy were more frequently
used in the later era. Patients in the early era had an unadjusted hazard ratio
(HR) of 1.22 (p=0.0006). After controlling for stage, tumor size, neoadjuvant
therapy, comorbidity score, grade, extent of surgery, patients in the pre-era POSTER SESSION 1 - P1.08: SURGERY
had a HR of 1.49 (p<0.0001). EPIDEMIOLOGIC STUDIES IN SURGERY FOR NSCLC –
P1.08-028 NATIONWIDE TRENDS IN SURGERY FOR LUNG CANCER

IN FINLAND FROM 2004 TO 2014
Jarmo Gunn1, Ville Kytö2
1
Cardiothoracic Surgery, Heart Center, Turku University Hospital, Turku/Finland,
2
Heart Center, Turku University Hospital, Turku/Finland
Background: Surgical treatment for lung cancer has developed in recent

decades and has enabled surgical treatment of patients with increasingly
severe comorbidities. The aim of this study is to describe nationwide trends
in lung surgery: incidence of surgical treatment, operative mortality, changes
in surgical approaches, long term survival and predictors thereof in Finland
between 2004 and 2014. Methods: Patients with any type of lung surgery and
pre- or postoperative diagnosis of C34.* were identified from the national
Care Register for Health Care which collects discharge data on all patients EXPERIENCE
discharged from inpatient care as well as outpatients treated in specialized Fatmir Caushi1, Danjela Xhemalaj2, Alban Hatibi2, Ilir Skenduli2, Irma Bani2,
care. Patients were verified as lung cancer patients by linking data with Hasan Hafizi3, Eljana Shima2, Rinaldo Kortoci2
diagnoses from the Finnish Cancer Registry. Mortality data were linked from 1
Statistics Finland. Results: During the study period 3912 patients underwent Surgery, University Hospital of Lung Diseases, Tirana/Albania, 3Pneumology,
lung surgery for cancer. Mean age was 66 years (SD 9.6), 62% were males. The University Hospital of Lung Disease “shefqet Ndroqi”, Tirana/Albania
number of operations increased over the years (p=0.02). Extent of surgery was
pneumonectomy in 10%, lobectomy in 79.8% and sublobar resection in 10.2%. Background: Lung cancer is one of the leading causes of mortality in the
Women underwent sublobar resection more often than men (8.2% vs 13.5%, world. The incidence of lung cancer in females is increasing, in contrast to
p<0.001). Overall 1 year survival was 85.5% and 5 -year survival was 51.4%. that seen in males. However, according to a lot of publications, lung cancer is
Age, stage of cancer, Charlson comorbidity index (CCI) and the proportion of almost six times more frequent in men than in women. The literature shows
lobectomy increased during the study period while survival remained stable. clearly that lung cancer in women differs from that in men in several aspects
Predictors of mortality on multivariable regression were age, male gender, and environmental factors and lifestyle plays an important role in the female
stage, CCI, pneumonectomy and adjuvant therapy. Conclusion: Despite a lung carcinogenesis. The objectives of this study were to evaluate clinic-
growing number of patients with increasing comorbidities treated surgically morphologic features of lung cancer in women and the role of the surgery
in a country with declining incidence of lung cancer and despite more in their treatment. Methods: This was a descriptive retrospective study,
advanced disease postoperative mortality for surgically resected lung cancer conducted for five years. We analyzed all patients hospitalized diagnosed
has remained stable. This suggests that modern surgical treatment could be and treated for lung cancer and using Pearson Chi-Square test. Results: The
offered more confidently to more patients with heavier disease burden. ratio men to women for patients diagnosed with lung cancer was 8 to1.The
most common histotype was Adenocarcinoma 76%, Squamous cell carcinoma
Keywords: Surgery, outcomes, lung cancer 11%, Small cell carcinoma 5%, others 8%.The average age was 57.5 with SD±12
years. 6% of females were in I stage, 22% of them were in II stage, 15% of them
were in IIIA stage, 10% of them in IIIB stage and 47% in IV stage. Only 9% of
our patients were smokers. Dyspnea was the main clinical sign, found in 67%
of women. The standardized incidence of female lung cancer patients was
EPIDEMIOLOGIC STUDIES IN SURGERY FOR NSCLC – 5/100.000. The surgery was performed in 20% of them meanwhile in men
MONDAY, DECEMBER 5, 2016 it was performed in 12.5% of cases. Conclusion: Most of women diagnosed
with lung cancer were in advanced stages. Adenocarcinoma is the common
histotype. This study shows that lung cancer in female is eight time less
P1.08-029 SURGICAL EXPERIENCE OF PRIMARY SALIVARY GLAND
frequent in women than in men. Since the ratio men to women regarding to
TUMORS OF LUNG: EXPERIENCE FROM TERTIARY CARE CANCER being operable is in the favor of women because they are diagnosed earlier
CENTER IN NORTH INDIA comparing to men, women are more subject of surgery. Because the clinical
Ashish Jakhetiya1, Pankaj Garg2, Surayanarayana Deo1, Nootan Shukla1, signs of lung cancer are far from being specific, a substantial portion of lung
Durgatosh Pandey1, Mukurdipi Ray1, Prabhat Malik1, Deepali Jain3, Sunil cancer cases and deaths could be prevented by applying effective prevention
Kumar 1 measures, such as tobacco control and the use of early detection tests.
1
Surgical Oncology, All India Institute of Medical Sciences, New Delhi/India,
2
Surgical Oncology, All India Institute of Medical Sciences and University College Keywords: female lung cancer, Surgery
of Medical Sciences, New Delhi/India, 3Pathology, All India Institute of Medical
Sciences, New Delhi/India
Background: Primary salivary gland type tumors of lung (PSGTTL) are rare intra-
thoracic malignant neoplasm. Their description in literature is largely limited to POSTER SESSION 1 - P1.08: SURGERY
EPIDEMIOLOGIC STUDIES IN SURGERY FOR NSCLC –
a few case series/case reports. We herewith present our surgical experience and MONDAY, DECEMBER 5, 2016
review its clinical presentation, management options and survival outcomes.
Methods: We performed a retrospective analysis of prospectively maintained
computerized data-base of lung cancer patients at department of surgical P1.08-031 NON-SMALL CELL LUNG CANCER IN PATIENTS AGED
oncology, Dr BRA-IRCH, AIIMS, Delhi. A total of nine patients underwent 40 YEARS OR YOUNGER: CLINICAL, SURGICAL, AND LONG-TERM
treatment for PSGTTL during the period from January 2012 to December 2015. OUTCOMES
Details concerning the clinical presentation, preoperative therapy, operative
procedure, histopathological examination, postoperative complications and
Lorenzo Spaggiari
outcome were retrieved and analysed. Results: Median age of patients was
Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy
42 years (range 24-52 years) with male: female ratio of 7:2. Median duration
of symptoms before presentation was 12 months (range 4-24 months). Most Background: Non-small cell lung cancer (NSCLC) in young patients is
common symptoms were Hemoptysis (77%) and dyspnoea (66%). Fiber-optic uncommon and has clinical characteristics different from that in older
bronchoscopy revealed endobronchial growth in all patients with six patients patients. We report the outcomes of a single institutional experience in the
had growth in left main bronchus while one had growth in right main bronchus treatment of young patients with NSCLC. Methods: Records of patients with
and two in right intermediate bronchus. Biopsy confirmed adenoid cystic NSCLC operated on between 1998 and 2013 were retrospectively analyzed
carcinoma in 6 (66%) and muco-epidermoid carcinoma in 3 (33%) patients. from a prospective database.We identify two groups: G1 with patients
Total seven patients underwent R‘0’ resection with pneumonectomy in five, resected with intention-to-treat, and G2 who underwent only diagnostic
bilobectomy in one, lower lobectomy in one patient. One patient developed surgical procedures due to advanced NSCLC. There were 47 patients (27 in
pneumonia after left carinal pneumonectomy and succumbed to it. No major G1, 13 men; and 20 in G2, 10 men) with a median age of 37 years in G1 (range,
postoperative complication was encountered in remaining six patients. One 16-40) and 38 years in G2 (range, 24-40).Survival was calculated by using
patient refused surgery and one found unresectable in view of dense adhesions Kaplan-Meier method. Results: Induction treatment (IT) was administered in
between lung and heart. Both patient received chemo-radiation and underwent 17 patients in G1; no patient in G2 received IT. In G1, surgery included 3 wedges,
bronchoscopic debulking and are in follow up. Median pathological tumor size 1 segmentectomy, 18 lobectomies, 5 pneumonectomies; in G2, surgery
was 3 cm. Median number of node harvested was 10 (range 4-18) however none included 3 explorative thoracotomies, 8 nodal biopsies, and 6 pleural biopsies.
showed metastasis. None of the operated patient developed relapse and overall Histological diagnosis was adenocarcinoma in all the patients. Median tumor
eight patients are alive after a median follow up of 18 months. Conclusion: size was 22 mm (range, 5-125) in G1. Postoperative staging in G1 included 11
Primary salivary gland type tumors of lung (PSGTTL) are low grade malignancy stage I, 4 stage II, and 12 stage III; all patients in G2 were stage IV and none was
and greater awareness of these tumors is necessary to avoid misdiagnosis and alive at 5-year. Five-year overall survival and disease-free survival in G1 were
delay in treatment. Aggressive anatomical lung resection with preservation of 55% and 51%, respectively (median, 30 and 16 months, respectively). In G1
functional lung parenchyma offers optimal outcome in such patients. recurrence occurred in 12 patients most of them at extra-thoracic sites (9/12
[75%]). Factors associated with increased survival in G1 included IT (p=.0002)
Keywords: adenoid cystic carcinoma, mucoepidermoid carcinoma, Primary
and right side disease (p=.01). At multivariate analysis in G1, IT [p=.03 (95% CI:
salivary gland type tumors of lung
0.67-0.89)] influenced long-term survival. Conclusion: In our experience, all
young patients had adenocarcinoma with a predominance of women. Patients
receiving pulmonary resection for curative intent had the best prognosis and
among these, those receiving IT had the best long-term survival.
EPIDEMIOLOGIC STUDIES IN SURGERY FOR NSCLC – Keywords: young, lung tumor
P1.08-030 FEMALE LUNG CANCER AND OUR FIVE YEAR

POSTER SESSION 1 - P1.08: SURGERY Clinicopathological factors were reviewed for time to recurrence (TTR), and
recurrence patterns were compared according to oncogenic status and
Translational Studies –
examined according to EGFR mutational subtype. Results: Among 401 patients,
MONDAY, DECEMBER 5, 2016 185 with EGFR mutation, 46 with KRAS mutation, 15 with ALK rearrangement,
and 155 with triple negative mutation (TN) were identified. Multivariate
analysis following univariate analyses showed that younger age, well–
P1.08-032 IMPACT OF THE ONCOGENIC STATUS ON THE MODE OF moderately differentiated histology, earlier pathologic stage, and presence of
RECURRENCE IN RESECTED NON-SMALL CELL LUNG CANCER EGFR or ALK mutation were favorable prognostic factors for TTR. Locoregional
Tetsuya Mizuno 1, Yasushi Yatabe2, Shozo Sakata1, Katsutoshi Seto1, Hitoshi recurrence was observed in 53.3% of ALK-positive patients, being significantly
Dejima1, Hiroaki Kuroda1, Noriaki Sakakura1, Yukinori Sakao1 common in these patients than in EGFR- and KRAS-positive patients.
1
Division of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya/Japan, EGFR-positive patients mostly experienced pleural recurrence, the incidence of
2
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya/ which was significantly higher in TN patients. Adrenal recurrence was observed
Japan in 7.2% of TN patients, but it was rarely identified in EGFR-positive patients.
(Figure) Among EGFR-positive patients, the incidence of brain metastases was
Background: Surgical resection is employed in patients with resectable significantly higher in L858R cohort than in Del Ex19 cohort.
non-small cell lung cancer (NSCLC). Despite complete resection, recurrence is
sometimes observed. Oncogenic mutations promote initiation and progression Conclusion: In resected NSCLC, younger age, well–moderately differentiated
of lung cancer, and mutation status predicts treatment outcome of advanced histology, earlier pathologic stage, and presence of EGFR or ALK mutation
NSCLC; however, their impact on the recurrence patterns remain poorly were favorable factors for TTR, and distinct recurrence patterns were revealed
understood. Methods: We retrospectively studied 401 patients showing according to oncogenic mutation status and mutational EGFR subtype. Our
recurrence after complete resection of NSCLC. results may provide suggestions for developing a strategy for follow-up and
adjuvant therapies after resection.
Keywords: recurrence, oncogenic status
POSTER SESSION 1 - P1.08: SURGERY of p-I-II and IIIA mutant/wild were 96.8%/92.1% and 81.6%/61.8% respectively.
TRANSLATIONAL STUDIES –
The median survival time of p-stageIIIA mutant was 80.5 months, and those
of others were not reached. The 3-year DFS of p-I-II and IIIA mutant/wild
were 78.3%/69.2% and 27.1%/45.1%, respectively. There were no significant
P1.08-033 EFFECT OF EGFR MUTATIONS ON SURVIVAL IN PATIENTS difference in OS and DFS at each p-stage despite the EGFR mutational
FOLLOWING SURGICAL RESECTION OF LUNG ADENOCARCINOMA status. Compared to the wild type, the p-IIIA mutant group had a poor DFS.
Grace Laidlaw 1, Rebecca Gao1, Kelsey Ayers2, Leah Backhus2, Mark Berry2, conversely, compared to wild type, the p-I mutant group showed a favorable
Joseph Shrager2 DFS. According to the subtypes of EGFR mutation, there were no significant
1 differences among EGFR subtypes, but pts with 19del tended to have the
Stanford University School of Medicine, Stanford/CA/United States of America,
2
Cardiothoracic Surgery, Stanford University School of Medicine, Stanford/United worst DFS. In subgroup analysis of 131 pts with recurrence, 3-year survival
States of America rate of p-I-II and IIIA mutant/wild were 92.0%/75.8% and 80.8%/45.6%
respectively. Pts with p-IIIA mutant showed significantly favorable OS than
Background: While numerous trials have evaluated the effects of EGFR those of wild type (p=0.014) as well as with p-I-II wild type. Although OS was
mutations on survival in patients undergoing treatment with tyrosine kinase not significantly different among the subtypes of EGFR mutation, pts with
inhibitors (TKIs), research on the influence of EGFR mutations in patients 19del showed statistically better prognosis than shown by the wild type
undergoing surgical resection as their primary intervention is limited and (p=0.038). Conclusion: EGFR status was an independent prognostic factor in
conflicting. We hypothesized that patients with resectable EGFR-mutant pts with surgically resected lung adenocarcinoma. Particularly, EGFR exon 19
tumors have a better postoperative prognosis than those with wild-type (WT) deletion might be the strongest predictive factor of poor DFS and good OS in
tumors, as EGFR-mutant tumors often include an in-situ component that resected lung adenocarcinoma.
portends an improved prognosis. We further hypothesized that the two most
common EGFR mutations may impact post-resection prognosis differentially. Keywords: lung adenocarcinoma, Epidermal growth factor receptor, exon 19
Methods: We carried out a single-center, retrospective study evaluating the deletion
influence of EGFR mutation status on progression-free (PFS) and overall
survival (OS) after resection, adjusting for tumor stage and ethnicity.
Kaplan-Meier plots and Cox proportional hazard models were used to
generate crude and adjusted hazard ratios. Results: 249 patients underwent
lung adenocarcinoma resection and had mutational analysis and ≥1 year of TRANSLATIONAL STUDIES –
follow-up at our institution between 2008-2015. These resections included MONDAY, DECEMBER 5, 2016
200 lobectomies, 12 segmentectomies, and 32 wedge resections. Ninety-
three (37.3%) patients had EGFR-mutant tumors. Relative to WT tumors,
P1.08-035 ANALYSIS OF POST-OPERATIVE RECURRENCE IN A
EGFR-mutant tumors were more likely to exhibit well-differentiated (44.0% vs
29.0%, p=0.009) or lepidic (61.3% vs 36.5%, p <0.0001) histology, and trended POPULATION WITH NSCLC HARBORING AN EGFR MUTATION: A
towards presenting as pathologic stage IA/IB (p=0.082). EGFR mutation SINGLE INSTITUTIONAL RETROSPECTIVE STUDY
improved crude OS (HR 0.39, 95% CI 0.159-0.931, p=0.034), but this difference Hayashi Kosuke 1, Ito Kentaro1, Watanabe Fumiaki1, Yada Isao1, Motoshi
became nonsignificant when adjusted for tumor stage and ethnicity (OS HR Takao2, Shimpo Hideto2, Suzuki Yuta1, Saiki Haruko1, Sakaguchi Tadashi1,
0.549, 95% CI 0.200-1.508, p=0.245). PFS did not differ between mutant and Nishii Yoichi1, Hataji Osamu1
WT cohorts (adjusted HR 0.94, 95% CI 0.550-1.603, p=0.817). In comparing 1
Respiratory Center, Matusaka Municipal Hospital, Matusaka/Japan, 2Department
L858R and Exon 19, neither PFS (adjusted HR 0.91, 95% CI 0.350-2.379, of Thoracic & Cardiovascular Surgery, Mie University Graduate School of Medicine,
p=0.851) nor OS (HR 0.88, HR 0.160-4.790, p=0.879) significantly differed. Tsu/Japan
Lastly, sublobar resection did not interact with EGFR mutation presence to
affect PFS (interaction p-value=0.735) or OS (interaction p-value=0.771). Background: The post-operative recurrence in the patients resected EGFR
Conclusion: Patients with EGFR-mutant adenocarcinomas exhibit improved mutated NSCLC was higher than wild-type, as previous reported. However,
crude post-resection OS vs. those with WT tumors, but this difference whether EGFR mutational status is prognostic factor or not had not been
disappears after adjustment for tumor stage and ethnicity. These findings yet proven, and we assessed the background of the patients with surgically
appear attributable to EGFR-mutant tumors presenting at earlier stages. We resected NSCLC harboring EGFR mutation and the post-operative clinical
hypothesize that this occurs because lepidic tumors spend a longer phase in course. Methods: We reviewed all patients with EGFR mutated NSCLC who
stage I before developing a more aggressive phenotype. Our finding that EGFR received surgical therapy for lung cancer between March 2007 and April 2016
mutation status does not interact with resection extent (sublobar vs. ≥ lobar) at Matsusaka Municipal Hospital in order to assess post-operative recurrence
suggests that mutation status should not affect surgical planning prior to and overall survival retrospectively. Survival curves of time to post-operative
resection. recurrence and overall survival were calculated using the Kaplan-Meier
method and were compared using the log-rank test. Subgroup analyses were
Keywords: EGFR, lung adenocarcinoma, sublobar resection conducted to evaluate predictive factors for post-operative recurrence.
Results: A total of 116 patients were enrolled. The median age was 72.5,
ranging from 37-88 years of age. Of the total, 83 patients (71.6%) were female,
and 90 patients had never smoked. All patients except one with squamous
cell carcinoma were diagnosed pathologically with adenocarcinoma. Of
POSTER SESSION 1 - P1.08: SURGERY the patients 41.9% were diagnosed with Ex19 deletion and 50.0% were
TRANSLATIONAL STUDIES –
MONDAY, DECEMBER 5, 2016 diagnosed with Ex21 L858R. Median time to post-operative recurrence was
70.5 months for the entire population. Multivariate analysis revealed that
age (p=0.008), subtype of EGFR mutation (p=0.034), and pathological stage
P1.08-034 PROGNOSTIC IMPACT OF EGFR MUTATION IN PATIENTS (p=0.00033) were predictive factors for post-operative recurrence. Subgroup
WITH SURGICALLY RESECTED LUNG ADENOCARCINOMA; ANALYSIS analysis revealed there was a significant difference in time to post-operative
ABOUT SUBTYPES OF EGFR MUTATIONS recurrence between patients over 75 y.o and those under 74 y.o even in the
Yohei Kawaguchi, Tetsuya Okano, Ken Taro Imai, Sachio Maehara, Junichi population who received a lobectomy. (p=0.031) Conclusion: Elderly patients,
Maeda, Koichi Yoshida, Masaru Hagiwara, Masatoshi Kakihana, Naohiro and those with the Ex21 L858R point mutation, had a tendency to relapse
Kajiwara, Tatsuo Ohira, Norihiko Ikeda after surgical therapy among the EGFR mutated NSCLC population. The rate
of post-operative recurrence in EGFR mutated patients tended to be higher
General Thoracic Surgery, Tokyo Medical University Hospital, Tokyo/Japan
compared to historical data. Because of differences with retrospective data
Background: Epidermal growth factor receptor (EGFR) gene mutations have and the small sample size, further investigations are warranted to confirm
an important role for predicting the prognosis in advanced or recurrent lung these results.
cancer patients. However, the significance of EGFR mutation as a prognostic
Keywords: NSCLC, EGFR mutation, Post-Operative Recurrence
factor for survival after complete resection remains controversial. The aim
of this study is to evaluate the impact of mutational status in patients with
surgically resected lung adenocarcinoma. Methods: We retrospectively
investigated the data of 414 patients (pts) with p-stage I-IIIA adenocarcinoma
who underwent completely tumor resection in our hospital from 2009 to 2013.
Overall survival (OS), disease-free survival (DFS), and clinico-pathological POSTER SESSION 1 - P1.08: SURGERY
factors affecting these factors were evaluated. Results: There were 202 males Minimal Invasive Surgery –
and 212 females (median age, 67 years). In total, 270 (65%), 66 (16%) and 78 MONDAY, DECEMBER 5, 2016
pts (19%) had p-stageI, II and IIIA disease respectively. In all 210 pts (51%) with
EGFR mutation were detected. Eighty-six pts (21%) had exon 19 deletion (19
del) and 113 pts (27%), exon 21 mutation (L858R). Among 414 pts, 131 pts (31%)
P1.08-036 THORACOTOMY AND VATS-SURGERY IN LOCAL NON-
had lung cancer recurrence. The median follow-up period was 38.6 months.
SMALL CELL LUNG CANCER: DIFFERENCES IN LONG-TERM HEALTH
p-stageI mutant/wild:145/125, II:24/42, and IIIA:41/37. The 3-year survival rates

RELATED QUALITY OF LIFE thoracoscopic guidance. Results: The marking procedure took 11 to 49 minutes
Ville Rauma1, Saana Andersson1, Jari Räsänen1, Harri Sintonen2, Jarmo Salo1, from insertion to removal of the bronchoscope. There were no complications
Ilkka Ilonen1 from the marking, and all 16 nodules were easily localized by means of
1 thoracoscopy. The metallic coil showed the nodules on the fluoroscopic
Department of General Thoracic Surgery, Heart and Lung Center, Helsinki
University Central Hospital, Helsinki/Finland, 2Department of Public Health monitor, which aided in nodule manipulation. Nodules were completely
Science, University of Helsinki, Helsingin Yliopisto/Finland resected under thoracoscopic guidance in segmentectomy. The pathologic
diagnosis was primary adenocarcinoma in 10 nodules, pulmonary metastases
Background: Older and more fragile NSCLC patients are operated on through in 3 nodules, an atypical adenomatous hyperplasia in 1 nodule, a hamartoma
video-assisted thoracic surgery (VATS), compared to thoracotomy. In this in 1 nodule and a nontuberculous mycobacteriosis in 1 nodule. One case of an
study we compare the long-term health related quality of life (HRQoL) adenocarcinoma in situ with an extensive two segments was performed a
among early stage and locally advanced NSCLC patients between these two curative segmentectomy. Conclusion: In this study, CT-guided transbronchial
operative methods. Methods: 687 NSCLC patients underwent lobectomy or metallic coil marking with an ultrathin bronchoscope with a coin on a patient’s
segmentectomy in our clinic between January 2000 and January 2013, of these chest wall under bi-plain fluoroscopy after CT-assisted stimulation was found
430 were operated before July 2009 and 257 after this. HRQoL questionnaire to be feasible and safe. In our previous report, CT had been needed at least
15D was sent to patients alive in June 2011 and February 2016 (min. 2 years three times, but this method needed only twice CT scan. It might be a useful
from operation). After the exclusion of patients with clinically extensive method not only for making a diagnosis but also for therapeutic resection in
disease (T4, N2 or M1), lacking data (n=5) or receiving neoadjuvant therapy, selected early lung cancers.
345 (191+154) patients were included in the study. Results: 289 (84%) patients
answered, 155 from the first and 134 from the second period. Respectively, 42 Keywords: VATS, coil marking, CT assisted bronchoscopy, segmentectomy
and 68 respondents had had VATS. The two groups differed in the following
features: thoracotomy group had on average more advanced clinical and
pathological stage (26% vs 7% and 28% vs 16% stage II & III, respectively),
younger age at operation (63.5 vs 66.8 years), and higher frequency of
adjuvant therapy (18% vs 5%) (p<0.05 in each). The VATS group scored MINIMAL INVASIVE SURGERY –
statistically (p<0.05) and clinically significantly lower on the dimensions MONDAY, DECEMBER 5, 2016
Breathing (0.63 vs 0.70), Excretion (0.78 vs 0.85), Usual activities (0.75 vs 0.81),
Mental function (0.83 vs 0.89), Depression (0.82 vs 0.88), Distress (0.82 vs
P1.08-038 VATS SUB-LOBAR ANATOMICAL PULMONARY
0.88), Vitality (0.76 vs 0.82), Sexual activity (0.72 vs 0.80) and on the 15D score
representing overall HRQoL (0.81 vs 0.85) (Figure). RESECTIONS: INDICATIONS AND OUTCOMES IN THORACIC
ONCOLOGICAL PRACTICE
Bibhusal Thapa1, Kalhara Perera2, Renee Manser3, Simon Knight4, Thomas
John5, Stephen Barnett6
1
Olivia Newton John Cancer Research Institute, Melbourne/VIC/Australia,
2
Depatrtment of Thoracic Surgery, Austin Health, Melbourne/ACT/Australia,
3
Department of Respiratory Medicine, Royal Melbourne Hospital, Melbourne/
VIC/Australia, 4Department of Thoracic Surgery, Austin Health, Melbourne/ACT/
Australia, 5Olivia Newton-John Cancer Centre, Austin Health, Melbourne/VIC/
Australia, 6 Austin Hospital; Peter MacCallum Cancer Institute, Melbourne/VIC/
Australia
Background: In patients with limited pulmonary reserve, sub-lobar anatomic

pulmonary resection (SLAPR) may have reduced perioperative morbidity and
mortality and additionally may better preserve long-term pulmonary function
compared to lobectomy. SLAPR may also mitigate the oncological deficiencies
of wedge resection. However, the safety and oncological efficacy of video
assisted thoracoscopic surgical (VATS) SLAPR has not been well described.
We therefore audited our recent experience of VATS SLAPR to evaluate:
Conclusion: Even with less invasive surgical techniques, the older and more indications, safety, and oncological outcomes. Methods: We retrospectively
comorbid patients seem to have lower long-term HRQoL. This is contrary to reviewed a prospectively maintained database to identify all consecutive
previous results of short-term reports. patients who underwent planned VATS SLAPR with curative intent.
Demographics, co-morbidities, indications and treatment outcomes were
Keywords: NSCLC, HRQoL, Surgery, Long-term retrieved, with supplemental chart review where necessary. Results: Seventy
seven VATS SLAPRs were performed between December 2010 and May 2016.
Median age of patients was 67 (44-83) years and 57% (44/77) were male. The
majority (47/77; 61%) of SLAPRs were undertaken for resection of NSCLC.
Indications for SLAPR in NSCLC patients included: inadequate pulmonary
POSTER SESSION 1 - P1.08: SURGERY reserve (DLCO <60% or predicted post-operative DLCO <40%) in 21/47 (44%),
MINIMAL INVASIVE SURGERY –
MONDAY, DECEMBER 5, 2016 excessive (≥2 major) comorbidities in 18/47 (38%), advanced age (≥75 years)
in 13/47 (27%) or a combination of these factors precluding lobectomy. In
patients with metastatic 22(28%) and benign 8(10%) nodules, indications
P1.08-037 THORACOSCOPIC SEGMENTECTOMY OF PULMONARY included proximity to vascular structures or inability to palpate lesion
NODULES AFTER COMPUTED TOMOGRAPHY–ASSISTED precluding simple wedge resections. Superior segmentectomy (22/77; 28%)
BRONCHOSCOPIC METALLIC COIL MARKING (2ND VERSION) and lingula sparing left upper lobectomy (17/77; 22%) were the commonest
Takanori Miyoshi, Hiroyuki Sumitomo, Koh Uyama, Naoki Hino SLAPRs performed. Seventy one (92%) were completed via VATS. Emergency
Department of Thoracic Surgery, Tokushima Municipal Hospital, Tokushima City/
conversion occurred in one case. Morbidity rate was 30% (23/77) and 30
Japan day mortality rate was 2.5% (2/77). Pre-operative DLCO was not associated
with post-operative pulmonary complication (P=0.7) or length of hospital
Background: With advances in computed tomography (CT), small pulmonary stay (P=0.20). In the NSCLC sub group, all patients were clinically stage I; R0
lesions previously unseen on chest radiographs are being increasingly resection was achieved in 100%. Median of 12(4-27) nodes were excised with
detected. Among lesions less than 10 mm in size, a considerable number a nodal upstaging rate of 25% (12/47) and pathological stage was I in 65%.
of malignancies have been reported. To localize small and deeply situated Median disease free survival (DFS) was 40 months and median overall survival
pulmonary nodules during thoracoscopy with roentgenographic fluoroscopy, (OS) was not reached. Loco regional recurrence rate was zero. Pre-operative
we developed a marking procedure that uses a metallic coil and a coin for DLCO dichotomised using median did not correlate with OS (P=0.8) or DFS
thoracoscopic segmentectomy. Methods: Fifteen patients underwent (P=0.29). Conclusion: A variety of VATS SLAPRs may be performed safely
video-assisted thoracoscopic surgery for removal of 16 pulmonary lesions with acceptable morbidity and mortality in high risk patients. Complete
between January 2011 and January 2016. There were 6 males and 9 females, microscopic resection and adequate nodal dissection can be achieved.
with an average age of 68.3 years (range 54 to 78 years). Fluoroscopy-assisted Although larger studies and longer follow is needed, our findings suggest that
thoracoscopic surgery after CT-assisted bronchoscopic metallic coil marking VATS SLAPR achieves comparable oncological outcomes in high risk patients
was performed using an ultrathin bronchoscope under bi-plain fluoroscopy to formal lobectomy.
viewing a coin on a patient’s chest wall. The coin was simulated a pulmonary
lesion by the CT findings, and it was put on the patient’s chest wall. During Keywords: Sub-lobar anatomic pulmonary resection, Video-assisted
thoracoscopy, a C-arm-shaped roentgenographic fluoroscope was used to thoracoscopic surgery
detect the radiopaque nodules. The nodule with coil markings was grasped
with forceps and resected in segmentectomy under fluoroscopic and

P1.08-039 SYSTEMATIC REVIEW AND UPDATED META-ANALYSIS

OF UNIPORTAL VERSUS MULTIPORTAL VIDEO-ASSISTED
THORACOSCOPIC SURGERY FOR LUNG CANCER
Mariusz Kowalewski1, Maciej Dancewicz2, Mariusz Bella2, Tomasz Szczęsny2,
Przemysław Bławat2, Marzena Lewandowska2, Aleksandra Chrzastek 3, Janusz
Kowalewski3
1
Department of Hygiene, Epidemiology and Ergonomics, Division of Ergonomics
and Physical Effort, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus
University in Torun, Bydgoszcz/Poland, 2Department of Thoracic Surgery and
Tumors, Franciszek Lukaszczyk Memorial Oncological Center in Bydgoszcz,
Bydgoszcz/Poland, 3Department of Thoracic Surgery and Tumors, Collegium
Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz/Poland
Background: Uniportal video-assisted thoracoscopic surgery (VATS) is a

challenging surgical procedure that poses substantial technical difficulties
compared to multiportal VATS but has been associated with favorable
outcomes in studies reported to date. Methods: On-line databases were
screened until June 2016. Meta-analysis aimed to compare clinical outcomes of
uniportal and multiportal VATS lobectomy for patients with lung cancer.
Endpoints assessed included perioperative mortality, operative time and
blood loss; length of hospital stay; duration of postoperative drainage; rates
of conversion to open thoracotomy; number of harvested lymph nodes and
overall morbidity. Risk Ratios (RR)/Mean Difference (MD) and corresponding
95% Confidence Intervals (95%CIs) served as primary statistics. Results:
Twelve studies were included (among them 1 randomized trial) that enrolled
N=2,476 patients. There was no difference in the 30-day mortality: (N=2,476);
RR (95%CIs) 0.32 (0.03-3.01); p=0.32; Event rates: 0.10% (1/1,021) vs 0.07%
(1/1,455); no difference were demonstrated for conversion-to-thoracotomy:
0.91 (0.48-1.73); p=0.77; similarly there were no differences in regard to
operative times: MD (95%CIs): 3.50 ([-12.35]-19.34) min; p=0.67 and blood loss:
-2.15 ([-17.13]-12.83) ml; p=0.78. There was no statistically significant difference
between number of harvested lymph nodes: 18.4±6.6 vs 19.4±8.5; MD
(95%CIs): -0.34 ([-1.39]-0.70) node; p=0.52. Uniportal VATS was associated
with significantly shorter duration of chest tube drainage: -0.61 ([-0.99]-[-
0.23]) days; p=0.002 (Figure 1A); and length of hospital stay: -0.58 ([-0.77]-[-
0.40]) days; p<0.001 (Figure 1B). Overall morbidity was significantly reduced
with uniportal VATS as well: RR (95%CIs) 0.77 (0.63-0.95); p=0.01.
Figure 1. Individual and summary point estimates. Uniportal vs multiportal

VATS. Length of hospital stay (A) and duration of chest tube drainage (B).
Conclusion: Uniportal VATS is at least as safe and effective as multiportal
VATS for patients with lung cancer. Whether clear postoperative benefits
with uniportal VATS further translate into reduction of clinical endpoints and
potentially improved survival remains to be confirmed in adequately powered
randomized trial.
Keywords: VATs lobectomy, uniportal VATS, meta-analysis, VATS

segmentectomy

POSTER SESSION 1 - P1.08: SURGERY either with open or VATS resection. Methods: A total of 359 patients with
early stage (cN0) lung cancer with available survival data in our institutional
database were treated between 2004 and 2015. VATS was introduced in 2009,
since that time all clinically nodal negative patients were treated with an
P1.08-040 LYMPH NODE SAMPLING IN 3-PORT VIDEO ASSISTED intended VATS approach. Results: There were 198 male patients; median age
THORACOSCOPIC SURGERY (VATS) VS UNIPORTAL VATS was 65 (range 38-85) years. 256 (71.3%) patients were treated with a
Cheng Yi1, Sanjeet Avtaar Singh2, Peter Lang2, Amy Gardiner2, Alan Kirk1, minimally invasive approach. There were significantly more female patients
Michael Klimatsidas2 (p=0.002) and lower pT-stages (p=0.002) in the VATS group. Nodal upstaging
1 was found in 19.1% in the VATS group and 23.3% in the open group (p=0.486).
Thoracic Surgery, Golden Jubilee National Hospital, Clydebank/United Kingdom,
2
Golden Jubilee National Hospital, Clydebank/United Kingdom 5-year disease free survival was 61.2% in the VATS group and 63.8% in the
open group (p=0.492). 5-year overall survival was 84.3% in the VATS group and
Background: VATS is fast overtaking thoracotomy as the approach to 73.3% in the open group (p=0.139), Figure 1. In a multivariate analysis including
lobectomies due to faster recovery times. Uniportal VATS lobectomies are age, gender, pT-status, pN-status and surgical approach, none of the factors
slowly becoming more popular throughout the world but the advantages of proofed to independently predict disease free survival. In overall survival, a
Uniportal VATS over the standard 3-port approach is unclear. The lung positive pN status was found to be the only independent negative prognostic
resection can often be performed via a Uniportal approach although factor (HR: 2.2, 95% CI: 1.2-4.1).
concurrent lymphadenectomy/lymph node sampling, may be more
challenging. We explored the adequacy of lymph node sampling at our unit as
per the ESTS 2006 guidelines on intraoperative lymph node staging. Methods:
All Primary Lung cancers (Non-small cell lung cancers) performed by 4 VATS
surgeons from May 2015-July 2016 were included in the study. A single surgeon
performed all the Uniportal VATS lobectomies. The standard 3-port approach
was employed by 4 VATS surgeons. Patient demographic details and length of
stay were obtained from our Cardiothoracic Database (CaTHi) alongside
pathological findings. Results:
Conclusion: Overall and disease free survival are not influenced by the type of
surgical approach. Due to perioperative benefits with shorter length of
hospital stay and less complications, a minimally invasive approach as the
gold standard of surgical treatment for clinically nodal negative lung cancer
patients should be advocated.
Keywords: VATS, early lung cancer, overall survival

The patients in the standard cohort had a higher ThoracoScore indicating P1.08-042 OVERALL SURVIVAL AND TUMOR RECURRENCE AFTER
increased risk of surgery. There was no statistically significant demographic VATS LOBECTOMY OF N1 POSITIVE NSCLC IS EQUAL TO OPEN
difference between the two groups. The rate of lymph node dissection was RESECTION
similar in both groups. Conclusion: Despite the perceived limited access, Herbert Maier 1, Caecilia Ng1, Florian Kocher2, Magdalena Sacher 1, Gregor
uniportal VATS has shown to be as good as standard 3 port VATS for lymph Laimer 1, Paolo Lucciarini1, Thomas Schmid1, Florian Augustin1
node sampling intraoperatively. 1
Department of Visceral, Transplant and Thoracic Surgery, Medical University
Innsbruck, Innsbruck/Austria, 2Department of Hematology and Oncology, Medical
Keywords: lobectomy, uniportal, VATS University Innsbruck, Innsbruck/Austria
Background: Video-assisted thoracoscopic surgery (VATS) is an accepted

alternative to open resection for early stage non-small cell lung cancer.
This study was performed to analyze survival after primary VATS anatomic
resection for nodal positive NSCLC compared to an open approach. Methods:
MONDAY, DECEMBER 5, 2016 The prospective institutional VATS database was searched for pN1 patients
after primary surgery for NSCLC (62/504 patients between February 2009
and December 2015). Exclusion criteria were neoadjuvant treatment and
P1.08-041 DISEASE FREE AND OVERALL SURVIVAL IS EQUAL conversion to thoracotomy. Demographics and survival were compared to a
IN OPEN AND VATS RESECTION FOR EARLY LUNG CANCER IN A historic group of N1 positive patients, who underwent primary open surgery
MULTIVARIATE ANALYSIS via a standard posterolateral thoracotomy for lung cancer between 2002
Caecilia Ng 1, Florian Kocher2, Herbert Maier 1, Magdalena Sacher 1, Gregor and 2007 (57 patients). Results: Age (65 vs 61.5 years), gender and stage
Laimer 1, Michael Fiegl2, Paolo Lucciarini1, Thomas Schmid1, Florian Augustin1 distribution (UICC IIA vs >IIA) did not differ between the VATS and open group.
1
Department of Visceral, Transplant and Thoracic Surgery, Medical University Half of the patients in the VATS group had clinical stage N0 (31/62) confirmed
Innsbruck, Innsbruck/Austria, 2Department of Hematology and Oncology, Medical by PET-CT. More people received adjuvant therapy after VATS lobectomy
University Innsbruck, Innsbruck/Austria (50/62 vs 31/57, p=0.003). Median follow up was 22 months in the VATS group
and 47 months in the open group (p<0.0001). Disease recurrence occurred in
Background: Video-assisted thoracic surgery (VATS) has become a valid 16/62 and 22/57 patients after a median of 13 and 12 months, respectively,
alternative to open resection for lung cancer treatment. However, robust data (p=0.1692). Overall survival did not differ between the two groups (Figure 1,
on the oncologic equality are still missing. This study evaluates disease free log rank, p=0.4006). No survival difference was found between unforeseen
and overall survival for patients with early stage (cN0) lung cancer treated and clinically evident nodal positive patients in the VATS group (p=0.9686).
Maria Echavarria1, Anna Cheng1, Frank Velez1, Emily Ng1, Carla Moodie2, Joseph
Garrett2, Jacques-Pierre Fontaine2, Eric Toloza2
1
University of South Florida, Tampa/FL/United States of America, 2Thoracic
Oncology, Moffitt Cancer Center, Tampa/United States of America
Background: Lobectomy is the standard procedure for early stage lung cancer.
The role of sub-lobar resection is currently under investigation. Published
comparisons between VATS, R-VATS, and open lobectomy vs. segmentectomy
have been reported. The goal of our study was to compare peri-operative
outcomes after R-VATS lobectomy vs segmentectomy. Comparison between
these two procedures using robotic instruments has not been published.
Methods: We retrospectively analyzed prospectively collected data from 253
consecutive patients who underwent lobectomy(N=208) and
segmentectomy(N=45) via R-VATS performed by one surgeon. Unpaired
Student’s t-test and Chi-square test were used to determine statistical
significance(p≤ 0.05) of intra- and post-operative outcomes between these 2
groups. Results:
Conclusion: VATS lobectomy in nodal positive lung cancer patients is
oncologically equal to open resection with similar survival and recurrence
rates. Half of the lymph node metastases have been missed by clinical staging.
Interestingly, the higher rate of patients receiving adjuvant chemotherapy
after VATS lobectomy did not result in significant better survival.
Keywords: nodal positive, VATS, thoracotomy

P1.08-043 PERIOPERATIVE AND MID-TERM OUTCOMES AFTER

SINGLE PORT VERSUS MULTI-PORTS THORACOSCOPIC LOBECTOMY
FOR LUNG CANCER: A PROPENSITY MATCHING STUDY
Bong Soo Son, Do Hyung Kim
Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital,
Mulgeum-Eup, Yangsan-Si/Korea, Republic of
Background: Recently, single incision thoracoscopic lobectomy for non-

small cell lung cancer has been performed at several centers worldwide. But
compared with conventional multi-ports thoracoscopic lobectomy, Reports
for perioperative and oncologic outcomes after single incision thoracosopic
lobectomy are limited. This study aimed to compare single incision
thoracoscopic lobectomy against conventional multi-ports thoracoscopic
lobectomy for non-small cell lung cancer. Methods: Between January 2009 and
December 2016, 141 single-incision thoracoscopic lobectomies and 159 multi-
ports thoracoscopic lobectomies were enrolled on patients with non-small
cell lung cancer in our institute. Preoperative patient characteristics including
gender, age, smoking history (P/Y), comorbidities, histologic type, tumor size,
pathological stage, histology and forced expiratory volume in 1 s (FEV1) and
pathologic stage were compared between two groups. Age and previous caner
history were used for propensity matching because age and previous caner
history were a statistically significant difference among parameters. After
propensity score matching, 141 single incision thoracoscopic lobectomies
and 141 multi-ports thoracoscopic lobectomies were selected and compared.
Results: There were no differences significantly between single incision
and multi-ports thoracoscopic lobectomy with regard to operation time
(233.3 ± 70.8 vs. 222.7 ± 79.5, P=0.236), hospital stay (15.6 ± 31.8 vs. 21.3 ±
114.4, P=0.572), number of lymph node (23.6 ± 11.6 vs. 25.5 ± 12.9, P=0.209),
the number of units transfused pack RBC (0.3±0.7 vs. 0.5±1.4, P=0.055), FFP
(0.0 ± 0.3 vs. 0.1 ± 0.8, P=0.145) and PLT(0.1 ± 1.5 vs. 0.1 ± 1.1, P>0.05) during
perioperative period. Overall survival rate and disease free survival also were
no difference between two groups. Chest tube drainage for 24 hours after
operation (410.2 ± 205.6ml vs. 571.0 ± 289.3ml, P<0.01) and intraoperative
blood loss (314.6 ± 348.6ml vs. 555.0 ± 460.5ml, P<0.01) are better with
single incision thoracoscopic lobectomy group. Conclusion: Single incision
thoracoscopic lobectomy could achieve similar short-term surgical results
and mid-term outcomes compared with multi-ports thorscoscopic lobectomy
except
Keywords: multi-port thoracoscopic lobectomy, signle incision thoracoscopic

lobectomy, propensity matching study, lung cancer

P1.08-044 COMPARISON OF PERI-OPERATIVE OUTCOMES AFTER

ROBOTIC-ASSISTED VIDEO-THORACOSCOPIC LOBECTOMIES
VERSUS SEGMENTECTOMIES

No significant difference was found on intra-operative complications (18/208 of the lung metastases. 4 patients had bilateral lung operations, and only
vs. 4/43; p=0.70). However, the mean duration of R-VATS segmentectomy was one lung metastasis was resected in three cases and the median number of
longer than lobectomy(258min vs. 207.5min: p<0.01). Total post-operative metastases resected was 1.94. Results: The median overall survival was 34.9
complications didn’t differ between the groups(24/43 vs. 84/208; p=0.071). months (range, 10-129). At follow up, 4 patients were dead with a median
Individual complications reviewed included cardiovascular, wound infections, follow-up of 21.9 months. 5 patients were alive, and 4 patients were disease-
and respiratory adverse outcomes. Only pneumothorax after chest tube free survivors, and 2 of 4 patients had only one pulmonary metastasis at the
removal(p=0.032) and effusion/empyema(p=0.011) requiring intervention first lung matstasectomy. Conclusion: In selected patients, thoracoscopically
were significant. Conclusion: R-VATS segmentectomy on average take longer pulmonary metastasectomy for osteosarcoma is safe, and may confer a good
and has more postoperative complications which can be explained by survival. Recurrent metastasis after resection confers a good prognosis.
patients’ underlying pulmonary disease. R-VATS segmentectomy may be
considered as an alternative procedure to R-VATS lobectomy in order to Keywords: osteosarcoma, VATS, pulmonary metastasis, Surgery
conserve lung function.
Keywords: segmentectomy, Robotic surgery, complications, lobectomy


P1.08-047 DECREASING USE OF EPIDURAL ANALGESIA WITH
INCREASING MINIMALLY INVASIVE LOBECTOMY: IMPACT ON
POSTOPERATIVE MORBIDITY
P1.08-045 PARTIAL LUNG RESECTION AFTER BRONCHOSCOPIC
Masha Zeltsman, Alexandra Poch, Takashi Eguchi, Sarina Bains, Bernard Park,
METALLIC COIL MARKING USING TWO COINS AND C-ARMED David Jones, Prasad Adusumilli
SHAPED FLUOROSCOPIC GUIDANCE Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center,
Koh Uyama, Takanori Miyoshi, Hiroyuki Sumitomo, Naoki Hino New York/NY/United States of America
Department of Thoracic Surgery, Tokushima Municipal Hospital, Tokushima City/
Japan Background: The goal of this study is to assess the impact of the decreasing
use of epidural analgesia (infusion ≥24 hours) on the incidence of
Background: The opportunities detecting small pulmonary lesions are postoperative morbidity following minimally invasive surgical (MIS; includes
increasing because of the spread of CT screening, however, it is sometimes VATS and robotic-assisted) lobectomy in patients with non-small cell lung
hard to localize the non-palpable tumors located in deep part of the lungs or cancer (NSCLC). Methods: We reviewed 1206 patients who underwent MIS
showing grand- glass opacity lesions. Therefore, it is necessary to mark the lobectomy for pathological stage I-III NSCLC in 2009-10 (n=506) and 2014-15
location of these tumors before operation. We developed the simple and (n=700) at our institution. Clinical data was obtained from a prospectively
easy marking technique using two coins and a metallic coil, and examined maintained database and by review of individual patient medical records.
its reliability, safety, and usefulness. Methods: 23 patients with 24 small Patients with induction therapy (n=225) or conversion from MIS to
peripheral pulmonary lesions less than 20 mm in size underwent fluoroscopy- thoracotomy (n=99) were excluded. Postoperative morbidity (≤30 days) was
assisted thoracoscopic partial lung resection after bronchoscopic metallic graded based on the Common Terminology Criteria for Adverse Events
coil marking using two coins and C-armed shaped fluoroscopic guidance. (CTCAE). Statistical comparison was performed using Chi-squared analysis
The average diameter of the lesions was 10.33mm, and the average distance and Fisher’s exact test. Results: A total of 884 patients were included in this
from the pleural surface was 8.37mm. At first we conducted chest CT scan study (2009-10, n=401; 2014-15, n=483). The rate of MIS lobectomy
and confirmed the number of the CT slice in which the tumor exist. Two coins significantly increased in 2014-15 compared to 2009-10 (74% vs. 53%, p<0.001)
were put on the patient’s chest wall according with the slice number of the with a simultaneous decrease in the use of epidural analgesia (92.9% vs.
antecedent CT scan. A metallic coil was installed in the bronchus near the 53.6%, p<0.001; Figure 1A and 1B). In the MIS group, there was no difference in
lesion where the shadows of two coins overlap using ultrathin bronchoscopy age, sex, or pathological stage between the 2009-10 and 2014-15 cohorts.
under C-armed shaped fluoroscopic guidance. Afterwards, we performed There was no significant change in the incidence of any, severe respiratory or
wide wedge resection of the nodules with coil marking under fluoroscopic and cardiovascular morbidity (CTCAE grade ≥3) following MIS lobectomy between
thoracoscopic guidance. Results: We could install coils in the objective bronchi the two time periods evaluated (Figure 1C). However, the incidence of CTCAE
in all cases. The marking procedure took 13 to 39 minutes from insertion to grade ≥2 respiratory morbidity in 2014-15 was higher than that in 2009-10
removal of the bronchoscope. There were no complications from the marking, (7.1% vs. 12.6%, p=0.047).
and all 24 nodules were easily localized at the time of VATS resection. The
pathologic diagnosis was primary adenocarcinoma in 9 nodules, pulmonary
metastases in 8 nodules, a primary squamous carcinoma in 2 nodules,
small cell carcinoma in 2 nodules, an atypical adenomatous hyperplasia in 1
nodule, and a nontuberculous mycobacteriosis in 1 nodule. Conclusion: The
fluoroscopy-guided coil marking using ultrathin bronchoscope with two coins
on a patient’s chest wall after CT-assisted stimulation was a safe, convenient,
and reliable method for localization of small pulmonary lesions before VATS
partial resection.
Keywords: VATS, coil marking, partial lung resection

P1.08-046 SURVIVAL FOLLOWING THORACOSCOPIC PULMONARY

METASTASECTOMY FOR OSTEOSARCOMA
Takashi Tojo, Takeshi Kawaguchi, Motoaki Yasukawa, Norikazu Kawai, Shigeki
Taniguchi Conclusion: In our study cohort, the observed decrease in use of epidural
Thoracic and Cardiovascular Surgery, Nara Medical University, Kashihara/Japan analgesia with the increasing rate of MIS lobectomy did not affect the
incidence of severe postoperative morbidity.
Background: Osteosarcoma is the malignant primary bone tumors which often
develop in young people, 5-year overall survival in patients with pulmonary Keywords: Postoperative Morbidity, Minimally Invasive Surgery, Epidural
metastasis is around 50%. The objective of this study was to report the overall Analgesia, VATS
survival in a group of patients with metastatic osteosarcoma treated with
surgical removal of the lung metastases. Methods: A retrospectic review from
our data base revealed 9 patients performing 18 pulmonary metastasectomies
between August 2005 and May 2016. The mean age was 18 years (range, 15-24)
and 5 patients were male. All patients were treated with chemotherapy and
oncologic resection of the primary tumor and thoracoscopic surgical removal
POSTER SESSION 1 - P1.08: SURGERY POSTER SESSION 1 - P1.08: SURGERY

MINIMAL INVASIVE SURGERY – MINIMAL INVASIVE SURGERY –
P1.08-048 COMPARISON OF PULMONARY FUNCTION AFTER P1.08-049 CT GUIDED LABELING WITH INDOCYANINE GREEN OF
ROBOTIC-ASSISTED VIDEO-THORACOSCOPIC LOBECTOMIES VS SMALL LUNG NODULES FOR SUBLOBAR RESECTION UTILIZING
SEGMENTECTOMIES ROBOTIC ASSISTED THORASCOPIC SURGERY (RATS)
Maria Echavarria1, Anna Cheng1, Frank Velez1, Emily Ng1, Carla Moodie2, Joseph K Adam Lee 1, Lee Fox 2, Andrew Hall2, Vincent Turiano2
Garrett2, Jacques-Pierre Fontaine2, Eric Toloza2 1
Thoracic Surgery and Lung Center, Jupiter Medical Center, Jupiter/FL/United States
1
University of South Florida, Tampa/FL/United States of America, 2Thoracic of America, 2Radiology, Jupiter Medical Center, Jupiter/FL/United States of America
Oncology, Moffitt Cancer Center, Tampa/United States of America
Background: Localization of deep and small pulmonary lung nodules
Background: Lobectomy is the standard surgical procedure for early stage undergoing a wedge or sublobar resection may be challenging during
lung cancer, but sub-lobar resection is being debated. We compared thoracoscopy, and may necessitate greater resection or conversion to
pulmonary function after robotic-assisted video-assisted Thoracoscopic thoracotomy. Particularly in robotic surgery, with the absence of tactile
(R-VATS) segmentectomy versus lobectomy; comparison using robotic feedback. Percutaneous CT guided Indocyanine Green injection provides
instruments hasn’t been published. Methods: We retrospectively analyzed a means to pinpoint these nodules. Methods: A retrospective study of 40
prospectively collected data from 251 consecutive patients who underwent consecutive patients who underwent preoperative CT-guided localization of
lobectomy (N=208) and segmentectomy (N=43) via R-VATS by one surgeon. solitary pulmonary nodules with ICG. Nodules < 15mm were 21/40 (52.5%), <
Unpaired Student’s t-test and Chi-square tests were used to determine 20mm 30/40 (75%), and < 30mm 38/40 (95%). A 22-gauge spinal needle (BD,
statistical significance(p≤ 0.05). Majority of patients had no prior lung NJ) or Chiba needle (Cook, IA) was positioned into or adjacent to the nodule.
surgery. We used “Predicted(PFT)=Preop(PFT)x(1-(Segments x 0.0556))”, 0.4cc Indocyanine Green was injected and the inner stylet withdrawn. The
where 0.0556=1seg/18seg. For patients with prior resections, the number of Xi daVinci robot (Intuitive Surgery, CA) was docked and the firefly filter of
segments previously resected was taken into account(1seg/(18-Prior the 8mm camera was activated, and the nodule illuminates in a flouresence
resection)). Results: green color. A wedge or sublobar resection was performed, with progression
to lobectomy when indicated. Results: CT guidance successfully localized
the nodules in 100% of 40 patients employing this technique. Success was
measured in nodule illumination as seen by the surgeon upon activation of the
camera filter and confirmed on frozen and permanent section by pathology.
Initial wedge resection for diagnosis prior to lobectomy and sublobar
resection for decreased PFTs or decrease cardiac function were performed
by Robotic Assisted Thoracoscopy (RATS). There were no conversions to
thoracotomy. Diagnosis were adenocarcinoma in 18 patients (45%), squamous
cell carcinoma in 7 patients (17.5%), carcinoid in 1 patient (2.5%), metastatic
in 8 patients (20%), and benign in 6 patients (15%). There were no 30 or 90
day mortalities. A chest tube reinsertion in one patient for pneumothorax.
Economically the cost for the vial of ICG is $79.56 compared to a fiducil marker
at a cost of $128.00. Thoracic Surgery has access to CT scanners, without an
extra cost, electromagnetic navigation systems come with significant added
costs. Conclusion: Percutaneous CT guided labeling with ICG is quick and
economical for the localization of small and deep nodules undergoing RATS
wedge or sublobar resection. This technique may be supportive in preserving
lung parenchyma and reduce the need for conversion to thoracotomy,
maintaining minimal invasive thoracic surgery, especially where palpation or
tactile feedback is absent.
Keywords: pulmonary nodules, sublobar resection, Minimal Invasive thoracic

surgery, CT guided labeling

P1.08-050 VATS LOBECTOMY IN LOCALLY ADVANCED NSCLC: A

SINGLE CENTRE EXPERIENCE
Davide Tosi, Lorenzo Rosso, Paolo Mendogni, Alessandro Palleschi, Ilaria
Righi, Matteo Montoli, Francesco Damarco, Mario Nosotti
Fondazione IRCCS Ca’ Granda Policlinico, Milan/Italy
Background: VATS lobectomy has become the gold standard in early

stage lung cancer treatment, but its role is still debated in case of locally
advanced disease (tumor larger than 5 cm, chest wall involvement, hilar
Preoperative FEV1(%) and DLCO(%) were statistically significant between the adenopathy, need for sleeve resection). The aim of this study was to evaluate
two groups. Also, FEV1 and DLCO were lower in segmentectomy patients. As the main differences between VATS lobectomy performed for early stage
expected, predicted changes between preoperative and postoperative values NSCLC and the ones performed for locally advanced disease. Methods: We
were significant. Predicted post-operative FEV1 and DLCO did not show any retrospectively analyzed patients that underwent VATS lobectomy for tumor
significant difference between the two groups. Conclusion: While pre- resection in our centre, from July 2011 till December 2015. Patients included
operative PFTs were significantly lower in segmentectomy patients compared in the study were similar for demographic characteristics and for number of
to lobectomy patients, predicted post-operative PFTs do not differ resected lymph nodes. We performed 136 VATS lobectomies: 124 following
significantly. Predicted changes for FEV1 and DLCO are significantly less in standard indications (group A); 12 following “extended” indications (group B).
segmentectomy. Thus, negate the difference in pre-operative PFTs. In Group B is composed by: 3 VATS sleeve lobectomy; 3 VATS lobectomy followed
conclusion, R-VATS segmentectomy preserves lung function and may be by limited chest wall resection (hybrid technique); 6 VATS lobectomy for
considered a viable alternative NSCLC larger than 5cm. We evaluated the conversion rate to open surgery, the
intraoperative blood loss, the operation lenght, the chest drain maintenance
Keywords: Robotic surgery lobectomy segmentectomy and the length of hospitalization. Results: Intra-operative conversion rate
was higher in group A than in Group B, but not statistically different (13,7%
vs 9%; p>0,05). No differences were detected in the intraoperative blood
loss. Instead we observed differences in terms of operation length, of chest
drain maintenance (4,8 vs 7,4 days; p<0,05) and of length of hospitalization
(6,2 vs 10,3 days; p<0,05). Conclusion: We believe that VATS lobectomy can be
proposed even in “complex cases”. Minimal invasive approach didn’t increase

the intraoperative blood loss and didn’t imply a significant impact in terms were compared for differences in perioperative outcomes. Results: Total
of intraoperative conversion to open surgery. We detected differences in 422 patients (43 robotic, 265 VATS, 30 open conversion from VATS, and
the operation length and in chest drain maintenance. Other studies with an 84 thoracotomy) were included in the analysis. Clinical and pathological
higher population of “complex cases” are needed, but we are trustful that stage showed earlier in robotic and VATS cases. Operative time (min),
VATS lobectomy indications will be extended in the short term. bleeding amount (gram) and drainage period (days) for robot, VATS,
conversion and thoracotomy were 247/20/2, 188/10/2, 246/100/2, 225/
Keywords: lobectomy, NSCLC, VATS, sleeve 92.5/2 respectively(p<0.0001). In the incidence of all, over G3, respiratory
over G3 postoperative complications robotic surgery showed significantly
lowest among them and there were neither conversion to thoracotomy nor
operative/hospital mortality in robotic surgery. Conclusion: In our initial
results of robotic surgery, lower incidence of operative morbidities is one
MINIMAL INVASIVE SURGERY – of the advantageous features. Important issue whether robotic surgery is
MONDAY, DECEMBER 5, 2016 established as a minimally invasive approach for NSCLC or not should be
verified.
P1.08-051 VATS LOBECTOMY COMBINED WITH LIMITED Keywords: NSCLC, thoracotomy, Robotic surgery, VATS
THORACOTOMY FOR TREATMENT OF SUPERIOR SULCUS TUMORS
Davide Tosi, Lorenzo Rosso, Alessandro Palleschi, Paolo Mendogni, Ilaria
Righi, Matteo Montoli, Claudia Bareggi, Mario Nosotti
Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda -
Ospedale Maggiore Policlinico, Milan/Italy MINIMAL INVASIVE SURGERY –
Background: Despite the increasing of VATS procedures even for locally
advanced NSCLC, Pancoast tumors have been rarely approached with VATS
combined with chest wall resection. This report describes an hybrid surgical P1.08-053 THORACOSCOPIC PARTIAL RESECTION FOR PERIPHERAL
technique to approach “en block” chest resection and pulmonary lobectomy PULMONARY NODULES WITHOUT USING STAPLER
for superior sulcus tumors Methods: We present two cases of patients Toshiya Toyazaki, Tatsuo Nakagawa, Yasuaki Tomioka, Yuichiro Ueda, Masashi
referred to our Institution. A female patient affected by right anterior Gotoh
Pancoast tumor surgically staged as cT4N0M0 for suspected anonymous Thoracic Surgery, Tenri Hospital, Tenri/Japan
vein invasion, underwent induction therapy with four cycles of cisplatin and
Pemetrexed plus 60 Gy irradiation, with satisfactory tumor reduction. The Background: Advances in radiologic studies, such as high resolution computed
surgical operation comprised an initial VATS approach to the hilar structures tomography (HRCT), have enabled frequent detection of small lung nodules.
followed by a limited C-shaped anterior contra-incision; finally, the right upper Accordingly, opportunity for sublobar resections for small lesions has
lobe “en block” with the anterior part of the first and second rib was removed. increased. Recently, we have introduced thoracoscopic partial resection
The second case is a 57-year-old man, affected by a cT3N0M0 posterior for peripheral pulmonary small nodules without using stapler to reduce the
Pancoast tumor, treated with induction chemoradiotherapy prior to the cost of operation. Methods: After detecting the peripheral nodules, partial
hybrid surgical approach. After thoracoscopic pleural cavity inspection, an resection was performed with electrocautery and two different methods
upper right VATS lobectomy by a 3-port standard approach was performed. of surface sealing were followed. Coagulation method (C method) with
The chest wall was resected through a limited paravertebral incision, allowing SOFT COAG alone and Coagulation-suturing method (CS method) with SOFT
the extraction of the lobe together with the rib segments. The posterior chest COAG combined with continuous suturing by an absorbable barbed suture.
wall defect was repaired with a synthetic patch. Results: The postoperative The clinical outcome of the two methods was retrospectively compared in
period was uneventful in both cases, and the pain never exceed a score of 4 this study. Results: C method was performed in 19 lesions of 18 cases and
on a visual analogue scale. The patients were discharged respectively 9 and CS method was performed in 17 lesions of 16 cases. Primary lung cancer was
11 days after surgery. Pathological results revealed in both cases nonvital most frequent as 19 lesions of 18 cases. There was no significant difference
tumor cells in the specimen (ypT0N0M0). The patients are free from disease between the two groups in size and depth of the lesions. Operation time was
and post-thoracotomy syndrome at 14 and 18 months’ follow-up Conclusion: significantly longer in CS method than in C method. Postoperative air leakage
VATS combined with thoracotomy approach leads to asses with precision the was complicated to 4 cases in C method and one of them needed re-do surgery,
thoracic wall resection and reduce surgical trauma with very good results in whereas only one case in CS method had temporary air leakage. Postoperative
term of postoperative morbidity. We strongly support the “VATS observation computed tomography revealed cavitation in 3 cases of C method and in
first” philosophy, to exclude previously undetected pleural dissemination 4 cases of CS method all without related symptoms. There was no local
and to precisely define the tumor location. Further experiences are needed to recurrence in resected sites. Conclusion: C method was technically easy to
validate the role of VATS lobectomy in the multidisciplinary management of perform, but air leakage may be possibly prolonged after surgery. CS method
Pancoast tumor may have an advantage of less air leakage than C method, but technical
learning is important to shorten operation time.
Keywords: VATS, Surgery, Pancoast
Keywords: partial lung resection, SOFT COAG, continuous suturing,
Thoracoscopic surgery

P1.08-052 COMPARISON STUDY OF PERIOPERATIVE OUTCOMES IN
ROBOTIC, VIDEO-ASSISTED THORACIC SURGERY, AND
THORACOTOMY APPROACHES FOR LUNG CANCER P1.08-054 UNIPORTAL VATS LOBECTOMY IN THE TREATMENT OF
Hiroshige Nakamura1, Yuji Taniguchi1, Ken Miwa1, Kunio Araki1, Tomohiro NSCLC
Haruki2, Makoto Wakahara1, Yohei Yurugi1, Yasuaki Kubouchi1, Yoshiteru Nenad Ilic, Josko Juricic, Dragan Krnic, Duje Orsulic, Ivan Simundza, Marijan
Kidokoro1, Takashi Ono1 Urlic, Nives Frleta Ilic, Darko Ilic
1
Division of General Thoracic Surgery, Tottori University Hospital, Tottori/Japan, 2Tu Thoracic Surgery Dept., University Surgical Hospital, Split/Croatia
Southwestern Medical Center, Dallas/TX/United States of America
Background: Uniportal Video-Assisted Thoracic Surgery (uniportal VATS)
Background: Robotic surgery for lung cancer has not widely spread because lobectomy represents the pinnacle of evolution for minimally invasive
of the lack of definitive advantage compared to conventional approaches, techniques in surgical management of lung cancer. Growing evidence suggest
specifically video-assisted thoracic surgery (VATS). Some studies have that Uniportal VATS procedures are technically feasible and safe with
reported that postoperative complication in robotic surgery is superior immediate outcomes comparable to traditional VATS approach. Uniportal
for unclear reasons. The aim of this study is to compare the perioperative approach has demonstrated equivalent disease-free survival, at intermediate
outcomes, particularly pointing out postoperative complication among follow-up for patients with early stage NSCLC, compared to conventional
robotic, video-assisted thoracic surgery (VATS) and thoracotomy approach in VATS. It represents a less invasive approach, and offers the advantage
non-small cell lung cancer (NSCLC). Methods: We performed a retrospective of minimizing the extent of the surgical access trauma thus resulting in
review of NSCLC patients who underwent curative anatomical resection postoperative pain reduction, muffled inflammatory response, early recovery
in our hospital from January 2011 to April 2016. There were 346 lobectomy and better cosmesis. Some authors described minimal changes in pulmonary
cases and 76 segmentectomy cases. The patients were classified into four function after uniportal surgery in patients with poor cardio-respiratory
groups (robotic, VATS, open conversion from VATS, and thoracotomy) and function. Here we present our experiences with uniportal VATS lobectomies
for NSCLC. Methods: Between October 2015. and March 2016. twenty-four in diameter; a low tumor standardized uptake value (SUV) evaluated in (18)F
(24) patients with non-small lung cancer (NSCLC) underwent uniportal VATS fluorodeoxyglucose-positron emission tomography/computed tomography
lobectomy and mediasitnal lymph node dissection. Surgical access was (FDG-PET) ; predominantly ground-glass appearance on CT imaging. The high
performed through a 4-5 cm long utilitarian incision at the 5th intercostal resolution CT scanner, Philips Brilliance iCT (Medical Imaging Resources, An
space in the anterior axillary line. Anatomical resection of veins, arteries, Arbor, MI) with both 128 and 256 slice configurations was used. CT data were
bronchi and mediastinal lymph nodes followed established oncological transferred to an imaging analysis system (Zio station ver.2, Tokyo, Japan)
principals. Once the operation was completed a single chest tube was inserted for image reconstruction and we performed preoperative CT-guided marking
in the anterior part of the incision for uniportal VATS. Results: Fifteen male in surface of near the tumor. Results: In all 20 cases, the reconstruction of
and nine female patients with an average age of 62.6 years (49-76) were the pulmonary artery and vein could image branches and resected in lung
enrolled in the study. Average procedural time was 108 minutes (75min- segment. Right side: One case of the upper lobe S1; 5 cases of the lower lobe
154min). None of the patients required blood transfusion after the procedure S6 (3), S8 (1) and S10 (1). Left side: 10 cases of the upper lobe S1+2a, S1+2c,
or during the rest of their hospital stay. Average duration of chest drainage S1+2a+b, S1+2c+S3a, S3b+c, apicoposterior segmentectomy, S3(2) and upper
was 3.6 days (2-8) and mean hospital stay was 6.3 days (3-10). There were 14 lober trisegmentectomy (2); 4 cases of the lower lobe S6, S8+S9, S10 and
patients with adenocarcinoma and 10 with squamous cell carcinoma. Two basal segmentectomy. All pulmonary nodules were found in the excised
patients had prolonged air leak and were treated conservatively. There was target segments with safety margin. According to postoperative pathological
no perioperative mortality. Conclusion: Our initial experiences with Uniportal examination of the all operative specimens were adenocarcinoma, and the
VATS lobectomy is encouraging as it demonstrated benefits to patients due diameters of pulmonary tumors resected were 15.8±3.3 and invasive size
minimal surgical stress, faster recovery, reduced postoperative pain and were 6.2±3.1 mm. Furthermore, the pathological results were given Atypical
shorter hospital stay.The authors strongly believe uniportal VATS surgery adenomatous hyperplasia (2), adenocarcinoma in situ (2), minimally invasive
should be considered for primary surgical treatment of NSCLC. adenocarcinoma (5), Lepidic predominant adenocarcinoma (10) and papillary
predominant adenocarcinoma (1). Conclusion: At the time of writing,
Keywords: VATS, uniportal, NSCLC local recurrences had not occurred in sublobar resection, so we should be
considered for early stage lung cancer in these conditions. Moreover the 3D-
CT angiography could be used preoperatively as a tracing method to identify
the resected line of lung segment and very useful for anatomic sublobar
resections, especially in thoracoscopic surgery.
MONDAY, DECEMBER 5, 2016 Keywords: 3D-CT angiography, Early-stage lung cancer., Thoracoscopic
surgery, Anatomic sublobar resection
P1.08-055 HAND ASSISTED THORACOSCOPIC SURGERY (HATS) FOR

METASTATIC LUNG TUMORS - IMPROVED TECHNIQUE FOR MORE
SAFETY AND ACCURACY
Shozo Fujino, Masato Watanabe, Takehiro Okumura MINIMAL INVASIVE SURGERY –
Department of Surgery, University Hospital Mizonokuchi, Teikyo University School MONDAY, DECEMBER 5, 2016
of Medicine, Kawasaki, Kanagawa/Japan
Background: Small pulmonary lesions, the localization of which cannot be P1.08-057 OUTCOMES BETWEEN SINGLE PORT, TWO PORT AND
confirmed by the sight, are often removed surgically with help of several THREE PORT VATS PULMONARY RESECTION
type markers. But they sometimes drop off or dislocate before surgery. Juwei Mu, Shugeng Gao, Qi Xue, Yousheng Mao, Dali Wang, Jun Zhao, Yushun
It is the most certain to confirm local existence of tumors with help of Gao, Jinfeng Huang, Jie He
palpation and remove them surgically. I reported the usefulness of hand Department of Thoracic Surgical Oncology, National Cancer Center / Cancer
assisted thoracoscopic surgery (HATS) for such cases. We removed about Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College,
15% more lesions than the number that we expected before surgery using Beijing/China
this technique. Methods: A hand of surgeon was inserted into the bilateral
thoracic cavities of patients through a subxiphoid skin incision in supine Background: To investigate the difference of outcome between single port,
position in the method of original HATS. Results: HATS is relative safe and two port and three port VATS pulmonary resection. Methods: The data of
useful technique. But there is only one problem in this technique. Surgeon can 3217 cases of VATS pulmonary resection from November 2014 to August
palpate whole lungs from the pulmonary apex to a base of lung in right side 2016 in the Department of Thoracic Surgery of National Cancer Center /
without circulatory complication. But, in left side, blood pressure sometimes Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively
decreases by a surgeon’s arm pressing left ventricle. In such a case, we change reviewed. The following data were compared between two groups: duration
patients’ position from supine to left side up. Circulatory complications of operation, intraoperative blood loss, lymph nodes retrieved, volume of
decreases in this improved technique. Conclusion: HATS in supine position for drainage, duration of chest tube, complication rate, postoperative length
right side and in left side up position for left side is safer and more accurate of stay, hospital cost and surgery cost. Results: There were 516 patients in
method. Improved data got with improved technique will present on the single port, 178 patients in two port group and 2523 patients in three port
poster of congress. group. Compared with three port group, patients in the single port and two
port group had decreased operative time (136.69±55.90 vs 129.09±57.36 vs
Keywords: hand-aasisted, small lesion, palpation, circulatory complication 122.23±58.38min; P=0.002), decreased intraoperative blood loss(71.06±106.94
vs 57.32±45.21 vs 67.39±93.00ml; P=0.028), decreased chest tube
drainage(1037.58±797.56 vs 791.09±535.36 vs 926.21±766.82 mL; P<0.001),
reduced duration of chest tube (5.08±2.84 vs 4.53±1.77 vs 4.30±2.29 d;
P<0.001), and decreased postoperative length of stay (6.13±3.13 vs 5.73±2.39
POSTER SESSION 1 - P1.08: SURGERY vs 5.16±2.42 d; P<0.001). However, the number of lymph nodes retrieved was
MONDAY, DECEMBER 5, 2016 significantly less in single port and two port compared with that in three
port group (13.76±8.96 vs 11.13±9.76 vs 11.78±9.78; P<0.001). There was more
patients were diagnosed as benign pulmonary lesions in single port and two
P1.08-056 SURGICAL RESULTS OF THORACOSCOPIC ANATOMICAL port group than in three port group (19.6% vs 19.1% vs 18.6%, P<0.001). There
SUBLOBAR RESECTIONS FOR EARLY-STAGE LUNG CANCER were no significant difference in the complication rate between there three
Fumiaki Watanabe 1, Motoshi Takao2, Kosuke Hayashi1, Isao Yada1, Hideto groups(2.7% vs 5.6% vs 3.7%; P=0.789).
Shimpo2, Yuta Suzuki1, Haruko Saiki1, Tadashi Sakaguchi1, Kentaro Ito1, Yoichi
Nishii1, Osamu Hataji1
1
Respiratory Center, Matsusaka Municipal Hospital, Matsusaka,mie/Japan,
2
Department of Thoracic & Cardiovascular Surgery, Mie University Graduate School
of Medicine, Tsu, Mie/Japan
Background: High-resolution computed tomography (HRCT) has been used

to detect ground glass nodules (GGN), and sublobar resections might be
currently accepted for patients with early stage malignant GGN. Aim of
this study was to evaluate the surgical results of thoracoscopic sublobar
resections for early-stage lung cancer. Methods: Twenty patients (6 males
and 14 females, a mean age of 72.5 years) performed surgical treatment for
thoracoscopic anatomical sublobar resections from April 2012 to May 2016.
Anatomic sublobar resections were selected with the following criteria;
stage IA disease with no regional lymph node metastasis; tumor up to 2 cm

Background: The timing of surgery after induction chemoradiotherapy

(ChRT) for locally Advanced NSCLC is accepted crucial because of technical
difficulties, morbidity and related mortality. Although six to eight weeks’
time interval between induction ChRT and surgery is advocated, precise
analysis of the optimal waiting time that maximizes oncologic benefits of
ChRT has not been established. We aimed to review our results of pulmonary
resections performed after induction ChRT and to determine the effects of
time interval on postoperative morbidity, mortality and long term survival.
Methods: We retrospectively reviewed our records for patients undergoing
induction ChRT between 1996 and 2015. Timing of treatment was defined as
the difference between the last date of radiotherapy and the date of lung
resection. The dose of radiotherapy varied from 45Gy to 66Gy. The patients
were divided into two groups, surgery less than eight weeks (Group 1) and
more than eight weeks (Group 2) following induction ChRT. Type of resection,
postoperative complications, 90-days mortality and long-term survival were
analyzed. The impact of surgical timing on outcomes was studied through
univariable and multivariable analyses. Results: One hundred and forty-
two patients were included into study. The mean time interval between
ChRT and surgery was 92.3 days (21-900 days). Sixty-five lung resections
were performed less than eight and 77 more than eight weeks. Pulmonary
Conclusion: The outcomes between single port and multiple port VATS resections were classified as pneumonectomy in 20 patients, lobectomy
lobectomy were comparable. However, compared with three port VATS in 122 patients (of whom, 55 underwent extended resections, chest wall,
pulmonary resection, single port and two port VATS pulmonary resection was sleeve etc.). Final pathological examination revealed complete response in
associated with decreased number of lymph nodes retrieved, which may need 43 (30.3%) of the patients. Major morbidity was observed in 42.2% of the
further study. patients [43% (28 of 65pts) in group 1 and 41.5% (32 of 77pts) in group 2,
p=0.85]. The overall 90-day mortality rate was 6.3% [7.7% in group 1 and 5.2%
in group 2, p=0.54]. The mortality rate after pneumonectomy was 5% (1/20)
and 6.5% (8/122) after lobectomy. The 5-year survival rate was 61% vs 47% (p
= 0.16). Multivariate analysis showed that timing of surgery after ChRT was
MINIMAL INVASIVE SURGERY – not significantly associated with an increased morbidity and mortality that
MONDAY, DECEMBER 5, 2016 was also not effected by the dose of radiotherapy. Conclusion: These findings
indicate that lobectomy or pneumonectomy can be safely performed eight
weeks or more after induction ChRT without affecting surgical morbidity and
P1.08-058 VATS LUNG RESECTION ANALYSIS FROM BRAZILIAN
mortality. Pulmonary resection may be performed safely even one year after
SOCIETY OF THORACIC SURGERY DATABASE ChRT.
Maria Teresa Ruiz Tsukazan1, Ricardo Terra2, Gustavo Fortunato3, Spencer
Camargo4, Humberto De Oliveira5, Letícia Lauricella6, Darcy Pinto7 Keywords: Locally advanced NSCLC, Chemoradiotherapy, Surgery
1
Hospital São Lucas Da Pucrs, Porto Alegre/Brazil, 2Cirurgia Torácica Oncológica,
Instituto Do Câncer Do Estado de São Paulo - Icesp, São Paulo/Brazil, 3Santa Casa
de Misericórdia Da Bahia Hospital Santa Isabel, Salvador/Brazil, 4Santa Casa de
Porto Alegre, Porto Alegre/Brazil, 5Hospital de Base Do Distrito Federal, Brasilia/
Brazil, 6Cirurgia Torácica, Intituto Do Coração Do Hospital Das Clínicas Da Fmusp, POSTER SESSION 1 - P1.08: SURGERY
São Paulo/Brazil, 7Hospital Geral Fundação Universidade de Caxias Do Sul, Caxias SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
Do Sul/Brazil
Background: Lung cancer is the leading cause of cancer related death

P1.08-060 SURVIVAL OF PATIENTS WITH UNSUSPECTED N2 (STAGE
worldwide when considering both genders. The optimal treatment is
complete surgical resection. The objective of this study was to analyze VATS
IIIA) NON-SMALL CELL LUNG CANCER
anatomic lung resections in Brazil. Methods: The Brazilian Society of Thoracic Takashi Yamamichi, Masahiko Harada, Tsunekazu Hishima, Ayaka Asakawa,
Surgery (BSTS) uses a customized version of the ESTS platform as its national Masayuki Okui, Hirotoshi Horio
database (BSTS Database). From August to December 2015, 1367 patients Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center
were registered. In the current analysis, we included only patients who Komagome Hospital, Tokyo/Japan
underwent lung cancer anatomic lung resections by VATS; wedge resections
Background: There are few studies evaluating the N2 pattern and outcomes
and unspecified cases were excluded. Results: Out of the 902 anatomical
when a patient with non–small cell lung cancer (NSCLC) unexpectedly is found
lung resections registered, 516 were lung cancer and VATS performed in 389.
to have N2 disease at the time of thoracoscopy or thoracotomy. The objective
Patient’s mean age was 62.5 years, 57.7% were women. PFT were available
of this study was to determine the survival of patients who have completely
in 239 with FEV1 81.7% and CFV 88%. ASA score (n=352) was 1 in 19.3%, 2 in
resected, nonsmall-cell, stage IIIA, lung cancer from unsuspected (nonimaged)
49.7%, 3 in 27.3%, 4 in 3.4% and 5 in 0.3%. The resections performed were
N2 disease. Methods: A retrospective review of NSCLC patients treated with
lobectomy in 303 cases (77.9%), pneumonectomy in 9 (2.3%), bilobectomy
lobectomy for clinically unsuspected mediastinal nodal disease (cT1-cT3
in 5(1.3%) and segmentectomy in 72 (18.5%). Morbidity rate was 21.8% and
cN0-cN1, pN2 disease) at our institution between January 2008 and December
it varied according to the procedure performed. Overall mortality rate was
2011 was conducted. All patients underwent computed tomography scan
1.6% (6). Pathological staging was In situ in 1.3%, IA 55.6%, IB 20.1%, IIA 11.7%,
with contrast, R0 resection with complete thoracic lymphadenectomy, and
IIB 1.7%, IIIA 9.6% and no IV. Conclusion: Slightly female predominance and
had unsuspected, pathologic N2 NSCLC. Positron emission tomography scan
majority of early stage IA and IB lung cancer were found. Our BSTS Database
or invasive staging was added in the attending physician’s choice. Results:
has comparable complications and mortality rates to international series.
Unsuspected pN2 disease was found in 10.9% of patients (31 out of 284) who
Keywords: lung resection, lung cancer, early stage NSCLC underwent lobectomy as primary therapy for cT1-cT3 cN0-cN1 NSCLC. Of
these, cN0pN2 and cN1pN2 were 9.6% (26 out of 270) and 35% (5 out of 14),
respectively. Compare to cN0 group, unsuspected pN2 was more frequent
in the cN1group (p=.0023). In terms of the pattern of metastasis, multiple
and single pN2 was observed similarly in cN0 and cN1 group (p=.9484). The
POSTER SESSION 1 - P1.08: SURGERY 5-year overall survival of the entire unsuspected pN2 was 68.5%, and cN0pN2
cohort tended to have better prognosis than cN1pN2 cohort (71.1%(cN0pN2)
Surgery for Locally Advanced and Advanced NSCLC – vs. 50.0%(cN1pN2); p=.0898). No significant difference in 5y-OS between
MONDAY, DECEMBER 5, 2016 unsuspected single and multiple pN2 could be seen; (70.5%(single) vs.
66.7%(multiple); p=.07803). Conclusion: This analysis suggests that, in the
setting of unsuspected pN2 NSCLC, proceeding with anatomic surgery does
P1.08-059 TIMING OF SURGERY AFTER INDUCTION not appear to compromise outcomes. As unsuspected pN2 disease was more
CHEMORADIATION THERAPY FOR LOCALLY ADVANCED NSCLC frequent in cN1 cohort and revealed poor prognosis, perioperative invasive
mediastinal staging and additional therapy should be considered.
Huseyin Melek 1, Adalet Demir2, Gamze Cetinkaya1, Berker Ozkan3, Sureyya
Sarıhan4, Mehmet Erol1, Ahmet Sami Bayram1, Alper Toker2, Cengiz Gebitekin1 Keywords: Surgery, postoperative outcome, nodal staging, non-small cell lung
1
Thoracic Surgery, Uludag University, Bursa/Turkey, 2Thoracic Surgery, Istanbul cancer
University, Istanbul/Turkey, 3Department of Thoracic Surgery, Istanbul University,
Istanbul/Turkey, 4Radiation Oncology, Uludag University, Bursa/Turkey
POSTER SESSION 1 - P1.08: SURGERY study, we investigated the short and long-term outcomes of completion
SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
pneumonectomy compared with primary pneumonectomy in our single
institution. Methods: Between January 1997 and December 2014, 243 patients
who underwent pneumonectomy in our institution were enrolled in this
P1.08-061 CLINICAL EXPERIENCE OF RIB RESECTION FOR LUNG study. Retrospectively, we investigated the postoperative complication,
CANCER WITH CHEST WALL INVASION USING A PNEUMATIC HIGH short and long-term outcomes of the patients who underwent completion
SPEED POWER DRILL SYSTEM pneumonectomy (CP) and primary pneumonectomy (PP). CP was defined
as pneumonectomy in patients with previous lung resection conducting
Yuichiro Ueda, Tatsuo Nakagawa, Yasuaki Tomioka, Toshiya Toyazaki, Masashi
a hilar manipulation. Results: Thirty-three patients (14%) of 243 patients
Gotoh
underwent CP. CP was performed for 28 malignant tumors and 5 benign
Thoracic Surgery, Tenri Hospital, Tenri/Japan
diseases. Postoperative severe complication (CTCAE Grade3 or more) occurred
Background: Rib resection is sometimes required for chest wall tumors or in 36% of CP group and 12% of PP group (p<0.01).Especially, bronchopleural
lung cancer with localized chest wall invasion.There are some reports on fistula (BPF) was more likely to occur in patients undergoing CP (PP 5% vs
thoracoscopic rib resection, which may be much less invasive and provide CP 15%, p=0.03). The incidence of BPF in PP group was related to the side of
an excellent surgical view of the target. We have used a pneumatic high procedure (right 70% versus left 30%, p=0.01), but those in CP group was not
speed power drill system, commonly used as a dentist’s drill, in order to be related (right 60% versus left 40%, p=0.57). In the patient with BPF after CP,
accomplished less invasive thoracoscopic rib resection. Methods: A pneumatic Bronchial stump coverage was performed in 2 of 5 patients undergoing the
high speed power drill (HiLAN® GA520R B Braun Aesculap, Tokyo, Japan) was right-side procedure, not performed in other 3 of 5 patients (2 left-side and 1
inserted in the thoracic cavity and the head of the drill, which has a diamond right-side). The 30-day mortality for CP group (9%) was a significantly higher
burr, adequately attached to the rib surface. The rib was then sheared by compared with PP group (2%, p=0.04). However, the 90-day mortality (PP 5%
whittling until dislocated. Cut pieces of bone tissue were removed by suction vs CP 12%, p=0.14) and the overall survival (PP 47% vs CP 52%, p=0.44 ) were
with saline dropping on the head of the drill. Soft tissue including the parietal not significant difference between the two groups. Conclusion: Postoperative
pleura, intercostal muscle and vessels were dissected using power devices or morbidity and 30-days mortality rates in CP were higher than those in PP
an electrical scalpel after cutting the ribs. group, but the long-term survival of CP is acceptable compared with PP group.
The incidence of left-side BPF is similar to right-side in CP group in this study.
It will be also necessary to take preventive procedure against BPF (bronchial
stump coverage) in left-side CP.
Keywords: completion pneumonectomy

P1.08-063 DOUBLE PRIMARY MALIGNANCIES INVOLVING LUNG

CANCER AND HEPATOCELLULAR CARCINOMA
Han Pil Lee, Se Hoon Choi, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park,
Hyeong Ryul Kim
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center,
University of Ulsan College of Medicine, Seoul/Korea, Republic of
Background: The incidence of double primary malignancies (DPM) with lung

cancer and hepatocellular carcinoma (HCC) has increased in gradually.
However there was a lack of data about the clinical outcomes and factors. We
Results: From February 2014 to date, we have experienced seven patients performed a retrospective study to investigate overall survival and
with chest wall resection using a drill. Hybrid-VATS was performed for four characteristics in that patients. Methods: Between January, 2002 and
of the patients, while complete-VATS was performed for the remaining three December, 2013, total 52 patients had DPM. 7 patients were excluded because
patients.There were no intraoperative issues and the postoperative courses there was lack of medical record. 3 patients with other malignancies were
were all eventless. The mean follow-up period is about 13 months. Two of the excluded. We divided the patients into 2 groups. 19 patients were
7 patients had recurrence of the disease with distant metastasis. However, synchronous group that interval of diagnosis between 2 malignancies was
there is no local recurrence. Conclusion: A pneumatic high speed power drill is shorter than 180 days and other 23 patients were metachronous group.
easy to handle and useful for rib resection in lung cancer surgery and possibly Results: Among 42 patients with DPM, there were no significant differences in
better suited even when compared to the Gigli saw or endoscopic rib cutter basic characteristics. Median overall survival was 118.97 ± 6.39 months. There
for selective patients undergoing thoracoscopic surgery. Rib resection using a was no significant difference in overall survival between synchronous group
drill might be less invasive procedure. and metachronous group (p = 0.921). Multivariate analysis revealed that
higher lung cancer stage, postoperative therapy due to lung cancer, liver
Keywords: rib resection, drill, Thoracoscopy, chest wall cirrhosis, and history of hypertension were independent factors for overall
survival.

P1.08-062 THE SHORT AND LONG-TERM OUTCOMES OF

COMPLETION PNEUMONECTOMY COMPARED WITH PRIMARY
PNEUMONECTOMY
Takuya Ueda1, Keigo Sekihara1, Tomohiro Miyoshi2, Keiju Aokage3, Tomoyuki
Hishida1, Junji Yoshida1, Masahiro Tsuboi4
1
Thoracic Surgery, National Cancer Center Hospital East, Kashiwa/Japan, 2Thoracic
Surgery, National Cancer Center Hospital East, Chiba/Japan, 3Division of Thoracic
Surgery, Department of Thoracic Oncology, National Cancer Center Hospital East,
Kashiwa/Japan, 4Thoracic Surgery, National Cancer Center Hospital East, Kashiwa,
Chiba/Japan
Background: Completion pneumonectomy has been reported to be high

morbidity and mortality procedure in lung cancer patients. However, we
sometimes have no choice but to apply this procedure for the patients
who developed secondary lung cancer in the remaining lung after lung
resection, local recurrence, or postoperative complication. In this

Prolonged air leak 2
ARDS 1
Mortality 0 0%
Conclusion: Lobectomy with PA-resection and reconstruction was feasible to

avoid pneumonectomy for tumor invading proximal left PA.
Keywords: lung tumor, Angioplasty, Left main pulmonary artery

P1.08-065 RESECTION OF ISOLATED BRAIN METASTASIS

IMPROVES OUTCOME OF NON SMALL-CELL LUNG CANCER (NSCLC)
Conclusion: Lung cancer stage and underlying liver cirrhosis were strongly
PATIENTS: A RETROSPECTIVE MULTICENTER STUDY
related to overall survival in patients with DPM involving lung cancer and HCC. Julia Fuchs 1, Martin Früh2, Alexandros Papachristofilou3, Lukas Bubendorf4,
Absence of hypertension showed better prognosis in those patients. Catherine Schill5, Lorenz Jost6, Alfred Zippelius1, Sacha Rothschild1
1
Medical Oncology, University Hospital Basel, Basel/Switzerland, 2Kantonsspital
Keywords: lung cancer, hepatocellular carcinoma, double primary St. Gallen, St. Gallen/Switzerland, 3Radiation Oncology, University Hospital
malignancies Basel, Basel/Switzerland, 4Insitute of Pathology, University Hospital Basel,
Basel/Switzerland, 5Medical Oncology, Kantonsspital Baselland Liestal, Liestal/
SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC – Switzerland, 6Medical Oncology, Kantonsspital Baselland Bruderholz, Basel/
MONDAY, DECEMBER 5, 2016 Switzerland
Background: Metastatic non-small cell lung cancer (NSCLC) is an incurable

P1.08-064 SURGERY FOR MALIGNANT PULMONARY TUMOR disease. Selected patients with solitary brain metastasis from NSCLC can
INVADING PROXIMAL LEFT MAIN PULMONARY ARTERY achieve long-term survival following metastasectomy. We analyzed the
Fumihiro Tanaka1, Yusuke Nabe2, Akihiro Taira2, Taiji Kuwata2, Soichi Oka2, outcome of all consecutive and unselected patients undergoing resection of
Yasuhiro Chikaishi2, Ayako Hirai2, Kazue Yoneda2, Yuko Tashima2, Koji brain metastases in two cancer centers in Switzerland to assess safety and
Kuoroda2, Naoko Imanishi2 efficacy of brain metastasis resection in NSCLC. Methods: 119 consecutive
1
Thoracic Surgery, University of Occupational and Environmental Health,
NSCLC patients undergoing surgical resection of brain metastases from
Kitakyuushuu/Japan, 2 Second Department of Surgery (Chest Surgery), University of two centers in Switzerland (University Hospital Basel, Cantonal Hospital St.
Occupational and Environmental Health, Japan, Kitakyusyu/Japan Gallen) between 2000 and 2014 were analyzed. Measured outcomes were
extent of resection, resection status, postoperative complications and overall
Background: Surgery for tumor invading proximal left main pulmonary artery survival (OS). We used the log-rank test to compare unadjusted survival
(PA) may be technical challenge, and the current study conducted to assess its probabilities and multivariable Cox regression to investigate potential
feasibility. Methods: Patients who received surgery for malignant pulmonary prognostic factors with respect to OS. Results: Median age was 60.5 years,
tumor invading left main PA, PA proximal to the first branch (usually A3), from 56% were male, 74% were smokers, 55% had adenocarcinoma. Median OS
2011 through 2015 in our institute were retrospectively reviewed Results: of the whole cohort was 18.0 months. 1-year survival rate was 63%, 12% of
Among 32 eligible patients (Table 1), 31 (97%) patients received complete patients were alive after 5 years. In total, 146 brain metastases were resected;
resection with pneumonectomy (n=4) or lobectomy with PA-reconstruction the maximum number of resected metastases was 4 (median: 1). Median
(n=27). Pericardiotomy was necessary for proximal control of main PA in 12 diameter of resected metastases was 25 millimeters (range, 6-70 mm). About
patients, and combined bronchial sleeve resection and reconstruction were half of metastases were localized in the frontal cortex or the cerebellum.
performed in 11 patients. Postoperative complications occurred in 7 patients, 86% of patients received postoperative radiotherapy. 63% of patients were
but a > grade 3 complication (ARDS) occurred in only one patient who received treated with whole brain radiation, 12.6% received stereotactic radiotherapy.
pneumonectomy. There was no operative or in-hospital death. Median dose of postoperative radiotherapy was 30 Gy. Patients not receiving
adjuvant radiotherapy (n=11) had a significantly worse outcome (median OS
Characteristics of Patients (n=32) 9.0 vs. 20.2 months, p=0.002). Patients with more than one brain metastasis
(n=21) had a significantly worse outcome compared to those with a solitary
No. of Patients %
metastasis (median OS 13.5 vs. 19.5 months, p=0.006). Also patients with
Age, median (range) 70 years (47-85) extracerebral metastases (n=33) had a significantly poorer outcome (median
OS 14.0 vs. 23.1 months, p=0.005). Patients with non-squamous histology
Sex, Female / Male 6 / 26 19% / 81%
(n=98) had a better outcome than patients with squamous cell carcinoma
Histology (median OS 22.6 vs. 12.0 months, p=0.019). 21% of patients experienced
Primary lung cancer 30 94% postoperative complications, including need for surgical reintervention
(5.8%), neurological deficits (4.2%), infection (4.2%), stroke (3.4%) and others
Lung metastasis 2 6%
(11.8%). The occurrence of postoperative complications was not associated
Mode of lung resection with outcome. In the multivariate analysis existence of extracerebral
metastases and resection of more than one brain metastasis were
Upper lobectomy 27 84%
independent negative prognostic factors. Conclusion: Patients with isolated
Pneumonectomy 4 13% brain metastasis from NSCLC in the absence of extracranial metastasis
Exploratory thoracotomy 1 3% should be evaluated for metastasectomy. Prospective trials are needed to
Pericardiotomy 12 38% characterize the patient population experiencing the greatest benefit from a
surgical procedure.
PA-resection 31 97%
Circumferential resection 18 Keywords: Brain metastasis, metastasectomy, Radiotherapy, Prognosis
Partial resection 13
PA-reconstruction 27 84%
Direct closure 25 POSTER SESSION 1 - P1.08: SURGERY
Patch closure (with pericardium) 1 MONDAY, DECEMBER 5, 2016
Vascular conduit (pulmonary vein) 1

P1.08-066 PROGNOSTIC FACTORS OF POST-RECURRENCE
Bronchial sleeve resection 11 34%
SURVIVAL IN PATIENTS WITH COMPLETELY RESECTED STAGE III-N2
Morbidity 7 22%
NON-SMALL CELL LUNG CANCER
Arrythmia 5 Kyung Wook Shin, Sukki Cho, Sung Won Yum, Hyo-Jun Jang, Kwhanmien Kim,
Sanghoon Jheon
Department of Thoracic and Cardiovascular Surgery, Seoul National University was no significant difference in occurrence of post-operative complication.
Bundang Hospital, Seongnam/Korea, Republic of Conclusion: Ipsilateral surgery, especially completion pneumonectomy for 2nd
primary lung cancer was more difficult procedure. However, ipsilateral and
Background: Post-recurrence survival (PRS) after curative resection has
contralateral surgery was equivalent feasibility. Contralateral 2nd primary
been considered a multifactorial process dependent on clinicopathological,
lung cancer is indication for surgery. However, second surgery for ipsilateral
biological, and treatment modality in non-small cell lung cancer (NSCLC). The
2nd primary lung cancer requires careful consideration.
aim of this study is to investigate the prognostic factors for PRS in patients
with completely resected stage III-N2 NSCLC. Methods: Two hundred forty-
five patients who had complete resection for pathologic stage III-N2 NSCLC
between 2003 and 2014 were enrolled. First, a number of clinicopathological
factors were evaluated to find prognostic factors for recurrence by Cox POSTER SESSION 1 - P1.08: SURGERY
proportional hazards models. Second, the following additional data were SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
evaluated: presence of recurrent symptom, recurrence patterns, treatment
modality, use of targeted agents, and recurrence-free interval. The prognostic
effects of these factors were analyzed for PRS. Results: One hundred twenty- P1.08-068 SALVAGE SURGICAL RESECTION AFTER CURATIVE-
four patients experienced recurrence during a median follow-up period of INTENT CONCURRENT CHEMORADIOTHRAPY FOR N2-STAGE III
36.3 months. Univariate analysis showed that vascular invasion, lymphatic
LUNG CANCER
invasion, tumor size, number of positive lymph nodes (LNs), and multistation
N2 were poor prognostic factors for recurrence. Lymphatic invasion, tumor Motohiro Yamashita, Tsuyoshi Ueno, Yoho Maki, Ryusiro Sugimoto
size, and number of positive LNs were even worse independent prognostic Thoracic Surgery, Shikoku Cancer Center, Matsuyama/Japan
factors for recurrence by multivariate analysis. Of 124 recurred patients, 21
Background: A concurrent chemoradiotherapy (CRT) is thought to be the
patients (17%) were symptomatic at the time of initial recurrence, and the
curative treatment for N2 Stage IIIA locally advanced lung cancer (LALC).
remaining 103 patients (83%) were asymptomatic. In these asymptomatic
However, after the CRT the cancer sometimes remained the treatment
patients, recurrence was detected by tumor markers in 3, computed
field. The radical pulmonary resection of residual cancer after CRT is one of
tomography (CT) in 80, or positron emission tomography-CT (PET/CT) in 20
the option for the treatment. Methods: We retrospectively evaluated 20
patients. The mean recurrence-free interval was 14.0 months (≤ 12 months in
patients who received curative-intent CRT and radical surgical resection
72, > 12 months in 52 patients). The patterns of recurrence were presented as
for LALC from January 2003 to April 2016. The initial treatment for LALC
loco-regional recurrence in 37 (30%), distant metastasis in 33 patients (27%),
consisted of platinum based 2-drugs with concurrent curative thoracic
and both in 54 patients (43%). The types of initial treatment included surgery
radiotherapy (60Gy.). Results: The mean age at the surgery was 62.8 years
in 15 (12%), chemotherapy in 68 (55%), radiotherapy in 19 (15%), and chemo-
(range 46~ 80 years), two women and 18 men. The mean interval from CRT to
radiation in 16 patients (13%). The median duration of PRS was 30.5 (1-109)
the surgery was 25 months (range 3-96 months). All patients except two cases
months and the 2-year and 5-year of PRS were 54% and 23%, respectively.
underwent complete surgical resection with mediastinal nodal dissection
Univariate analysis identified no symptom of recurrence, only LN metastasis
including lobectomy in 15 cases, lobectomy with bronchoplasty in 2 cases,
without distant organ metastasis, treatment modality, and a longer
pneumonectomy in 2 cases and 1 wedge resection. The bronchial stump was
recurrence-free interval as good prognostic factors, while no symptom and a
covered with pericardial fat tissue or intercostal muscle. Histological type
longer recurrence-free interval were independent prognostic factors for PRS
was adenocarcinoma in 11 cases, squamous carcinoma in 6 cases, large-cell-
in a multivariate analysis. Conclusion: No symptom at the time of recurrence
carcinoma in 2 cases, and combined cell type small-cell carcinoma in one case.
and a longer recurrence-free interval were significant predictors of better PRS
The mean operation time was 320 minutes (range 163-649 minutes), and mean
in patients that have underwent complete resection of stage III-N2 NSCLC.
blood loss was 868g (range 90-6000g). There was no operative mortality and
Keywords: stage III-N2, Post-recurrence survival, non-small cell lung cancer 8 cases post-operative morbidity such as arrhythmia in 4 cases, atelectasis
in 2 cases, pneumonia, ileus and heart failure in each. There was no broncho-
pleural fistula or bronchial dehiscence. The 3 and 5 years survival after
surgical resection was 70% and 60 % with 43 months median follow-up period.
Conclusion: The radical pulmonary resection after curative-intent concurrent
POSTER SESSION 1 - P1.08: SURGERY chemoradiotherapy is feasible with careful patient selection, operative
procedure and meticulous perioperative care.
Keywords: trimodality treatment, salvage surgery, Stage III loclly advanced

P1.08-067 THE FEASIBILITY OF LUNG SECOND SURGERY FOR 2ND lung cancer, Curative treatment
PRIMARY LUNG CANCER
Kazunori Hata, Kenji Suzuki, Takeshi Matsunaga, Kazuya Takamochi, Shiaki
Oh
Department of General Thoracic Surgery, Juntendo University School of Medicine, POSTER SESSION 1 - P1.08: SURGERY
Tokyo/Japan SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
Background: 2nd primary lung cancer often has been encountered because of
improvement of treatment outcome for lung cancer. If close follow up was
P1.08-069 ONE SURGEON’S 30-YEAR EXPERIENCE OF SURGICAL
performed after first surgery, 2nd primary lung cancer often was detected in
TREATMENT FOR PANCOAST TUMOR
early stage. And local therapy was indicated for this 2nd primary lung cancer.
However, there is no rule whether stereotactic radiation therapy or surgery Hiroshi Niwa, Masayuki Tanahashi, Haruhiro Yukiue, Eriko Suzuki, Naoko
should be chosen. The aim of this study was to evaluate the feasibility of Yoshii, Masayuki Shitara, Toshio Fujino, Yasunori Kaminuma
second surgery. Methods: We reviewed retrospectively 123 consecutive Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital,
patients with past history of lung resection who underwent second surgery Hamamatsu/Japan
for 2nd primary lung cancer between 2008 and 2015 at our institution. i)
Background: Surgical treatment for Pancoast tumor has made marked
These 123 cases were divided into 2 groups, contralateral and ipsilateral
progress, and the patient outcome has improved significantly over the last
surgery groups. The difference between two groups of surgical difficulties
three decades. Developments of some new surgical approaches and the
(operation time and blood loss) and feasibility (post-operative complication
application of preoperative chemo-radiotherapy markedly contributed.
and length of hospital stay) were evaluated by using Mann-Whitney U-test
Methods: We retrospectively analyzed the patients who received surgical
and Fisher’s exact test. ii) 82 cases who underwent contralateral surgery
treatment in two institutes between 1984 and 2013. One surgeon planned
was picked up and divided into 3 groups, both lobectomy, lobectomy
the surgical treatment and performed the operation in all patients. Results:
and limited surgery and both limited surgery. The difference between 3
Seventy-two patients received surgical treatment. There were 61 males
groups of surgical difficulties and feasibility were evaluated by using same
and 11 females, with median age of 61 years old (33-83 years). There were 26
methods. iii) Furthermore, 41 cases who underwent ipsilateral surgery
adenocarcinomas, 26 squamous cell carcinomas, 10 large cell carcinomas, and
divided into 4 groups by procedure: completion pneumonectomy, lobectomy,
10 other pathologies. Forty patients received preoperative induction therapy.
segmentectomy and wedge resection. The difference between 4 groups of
Twenty-five patients were treated by induction chemo-radiotherapy with a
surgical difficulties and feasibility were evaluated by using same methods.
platinum doublet and 40-50 Gy of concurrent radiotherapy. Fourteen patients
Results: i) Not only operation time (161min vs 123min, p<0.001) but blood loss
received radiotherapy alone, and another one patient received chemotherapy
(30g vs 15g, p=0.002) were more in ipsilateral cases than in contralateral cases
alone. The surgical approach was selected based on the tumor location. An
significantly. However, there was no significant difference in feasibility. ii) In
anterior approach including Masaoka’s approach, Dartevele’s approach, and
contralateral cases, there were no significant difference between 3 groups
Grunennwald’s approach were adopted for 19 patients. Posterior approach,
in surgical difficulties and feasibility. iii) In ipsilateral cases, completion
all involving a hook approach was employed in 52 patients. One patient
pneumonectomy had more operation time and blood loss than other
was operated on using both anterior and posterior approaches. Combined
procedures significantly (p=0.005, p=0.002, respectively) However, there
resection excluding the chest wall was performed in 59 patients. The brachial

plexus (Th1) in 48 patients, thoracic vertebrae in 17, subclavian artery in through a median sternotomy (ND3 operation) for Left NSCLC, and reported
eleven, and subclavian vein in 5 were removed with the tumor. In 52 patients that it can allow for complete dissection of all stations of mediastinal
(72.2%), the tumors were completely removed. The morbidity rate was 37.5% lymph nodes. The aim of this study is to add knowledge on mediastinal
and mortality rate was 2.8%. One patient died of bleeding from rapture lymphadenectomy by evaluating the feasibility and efficiency of our ND3
of an aortic anastomosis, and another patient died of esophago-pleural operation. Methods: We retrospectively studied 283 patients who underwent
fistula. The 5-year survival rate for all patients was 44%, with a median ND3 operation due to Left NSCLC, from January 1988 till December 2015.
survival time of 19.5 months. The 5-year survival rate based on the operation All operations were performed through the median sternotomy. The lymph
date was 31.7% for the first half (1984-1999) and 59.1% for the second half nodes around the right and left recurrent laryngeal nerves directly under the
(2000-2013) (p=0.035). The 5-year survival rates of patients who received thyroid gland, and then a series of lymph nodes on the bilateral sides along
and did not receive induction chemo-radiotherapy were 63.0 and 34.8%, the trachea were dissected. Lymph node station #2R, #4R, #2L, #4L, #3a, #5,
respectively. Conclusion: The survival rate after surgical therapy for Pancoast #6, #7, ( #8, #9:Left lower NSCLC) and part of #1R, #1L were removed. Results:
tumor significantly improved over the three decades. Preoperative chemo- Overall 5-year survival rate in the 283 patients was 61.7%. Operative mortality
radiotherapy and the selection of an approach based on the tumor location was 3.1%,(1.1% after 2006) Lymph node metastasis to the mediastinum was
contributed to the improvement. confirmed in 91 (32.1%) patients (pN2 was 50,pN3α was 23, pN3β was 2,
pN3γ was 16).According to pathological stages, five-year survival rate was
Keywords: surgical approach, lung cancer, Pancoast tumor, induction chemo- 88.4% in stage IA, 74.5% in stage IB, 61.3% in stage IIA, 68.4% in stage IIB,
radiothearpy 46.8% in stage IIIA, 40.8% in stage IIB. Five-year survival rate were 47.9% in
cN2(n=45), 46.7% in cN3α(n=19),47% in pN2(n=50), and 47.5% in pN3α(n=23).
Conclusion: Surgery for Stage III-N2,N3 Lt. NSCLC achieved good long-term
survival . Our result suggest that ND3 operation　would provide better
prognosis in the patients with mediastinal lymph node metastasis, and it
SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC – does not increase mortality. We can assume that our ND3 operation in Lt.
MONDAY, DECEMBER 5, 2016 NSCLC with mediastinal lymph node involvement represent feasible, safe, and
effective option. It is important to perform curative operation with complete
dissection of all station of mediastinal lymph nodes. Surgery should be
P1.08-070 SALVAGE LUNG SURGERY: DIFFICULTIES AND RESULTS
considered as a first treatment for patients with stage III-N2,N3 Lt.NSCLC.
Banu Yoldas1, Soner Gursoy1, Ahmet Ucvet1, Berna Komurcuoglu2, Esra
Kirakli3 Keywords: non small cell lung cancer, Lymphadenectomy, mediastinal lymph
1
Thoracic Surgery, Izmir Dr. Suat Seren Chest Diseases and Thoracic Surgery Training node
and Education Hospital, Izmir/Turkey, 2Pulmonology, Izmir Suat Seren Education
Hospitall for Chest Disease, Izmir/Turkey, 3Radiation Oncology, Dr. Suat Seren
Göğüs Hastalıkları Ve Cerrahisi Eğitim Ve AraŞtırma Hastanesi, Izmir/Turkey
Background: Thoracic surgeons often encounter lung resections following POSTER SESSION 1 - P1.08: SURGERY
neoadjuvan treatments. Despite that, sometimes patients have curative SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
chemo or/and radiotherapy treatments according to being inoperable for
different reasons at the time of diagnosis. After these treatments due to
residual tumour or relapses, surgery might be performed and this kind of P1.08-072 THE RESULT OF COMPLETION PNEUMONECTOMY
surgery is called “salvage surgery”. This surgery has more difficulties and FOR THE LOCAL RECURRENT LUNG CANCER AFTER RADICAL
complications because of the adverse effects of definitive therapies. In this
LOBECTOMY
study we retrospectively analysed such patients undergone salvage surgery,
and looked for an answer if we have to avoid or not? Methods: Patients Takeshi Shiraishi, Shin-Ichi Yamashita, Akinori Iwasaki
operated after curative chemo or/and radiotherapy (4 cycles and more Dept. of General Thoracic, Breast, and Pediatric Surgery, Fukuoka University School
chemotherapy and 66 Gy radiotherapy is accepted as curative radiotherapy) of Medicine, Fukuoka City/Japan
between January 2010 and December 2014 were included in this study
Background: Retrospective review on the result of completion
and analysed retrospectively. Demographic data, surgical management,
pneumonectomy (CP) for the local recurrent non-small cell lung cancer
morbidity, mortality and survival results were collected. Results: Having the
(NSCLC) following the radical lobectomy, performed by a single institution.
described criteria 69 cases (62 male, 7 female) were included in the study.
Methods: From 1995 to 2015, 12 consecutive patients underwent CP for cure
Six of the cases had chemotherapy, 8 radiotherapy only and remaining 55
of loco-regional recurrent NSCLC. Eleven out of these were the cases with
had only chemotherapy (4-12 cycles). At the postoperative period, 5 cases
recurrent tumor at resection margin of previous surgery and the rest was
were undergone rethoracotomy, 10 had prelonged air leakage and were
the case with multiple metastatic tumors within the ipsilateral remaining
externed with “Heimlich Valve” system, 5 had intraoperative vascular injury;
lung lobe. The right CP was performed for 5 patients (41.6%) and the left for
1 chylothorax, 4 secretion retantion requiring bronchoscopy, and 2 (2.3%)
7 (58.3%). Results: Operative mortality was 0% and major complications
mortality occured. The mean follow up time was 27.6±20.5, ranging with
occurred to 3 patients (25%). The operations were performed by the
0.1-69.7 months. Five year survival was calculated as 51.9%. Conclusion:
posterolateral thoracotomy for 7 patients, and 5 by the anterior approaches
Complications after resective surgery following curative treatments are at
(median sternotomy or hemi-clamshell thoracotomy). The control of hilar
acceptable rates. Besides this, the 51.9% five year survival rate seems like a
components was achieved through an intra-pericardial route in all cases. In
last chance for such patients who have had their definitive treatment.
two cases, the infiltration of the recurrent tumors were confirmed in the
Keywords: salvage, Surgery, lung, Cancer carinal bifurcation. Thus, the completion “sleeve” pneumonectomy was
performed. The complete resections were achieved in all patients. Mean
observation period was 1313 days after CP at the time of this investigation.
Four patients deceased including 2 cancer re-relapse death and 2 cancer
unrelated death. There are 8 survivors for more than one year after CP
POSTER SESSION 1 - P1.08: SURGERY including 4 patients surviving without cancer relapse (mean survival time
SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC – [MST] of 1214 days) and 4 surviving with either local or distant cancer relapse
(MST = 1354 days). Among those 4 survivors with cancer relapse, 3 patients
were treated with molecular targeted drugs after gene-mutation survey for
P1.08-071 SURGERY FOR LUNG CANCER WITH MEDIASTINAL susceptibility of specific molecular targeted drugs using tumor specimen
LYMPH NODE METASTASIS - EFFECTIVENESS OF EXTENDED harvested from CP surgery. Another patient with cancer relapse was found
BILATERAL MEDIASTINAL LYMPHADENECTOMY to be unsuitable for any type of molecular targeted drugs, thus treated with
cisplatin based conventional anti-cancer protocol. Five year survival rate for
Toshiya Yokota, Shingo Ikeda
the entire series was 66.7%. Conclusion: Completion pneumonectomy has
Thoracic Surgery, Mitsui Memorial Hospital, Tokyo/Japan
been considered as a complex and high risk surgical procedure, however, due
Background: The role of surgery in the treatment of non-small-cell lung to the recent progresses made in the surgical techniques and post-operative
cancer (NSCLC) with clinically manifested mediastinal node metastasis management, the CP in the setting of locally recurrent NSCLC became safe
is controversial even in resectable cases. Hata et al. used scintigraphy in and favorable treatment option. More importantly, tumor specimen obtained
healthy volunteers to show that main lymphatic route from any pulmonary by the CP can be used for selecting the updated molecular target drugs which
lobe was connected with both sides of supraclavicular lymph nodes through might be helpful for patient’s long term survival.
the superior madiastinal nodes. They considered bilateral mediastinal Keywords: Surgery, completion pneumonectomy, recurrence, lung cancer
lymphadenectomy contributes the survival of the patient with NSCLC. Due
to anatomical limitation, it is difficult to perform complete dissection of
superior mediastinal lymph nodes through the left thoracotomy. We had
devised extended bilateral mediastinal lymphadenectomy and lung resection
POSTER SESSION 1 - P1.08: SURGERY 2007; of which, 20 patients showed to have EGFR mutation. Targeted agents
were used in 32 out of 51 patients. The mean overall survival was 36.4 months
(5.9-98.0); 28 patients died during the follow-up period. The 2-year and 5-year
survival rates were 75.7 % and 39.8%, respectively. The prognostic factors for
P1.08-073 EXPERIENCE OF THIRD PRIMARY LUNG TUMORS AFTER patients with overall survival of more than 36 months, seen in 19 patients,
TREATMENT OF FIRST AND SECOND PRIMARY LUNG CANCER were old age, negative post-IPHC pleural biopsy, and presence of EGFR
Takehiro Watanabe, Takahisa Koizumi, Tatsuhiko Hirono mutation. Conclusion: IPHC appears to be a safe procedure for advanced lung
cancer patients with pleural seeding, and IPHC may provide better survival to
Thoracic Surgery, Nishi-Niigata Chuo National Hospital, Niigata/Japan
only a highly selective group of patients. Old age, negative post-IPHC pleural
Background: Widespread adoption of lung cancer screening and development biopsy, and presence of EGFR mutation are the predictive factors for longer
of high-resolution computed tomography (HRCT) have led to a marked survivor.
increase in the detection of early lung cancer in Japan. After curative
Keywords: pleural seeding, non-small cell lung cancer, intrapleural perfusion
resection for early lung cancer, second primary lung cancers develop in a
hyperthermic chemotherapy
significant proportion. The majority of these cancers are detected at an
early stage because of careful follow-up using HRCT. In our experience, more
than 80% of these patients were treated with surgery or radiation therapy,
and some of them have acquired with long-term survival. Recently we have
experienced with third primary lung tumors in long-term survivors. In this POSTER SESSION 1 - P1.08: SURGERY
paper, we reviewed the incidence, management, and outcome of third primary SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
lung tumors. Methods: Between April 1996 and March 2016, 1194 patients MONDAY, DECEMBER 5, 2016
underwent complete resection for primary lung cancer in our institution. Of
these individuals, patients who developed a third primary lung tumor were P1.08-075 SALVAGE SURGERY FOR STAGE IV NON-SMALL CELL
selected for this study. Results: Of 1194 consecutive patient, 105 patients
LUNG CANCER
(8.8%) developed second primary lung cancers, and 11 patients (1%) of them
developed third primary lung tumors. The patients included 10 men and one Hideaki Kojima1, Shoko Hayashi1, Kiyomichi Mizuno1, Yoshiyuki Yasuura1,
woman. The initial resection for primary lung cancer was lobectomy in 9 Reiko Shimizu1, Hiroyuki Kayata1, Shoji Takahashi1, Mitsuhiro Isaka1, Toshiaki
patients and segmentectomy in 2. Surgical resection for second primary lung Takahashi2, Yasuhisa Ohde3
1
cancer was performed in 8 patients, and radiation therapy was performed in Division of Thoracic Surgery, Shizuoka Cancer Center, Shizuoka/Japan, 2Thoracic
3. Four of the 11 patients underwent resection for third primary lung tumors. Oncology, Shizuoka Cancer Center, Shizuoka/Japan, 3Thoracic Surgery, Shizuoka
Cancer Center, Shizuoka/Japan
One patient had completion pneumonectomy, 1 had segmentectomy, and
2 had wedge resections. Five patients were treated by radiation therapy. Background: There have been few reports regarding salvage surgery in
The two remaining patients received best supportive care. Survival after patients with primary lung cancer, and the efficacy of salvage pulmonary
resection of first primary lung cancer ranged from 50 months to 185 months, resection for primary lung cancer have not been fully elucidated. Furthermore,
with a median survival of 138 months and an average survival of 137 months. salvage surgery for stage IV non-small cell lung cancer have been rarely
Currently, 4 patients are alive without evidence of recurrence. Among them, performed. The purpose of this study is to evaluate the efficacy of salvage
three patients were treated by their third pulmonary resection, and one surgery for stage IV non-small cell lung cancer. Methods: We performed a
patient was treated by radiation therapy. Conclusion: During 20 years, third retrospective analysis of 4 patients who underwent salvage pulmonary
primary lung tumors were diagnosed in only 11 patients (1%). But long-term resection for stage IV non-small cell lung cancer between September, 2002
survivors after resection of lung cancer are increasing. Careful follow-up and and September, 2015 at the Shizuoka Cancer Center Hospital. Results: Of
early detection of second primary lung cancers using HRCT will induce the 2606 cases of surgically resected lung cancer in our hospital, 4 cases (0.15%)
increase of experience for treatment of third primary lung tumors. In our little of salvage surgery for stage IV non-small cell lung cancer patients were
experience, aggressive surgery for third primary lung tumors may improve performed. There were 2 men and 2 women. The range of age was 38-63 years
survival. old (median 57 years old). The histological type was 3 adenocarcinomas and
one large cell carcinoma. The reasons diagnosed stage IV non-small cell lung
Keywords: third primary lung tumor, radiation therapy, lung cancer, Surgery
carcinoma were 2 liver metastasis, 1 brain metastasis, and 1 abdominal lymph
node metastasis. All cases have administered chemotherapy, and salvage
pulmonary resection was performed for persistent or recurrent primary lung
tumors. The median period for surgery from chemotherapy was 17.5 months
POSTER SESSION 1 - P1.08: SURGERY (range 13-55 months). The lobectomy was performed in all cases. There were
SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC – no complications after surgery and the mean length of hospital stay was 9
days. Postoperative disease free survival of all patients was 2, 2, 5, 52 months
(median 3.5 months), respectively. 3 cases had recurred after surgery and all
P1.08-074 EFFECT OF INTRAPLEURAL PERFUSION HYPERTHERMIC of them were distant recurrence. 2 cases were died of disease (survival time
CHEMOTHERAPY IN NON-SMALL CELL LUNG CANCER WITH 15, 42 months, respectively), 1 case was alive with recurrent disease, and 1 case
was alive with no recurrent disease (survival time 52 months). Conclusion:
PLEURAL SEEDING
Although almost all cases had developed distant recurrence after surgery
Hyo-Jun Jang1, Kyung Wook Shin1, Sukki Cho1, Sook Whan Sung2, Kwhanmien early, one case was long-term survival. Salvage surgery might have been
Kim1, Sanghoon Jheon1 effective for highly selected stage IV non-small cell lung cancer patients.
1
Department of Thoracic and Cardiovascular Surgery, Seoul National University
Bundang Hospital, Seongnam/Korea, Republic of, 2 Seoul St.Mary’s Hospital, Seoul/ Keywords: salvage pulmonary resection, salvage surgery, stage IV, non-small
Korea, Republic of cell lung cancer
Background: Pleural seeding is generally associated with poor prognosis
in advanced non-small cell lung cancer (NSCLC). Although palliative
chemotherapy is the mainstay modality for these patients, intrapleural
perfusion hyperthermic chemotherapy (IPHC) may be a good alternative. The POSTER SESSION 1 - P1.08: SURGERY
aim of this study was to evaluate the efficacy of IPHC and predictive factors SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
for longer survival in NSCLC with pleural seeding. Methods: From 2003 to
2014, 51 patients who underwent IPHC for NSCLC with pleural seeding at the
first operation in 36 or after postoperative recurrence in 16 patients were P1.08-076 RECURRENCE PATTERNS IN LUNG CANCER PATIENTS
enrolled. IPHC was performed with cisplatin (dose:150mg/m2) for 90 minutes. TREATED WITH PROTOCOL BASED MULTIMODALITY TREATMENT
For patients with pleural seeding at first operation, parenchymal resection
AT A TERTIARY CARE CANCER CENTER IN INDIA
was performed and mediastinal LN was evaluated. We included some
procedures other than pre-IPHC pleural biopsy, pre-IPHC lavage cytology, Ashish Jakhetiya1, Vinay Kumar 1, Surayanarayana Deo1, Nootan Shukla1,
post-IPHC lavage cytology, and post-IPHC pleural biopsy. Subjects were Durgatosh Pandey1, Prabhat Malik2, Deepali Jain3, Sunil Kumar 1
1
divided into two groups: group I is shorter survivor of less than 36 months and Surgical Oncology, All India Institute of Medical Sciences, New Delhi/India,
2
group II is longer survivor of more than 36 months of overall survival duration. Medical Oncology, All India Institute of Medical Sciences, New Delhi/India,
3
Pathology, All India Institute of Medical Sciences, New Delhi/India
Results: There were 22 male patients and the mean age was 59.6 years. There
were 7 patients in pathologic stage T1, 28 in T2, 13 in T3, and 3 in T4. With Background: Wide disparity has been reported in lung cancer survival between
respect to N stage, 18 patients in N0, 9 in N1, 17 in N2, and 8 in Nx. Major post- high income countries (HIC) and low-middle income countries (LMIC). The
IPHC complication was acute renal insufficiency (n=4). All patients, except 3, aim of present study is to analyze treatment outcomes and relapse patterns
received systemic chemotherapy after IPHC. Pleural seeding aggravation was following protocol based multimodality management including quality
seen in 28 patients, and the development of pleural effusion was observed control surgery in lung cancer patients from a tertiary care cancer center in
in 5 patients after IPHC. EGFR mutation was examined in 38 patients after

India (LMIC). Methods: A retrospective analysis of computerized prospective patients is not widely accepted and chemotherapy is usually administered.
clinical database of lung cancer patients treated consecutively during January The study was aimed to evaluate the long-term results and prognosis after
2006 to June 2015, in the department of Surgical Oncology, Institute Rotary surgical resection of oligometastases in NSCLC patients. Methods: 139
Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India was patients with isolated distant metastases of NSCLC (M1a – 38, M1b – 101)
performed. The AJCC/ TNM (2010) staging system was referred for staging operated on in our clinic from 1998 to 2011 were included in the retrospective
purpose. All patients were offered protocol based trimodality therapy trial from the prospective database. Solitary brain metastasis was
(Surgery + Systemic therapy + Radiotherapy). Clinical spectrums, Follow diagnosed in 82, pleural metastases – in 21, contralateral lung – in 17, adrenal
up patterns, compliance to treatment and relapse patterns were analyzed. metastases – in 11, others – in 8 patients. Synchronous metastases were
Results: A total of 136 patients underwent surgery during this period. Mean detected in 61 (43,9%), metachronous – in 78 (56,1%) patients. In patients
age at presentation was 53.16 years (SD 13.56) with male predominance with pleural dissemination lung resection with pleurectomy followed by
(78%). Cough (58%) and Hemoptysis (42%) were most common presenting PDT was carried out. The primary lung cancer was completely resected in all
symptoms. Majority operated upfront (70%) and 126 (92.6%) underwent cases. Surgery included pneumonectomy – in 17, lobectomy/bilobectomy – in
curative resection. Most common procedure was lobectomy (52%) however 112 and sublobar resection – in 10 patients. Median follow up is 52 month.
42 patients (30%) underwent pneumonectomy due to advanced stage. Results: Postoperative complications were registered in 10 (7,2%) patients,
Most common histology was squamous cell carcinoma (45%) followed by mortality – 2,2%. Median survival after pulmonary resection and removal of
adenocarcinoma (36%). Most common stage was IIIA (30%) followed by IIB brain metastasis was 23,0 months, contralateral lung resection – 12,0, after
(27%). Median duration of surgery and hospital stay was 180 minutes and lung resection with pleurectomy – 11,0 and adrenalectomy – 9,0 months.
7 days respectively. One patient developed post operative pneumonia and 5-year survival after lung resection and brain metastasectomy was 20,6%,
succumbed to it while 15 others developed major postoperative morbidity contralateral lung resection – 12,0%, lung resection and pleurectomy
which was managed conservatively. Total of 30% received adjuvant (limited pleural spread) – 10,7%. No one survived more than 2 years after
chemotherapy and 11% received adjuvant radiotherapy. After median follow adrenalectomy. Survival of patients in N0-1 cases was significantly better
up of 7.26 months 16 (11.75%) patients had documented recurrences. Out of in all groups: after brain metastasectomy - 34,5% vs 0%, contralateral lung
16 patients 3 had isolated loco-regional, 4 had loco-regional with systemic resection – 28,0% vs 0%, pleural dissemination – 4,7% vs 0% in N2 positive
and 9 had systemic recurrence. Among systemic recurrences five had multiple patients with median survival 19,0 and 8,0; 15,0 and 8,0; 23,0 and 10,0
visceral, bone and brain in three each followed by contralateral lung in two months respectively. Overall survival was worse in synchronous group if
patients. Conclusion: Majority of lung cancer patients presents in advanced compare with metachronous detection: after brain metastasectomy 10,0%
stage. With good protocol based approach including quality-controlled and 19,8%; contralateral lung resection 0% and 32,0% with median survival
surgery excellent outcomes can be achieved which are comparable to western 18,0 and 25,0; 11,0 and 21,0 months respectively. Multivariate analysis
world even in resource constrained low middle income countries like India. confirmed that positive N2 status (p<0.001) and synchronous detection of
oligometastatic disease (p=0.002) were independent unfavorable prognostic
Keywords: low and middle income country, lung cancer, Surgery factors. Conclusion: Aggressive surgery in patients with oligometastatic
NSCLC is justified in selected patients with solitary brain, contralateral lung
metastasis and limited pleural dissemination, especially in N0-1cases and
metachronous disease. Surgical resection should be whenever avoided in
patients with oligometastatic lung cancer and positive N2 status.
MONDAY, DECEMBER 5, 2016 Keywords: lung cancer, Oligometastatic disease, Surgery
P1.08-077 COMPARISON OF PULMONARY RESECTION FOR LUNG

CANCER AFTER RADICAL CHEMORADIATION WITH THAT AFTER
INDUCTION CHEMORADIATION POSTER SESSION 1 - P1.08: SURGERY
Yasuhiro Hida, Kichizo Kaga, Masato Aragaki, Reiko Nakada-Kubota, MONDAY, DECEMBER 5, 2016
Haruhiko Shiiya, Hatsuki Usui, Yoshiro Matsui
Dept. Thoracic and Cardiovascular Suegery, Hokkaido University Hospital,
P1.08-079 SULVAGE SURGERY AFTER DEFINITIVE RADIOTHERAPY
Sapporo/Japan
OR CHEMORADIOTHERAPY FOR LUNG CANCER
Background: Induction chemoradiation (ICR) for advanced non-small cell Naoya Yamasaki1, Tomoshi Tsuchiya1, Keitaro Matsumoto1, Takuro Miyazaki1,
lung caner is often limited to 45Gy or less to avoid increase of perioperative Ryotaro Kamohara1, Tomohiro Obata1, Daisuke Taniguchi1, Takuya Yamasaki2,
complications. On the other hand, pulmonary resection after definitive Daisuke Nakamura2, Kazuhiro Tabata3, Takeshi Nagayasu1
chemoradiotherapy (DCR) is increasing. In this study, we compared three 1
Surgical Oncology Nagasaki Graduate School of Biomedical Sciences, Nagasaki
groups, pulmonary resection following low dose ICR (LCR), that following high University, Nagasaki/Japan, 2Radiological Sciences, Nagasaki University, Nagasaki/
dose ICR (HCR) and that after DCR. Methods: From 1997 to 2015, we had 24 Japan, 3Pathology of Nagasaki Graduate School of Biomedical Sciences, Nagasaki
pulmonary resections following CR. Among 13 ICR, 7 were LCR and 6 were HCR. University, Nagasaki/Japan
There were 11 DCR. Intercostal muscle flaps were used in 1 LCR, 6 HCR and 1
DCR. Omental flaps were used in 8 DCR. Results: There was no mortality in any Background: Reports of salvage surgery especially bronchoplasty after
groups. In comparison with LCR and HCR, operation time (min) were 352 and definitive radiation therapy for locally advanced lung cancer are small. In
344, estimated blood loss (ml) were 440 and 280, morbidity (%), 86 and 50. addition, reports of surgery after stereotactic body radiotherapy (SBRT)
Although operation time was longer (470 min) and there were more blood loss are also small. Methods: Between 2011 and 2015, 3 patients who underwent
(820 ml) in DCR, there was no significant increase of peri- and post-operative salvage pulmonary resection after definitive radiation therapy (Group A)
complications. 2-year recurrence free survival and 5-year over all survival rates and 3 patients after SBRT (Group B) were identified. Results: Group A: One of
(%) were 43 and 29 in LCR, 40 and 60 in HCR, and 58 and 52 in DCR. Conclusion: two patients who underwent boronchoplasty failed in anastomosis failure. A
High dose ICR may contribute to better local control and longer survival. 40-year-old woman underwent right upper sleeve lobectomy after chemo-
Pulmonary resection after DCR is as safe as that following ICR. radiation therapy including bevacizumab for primary lung adenocarcinoma
(cT3N2M0 Stage IIIA). Two months after surgery, anastomosis dehiscence
Keywords: Trimodality, advanced NSCLC, salvage surgery occurred. She underwent right completion pneumonectomy after preparing
an omental flap. Bronchial stump was closed in overholt method with
wrapping of omental flap. After surgery, left kidney and supraclavicular
lymph node metastasis were detected, she was administered crizotinib. She
is alive at 48 months after surgery. The other two patients are alive without
POSTER SESSION 1 - P1.08: SURGERY recurrence at 8 and 35 months, respectively. Group B: The dose of radiation
MONDAY, DECEMBER 5, 2016 was 48Gy (12 Gy x 4 fractions ). Period from SBRT until surgery was 14, 18, 30
months, respectively. One patient underwent SBRT for second lung cancer
after left upper lobectomy for first lung cancer. He died of respiratory failure
P1.08-078 DOES SURGERY HAVE REAL BENEFIT IN RESECTABLE on 103 days after surgery. The clinical courses of other two patients were
OLIGOMETASTATIC NSCLC? uneventful. One patient died of distant metastasis at 7 months, and other
Oleg Pikin1, Andrey Ryabov2, Vladimir Glushko1, Konstantin Kolbanov1, Ali one is alive without recurrence at 8months. There were no severe adhesion
Amiraliev1, Dmitriy Vursol1, Vladimir Bagrov1, Vitaliy Barmin1 on both hilar and chest wall after SBRT. Conclusion: Caution is needed in
1
Thoracic Surgery, Hertzen Research Institute of Oncology, Moscow/Russian the salvage pulmonary resection after chemo-radiation therapy including
Federation, 2Thoraco-Abdominal Surgery, Hertzen Research Institute of Oncology, bevacizumab. On the other hand, there was not strong influence to the
Moscow/Russian Federation bronchial stump after SBRT.
Background: The prognosis in patients with distant metastases of NSCLC is Keywords: definitive radiotherapy, lung cancer, Surgery
generally poor. Surgical resection of isolated distant metastases in NSCLC
POSTER SESSION 1 - P1.08: SURGERY POSTER SESSION 1 - P1.08: SURGERY

SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC – SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
P1.08-080 BILOBECTOMY FOR LUNG CANCER: ANALYSIS OF P1.08-082 SURGICAL TECHNIQUES AND LONG-TERM RESULTS OF
INDICATIONS, POSTOPERATIVE RESULTS AND LONG-TERM THE PULMONARY ARTERY RECONSTRUCTION IN PATIENTS WITH
OUTCOMES LUNG CANCER
Domenico Galetta, Alessandro Borri, Roberto Gasparri, Francesco Petrella, Domenico Galetta, Alessandro Borri, Roberto Gasparri, Francesco Petrella,
Lorenzo Spaggiari Lorenzo Spaggiari
Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy
Background: Bilobectomy for lung cancer is considered a high risk procedure Background: Pulmonary artery (PA) reconstruction for lung cancer is
for the increased postoperative complication rate and the negative impact on technically feasible with low morbidity and mortality. We assessed our
survival. We analyzed the safety and the oncologic results of this procedure. experience with partial or circumferential resection of PA during lung
Methods: We retrospectively reviewed patients who underwent bilobectomy resection. Methods: Between 1998 and 2015, we performed PA angioplasty
for lung cancer between October 1998 and December 2015. Age, gender, in 150 patients with lung cancer. Seventy-five patients received induction
bilobectomy type and indication, complications, pathology, stage, and chemotherapy (IC). Partial PA resection was performed in 146 cases. PA
survival were analyzed. Results: Bilobectomy was performed on 166 patients reconstruction was performed by running suture in 113 and using a pericardial
(122 men; mean age, 62 years. There were 87 upper-middle and 79 middle-lower patch in 33. A circumferential PA resection was performed in 4 patients and
bilobectomies. Indications were tumor extending across the fissure in 37 reconstruction was made in PTFE and by a custom-made bovine pericardial
(22.3%) patients, endobronchial tumor in 44 (26.5%), extrinsic tumor or nodal conduit each. Bronchial sleeve resection was associated in 56 cases. Thirty-
invasion of bronchus intermedius in 70 (42.2%), and vascular invasion in 15 two patients had stage I disease, 43 stage II, 51 IIIA, and 17 IIIB. Seven patients
(10%). An extended resection was performed in 25 patients (15.1%). Induction had a complete response after IC. Results: Thirty-day mortality was 3.3%
therapy was performed in 47 patients (28.3%). Thirty-day mortality was 1.2% (n=5); two of these patients had a massive hemoptysis leading to death;
(n=2). Overall morbidity was 43.4%. Mean chest tube persistence was 7 days 33 patients had pulmonary complications, 28 cardiac, 17 air leaks. Overall
(range, 6-46 days). Overall 5-year survival was 58%. Significance differences 5- and 10-year survival was 50% and 39%, respectively. Five- and 10-year
in survival were observed among different stages (stage I, 70%; stage II, survival for stages I and II versus stage III was, respectively, 66% versus
55%; stage III, 40%; p=.0003) and the N status (N0, 69%; N1, 56%; N2, 40%; 32% and 56% versus 20% (p<.0001). Five-year survival was 61% for N0 and
p=.0005). Extended procedure (p=.0003) and superior bilobectomy (p=.0008) N1 nodal involvement versus 28% for N2, respectively; 10-year survival was
adversely influenced survival. Multivariate analysis demonstrated that an 45% versus 28% (p=.001). IC did not influence survival. Multivariate analysis
extended resection (p=.01), an advanced N disease (p=.02), and an upper-mild yielded advanced stage, N2 status, and squamous cell carcinoma as negative
lobectomy (p=.02) adversely affected prognosis. Conclusion: Bilobectomy is prognostic factors. Conclusion: PA reconstruction is safe, with excellent long-
associated with a low mortality and an increased morbidity. Survival relates term survival. Our results support this technique as an effective option to
to disease stage and N factor. Optimal prognosis is obtained in patients with pneumonectomy for patients with lung cancer.
lower-middle lobectomy without extension of the resection.
Keywords: lung tumors, Surgery
Keywords: lung tumor, Bilobectomy, Surgery

POSTER SESSION 1 - P1.08: SURGERY SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC –
SURGERY FOR LOCALLY ADVANCED AND ADVANCED NSCLC – MONDAY, DECEMBER 5, 2016
P1.08-083 HYPERTHERMIC PLEURAL LAVAGE FOR PLEURAL

P1.08-081 RESECTION OF T4 NON-SMALL CELL LUNG CANCER METASTASES
INVADING THE SPINE Patricia Thompson1, Daniel Miller2, Jordan Whetstone2, Ioana Bonta1,
Domenico Galetta, Lorenzo Spaggiari Christopher Parks1, Rabih Bechara1
1
Division of Thoracic Surgery, European Institute of Oncology, Milan/Italy Thoracic Oncology, Cancer Treatment Centers of America, Newnan/United States
of America, 2Wellstar Health System, Newnan/United States of America
Background: Surgical treatment of non-small cell lung cancer (NSCLC)
invading the spine is controversial. We evaluated surgical results and long- Background: To evaluate the safety and efficacy of hyperthermic pleural
term outcome of patients with T4 NSCLC who underwent vertebral resection lavage (HTPL) with cisplatin in patients who have undergone cytoreductive
(VR) due to the infiltration by lung tumor.Methods: Retrospective analysis of surgery pleurectomy/decortication (PD) for isolated chemoresistant pleural
16 consecutive patients undergoing VR for NSCLC invading the spine between metastases (PM). This may be an alternative treatment for patients with
1998 and 2015 was performed. Ten patients (62.5%) received induction isolated pleural metastases with controlled primary disease. Methods:
therapy. Vertebral resection was divided into 5 types; type 1: only transverse After Health Care System and Cancer Committee approval, 10 patients with
process; type 2A: transverse process with a portion of the vertebral body; unilateral chemo resistant pleural metastasis were registered prospectively.
type 2B: a portion of vertebral body without transverse process; type 3, The patients’’ primary sites of malignancy were under control for a median
hemivertebrectomy; type 4: total vertebrectomy. Results: There were 15 men of 40 months (range, 28-76). Patients underwent a unilateral radical P/D and
and one woman with a median age of 62 years (range, 41-80). Ten patients had lymph node dissection, 60 minute pleural lavage (1,500 – 1,700 cc/min) with
induction therapy. Vertebral resection included 3 type 1 resection, 6 type 2A, 4 225 mg/m2 of cisplatin at 42°C. Cisplatin levels were drawn at time zero, 1
type 2B, 2 type 3, and 1 type 4. Pneumonectomy was performed in 3 patients, hour, 4 hours, and 24 hours after completion of HTPL. Results: Median age was
lobectomy in 7, segmentectomy in 3 and wedge in 3. Complete resection was 53 years (range, 38-64); 7 patients (70%) were women. Primary tumor: breast
achieved in 14 patients (87.5%). Surgical nodal status was N0 in 11 patients, N1 5, colon 2, and thymic, renal cell and anal cancer 1 each. Surgical approach was
in 2, and N2 in 3, each. There were no postoperative mortality. Morbidity was a thoracotomy in 9 patients (90%). Morbidity included atrial fibrillation in 3
observed in 7 patients (43.7%), including 1 (6.2%) neurologic complication, (30%), and acute respiratory distress syndrome in 1 (10%). Median hospital
3 (18.7%) ARDS, and 2 (12.5%) cardiac . Seven patients (43.7%) are alive stay 7 days (range, 4-14). Serum cisplatin levels peaked at 4 hours after lavage;
without disease after e mean follow up of 44.4 months. The 1- and 5-year none to toxic range. Median dose of cisplatin was 386 mg (range, 299-450); no
predicted survivals were 79% and 40.4%, respectively. Patients without nodal patient developed renal insufficiency. Median follow up was 10 months (range,
involvement had the best prognosis (56.3% vs 0%; p=0.0009). Induction 1-15). 8 patients had no signs of malignant disease at last follow up; 1 patient
therapy did not influence survival. Conclusion: Resection of NSCLC with (anal cancer – 6 months) developed local recurrence and 1 patient (renal cell
vertebrectomy is technically demanding and is associated with acceptable cancer – 9 months) developed contralateral pleural disease. All patients
morbidity. However, an encouraging long-term survival observed in this experienced improved quality of life, respiratory function, and reduced
series suggest that resection could be a valid option in selected patients with pleuritic pain. Conclusion: Surgical cytoreduction of chemoresistant PM
vertebral invasion by NSCLC. followed by HTPL with cisplatin was well tolerated with no cisplatin-related
toxicities. Early results are promising. This novel treatment for patients with
Keywords: lung tumor, Surgery, vertebra isolated secondary PM represents the first series reported. Longer follow-up
is warranted to determine a survival and quality of life advantage as well as
defined inclusion and exclusion criteria.
Keywords: pleural metastasis hyperthermic lavage


Miscellaneous –
P1.08-084 TREATMENT FOR ELDERLY PATIENTS WITH CLINICAL

STAGE I NON-SMALL CELL LUNG CANCER; SURGERY OR
STEREOTACTIC BODY RADIOTHERAPY?
Takuro Miyazaki1, Takuya Yamazaki2, Daisuke Nakamura2, Naoya Yamasaki1,
Tomoshi Tsuchiya1, Keitaro Matsumoto1, Ryotaro Kamohara1, Go Hatachi1,
Takeshi Nagayasu1
1
Surgical Oncology, Nagasaki Graduate School of Medicine, Nagasaki/Japan,
2
Radiological Sciences, Nagasaki Graduate School of Medicine, Nagasaki/Japan
Background: The number of elderly lung cancer patients requiring surgery

has been increasing due to the aging society and less invasive perioperative
procedures. Stereotactic body radiotherapy (SBRT) is one of the effective
treatments for early stage non-small cell lung cancer (NSCLC). The aim of this
retrospective study was to compare the outcome of pulmonary resection
to SABR for elderly clinical stage I NSCLC in our hospital. Methods: Over
80-year-old patients with clinical stage I NSCLC between August 2008 and
December 2014 were treated either surgery or SBRT at Nagasaki university
hospital. Propensity score matching (PSM) was performed to reduce selection
bias in various clinicopathological factors including age, gender, tumor size,
carcinoembryonic antigen (CEA), Charlson comorbidity index (CCI), Glasgow
prognostic scale (GPS) and forced expiratory volume in one second (FEV1.0)
were compared between surgery and SBRT. Results: Pulmonary resection was
performed in 57 cases, SABR in 41 cases. In surgery group, operations included
34 lobectomies, 23 limited resection (segmentectomy and wedge resections).
Systemic lymph node dissection was 16 and limited dissection was 41 cases.
In SABR group, 17 cases (41.5%) were not proven in histology. 27 cases were
given 48 Gy by 4 fractions, 14 were 60 Gy by 10 fractions, respectively. No
treatment deaths were observed. Before PSM, the 5 year overall survival (OS)
in surgery (68.3%) was significantly better than that in SBRT (47.4%, p=0.02).
the 5 year disease specific survival (DSS) (94.1%, 78.2%, p=0.17, respectively)
was not significant. Similar characteristics were identified in age (82 years),
gender, tumor size (2.2 cm), CEA (3.6 ng/ml), CCI (1), GPS (0) and FEV1.0 (1.7
Litter) after PSM. The difference in 5 year OS became insignificant between
the matched pairs (57.0%, 49.1%, p=0.56, respectively). 5 year DSS was not
significant (87.1%, 70.2%, respectively). Both treatments for elderly clinical
stage I NSCLC were acceptable though unknown histology and precise lymph
node status still existed as important bias. Conclusion: Surgery for early stage
NSCLC is a safe and feasible treatment. SABR could be effective and a good
option for early stage NSCLC.
Keywords: surgery, stereotactic body radiotherapy, elderly
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY

POSTER SESSION 2 - TUESDAY, DECEMBER 6, 2016 ANALYSIS OF BODY FLUIDS IN CANCER –

P2.01-002 SERUM PROTEIN SIGNATURE IN LUNG CANCER
Analysis of Body Fluids in Cancer –
PATIENTS AND IN PATIENTS WITH CHRONIC OBSTRUCTIVE
TUESDAY, DECEMBER 6, 2016 PULMONARY DISEASE
Janna Berg 1, Ann Halvorsen2, May-Bente Bengtson1, Kristin A. Taskén2,
Gunhild Mælandsmo2, Arne Yndestad3, Bente Halvorsen4, Odd Terje
P2.01-001 ENRICHMENT-FREE, RAPID METABOLIC ASSAY FOR Brustugun2, Pål Aukrust3, Thor Ueland3, Åslaug Helland2
DETECTION OF TUMOR CELLS IN PLEURAL EFFUSION AND 1
Dept. of Medicine, Vestfold Hospital Trust, Tønsberg/Norway, 2Cancer Genetics,
PHERIPHERAL BLOOD Institute for Cancer Research, Oslo/Norway, 3Dept. of Medicine, Rikshospitalet,
Qihui Shi1, Ying Tang2, Zhuo Wang2, Ziming Li3, Wei Wei4, Shun Lu3 Oslo/Norway, 4Reseach Inst. of Int. Medicine, Rikshospitalet, Oslo/Norway
1
Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University,
Background: Chronic inflammation plays an important role in lung
Shanghai/China, 2 Shanghai Jiao Tong University, Shanghai/China, 3Shanghai Lung
Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai/ carcinogenesis and in chronic obstructive pulmonary disease (COPD), and
China, 4University of California, Los Angeles, Los Angeles/CA/United States of is accompanied with alterations in specific serum-proteins. Both COPD and
America lung cancer are associated with smoking behavior, and 40-70% of lung cancer
patients have COPD. The aim of the study is to compare levels of specific
Background: Current methods for circulating tumor cell (CTC) detection are serum markers related to inflammation, extracellular matrix remodeling
mostly include an enrichment step and the subsequent immunostaining- (ECM) and endothelial cell activation in patients with lung cancer and COPD.
based identification of CTCs by epithelial and leukocytes markers. These Methods: Blood samples were collected from 208 lung cancer patients with
methods are limited by loss and damage of CTCs during the enrichment and stage I-IIIA disease before surgery in addition to blood samples from 47 COPD
fail to determine the malignancy and drug targets of putative CTCs. Methods: patients, stage I-IV (4 patients in stage I, 16 in II, 19 in III and 8 in IV). Six of
We describe an enrichment-free, metabolic-based assay for rapid detection of COPD-patients used oral steroids, 28 used inhaled corticosteroids. Serum
tumor cells in the pleural effusion and peripheral blood samples. All nucleated levels of various markers were measured by enzyme immunoassays. Results:
cells are plated on microwell chips that contain 200,000 addressable Of 17 proteins (table 1), 9 were significantly elevated in the COPD group
microwells. These cells are labeled with a fluorescent anti-CD45 antibody compared to lung cancer group including proteins associated with lung cancer
(leukocyte marker), a fluorescent glucose analog (2-NBDG) and a dead cell in other studies as OPG, PTX3, ePCR, GDF15 and endostatin. Only 3 proteins,
marker (EthD-1). The microwell chips are imaged by a computerized high-speed CRP, vWF og GDF15 reflecting systemic inflammation and endothelial cell
fluorescent microscope in three colors and the bright filed. A computation activation, were more abundant in serum from lung cancer patients, and one
algorithm analyzes the images and identify candidate tumor cells that are of these (CRP) significantly so.
viable, CD45 negative, and exhibit high glucose uptake (EthD-1- /CD45 - /2-
NBDGhigh). A micromanipultor is then utilized to retrieve single tumor cells Table 1. Serum proteins measured in our study.
based on recorded addresses for single-cell sequencing. Results: EthD-1- /
Protein short name Protein full name
CD45 - /2-NBDG>100 cells are identified as candidate tumor cells. Single-cell
sequencing based on a small panel of driver oncogenes (EGFR, KRAS, PIK3CA) OPG Osteoprotegrin
shows that >60% of candidate tumor cells are true tumor cells harboring ePCR Endothelial cell protein C receptor
mutations in the panel. Single-cell whole exome sequencing results show all vWF Von Willebrand factor
candidate tumor cells have high mutation frequency in dirver oncogenece and
PTX3 Pentraxin 3
tumor suppressors from Qiagen’s Human Lung Cancer Panel. Meanwhile,
CD45 - /EthD-1- /2-NBDG>100 tumor cells show heterogenieity in cytokeratin (CK) Axl Tyrosine-protein kinase receptor
expression, and only ~40% of these tumor cells are found CK positive. CXCL16 C-X-C motif chemokine ligand 16
DLL1 Delta-like protein 1
Cathepsin S (Chloramphenicol acetyl
Cats
transferase)
GDF15 Growth differentiation factor-15
Endostatin
Cluster of differentiation 147 (Basigin.
CD147
EMMPRIN)
sTNFR1 Tumor necrosis factor receptor 1
CRP C-reactive protein
Alcam (CD166) Activated leukocyte cell adhesion molecule
p53-associated parkin-like cytoplasmic
PARC
protein
sCD163 Cluster of differentiation 163
Gal3BP Galectin-3-binding protein
Conclusion: Chronic inflammation plays an important role in both diseases:

lung cancer and COPD. However, it seems that inflammation as determined
by these selected markers is more pronounced in patients with COPD as most
of the biomarkers levels were significantly higher in these patients than lung
cancer group.
Keywords: serum biomarkers, lung cancer, Chronic obstructive pulmonary

disease (COPD), serum protein

Conclusion: We have developed a simple and functional-based method to ANALYSIS OF BODY FLUIDS IN CANCER –
rapidly identify tumor cells with high glucose uptake in the clinical liquid TUESDAY, DECEMBER 6, 2016
samples without enrichment. These tumor cells are addressable, enabling
single-cell manipulation and sequencing. Clinical feasibility of this assay has
P2.01-003 SERUM VEGF, MMP-7 AND CYFRA 21-1 AS PREDICTIVE
been established by testing samples from a cohort of patients.
MARKERS OF LUNG METASTASES FROM COLORECTAL CANCER
Keywords: circulating tumor cell, lung cancer, enrichment-free, glucose uptake Franco Lumachi1, Paolo Ubiali2, Alessandro Del Conte3, Federica D’Aurizio4,
Renato Tozzoli5, Stefano Basso2
1
Department of Surgery, Oncology & Gastroenterology, University of Padua, School
of Medicine, Padova/Italy, 2Department of Surgery, General Surgery, S. Maria
Degli Angeli Hospital, Pordenone/Italy, 3Medical Oncology, S. Maria Degli Angeli

Hospital, Pordenone/Italy, 4Department of Laboratory Medicine, Clinical Pthology Institute of Mother and Child, Warsaw/Poland, 3Department of Pathomorphology,
Laboratory, S. Maria Degli Angeli Hospital, Pordenone/Italy, 5Department of National Institute of Tuberculosis and Lung Diseases, Warsaw/Poland,
4
Laboratory Medicine, Clinical Pathology Laboratory, S. Maria Degli Angeli Hospital, Department of Thoracic Surgery, National Institute of Tuberculosis and Lung
Pordenone/Italy Diseases, Warsaw/Poland, 5Iii Department of Lung Diseases, National Institute of
Tuberculosis and Lung Diseases, Warsaw/Poland
Background: Colorectal cancer (CRC) is one of the most common malignancy
and the most frequent cause of cancer-related death in Western countries. Background: Effective discrimination between lung cancer and benign
In patients with CRC, the presence of liver or lung metastases (LMs) seriously tumours is a common clinical problem in the differential diagnosis of solitary
affects survival, and the early diagnosis and resection of LMs significantly pulmonary nodules. While most solitary pulmonary nodules are benign,
improves the outcome. Unfortunately, the sensitivity of imaging studies around 20% of cases represent an early stage lung cancer. The presence
in detecting LMs is low, because the onset of solitary pulmonary nodules of cell-free DNA (cfDNA) in plasma of lung cancer patients demonstrates
is common during follow-up, the most part of them are not malignant. The promising diagnostic implications and could be considered as an auxiliary
aim of this study was to evaluate the accuracy of serum carcinoembryonic tool in the differential diagnosis of solitary pulmonary nodules by evaluating
antigen (CEA), vascular endothelial growth factor (VEGF) and matrix cancer-specific biomarkers, such as hypermethylated tumor DNA fragments.
metalloproteinase (MMP)-7 and cyrokeratin-19 fragment (CYFRA 21-1) as We developed a simultaneous methylation profiling of 21 distinct tumor
predictive markers of LMs from CRC. Methods: We retrospectively reviewed suppressor genes (TSGs) in plasma cfDNA using MS-MLPA assay. Methods:
the medical charts of 21 patients with a history of CRC who developed The methylation profiling of 21 TSGs in plasma cfDNA of 32 resectable NSCLC
histologically confirmed solitary or multiple PMs. There were 13 (61.9%) men (I-IIIa) patients and 8 subjects with benign lung nodules (hamartoma, fibrosis,
and 8 (38.1%) women, with an overall median age of 65 years (range 31-82 granuloma) was performed using optimized MS-MLPA assay. Results: 25/32
years). Controls were 24 age-matched patients with CRC in whom the presence (78%) NSCLC and 8/8 (100%) benign-nodule cfDNA samples presented at
of PMs was excluded using 18F-FDG PET. The receiver operating characteristic least one TSG methylation, however the number of hypermethylated TSGs
(ROC) curve was used to obtain the optimal threshold value (cutoff point) was much higher in NSCLC group. APC (frequency 18% samples), MLH1 (18%),
for each TM. Results: The optimal cutoff was set at 5 ng/mL, 7.5 ng/mL, 250 ATM (13.6%), DAPK1 (13.6%), HIC 1 (13.6%), and RARβ (9%) were the most
pg/mL, and 2.8 ng/mL for CEA, VEGF, MMP-7, and CYFRA 21-1, respectively. frequently methylated genes in NSCLC, while TIMP3 (75%), MLH1 (25%) and
The sensibility, specificity, positive (PPV) and negative (NPV) predictive TP73 (37.5%) – in benign patients. Conclusion: The optimized MS-MLPA assay
value, and accuracy are reported in the Table. The logistic regression analysis allowed simultaneous detection of multiple methylated TSGs in plasma
excluded CYFRA 21-1 from the model, and thus we calculated the results also cfDNA. The MS-MLPA showed good performance in samples with diverse
considering the combination of CEA+VEGF+MMP-7. The area under the ROC cfDNA concentrations suggesting that methylation detection rate depends
curve (AUC) was 0.712 (95% CI: 0.432-0.802). on the methylated DNA content in a sample. The study is on-going. The groups
are to be extended and other benign lung pathologies evaluated.
CEA
Keywords: cell-free DNA, non-small cell lung cancer, gene methylation,
RESULTS CEA VEGF MMP-7 CYFRA 21-1 +VEGF
+MMP-7 biomarker
71.4%
80.9% 85.7% 84.2% 90.5%
Sensitivity (52.1-
(64.2-97.7) (70.5-99.9) (67.8-99.9) (77.9-99.9)
90.7)
91.7% POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
95.8% 95.6% 91.7% 99.6% ANALYSIS OF BODY FLUIDS IN CANCER –
Specificity (80.6- TUESDAY, DECEMBER 6, 2016
(87.8-99.9) (87.8.99.9) (80.6-99.9) (98.7-99.9)
99.9)
Positive 88.2% 95.0%
94.4% 94.7% 88.9% P2.01-005 EVALUATION OF CIRCULATING TUMORAL MICROEMBOLI
predictive (72.9- (85.4-
(83.9.99.9) (84.7-99.9) (74.4-99.9) (CTM) AS A PROGNOSTIC FACTOR IN NON-SMALL CELL LUNG
value 99.9) 99.9)
Negative 78.6 % CANCER (NSCLC)
85.2% 88.5% 88.0% 99.1%
predictive (63.4- Marcelo Corassa1, Marcello Fanelli1, Aldo Dettino1, Milena Tariki1, Emne
(71.8-98.6) (76.2-99.9) (75.3-99.9) (97.9-99.9)
value 93.8) Abdallah2, Alexcia Braun2, Vladmir Cordeiro De Lima1, Helano Freitas1,
Likelihood Ludmilla Chinen2
1
ratio 28.57 19.43 20.57 10.11 212.62 Medical Oncology, A.C.Camargo Cancer Center, São Paulo/Brazil, 2International
positive Research Center, A.C.Camargo Cancer Center, São Paulo/Brazil
Likelihood Background: Much has been studied regarding the prognostic role of
ratio 0.31 0.20 0.15 0.17 0.10 circulating tumor cells (CTCs) in NSCLC. CTM (defined as clusters of 3 or more
negative cancer cells detected in peripheral blood) relationship to prognosis was
False previously published for small cell lung cancer (SCLC), demonstrating worst
positive 8.33% 4.17% 4.17% 8.33% 0.43% prognosis for the presence of CTM. No relevant data, however, was published
rate (α) for CTM in NSCLC. The objective of this study is to define the presence of CTM
False as a prognostic factor for survival in NSCLC and its molecular characteristics.
negative 28.57% 19.05% 19.05% 15.79% 9.52% Methods: It was performed a retrospective evaluation of 31 metastatic NSCLC
rate (β) patients positive for CTC, which were previously enrolled for CTC research
in a single institution. CTC and CTM were detected by ISET (Isolation by
Clinical
82.2% 88.9% 91.1% 84.4% 93.3% Size of Epithelial/Trophoblastic Tumor Cells, Rarecells, France®). Included
accuracy
patients had metastatic disease treated in multiple lines of cytotoxic
Conclusion: The periodic assay of CEA+VEGF+MMP-7 together may help treatment. Analysis included frequencies, demographic characteristics
to suspect the presence of LMs, suggesting the need to anticipate further and survival variables, including Progression Free Survival (PFS) and
evaluations. Overall Survival (OS), with PFS as primary endpoint. The PFS and OS were
calculated based on the date of first CTC collection and first progression after
Keywords: MMP-7, Lung metastasis, CYFRA-21-1, VEGF collection (PFS) or death (OS). Molecular characterization was performed
by immunocytochemistry for Transforming Growth Factor beta receptor
(TGFßR) and Matrix Metalloproteinase 2 (MMP2). Results: The primary
endpoint was not met. Presence of CTM did not have statistically significant
influence on PFS or OS in our population. Eight patients were positive (CTM+)
ANALYSIS OF BODY FLUIDS IN CANCER –
and 23 were negative (CTM-) for CTM. Median follow-up was 13.3 months
TUESDAY, DECEMBER 6, 2016 (m). Median age was 65.5 years in CTM- and 69.6 years in CTM+ patients.
Remaining demographic variables were balanced between groups. All patients
had progressive disease and 9 were still alive at the time of analysis. Median
P2.01-004 THE METHYLATION PROFILING OF MULTIPLE TUMOR PFS (mPFS) was 6.9m for CTM- and 4,5m for CTM+, with p=0.59. Median OS
SUPPRESSOR GENES IN PLASMA CELL-FREE DNA OF PATIENTS (mOS) was paradoxically greater in CTM+, without statistical significance
WITH NSCLC VS BENIGN TUMORS (27.3m for CTM- and 31.6m for CTM+; p=0.83). Molecular characterization
Mateusz Florczuk 1, Adam Szpechcinski1, Monika Gos2, Renata Langfort3, did not have any prognostic impact on both CTM- and CTM+ groups. No
Michal Komorowski1, Aleksandra Landowska2, Dorota Giedronowicz3, patient was positive for TGFßR and 2 CTM+ patients were positive for MMP2
Wlodzimierz Kupis4, Piotr Rudzinski4, Jolanta Zaleska5, Tadeusz Orlowski4, (10/31 patients with isolated CTCs positive for MMP2). Conclusion: This
Kazimierz Roszkowski-Sliz5, Joanna Chorostowska-Wynimko1 retrospective analysis showed no impact on survival for the presence of
1
Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung CTM in NSCLC, which was opposite to findings of positive prognostic value
Diseases, Warsaw/Poland, 2Department of Medical Genetics, National Research of CTM for SCLC where CTM was a negative factor for survival. Molecular
characterization also did not show differences between groups. The findings DNA was isolated from tissue biopsy and serum of all the subjects and
warrant further evaluation in dedicated research. methylation-specific PCR of APC, DAPK, and GSTP1 was carried out after
bisulfite conversion. Association of DNA methylation with various clinico-
Keywords: non-small cell lung cancer, Circulating tumor cells, survival, pathological parameters and survival was determined in lung cancer patients.
Circulating Tumoral Microemboli Results: The methylation rates of APC, DAPK, and GSTP1 in tissue biopsy were
83.1%, 83.1%, and 78.1% for lung cancer patients and 72.9%, 70%, and 70% for
cancer-free controls. The methylation rates of APC, DAPK, and GSTP1 in serum
were 52.5%, 30.6%, and 65.6% for lung cancer patients and 14.3%, 18.6%, and
30% for cancer-free controls. In lung cancer patients, all three genes were
ANALYSIS OF BODY FLUIDS IN CANCER – methylated at significantly higher frequency in tissue biopsy than matched
TUESDAY, DECEMBER 6, 2016 serum samples. No significant correlation was observed between methylation
of any of three genes with clinico-pathological parameters, including survival.
Conclusion: Present study did not demonstrating any evidence suggesting
P2.01-006 SENSITIVE DETECTION OF CTCS IN THORACIC
the role of promoter DNA methylation of APC, DAPK, and GSTP1 in lung
MALIGNANT TUMORS WITH “UNIVERSAL” CTC-CHIP carcinogenesis. However, follow-up of cancer-free controls, who were positive
Kazue Yoneda1, Taiji Kuwata1, Yasuhiro Chikaishi1, Kenichi Kobayashi1, Rintaro for DNA methylation, is required to confirm their role in early stages of lung
Oyama1, Sakiko Yura1, Hiroki Matsumiya1, Akihiro Taira1, Yusuke Nabe1, Masaru carcinogenesis.
Takenaka1, Soichi Oka1, Ayako Hirai1, Yuko Tashima1, Naoko Imanishi1, Koji
Kuroda1, Ohnaga Takashi2, Fumihiro Tanaka1 Keywords: DNA methylation, MS- PCR, Tumor suppressor genes, lung
1
Second Department of Surgery (Chest Surgery), University of Occupational and carcinoma
Environmental Health, Japan, Kitakyushu/Japan, 2Central Research Laboratories,
Toyama Industrial Technology Center, Takaoka/Japan
Background: Circulating tumor cells (CTCs) are tumor cells shed from
primary tumor and circulate in the peripheral blood. CTCs, as a surrogate of POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
distant metastasis, can be potentially useful in diagnosis and monitoring ANALYSIS OF BODY FLUIDS IN CANCER –
therapeutic effects in malignant tumors. Among a variety of systems for
detection of CTCs, the “Cellsearch” is the only approved system for clinical
use. However, EpCAM-negative tumor cells, such as those originating from P2.01-008 SIRE NEXT GENERATION SEQUENCING PANEL:
non-epithelial cells and those undergoing epithelial-mesenchymal transition EFFECTIVE DIAGNOSTIC TOOL FOR CIRCULATING FREE DNA
(EMT) cannot be captured with the “CellSearch” that is an EpCAM-based ANALYSIS
isolation system. Therefore, we have developed a novel polymeric microfluidic
Umberto Malapelle 1, Clara Mayo2, Danilo Rocco3, Monica Garzon2, Pasquale
device (“Universal” CTC-chip) that can capture CTCs with or without EpCAM
Pisapia1, Nuria Jordana Ariza2, Riccardo Smeraglio1, Roberta Sgariglia1,
expression (AACR 2015). In the present study, we examined CTCs-detection
Caterina De Luca1, Francesco Pepe1, Alejandro Martinez-Bueno2, Daniela
performance of the CTC-chip in patients with thoracic malignant tumors
Morales-Espinosa4, María González-Cao4, Niki Karachaliou4, Santiago Viteri4,
(lung cancer [LC] as an “EpCAM-positive” tumor and malignant pleural
Claudio Bellevicine1, Christian Rolfo5, Miguel Angel Molina Vila2, Rafael
mesothelioma [MPM] as an “EpCAM-negative” tumor) in comparison with
Rosell6, Giancarlo Troncone1
that of the CellSearch. Methods: Peripheral blood sampled from each patient 1
Public Health, University of Naples Federico Ii, Naples/Italy, 2Laboratory of
was divided and subjected to quantitative evaluation of CTCs with the CTC-
Cellular and Molecular Biology, Pangaea Biotech Sl, Ior Quirón-Dexeus University
chip as well as with the “CellSearch”. The CTC-chip, coated with an anti-EpCAM Institute, Barcelona/Spain, 3Medical Oncology, Monaldi Institute Aorn Dei Colli,
antibody, was used to capture CTCs in the blood samples (n=19) from lung Naples/Italy, 4 Medical Oncology, Instituto Oncológico Dr Rosell (IOR), Hospital
cancer patients. To capture CTCs in the samples (n=11) from MPM patients, the Universitario Quirón-Dexeus, Barcelona/Spain, 5Phase I-Early Clinical Trials Unit¢re
CTC-chip was coated with an antibody against podoplanin that is expressed for Oncological Research (Core), Antwerp University Hospital & Antwerp University,
on the mesothelioma. After immuno-staining for cytokeratin and CD45 on Edegem/Belgium, 6Thoracic Surgery, Dr. Rosell Oncology Institute, Quiron Dexeus
the chip, a captured cell containing Hoechst-positive nucleus and cytokeratin- University Hospital, Barcelona/Spain
positive/ CD45-negative cytoplasm was judged as a CTC. The CTC-count for
Background: Tissue availability is a crucial point in NSCLC. The introduction
each sample was represented as the number per 7.5mL of the blood. Results:
of Liquid Biopsies allows to determine circulant biomarkers, specifically
The median CTC-count detected with the CTC-chip in LC was 50 (range, 0-270),
using free DNA. To simultaneously analyze multiple patients sample at high
which was significantly higher than that (the median CTC-count, 0; range,
sensitivity, Next Generation Sequencing (NGS) can be narrowed to target
0-47) with the CellSearch (p<0.01). In the peripheral blood sampled from MPM
a limited number of actionable genes. Here we prospectically applied a
patients, CTC was detected in only one patient using the CellSearch, but was
lab-developed narrowed gene panel (SiRe) to produce a DNA library covering
detected in all 11 patients with the median CTC-count of 144 (range 0-470).
568 actionable mutations in six gene (EGFR, KRAS, NRAS, BRAF, cKIT and
Conclusion: The“universal” CTC-chip achieved higher performance in detection
PDGFRα). Methods: This daily clinical practice study was performed on cfDNA
of CTCs of thoracic malignant tumors as compared with the CellSearch.
obtained from Non Small Cell Lung Cancer blood samples (serum and plasma)
Keywords: Circulating tumor cell (CTC), lung cancer, Mesothelioma prospectically collected either prior to treatment administration in patients
without tissue availability (n = 46) or after a progressive disease (n = 19) from
a first line gefitinib (n = 14) or afatinib (n = 5) therapy. Results: SiRe detected
an activating EGFR mutation in 4/46 (8.9%) cases and in T790M in 9/19 (47.4%)
at the time of tumor progression. Using tissue data as gold standard, the SiRe
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY panel showed a sensibility of 90.5% and specificity of 100%. Conclusion: The
ANALYSIS OF BODY FLUIDS IN CANCER –
TUESDAY, DECEMBER 6, 2016 SiRe panel is an effective tool enabling the implementation of NGS for cfDNA
mutational profiling in molecular pathology practice.
P2.01-007 DETECTION OF PROMOTER DNA METHYLATION OF APC, Keywords: NGS, liquid biopsy, NSCLC, TKIs
DAPK, AND GSTP1 GENES IN TISSUE BIOPSY AND MATCHED SERUM
OF ADVANCED STAGE LUNG CANCER PATIENTS
Ashraf Ansari1, Sachin Kumar2, Vinod Kakaria3, Anant Mohan4, Kalpana
Luthra5, Ashish Upadhyay6, Randeep Guleria7 POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
1 ANALYSIS OF BODY FLUIDS IN CANCER –
Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, TUESDAY, DECEMBER 6, 2016
Delhi/India, 2 Amity Institute of Molecular Medicine & Stem Cell Research, Amity
University, Noida/India, 3Principal Regional Institute of Education (Ncert), Ajmer/
India, 4Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi/ P2.01-009 SERIAL QUANTITATIVE ASSESSMENT OF PLASMA
India, 5Biochemistry, All India Institute of Medical Sciences, New Delhi/India,
6
Biostatistics, All India Institute of Medical Sciences, New Delhi/India, 7Pulmonary
CIRCULATING TUMOR DNA BY DIGITAL NGS IN PATIENTS WITH
Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi/ LUNG CANCER
India Yue Zhao 1, Jay Gong2, Hong Li3, Weijie Ma4, Kimberly Banks5, Huiyu Wen6,
Elizabeth H Moore7, Richard Lanman8, Tianhong Li9
Background: Promoter DNA hypermethylation is a well characterized 1
Department of Thoracic Surgery,, Fudan University Shanghai Cancer Center,
epigenetic event and has been linked with early stages of lung carcinogenesis
Shanghai/China, 2University of California Davis Comprehensive Cancer Center,
through inactivation of tumor suppressor genes. In this study, we studied Sacramento/AL/United States of America, 3Department of Geriatrics, Peking
the methylation status of APC, DAPK, and GSTP1 genes in tissue biopsy University First Hospital, Beijing/China, 4Division of Hematology & Oncology,
and serum of lung cancer patients and cancer-free controls. Methods: In University of California Davis Comprehensive Cancer Center, Sacramento/AL/
this prospective study, 160 primary lung cancer patients and 70 cancer- United States of America, 5Guardant Health, Inc., Redwood City/AL/United States
free controls undergoing bronchoscopy for benign disease were recruited. of America, 6UC Davis Comprehensive Cancer Center, Sacramento/AL/United States

of America, 7University of California Davis School of Medicine, Sacramento/AL/ invasion in H1299 and 95C cells. Inhibition of PFTK1 decreased the expression
United States of America, 8 Guardant Health, Inc., Redwood City/CA/United States of β-catenin, vimentin, as well as ZEB1. Cytoskeletal protein F-actin was also
of America, 9Division of Hematology & Oncology, University of California Davis decreased by the down-regulation of PFTK1. Conclusion: We reported for
Comprehensive Cancer Center, Sacramento/CA/United States of America the first time that PFTK1 was overexpressed in samples of NSCLC. The high
expression of PFTK1 was associated with lymph node metastasis, T stage and
Background: Next generation sequencing (NGS) has been increasingly used
poor prognosis for NSCLC patients. Furthermore, our data indicated that
in oncology practice but proven practically difficult when serial tumor
PFTK1 promoted cells migration and invasion by regulating the expression
specimens are needed. The objectives of this study were to determine
of cytoskeletal protein F-actin and modulating EMT events. Therefore, our
feasibility and explore clinical utility of serial NGS analyses of circulating
findings suggest that PFTK1 would be a potential target to development of
tumor DNA (ctDNA) in patients (pts) with advanced solid tumors undergoing
therapies for NSCLC.
treatment. Methods: ctDNA digital NGS was performed by a CLIA-certified
lab (70-gene panel with mutant allele fraction (MAF) quantification). ctDNA Keywords: cell migration, PFTK1, cell invasion, actin cytoskeleton
results were retrospectively analyzed and decreases/increases/stability of
molecular tumor load (MTL) defined here as MAFs of truncal driver mutations
were correlated with clinical and radiographic response to treatment
(response, progression, or stable disease, respectively). Results: From Jan
2015 to July 2016, 38 consecutive pts with advanced lung tumors (84% LUAD, POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
5% LUSC, 5% SCLC, 5% NOS) receiving treatment (Table) had serial ctDNA ANALYSIS OF RNA –
analyses (median 2, range 2-7). ctDNA alterations were detected at least once
in 37 (97.4%) pts. Changes in MTL correlated with or predicted all (95% CI,
82.0-99.8%) radiological and/or clinical responses except for the patient with P2.01-011 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED
no genomic alteration detected. MTL results clarified response status when CIRCULATING MIRNAS IN THE SERUM OF NSCLC PATIENTS USING
radiographic responses were difficult to assess in 9 (28%) of pts with either NEXT GENERATION SEQUENCING
complex pleural disease (n=6), pneumonitis during PD-1 inhibitor therapy (2).
Sachin Kumar 1, Ashraf Ali2, Randeep Guleria2
Two MTL change patterns were observed: 1) clonal changes while receiving 1
Amity Institute of Molecular Medicine & Stem Cell Research, Amity University
targeted therapy, including EGFR (12), ALK (3), MET (2), ERBB2 (2); 2) global
Uttar Pradesh, Noida/India, 2Dept. of Pulmonary Medicine and Sleep Disorders, All
changes to PD-1 inhibitors, chemotherapy or radiation. Representative tumor India Institute of Medical Sciences, New Delhi/India
response maps will be presented. Table. Summary of tumor types and cancer
treatment. Background: Aberrant expression of miRNAs has been found in human
cancers and has not only been used as diagnostic, prognostic, and predictive
Targeted Immuno- Chemo- biomarkers, but also as potential therapeutic target. In this study, we
Cancer Type Radiation TOTAL
Therapy therapy therapy compared the expression profile of miRNAs in the serum of NSCLC patients
LUAD 14 8 7 3 32 with that of non-malignant respiratory disease patients and healthy controls.
Methods: For this prospective pilot study, a total of 10 subjects were
LUSC 1 1 0 0 2
recruited, 2 each of lung adenocarcinoma (ADC), squamous cell carcinoma
SCLC 0 0 2 0 2 (SQC), pulmonary tuberculosis (TB), chronic obstructive pulmonary disease
NOS 1 0 1 0 2 (COPD), and healthy controls, from Outpatient Department of Pulmonary
All 16 9 10 3 38 Medicine and Sleep Disorders, AIIMS, New Delhi. Approximately 5 ml. of
peripheral blood was collected; serum was separated and total RNA was
Conclusion: Serial liquid biopsies and ctDNA digital NGS are feasible and isolated using miRNeasy serum/plasma kit (QIAGEN). Small RNAs were
clinically useful in monitoring MTL and genomic alterations during cancer purified from total RNA; libraries of 18 to 50 nt small RNAs were prepared with
treatment, especially in situations when radiographic responses are the TruSeq RNA Library Prep Kit (Illumina), and mature miRNAs were profiled
equivocal. Prospective evaluation of impact on clinical decision making is using illumina TruSeq Sequencing Chemistry on illumina HiSeq 2000 next
warranted. generation sequencing (NGS) platform. Quality check was performed and
high quality raw data was mapped on to miRBase database. The expression
Keywords: plasma, Circulating Tumor DNA, lung cancer, digital next profile of miRNAs in each subject was analyzed using miRNAkey software and
generation sequencing fold change was performed to identify differentially expressed miRNAs in
NSCLC as compared to controls. Results: Using NGS, we were able to detect
1074, 1013, 299, 268, and 907 known miRNAs in the serum of lung ADC, SQC,
TB, COPD and healthy controls, respectively. A number of miRNAs, such as
let-7, miR-10b-5p, miR-15a-5p, miR-23b-5p, miR-92a-3p, miR-148b-3p, miR-
ANALYSIS OF RNA – 185-3p, miR-192-5p, miR-320a, miR-329-3p, miR-342-3p, miR-375, miR-449a,
TUESDAY, DECEMBER 6, 2016 miR-486-5p, miR-497-5p, miR-584-3p, miR-1908-5p, and miR-3195 were found
to be downregulated, while miR-10a-5p, miR-148a-3p, and miR-197-3p were
found to be upregulated in NSCLC as compared to non-malignant respiratory
P2.01-010 DOWNREGULATION OF PFTK1 BY SHRNA INHIBITS
disease controls and healthy controls (>2 fold change; p<0.05). Further, few
MIGRATION AND INVASION OF HUMAN NON-SMALL CELL LUNG
miRs, including miR-93-3p, miR-130b-5p, miR-196b-5p, miR-337-3p, miR-378f,
CANCER CELL LINES miR-382-5p, miR-424-3p, and miR-1271-3p were found to be specifically
Wentao Yue1, Xiaoting Zhao2, Mei Jiang1, Yu Teng1, Lina Zhang1, Li Ma1 expressed in NSCLC. Conclusion: A number of miRNAs were found to be
1
Beijing TB and Thoracic Tumor Research Institute/beijing Chest Hospital, Capital dysregulated in the serum of NSCLC patients than controls. The present study
Medical University, Beijing/China, 2Department of Cellular Biology, Beijing TB is being continued in a larger set of subjects to validate the findings & also
and Thoracic Tumor Research Institute/beijing Chest Hospital, Capital Medical the expression patterns of target genes of differentially expressed miRNAs is
University, Beijing/China being analyzed by real-time reverse-transcriptase PCR to find their relevance
in lung carcinogenesis. This may prove to be useful for developing non-invasive
Background: PFTK1, a novel cyclin-dependent kinases, plays pivotal roles
diagnostic and prognostic tools as well as tools to monitor therapeutic
in cell proliferation, differentiation and cell cycle regulation. It has been
efficacy in NSCLC.
reported that cell motility and invasiveness could be enhanced by PFTK1
in kinds of tumors. However, the function of PFTK1 in NSCLC metastasis is Keywords: microRNA, Biomarkers, non-small cell lung cancer, next generation
not clear. The aim of this study was to explore the potential role of PFTK1 sequencing
in NSCLC metastasis. Methods: Expression of protein PFTK1 was assessed
by immunohistochemistry staining in tissue microarrays, containing
paired tumor tissue and adjacent NSCLC tissue from 119 cases of human
lung cancer. PFTK1 was knocked down by shRNA interference method both
in human H1299 and 95C cells. Then we applied H1299 and 95C cells that POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
PFTK1 expression was inhibited into the next study. The effect of PFTK1 on ANALYSIS OF RNA –
cell migration and invasion was explored by cell wound healing assay and
transwell assay. Western blot was used to detect whether PFTK1 influences
the expression of EMT related proteins β-catenin, vimentin and ZEB1. P2.01-012 ACQUIRED CHEMOTHERAPY RESISTANCE IN VITRO:
Cytoskeleton preotein F-actin was observed using cell immunofluorescence MIRNA PROFILES OF CHEMOTHERAPY RESISTANT SQUAMOUS
test. Results: Immunohistochemistry staining of 119 NSCLC patients showed LUNG CANCER CELL LINES
that a high level of PFTK1 expression was correlated with lymph node
Simon Haefliger, Amanda Hudson, Sarah Hayes, Nick Pavlakis, Viive Howell
metastasis and T stage(P<0.05). And detailed analysis indicated that the high
expression of PFTK1 was associated with poor prognosis for NSCLC patients Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical
Research, University of Sydney, St Leonards/Australia
(P<0.05). In addition, suppression of PFTK1 inhibited cell migration and
Background: Lung cancer is the leading cause of cancer death worldwide.

25 -30% of lung cancers are histologically squamous cell carcinomas (SCC).
Despite recent advances in immunotherapy for lung SCC, traditional cytotoxic
chemotherapies currently remain the mainstay of treatment. However,
over the course of treatment, patients with lung SCC inevitably acquire
chemotherapy resistance. This results in poor overall survival of advanced
stage lung SCC of only 9 to 11 months. Repetitive exposure of lung cancer
cell lines to chemotherapeutic drugs enables investigation of molecular
mechanisms of acquired chemotherapy resistance in vitro. We are studying
the role of miRNAs in this process. MiRNAs are small non-coding nucleic
acids that regulate gene expression. They are involved in numerous cellular
pathways, including therapy resistance. MiRNA serve as biomarkers and have
recently become therapeutic targets or therapeutics themselves. Methods:
We induced chemotherapy resistance in lung SCC cell lines LUDLU-1, Calu-1,
SK-MES-1 in vitro by repetitive drug treatment over a period of 6 – 12 months.
Agents used to develop resistance included Cisplatin, Gemcitabine, Paclitaxel
and Vinorelbine. Cell viability after 3 days of chemotherapy treatment was
measured by MTT assay and drug dose causing a 50% growth inhibition (IC50)
was calculated. Total RNA including miRNA was extracted. Expression of
754 miRNA was measured by TaqMan OpenArray Human MicroRNA array.
Results: After 15 -25 cycles of chemotherapy lung SCC resistant cells showed
a statistically significant increase in IC50 values: Cisplatin up to 12.4 (n-fold);
Gemcitabine 40.2 – absolute resistance (n-fold); Paclitaxel 30.9 – 110.1 (n-fold);
Vinorelbine 4.8 -19.3 (n-fold). Resistance was stable and passed on to daughter
cells. MiRNA expression of resistant cells was compared to parental, drug
sensitive cells and is illustrated by heatmaps and volcano plots. Analysis of
expression patterns revealed upregulation and downregulation of specific
miRNAs in drug resistant cells. We are currently investigating the function of
these dysregulated miRNAs in promoting chemotherapy resistance. Further,
we are testing if certain miRNA are suitable targets to improve chemotherapy
response. Conclusion: We identified changes of miRNA expression patterns
after induction of chemotherapy resistance with various drugs used for lung
SCC treatment. These findings may lead to development of new predictive
biomarkers and to new miRNA-based drugs.
Keywords: chemotherapy, Squamous cell carcinoma, miRNA, Resistance
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY Chemo-sensitivity of resistant cells are directly associated with expression
ANALYSIS OF RNA –
TUESDAY, DECEMBER 6, 2016 of CD44 by knockdown of CD44 expression using siRNA. For overcoming
drug-resistance in lung cancer, we developed a HA-liposome drug delivery
system which can specifically target to CD44, effectively delivered CD44
P2.01-013 HA-LIPOSOME NANOCARRIER CONTAINING CD44 siRNA to CD44 overexpressed resistant NSCLC cells. And, the HA-liposome
SIRNA AS A TARGETED CHEMOTHERAPY TO CD44 RELATED (CD44 siRNA) successfully inhibited the expression of CD44 on resistant
CHEMORESISTANT NON-SMALL CELL LUNG CANCER cells and improved the sensitivity to cisplatin. Conclusion: We demonstrated
Hyun Koo Kim1, Yu Hua Quan1, Ji-Young Lim2, Byeong Hyeon Choi1, Ji-Ho Park2, the corelation of chemoresistance and expression of CD44 in NSCLC, and
Young Ho Choi1 successfully developed HA-liposome drug delivery system for significantly
1
Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, Seoul/Korea, inhibit the expression of CD44. This study supported future investigation HA-
Republic of, 2Bio and Brain Engineering, Korea Advanced Institute of Science and liposome (CD44 siRNA) as possible chemotherapy carrier for targeting CD44,
Technology, Daejeon/Korea, Republic of to assess for inhibiting chemoresistance using various drug delivery in NSCLC.
Background: Chemotherapy to non-small cell lung cancer (NSCLC) remains a Keywords: lung cancer, chemoresistance, drug delivery
big limitation; chemo-resistance which has been reported regulating by one
of cancer stem cells (CSC) marker cluster determinant (CD) 44 expression
in NSCLC. Here, we demonstrated that the importance of CD44 in chemo-
resistance of NSCLC, subsequently, develop and evaluate the hyaluronan
(HA)-liposome as a drug delivery system for overcoming chemoresistance by ANALYSIS OF RNA –
efficiently delivery CD44 targeting siRNA to NSCLC cells. Methods: First, the TUESDAY, DECEMBER 6, 2016
relationship between expression of CD44 and sensitivity of the chemotherapy
was evaluated in NSCLC cells (H1299, H1703, H1793, H1435, H2087, H358,
H522, H460) using flow cytometry (FACS) and MTT assay. The expression P2.01-014 MIR-3941: A NOVEL MICRORNA THAT CONTROLS
of CD44 was confirmed as inversely proportion to the sensitivity of the IGBP1 EXPRESSION AND IS ASSOCIATED WITH MALIGNANT
chemotherapy in these NSCLC cells. Furthermore, in order to confirm that PROGRESSION OF LUNG ADENOCARCINOMA
correlation between CD44 expression and chemo-resistance of NSCLC, we Taiki Sato 1, Aya Shiba2, Yun-Jung Kim1, Tomoko Dai1, Shingo Sakashita2,
generated and characterized cisplatin resistant cell lines, and indicated that Masayuki Noguchi2
CD44 expression on resistant cells significantly increased compared to wild 1
Graduate School of Comprehensive Human Science, Department of Pathology,
type cells. Results: University of Tsukuba, Tsukuba/Japan, 2Department of Pathology, Faculty of
Medicine, Univerysity of Tsukuba, Tsukuba/Japan
Figure 1. CD44 siRNA effectively improved the resistance of cisplatin by
HA-liposome carrier for resistant NSCLC therapy. Background: Immunoglobulin (CD79A) binding protein 1 (IGBP1) binds to
PP2Ac and exerts an anti-apoptotic effect. We have already reported that
IGBP1 overexpression occurs during the course of malignant progression of
lung adenocarcinoma (Sakashita S et al., Pathol Int. 2011). However, the
molecular mechanism of IGBP1 overexpression is still unclear. A few reports
have documented mutation, hypomethylation, or amplification of IGBP1, but
only one study has suggested that down-regulation of miR-34b leads to high
expression of IGBP1 (L-P Chen et al. Oncogene. 2011). In this study, we have
detected miR-3941 as another functional microRNA that influences the
expression status of IGBP1. Methods: We performed microRNA array analysis
using total RNA extracted from fresh specimens of invasive lung
adenocarcinoma (IGBP1+) and minimally invasive adenocarcinoma (IGBP1-).
We compared the results of microRNA array with microRNAs listed in

TargetScan (a microRNA database) that would potentially bind to IGBP1. contrasts the aberrations of their copy numbers. 70 genes were validated
Using reverse transcription-quantitative PCR (RT-qPCR), we analyzed the using TCGA-LUAD data. We showed that paradoxical expression of these
expression levels of candidate microRNAs in frozen specimens of lung genes is associated with 19 microRNAs, whose significant deregulation in
adenocarcinoma. We also validated these microRNAs by checking IGBP1 LUAD has been consistently reported. Importantly, these genes form a
expression and cell proliferation after they had been transfected into lung clinically significant prognostic signature.
adenocarcinoma cell lines (A549, PC-9) and confirmed the direct effect of the
microRNAs by luciferase reporter assay. Results: Using microRNA array and
TargetScan, we selected 6 microRNAs (miR-34b, miR-138, miR-374a, miR-374b,
miR-1909, miR-3941). RT-qPCR analysis showed that these microRNAs were
down-regulated in invasive adenocarcinoma (IGPB1+) relative to adjacent
normal lung tissue (IGBP1-) (Fig1A). We transfected these microRNAs into lung
adenocarcinoma cell lines, and all of the microRNAs suppressed IGBP1
expression. Among these microRNAs, miR-34b and miR-3941 depressed
luciferase activity by targeting 3’UTR-IGBP1 in the luciferase vector (Fig1B).
Conclusion: We have found that miR-3941 targets IGBP1 in addition to

miR-34b. Down-regulation of both microRNAs can lead to high expression of
IGBP1, and this is thought to be associated with progression of lung
adenocarcinoma.
Keywords: IGBP1, microRNA, Adenocarcinoma, lung
Conclusion: Paradoxical gene expression, caused by microRNA deregulation, is

preserved across patient cohorts, and forms a prognostic LUAD signature.
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY Keywords: microRNA, prognostic signature, Copy number aberrations, lung
ANALYSIS OF RNA – adenocarcinoma
P2.01-015 DIFFERENTIALLY EXPRESSED MICRORNAS IN LUNG

ADENOCARCINOMA INVERT EFFECTS OF COPY NUMBER POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
ABERRATIONS OF PROGNOSTIC GENES ANALYSIS OF RNA –
Tomas Tokar 1, Emily Vucic2, Chiara Chiara Pastrello1, Varune Ramnarine1,
Chang-Qi Zhu3, Kenneth Craddock 3, Frances Shepherd4, Ming Tsao3, Wan
Lam2, Igor Jurisica1 P2.01-016 ANALYSIS OF 5 DIFFERENTIAL MIRNA EXPRESSION IN
1
Jurisica Lab, University Health Network, Toronto/ON/Canada, 2Department NSCLC PATIENTS
of Integrative Oncology, British Columbia Cancer Research Center, Vancouver/ Marzena A Lewandowska1, Lukasz Zolna2, Aleksandra Chrząstek2, Janusz
BC/Canada, 3Tsao Laboratory, University Health Network, Toronto/ON/Canada,
4 Kowalewski2
Cancer Clinical Research Unit, University Health Network, Toronto/ON/Canada 1
Molecular Oncology and Genetics Departament, The F. Lukaszczyk Oncology
Background: Across multiple cancer histologies, many significantly down- Center, Collegium Medicum, Nicolaus Copernicus Univeristy, Bydgoszcz/Poland,
2
regulated genes reside within chromosomal regions with increased number of Department of Thoracic Surgery and Tumors, Collegium Medicum in Bydgoszcz,
Nicolaus Copernicus University in Torun, Bydgoszcz/Poland
copies, and vice versa. These “paradoxical genes” have been usually ignored as
a noise, but could be a consequence of epigenetic regulatory mechanisms, Background: There are two main types of lung cancer: non small cell lung
including microRNA-mediated control of mRNA transcription. Methods: To cancer (NSCLC) which represents 80-85% cases of lung cancer and small cell
identify paradoxical genes in lung adenocarcinoma (LUAD) we curated and lung cancer (SCLC) which is about 10-15% cases of lung cancer. The 5-year
analyzed gene expression and copy number aberrations across 1,064 LUAD survival rate for patients with lung cancer vary depending on the stage of the
samples, including newly-generated aCGH data from 65 samples. We then cancer when it is diagnosed. Unfortunately, most of patients with lung cancer
analyzed 9 LUAD microRNA expression studies to compile a list of consistently are diagnosed on later stage of disease (stage III and IV). In our research we try
deregulated microRNAs. Finally, using microRNA:gene networks from mirDIP to find marker among miRNA that can predict occurring of lung cancer on the
we examined possible association between microRNAs and paradoxical genes. earlier stage. Methods: Isolation of miRNA from plasma was performed by
Results: We identified 85 genes whose differential expression consistently miRCURY RNA Isolation Kit – Biofluids (Exiqon) from NSCLC patients and
controls. Synthesis of cDNA and qPCR were carried out using miRCURY LNATM mir-19b and mir-320 was observed whereas mir-15b and mir-197 were up-
Universal RT microRNA PCR with LNATM enhanced PCR Primers (Exiqon). regulated in the conversion of macrophages into M2 phenotype. Modulation
Statistical calculations were executed on 11 samples as a Pre-eliminary data. of miRNAs in immune and stromal cells was consistent with up-regulation of
Results: Results are shown in the following table. the same miRNAs observed in plasma samples. Conclusion: Our findings on
the origin of circulating miRNAs support the conclusion that plasma miRNAs
are heterogeneous and secreted by different cellular components of lung
microenvironment rather than by tumor cells. In particular, we demonstrated
that a pro-tumorigenic and immunosuppressive microenvironment
contributes to the de-regulation of miRNAs observed in plasma of lung cancer
patients.
Keywords: lung cancer, microRNA, microenvironment

ANALYSIS OF RNA –
Conclusion: We assed level of 5 different miRNAs circulating in the blood of
NSCLC patients using qPCR. Our initial results show that different miRNA can
P2.01-018 DIFFERENTIAL MICRORNA EXPRESSION PROFILE
be used to stratify patients and miRNA. Expression of hsa-miR-451a is
decreasing in NSCLC versus negative control. Interestingly up-regulated
BETWEEN YOUNG AND OLD LUNG ADENOCARCINOMA PATIENTS
hsa-miR-660-5p was recently described as a prognostic marker in breast Mirella Giordano 1, Laura Boldrini1, Adele Servadio1, Marco Lucchi1, Franca
cancer but our result preliminary results showed constant decrease in Melfi2, Alfredo Mussi3, Gabriella Fontanini1
1
hsa-miR-660-5p expression in all patients’ groups vs controls. The Department of Surgical, Medical, Molecular Pathology and Critical Area, University
examination on the bigger cohort of patients is necessary to receive a more of Pisa, Pisa/Italy, 2Unit of Thoracic Surgery, University Hospital of Pisa, Pisa/Italy,
3
statistically significant and conclusive data. Department of Surgical Medical Molecular Pathology and Critical Care, University
Hospital of Pisa, Pisa/Italy
Keywords: cell-free microRNA, biomarkers, miRNA expression profiling,
NSCLC. Background: Lung cancer is the leading cause of cancer related mortality and
approximately 80% is represented by non-small cell lung cancer (NSCLC). In
the last decade, age of patients at diagnosis has decreased, with an incidence
of approximately 13.4% in patients under 50 years. Previous studies have
hypotesized that lung cancer in young patients could represent a separated
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY clinicalpathological entity, however it is still controversial whether younger
ANALYSIS OF RNA – patients have a different outcome compared with their older counterparts.
MicroRNAs (miRNAs) have recently been defined to play a key role in cancer
pathogenesis and their aberrant expression has been suggested as a potential
P2.01-017 CIRCULATING MIRNAS IN LUNG CANCER ARE biomarker of prognosis in lung adenocarcinoma. To understand the molecular
ASSOCIATED TO PRO-TUMORIGENIC AND IMMUNOSUPPRESSIVE features of young and old adenocarcinoma patients, we investigated the
MICROENVIRONMENT expression levels of a panel of miRNAs selected from recent literature.
Methods: Thirty-five lung ADC from patients under 50 years old were enrolled
Orazio Fortunato 1, Cristina Borzi1, Giovanni Centonze1, Massimo Milione2,
as the younger group and thirty-five ADC older than 50 years were collected
Davide Conte1, Mattia Boeri1, Carla Verri1, Linda Calzolari1, Francesca
as the older group. After miRNA isolation from formalin-fixed and paraffin-
Andriani1, Luca Roz1, Veronica Huber3, Agata Cova3, Chiara Camisaschi3, Chiara
embedded tumor tissues, the expression levels of 30 miRNAs were analyzed
Castelli3, Licia Rivoltini3, Claudio Tripodo4, Ugo Pastorino5, Gabriella Sozzi1
by NanoString technology and compared between the two groups. Survival
1
Tumor Genomics Unit, Department of Experimental Oncology and Molecular data were used to assess the prognostic impact of miRNAs. The software
Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori Int, Milano/Italy,
2 miRgator v3.0 was used to predict the putative pathways targeted by
Anatomic Pathology Unit, Department of Pathology and Laboratory Medicine,
Fondazione IRCCS Istituto Nazionale Dei Tumori Int, Milan/Italy, 3Unit of
miRNAs. Results: The analysis revealed that 7 miRNAs (miR-25-3p, miR-29c-
Immunotherapy of Human Tumors, Department of Experimental Oncology and 3p, miR-33a-5p, miR-144-3p, miR-153-3p, miR-342-5p and miR-485-3p) were
Molecular Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori Int, Milano/ differently expressed in the two groups (Mann-Whitney U test, p<0.05). All
Italy, 4Tumor Immunology Unit Department of Health Science, Human Pathology these miRNAs showed higher expression levels in young compared to old
Section, University of Palermo School of Medicine, Palermo/Italy, 5Thoracic patients, and their predicted targets included EGFR, MET, VEGF-A, TP53 and
Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumori Int, Milano/Italy PDGFRa. miR-144-3p had an opposite influence on overall survival, since its
upregulation was associated with a better outcome in young patients (p=
Background: We previously reported the identification of diagnostic miRNA
0.01) and a worse prognosis in the old group (p= 0.03). Conclusion: Our study
signatures in plasma samples of lung cancer patients detected by low dose
provides new insights about the role of miRNAs in lung adenocarcinoma
computed tomography (LDCT) screening. Circulating miRNAs are released
occurring in young patients. We observed that lung cancer in young and
into the bloodstream by different mechanisms such as passive leakage from
old patients may be influenced by different regulatory mechanisms since
damaged cells or active secretion through extracellular-vesicles or protein
we found 7 miRNAs as downregulated in the older group, probably due to
complexes Methods: To evaluate the potential origin and the release of the
distinct age-related genetic and epigenetic alterations. Moreover, one of
24 miRNAs of the diagnostic signature we analyzed their expression by real-
the deregulated miRNAs showed a different prognostic impact in the two
time or digital PCR in both cells and conditioned medium (CM) from cancer
groups thus confirming that young and old patients deserve a specific clinical
cell and different cell types of the lung microenvironment. Lung tissues and
approach. Further validations are needed to better define if an age-based
cell-blocks were analyzed by miRNAs in situ hybridization (ISH). Modulation
genomic signature could be used as prognostic marker in lung cancer.
of miRNAs after in vitro treatments known to induce changes associated
with cancer progression, in different cell types was assessed and correlated Keywords: MicroRNAs, lung adenocarcinoma of the young, Prognosis
to changes observed in circulating miRNAs signatures. Results: 24-miRNAs
analysis showed higher abundance in specific cellular components such as mir-
145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells
or mir-451 and 142-3p in hematopoietic cells. Generally, tumor cells showed
lower levels of miRNAs compared to bronchial epithelial cells. MiRNAs specific POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
ANALYSIS OF RNA –
localization in lung tissue was confirmed by ISH. We observed that mir-451 TUESDAY, DECEMBER 6, 2016
is specifically expressed in lung interstitial alveolar walls while mir-126 by
endothelial cells outside the tumor bulk; miR-145 is characteristic of fibroblast
and muscle cells and miR-142-3p of hematopoietic cells, fibroblast and muscle P2.01-019 THREE MICRORNAS ASSOCIATED WITH POOR
whereas mir-21 is over-expressed in the tumor. The analysis of miRNAs in PROGNOSIS ARE UP-REGULATED IN AMPLIFIED REGIONS OF
CM showed that miRNAs secretion is correlated with cellular expression for SQUAMOUS CELL LUNG CARCINOMA
most cell types (Pearson correlation range: 0.41-0.80). Interestingly, platelets
Sana Yokoi1, Endi Xia1, Yasumitsu Moriya1, Toshihiko Iizasa2, Ichiro Yoshino3
and granulocytes were the components that mostly secreted miRNAs. In 1
Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba/Japan,
vitro experiments showed that endothelial cells under hypoxic condition 2
Thoracic Surgery, Chiba Cancer Center Hospital, Chiba/Japan, 3General Thoracic
up-regulate mir-126 and that mir-145 was up-regulated and secreted in lung Surgery, Chiba University, Chiba/Japan
cancer-associated compared to normal fibroblasts. Interestingly, during
conversion of T lymphocytes into T regulatory cells up-regulation of mir-15b, Background: Squamous cell carcinoma (Sq) is second major histological

subtype of lung cancer. Unlike in the case of adenocarcinoma (Ad), Sq Daniela Petriella1, Stefano Cagnin2, Annamaria Catino3, Sara Montagna3,
has only few molecular target drug. MicroRNA (miR) is a major part of Francesco Zito4, Barbara Barrettara5, Beniamina Pacchioni2, Caterina
post-transcriptional regulators functioning as tumor suppressor genes or Millino2, Simona De Summa1, Domenico Galetta3, Stefania Tommasi1, Rosanna
oncogenes. MiR will regulate target molecules related to carcinogenesis and Lacalamita1
malignancy in Sq. Methods: Using The Cancer Genome Atlas dataset including 1
Molecular Genetics, IRCCS, Istituto Tumori Giovanni Paolo Ii, Bari/Italy, 2Università
copy number variation, RNA sequence, miR sequence, clinicopathological Di Padova, Padova/Italy, 3Medical Oncology, IRCCS, Istituto Tumori Giovanni Paolo
feature from 484 lung cancer cases, the correlation between genomic copy Ii, Bari/Italy, 4Pathology Unit, Asl Ba, Bari/Italy, 5Division of Thoracic Surgery, “san
number and expression of miR was analyzed. 245 samples of Sq and 239 Paolo” Hospital, Bari/Italy
samples of Ad were included. The raw counts of each mature miR fragments
with different precursor were merged and calculated from miR-seq isoform Background: Early-stage lung cancer patients have a five-year survival rate
files by R project (http://www.r-project.org/) Segmented copy number greater than 70%, however this benefit is not exploited due to late diagnosis.
variation datasets were processed with R package CNTools of Bioconductor Moreover, for the early-stage patients eligible to surgical intervention the
project. Independent two-group Mann-Whitney U test was used to compare long-term survival is also reduced by the high risk of relapse following surgery.
different expression between Sq and Ad. MiR expression according to copy The identification of circulating biomarkers is an attractive and less invasive
number variation was analyzed using Pearson correlation coefficient r-score. way to improve the management of lung cancer patients. MicroRNAs
To identify the miR target sites of mRNAs, targetscan-Perl scripts were used (miRNAs) post-transcriptionally modify gene expression and are thus involved
(http://www.targetscan.org/). Results: From 1,001 mature miR fragments, in cancer through controlling different cellular processes. Dysregulation of
34 miRs were identified as the candidates especially for Sq distinguished their expression contributes to lung cancer progression both in tissue samples
from Ad. Furthermore, four miRs were up-regulated in amplified regions and and in the blood stream (plasma/serum). The aim of our study is to assess a
independently associated with poor prognosis in Sq. Moreover, those who had miRNA profile from serum patients to identify circulating biomarkers useful
the tumor with high expression in three of four miR simultaneously showed to predict surgery outcome in the early-stage NSCLC patients Methods: 16
worst prognosis. To explore miR-mRNA network, we also predicted the target early-stage NSCLC patients were enrolled. Serum samples before (pre) and
genes for each miR. From 734 common target genes, three showed positive after (post) surgery together with surgical tumor tissue were collected from
correlation with the expression of three miRs. Conclusion: Three miRs up- each patient. Extracted RNA was enriched to construct library. Raw
regulated in Sq were associated with poor prognosis through the regulation of sequencing reads were aligned to hg19 human genome and miRNAs were
three common target genes. annotated using miRBase v21. After reads normalization, differentially
expressed miRNAs were identified through edgeR package. pvalue < 0.01 was
Keywords: Squamous cell carcinoma, micro RNA considered as statistically significant. Results: miRNA deep sequencing
analysis on 16 NSCLC patients: surgical tissue, pre-surgical and post-surgical
serum samples lead to detect a total of 2500 miRNAs. MiRNA expression
profile data were explained by the Venn diagram (figure1)

ANALYSIS OF RNA –
P2.01-020 IDENTIFICATION OF A THREE-LNCRNA SIGNATURE FOR

LUNG CANCER DIAGNOSIS AND PROGNOSIS
Bin Zhang1, Hua Zhang2, Liuwei Gao2, Changli Wang 1
1
Department of Lung Cancer, Tianjin Medical University Cancer Institute and
Hospital, Tianjin/China, 2Tianjin Medical University Cancer Institute and Hospital,
Tianjin/China
Background: Lung cancer is one of the leading causes of cancer-related death

in the world. Metastasis is the main cause of death. There is still lack of
ideal predictive and prognostic biomarkers. Human lncRNA plays important
structural and functional roles in many biology progresses. Increasing studies
have demonstrated that the abnormal expression of lncRNA is correlated
to cancer progress in variant types of cancer, and lncRNA is considered as
a potential valuable biomarker for diagnosis, treatment and prognosis of
cancer. Methods: Here, we investigated the lncRNA expression profile in
lung adenocarcinoma with lymph node metastasis and without lymph node
metastasis (n=5 vs 5) by microarray assay. Three lncRNAs were selected
for further verification by qRT-PCR in a training cohort including 118 paired
lung cancer and the adjacent normal tissues and a test cohort including
60 paired tissues. In addition, we analyzed the correlation of the lncRNAs
with clinicopathological features and survival. Results: We observed 245
significantly differentially expressed lncRNAs between lung adenocarcinoma
with lymph node metastasis and without lymph node metastasis. Gene
ontology analysis showed that the lncRNAs may be involved in several
important biological progresses. ROC curves revealed that a 3-lncRNA
signature distinguished not only lung cancer with lymph node metastasis
from lung cancer without lymph node metastasis but also lung cancer from
normal tissue. Moreover, the 3-lncRNA signature showed prognostic value MiR-125b-5p resulted significantly down-regulated in serum samples (pre
by survival analysis. Multivariable Cox regression analysis showed that the and post-operative) compared to tumor tissue, while it increased in serum
signature was an independent prognostic factor for lung cancer patients. In of patients after tumor removal. Therefore miR-125b-5p expression could
another independent test cohort including 60 paired lung cancer and normal be influenced by tumor resection because of its involvement in different
tissues, we validated the diagnostic and prognostic values of the 3-lncRNA tumorigenic processes. Conclusion: miRNA deep sequencing revealed
signature. Conclusion: Our results identified a new 3-lncRNA signature for the circulating biomarkers potentially involved in lung tumor progression after
diagnosis and prognosis of lung cancer, suggesting the potential clinical utility surgery. MiRNAs could be useful to follow disease recurrence and to improve
of lncRNA biomarkers in lung cancer. survival rate of early-stage patients.
Keywords: lncRNA, lung cancer, biomarker, microarray Keywords: Biomarkers, liquid biopsy, miRNA, next-generation sequencing
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY

ANALYSIS OF RNA – ANALYSIS OF RNA –
TUESDAY, DECEMBER 6, 2016 TUESDAY, DECEMBER 6, 2016
P2.01-021 MIRNA DEEP SEQUENCING OF EARLY-STAGE LUNG P2.01-022 A PIWI-INTERACTING RNAS CO-EXPRESSION NETWORKS
CANCER PATIENTS TO EVALUATE THE DYNAMIC CHANGE OF AS A PROGNOSTIC FACTOR IN LUNG CANCER
CIRCULATING BIOMARKERS IN RESPONSE TO SURGERY Brenda Minatel1, Victor Martinez1, Erin Marshall1, Kevin Ng1, Katey Enfield1,
Stephen Lam2, Wan Lam1 combined miRNA/piRNA signature improved both OS and RFS predictions
1
Integrative Oncology, British Columbia Cancer Research Centre, Vancouver/BC/ compared to signatures of miRNAs or piRNAs alone. In TCGA, log-rank analysis
Canada, 2Department of Integrative Oncology, British Columbia Cancer Research of risk groups indicated only the miRNA/piRNA signature significantly
Centre, Vancouver/BC/Canada stratified patients (OS p=0.0038, RFS p=0.0229) into low, intermediate,
and high risk groups compared to separated miRNA or piRNA signatures.
Background: PIWI-interacting RNAs (piRNAs) are small (24-32 nucleotides) Similarly, in the BCCA dataset, only the combined miRNA/piRNA signature
non-coding RNAs. Their functions, widely conserved across species, are significantly stratified high, intermediate, and low risk groups (p=0.0019).
associated to epigenetic control of gene expression and maintenance of Target prediction of piRNAs and miRNAs from the signature indicated that
genomic stability by the repression of mobile elements. In humans, >23,000 34 genes may be regulated at both the DNA (piRNA) and mRNA (miRNA)
piRNAs are known, showing tissue-specific expression patterns. While the level. Conclusion: We find the combination of miRNA and piRNA expression
aberrant expression of individual piRNAs has been identified in some cancer derived from the DLK1-DIO3 locus produces a superior stratification of
types, the role of piRNA co-expression networks in the development of patient outcome than either metric alone. While the contribution of miRNAs
lung tumors and their utility as molecular markers remains unexplored. By to patient risk stratification is established, the improved model performance
analyzing over 7000 piRNA transcriptomes from human tumors and non- derived from the addition of piRNAs adds another layer of gene regulation
malignant tissues, we have identified lung cancer (LC) specific expression at the DNA-level. Model performance is optimal when these two small
networks associated with clinically-relevant tumor features and patient RNA species are considered simultaneously; suggesting their coordinated
prognosis. Methods: We developed a custom small-RNA sequence analysis biological effects as a result of deregulation at this locus in LUAD.
pipeline to generate >7,000 human piRNA transcriptomes. piRNA expression
baseline was deduced from 6,378 piRNA transcriptomes (non-malignant/ Keywords: Imprinted locus, Small non-coding RNA, lung cancer, survival
tumors) from 11 organ sites. In lungs, we analyzed 1,082 tumors and 209
non-malignant samples from two cohorts: BC Cancer Agency (BCCA) and
The Cancer Genome Atlas (TCGA). Network analysis was performed using
the weighted gene co-expression network analysis (WCGNA). We evaluated
tumour aggressiveness by considering correlation to several clinical POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
ANALYSIS OF RNA –
parameters, including stage, number of mutations, nodal/distant metastasis, TUESDAY, DECEMBER 6, 2016
and overall/disease-free survival. piRNA survival signatures were identified
using a Cox Proportional Hazard model. Results: A subset of piRNA showed
robust expression in somatic tissues. Expressed piRNAs display organ-specific P2.01-024 EXPRESSION OF MIR-106 PARALOGS IMPROVES
patterns and mainly map to coding transcripts, suggesting a role in regulation PROGNOSTIC VALUE OF MESENCHYMAL SIGNATURES BUT ONLY
of gene expression. In lungs, 204 piRNAs were consistently expressed in both MIR-106B PROMOTES INVASIVENESS
LC cohorts. Tumor piRNA expression profiles are markedly different from their Sonia Kung 1, Katey Enfield1, David Rowbotham1, Erin Marshall1, Alice Holly2,
non-malignant counterparts (133 piRNAs were differentially expressed). The Chiara Pastrello3, Brenda Minatel1, Graham Dellaire2, Jason Berman2, Igor
patterns differ between the adenocarcinoma and squamous cell carcinoma, Jurisica3, Calum Macaulay1, Stephen Lam1, Wan Lam1
and were influenced by smoking status. Network-based analysis identified 1
Integrative Oncology, British Columbia Cancer Research Centre, Vancouver/BC/
piRNA expression changes in two modules of piRNAs are associated with Canada, 2Dalhousie University, Halifax/NS/Canada, 3Princess Margaret Cancer
aggressiveness tumor features, such as increased number of mutations, Centre, Toronto/ON/Canada
tumor size and nodal metastasis. Finally, combined expression of piRNAs
define signatures associated with patient overall and recurrence free survival. Background: Improved understanding of the molecular mechanisms driving
Conclusion: We provide evidence of somatic, tissue-specific human piRNA lung cancer progression can lead to novel therapeutic strategies to improve
expression. In lungs, aberrant expression patterns are associated with well- the currently poor patient treatment outcome. Deregulation of microRNA
established etiological factors of cancer and seem to contribute to lung cancer (miRNA) expression in malignant cells activates molecular pathways that
subtype-specific biology. We discover that specific piRNA-based expression drive tumor progression such as epithelial-mesenchymal transition (EMT).
patterns characterize aggressive lung tumors and also exhibit prognostic We identify miRNA paralogs, miR-106a and miR-106b, to be elevated in
value. The unique expression patterns of piRNAs offer an opportunity to metastatic lung adenocarcinoma (LUAD). We assess whether these two highly
better understand lung cancer-specific biology as well as develop novel similar miRNAs share the same functions in vitro, and measure how their
prognostic markers for clinical application. elevated expression increases invasiveness or induces EMT in LUAD tumor.
Methods: MiRNA expression was obtained from small RNA sequencing data
Keywords: piRNA, expression networks, tumor aggressiveness, lung cancer derived from clinical primary LUAD specimens and paired non-malignant
tissues (60 localized, 27 with lymph node invasion). Non-invasive, epithelial
LUAD cell lines with low endogenous miR-106a/b levels were transfected
and co-transfected with overexpression vectors for miR-106a and miR-
106b. Invasiveness of experimentally-modulated tumor cells was assessed
ANALYSIS OF RNA – in vitro by Boyden chamber assay and in vivo using a zebrafish model, and
TUESDAY, DECEMBER 6, 2016 expression of EMT markers was determined by Western Blot. Predicted
miRNA targets were identified using mirDIP portal. To identify putative
genetic mechanisms of mir-106a/b overexpression, DNA copy number,
P2.01-023 DEREGULATION OF SMALL NON-CODING RNAS methylation, and Gene Set Enrichment Analysis (GSEA) were performed.
AT THE DLK1-DIO3 IMPRINTED LOCUS PREDICTS LUNG Clinical associations were computed in an independent cohort of TCGA LUAD
ADENOCARCINOMA PATIENT OUTCOME samples. Results: Both miR-106 paralogs were significantly overexpressed in
John Enterina, Katey Enfield, Victor Martinez, Erin Marshall, Greg Stewart, LUAD samples with lymph node invasion. However, increased expression of
Wan Lam miR-106b alone or together with miR-106a, but not miR-106a alone, enhanced
Integrative Oncology, BC Cancer Research Centre, Vancouver/BC/Canada metastatic phenotypes, and correlated with increased mesenchymal and
decreased epithelial marker expression. Predicted targets include EP300, a
Background: Deregulation of small RNAs at the imprinted DLK1-DIO3 locus transcriptional activator of E-cadherin, and members of the TGFβ signaling
has been linked to lung adenocarcinoma (LUAD) patient outcome. While pathway. Copy number and methylation status did not correlate with miRNA
the contribution of microRNAs (miRNAs) is established, the role of Piwi- expression; however, GSEA analysis revealed enrichment of E2F transcription
interacting RNAs (piRNAs), small RNAs involved in epigenetic regulation factor targets in LUAD with high expression of either miR-106 paralogs.
of gene transcription, is unexplored. We quantified expression of piRNAs Furthermore, expression of miR-106 paralogs was significantly positively
and miRNAs mapping to this locus in two independent cohorts of LUAD and correlated with E2F1 and E2F2, suggesting that upstream regulation by E2F
assessed the ability of a combined miRNA/piRNA signature to improve patient is a potential mechanism. Interestingly, miR-106a and miR-106b expression
outcome stratification. Methods: Expression levels (RPKM) for miRNA/piRNA was associated with poor survival and advanced stage when stratified by
were determined from small RNA sequencing experiments from two cohorts mesenchymal marker vimentin. Conclusion: Although both miR-106a and
(TCGA, n=154, 5-year follow up; BCCA, n=77, 8-year follow up). Associations miR-106b are overexpressed in metastatic LUAD, the strongest prognostic
with patient overall survival (OS) and recurrence free survival (RFS) were association was found in LUAD with a mesenchymal expression signature
calculated by inputting miRNA and piRNA expression combinations into a and high expression of both miRNAs. Our cell models suggest that miR-106b
Cox proportional hazard model. Risk scores were calculated by multiplying may play a direct role in EMT, with miR-106a influencing tumor progression
the expression value for each gene by its hazard coefficient, and summed per via alternative mechanisms. Inhibition of one or both of these miRNAs may
sample. Risk scores were ranked and divided into tertiles for log-rank survival provide a strategy for treating advanced stage disease.
analysis. DNA-level piRNA targets were predicted using MiRanda based on
sequence complementarity in the region 3.5kb upstream of the transcription- Keywords: Epithelial-mesenchymal transition (EMT), miRNA, metastasis,
start site of all human transcripts from ENSEMBL. Transcript-level miRNA Genomics
targets were predicted using the miRDIP algorithm, which integrates 13
miRNA target prediction algorithms and six miRNA prediction databases.
Results: Only 7 out of 138 piRNAs mapping to the locus were expressed. A


ANALYSIS OF RNA –
P2.01-025 MIR-146B FUNCTIONS AS A SUPPRESSOR MIRNA AND

PROGNOSIS PREDICTOR IN NON-SMALL CELL LUNG CANCER
Jun Chen
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital,
Tianjin/China
Background: Non-small cell lung cancer (NSCLC) is the leading cause of

cancer-related death worldwide; however, science has not yet been able to
substantially improve the prognosis of lung cancer patients. Accumulating
evidence suggests that microRNAs (miRNAs) are key players in the regulation
of tumor development and metastasis. Expression of six miRNAs previously
shown to play roles in tumor development (miR-146b, miR-128b, miR-21, miR-
221, miR-34a, and Let-7a) in other tumor types Methods: Expression of six
miRNAs previously shown to play roles in tumor development (miR-146b, miR-
128b, miR-21, miR-221, miR-34a, and Let-7a) in other tumor types was examined
using real-time RT-PCR in 78 specimens of NSCLC. Results: The results revealed
that patients with low expression of miR-146b had significant shorter median
and mean survival time than those with high miR-146b expression (33.00
and 30.44 months versus 42.0 and 36.90 months, respectively; log-rank
test P=0.048), thus low miR-146b expression level was associated with poor
prognosis in NSCLC patients. Univariate Cox hazard regression analysis
demonstrated that miR-146b expression levels tended to be a significant
prognostic indicator of NSCLC (adjusted hazard ratio=0.482, 95% CI: 1.409-
29.593, P=0.016). Multivariate Cox proportional hazard regression analysis
showed that miR-146b expression levels were an independent prognostic
factor for NSCLC patients (hazard ratio=0.259, 95% CI: 0.083-0.809, P=0.020).
Furthermore, the effects of miR-146b on NSCLC cell growth and invasion in
vitro were investigated. Our findings demonstrate that ectopic expression of
miR-146b suppresses proliferation and colony formation ability of lung cancer
H1299 cells in vitro. In addition, miR-146b induced G0/G1 phase arrest in H1299
cells and over-expression of miR-146b inhibited lung cancer cell migration
and invasion in vitro. Conclusion: Our findings demonstrate that miR-146b
functions as a suppressor miRNA and prognosis predictor in NSCLC.

Proteins in Lung Cancer and Proteomics –
Conclusion: Construction of a phylogenetic tree of lung ACA subclones
oriented to stem cells demonstrated that the degree of disruption of a
subclone correlated with the degree of similarity of the subclone to stem cells,
P2.01-026 A MASS SPECTROMETRY BASED STEM CELL-ORIENTED
and with prognosis.
PHYLOGENY OF INTRA-TUMORAL NSCLC SUBCLONES
Robert Downey 1, Erin Seeley2, Andre Moreira3, Hua-Jun Wu4, Charlotte Lee4, Keywords: stem cells, mass spectrometry, Phylogeny, Subclone heterogeneity
Prasad Adusumilli1, Greg Kilby2, Franziska Michor5
1
Surgery, Memorial Sloan Kettering Cancer Center, New York/United States of
America, 2Protea Biosciences Inc., Morgantown/WV/United States of America,
3
Pathology, Memorial Sloan Kettering Cancer Center, New York/United States of
America, 4Biostatistics and Computational Biology, Dana-Farber Cancer Institute, POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
Boston/United States of America, 5Biostatistics and Computational Biology, Dana- PROTEINS IN LUNG CANCER AND PROTEOMICS –
Farber Cancer Institute, Boston/MA/United States of America
Background: Sub-clones within a cancer diverge due to ongoing accumulation

P2.01-027 A COMPARISON OF FIVE DIFFERENT
of mutations. We sought to characterize the intratumor heterogeneity and
IMMUNOHISTOCHEMISTRY ASSAYS FOR PROGRAMMED DEATH
phylogenetic relationships among different histological patterns present in
lung adenocarcinomas based on mass spectrometric analysis of tumor LIGAND-1 EXPRESSION IN NON-SMALL CELL LUNG CANCER
subclones. Methods: MALDI-TOF mass spectrometry was used to generate SAMPLES
proteomics data from different histological regions of 35 resected lung Ross Soo1, Joey Lim2, Bernadette Reyna Asuncion2, Zul Fazreen2, Maria
tumors, as well as from 3 basal cell and 3 mesenchymal cell samples. A total of Herrera2, Feroz Omar2, Ju Ee Seet3, David Bryne4, Shona Hendry4, Stephen
1985 different histological regions were analyzed from the 35 resected tumors Fox4, Richie Soong2
along with the 3 samples each of airway basal cells and mesenchymal stem 1
Department Hematology-Oncology, National University Hospital, Singapore/
cells. For each of the 1991 samples, a spectral profile was generated with Singapore, 2Cancer Science Institute of Singapore, National University of
expression data from 217 peptide mass peaks to allow comparison of the Singapore, Singapore/Singapore, 3National University Hospital, Singapore/
proteomics profiles from the different histological regions from each cancer Singapore, 4Peter MacCallum Cancer Centre, Melbourne/VIC/Australia
to the basal and mesenchymal stem cell profiles. Weighted protein co-
Background: Randomised trials have shown treatment with programmed
expression networks were analyzed by using WGCNA package in R. Global and
death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors can provide a
histologic specific networks were generated through using a power adjacency
survival benefit to patients with advanced stage non-small cell lung cancer
function which defines the similarity between any pairs of proteins The
(NSCLC). PD-L1 expression, determined by immunohistochemistry (IHC) using
network modules were decided by using average linkage hierarchical
different protocols, antibodies and thresholds for positivity for different
clustering and a dynamic tree-cut algorithm. Networks of the different
inhibitors, has been reported to be potentially predictive of clinical outcome.
histologies and normal were compared and visualized by heat map methods.
The objective of this study was to compare the staining patterns of prominent
Results: The clinically more aggressive histologies ( micropapillary/solid)
PD-L1 IHC assays in clinically relevant NSCLC samples. Methods: Consecutive
clustered with stem cells and away from normal alveolar tissue (Fig 1) and had
full sections of 20 NSCLC samples, comprising five each of resection, core
severe loss in peptide connectivities (Fig 3). Applying t-SNE dimensionality
biopsy, cytology, and pleural fluid samples, underwent IHC with the following
reduction method showed that subclones from one specimen cluster
anti-PD-L1 antibodies/autostainers: 22C3/Link 48, 28-8/Bondmax, SP142/
differently from each other suggesting underlying heterogeneity, with more
Bondmax, SP263/Benchmark XT, E1L3N/Benchmark XT according to publicly-
heterogenous tumors being associated with worse prognosis (Fig 2).
available protocols. PD-L1 expression were scored manually by pathologists
according to the percentage of tumour cells (%TC) stained on a continuous POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
PROTEINS IN LUNG CANCER AND PROTEOMICS –
scale. Results: Using published tumour cell percentage thresholds for 22C3, TUESDAY, DECEMBER 6, 2016
28-8, SP142 and SP263 of ≥50%, ≥1%, ≥5%, and ≥25%, the frequency of PD-L1
positive cases were 10%, 15%, 70%, and 15% of cases respectively. When a ≥1%
threshold was applied, the corresponding frequencies were 70%, 15%, 95%, P2.01-029 TUMOR B7-H3 (CD276) PROTEIN EXPRESSION, SMOKING
65% respectively, and 55% for E1L3N. Using published thresholds, cases were HISTORY, AND SURVIVAL IN LUNG ADENOCARCINOMA PATIENTS
positive according to 1, 2, 3, 4 and 5 antibodies in 15%, 25%, 25%, 0% and 5% Kentaro Inamura1, Yusuke Yokouchi2, Maki Kobayashi1, Rie Sakakibara1,
of cases respectively. Sorting of cases according to increasing %TC staining Hironori Ninomiya1, Sophia Subat1, Hiroko Nagano1, Kimie Nomura1, Sakae
revealed a similar order of cases between antibodies, albeit with differences Okumura3, Tomoko Shibutani2, Yuichi Ishikawa1
in %TC quanta and occasional exceptions to the order. Spearman rho analysis 1
The Cancer Institute, Jfcr, Tokyo/Japan, 2Daiichi Sankyo Co., Ltd., Tokyo/Japan, 3The
indicated %TC staining significantly (p<0.05) correlated between most Cancer Institute Hospital, Jfcr, Tokyo/Japan
antibody pairs, except 28-8 and 22C3, 28-8 and SP142, and 28-8 and E1L3N.
Unsupervised hierarchical clustering revealed two subgroups, comprising of Background: Compared with non-smoking counterparts, smoking-associated
SP142/SP263 and 22C3/28-8/E1L3N. Conclusion: The classification of cases as lung cancers is characterized by a high frequency of somatic mutations,
PD-L1 positive can vary significantly according to the antibody and protocol including mutations of DNA repair genes, a high burden of neoantigens,
used. Differences were more likely due to protocol dependent staining and increased immunogenicity. B7-H3 (also known as CD276) belongs to
intensities and nominated thresholds for positivity, rather than differences in a family of immune modulators that includes PD-1 and PD-L1 (also known
antibody affinity for different epitopes. as B7-H1 or CD274). Considering the better response to PD-L1 inhibitors in
smokers’ lung cancer, we examined the prognostic interaction of tumor B7-H3
Keywords: immunohistochemistry assays, PD-L1 expression expression with smoking history in lung adenocarcinoma patients. Methods:
Using tissue microarrays of consecutive 270 cases of lung adenocarcinoma,
we evaluated tumor B7-H3 expression by immunohistochemistry. We
examined the prognostic association of B7-H3 expression in strata of
smoking history, using Cox proportional hazards regression analysis and the
PROTEINS IN LUNG CANCER AND PROTEOMICS – log-rank test. Additionally, we used logistic regression analysis to examine
TUESDAY, DECEMBER 6, 2016 the correlations between B7-H3 expression levels and clinicopathological/
molecular features of lung adenocarcinoma. Results: The association of B7-H3
expression with survival significantly indeed differed by smoking history
P2.01-028 PROGNOSTIC SIGNIFICANCE OF GLUT1 AND CAIX
(Pinteraction=0.014); B7-H3 high-expression was associated with inferior
EXPRESSION: CORRELATION WITH VOLUME-BASED PET
survival in moderate/heavy-smoking patients (smoking index [SI]≥400)
PARAMETERS IN NON-SMALL CELL LUNG CANCER (hazard ratio [HR]=3.07, 95% confidence interval [CI]=1.74-5.49, P=0.0001)
Young Wha Koh1, Seong Yong Park2, Su Jin Lee3 (log-rank test: P<0.0001), but not in non/light-smoking patients (SI<400)
1
Pathology, Ajou University School of Medicine, Suwon/Korea, Republic of, (HR=2.24, 95% CI=0.63-1.96, P=0.64) (log-rank: P=0.64). High B7-H3 expression
2
Department of Thoracic and Cardiovascular Surgery, Ajou University School was associated with smoking patients (univariable odds ratio [OR]=2.63, 95
of Medicine, Suwon/Korea, Republic of, 3Department of Nuclear Medicine and % CI=1.51-4.65, P=0.0005) and independently associated with EGFR wild-type
Molecular Imaging, Ajou University School of Medicine, Suwon/Korea, Republic of status (multivariable OR=2.80, 95% CI=1.38-5.84, P=0.0042). Conclusion:
We demonstrated that the prognostic association of B7-H3 expression
Background: Glucose transporter type 1 (GLUT1) and carbonic anhydrase
indeed differed according to smoking history. The current study also showed
IX (CAIX) represent glucose metabolism and tissue hypoxia, respectively.
significant association of high B7-H3 expression with EGFR wild-type and
The purpose of this study is to measure the GLUT1 and CAIX expression
smoking patients, indicating the potential effectiveness of anti-B7-H3
and volume-based 18F-fluorodeoxyglucose positron emission tomography
therapy for EGFR wild-type or smokers’ lung adenocarcinoma.
(FDG PET) parameters in non-small cell lung cancer (NSCLC) patients and
examined the correlations between above parameters and their prognostic Keywords: smoking, immune checkpoint, B7-H3, prognostic interaction
significance. Methods: We evaluated GLUT1 and CAIX expression by
immunohistochemical methods and volume-based FDG PET parameters in
269 NSCLC patients treated with surgical resection (158 adenocarcinoma,
93 squamous cell carcinoma and 18 other type carcinoma). Metabolic tumor
volume (MTV) and total lesion glycolysis (TLG) of NSCLC were measured POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
using pretreatment 18F-FDG PET/CT. Receiver operating characteristic (ROC) PROTEINS IN LUNG CANCER AND PROTEOMICS –
curve analysis was used to determine the optimal cut-off values of MTV or
TLG. Correlations between GLUT1, CAIX, MTV, TLG, and clinicopathological
factors were assessed, and prognostic significance was determined. Results: P2.01-030 PROGNOSTIC IMPACT OF STATHMIN1 EXPRESSION IN
The GLUT1 expression was identified in 99% of squamous cell carcinoma and PATIENTS WITH NON-SMALL LUNG CANCER
50% of adenocarcinoma. In patients with adenocarcinoma, GLUT1 expression
Kimihiro Shimizu1, Toshiteru Nagashima2, Yoichi Ohtaki2, Kai Obayashi2,
showed positive correlation with MTV or TLG (P = 0.012 and P = 0.037,
Seshiru Nakazawa2, Yoko Azuma2, Misaki Iijima2, Takayuki Kosaka2, Toshiki
respectively). In patients with squamous cell carcinoma, correlation analyses
Yajima2, Akira Mogi2, Hiroyuki Kuwano2
between GLUT1, MTV and TLG were not performed because most cases of 1
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate
squamous cell carcinoma showed GLUT1 positivity. There was no correlation
School of Medicine, Maebashi/Japan, 2Division of General Thoracic Surgery,
between CAIX expression, MTV and TLG in squamous cell carcinoma and Integrative Center of General Surgery, Gunma University Hospital, Maebashi/Japan
adenocarcinoma. In cases with adenocarcinoma, GLUT1-positive patients
had lower overall survival (OS) rates and lower recur-free survival (RFS) Background: Stathmin 1 is a cytosolic phosphoprotein that plays a crucial
rates than GLUT1-negative patients (P < 0.001 and P = 0.004, respectively). role in the control of cellular division and proliferation by regulating
CAIX expression was not significantly associated with either OS or RFS in microtubule dynamics. In addition, Stathmin1 is associated with tumor
squamous cell carcinoma and adenocarcinoma. Patients with high MTV or TLG growth and progression. Our study aimed to determine differences in
had significantly lower OS rates and lower RFS rates than patients with low overall (OS) and disease free survival (DFS) in patients with non-small lung
MTV or TLG in adenocarcinoma. High GLUT1, TLG and MTV were significantly cancer (NSCLC) stratified by STMN1 tumor expression. Methods: Using
associated with adverse clinicopathologic variables. When patients with inmmunohistochemistry, Stathmin1 expression was determined in resection
adenocarcinoma were stratified into two groups (High GLUT1 and TLG vs. the specimens from 423 NSCLC patients. The relationship between Stathmin1
other 3 groups), high GLUT1 and TLG was an independent prognostic marker protein expression and overall and disease free survivalwas assessed
for OS in multivariate analysis (P = 0.003). Conclusion: Our results show that using Kaplan Meier survival curves and compared using log-rank statistics.
high GLUT1 expression levels were significantly associated with MTV or TLG Cox proportional hazards regression determined the hazard for death
in patients with adenocarcinoma. High GLUT1 and TLG was an independent stratified by Stathmin1, adjusting for clnicopathological characteristics.
prognostic marker for OS. High GLUT1 and TLG can be used to identify a Results: The STMN1 protein was expressed in 58% of NSCLC cases, 54% of
subgroup of patients with adenocarcinoma at high risk of recurrence or Adenocarcinoma, 63% of Squamous cell carcinoma, and 100% of large cell
progression who may benefit from aggressive chemotherapy or radiotherapy. neuroendocrine carcinoma (LCNEC) and its expression was significantly
associated with advanced T and N factors, advanced pathological stages,
Keywords: glucose transporter type 1, total lesion glycolysis, lung positive lymphatic permeation, positive vascular invasion, and poor or
adenocarcinoma, Metabolic tumor volume mediate differentiation. STMN1 was a negative prognostic factor for OS
(hazard ratio [HR], 2.212; 95% confidence interval [CI]: 1.544-3.169; p< 0.001)
and DFS (HR, 2.685; 95% CI: 1.897-3.798; p< 0.001). Multivariable analysis
confirmed that STMN1 protein expression was an independent predictor
of an unfavorable OS (HR, 1.480; 95% CI, 1.006 to 2.176; p = 0.046) and DFS
(HR, 1.605; 95% CI, 1.105 to 2.329; p = 0.013) in all NSCLC patients, and of an
unfavorable DFS (HR: 2.128, 95% CI, 1.293 to 3.503; p = 0.003) in Stage I NSCLC

patients. Conclusion: STMN1 expression was an independent prognostic Surgery, Yamaguchi-Ube Medical Center, Ube/Japan
factor for NSCLC, even when restricted to early stage patients.
Background: Ribosome is a subcellular organelle, which serves as the site
of biological protein synthesis. Ribosomal protein L29 (RPL29) is one of
the proteins composing ribosome, and it expresses in cell surface as well
as in cytoplasm, especially showing its high expression in cancer cells.
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY Methods: We retrospectively reviewed 92 patients who underwent surgical
TUESDAY, DECEMBER 6, 2016 resection for non-small cell lung cancer between June 2010 and January
2012. Preoperative serum anti-RPL29 levels were measured by the indirect
enzyme-linked immunosorbent assay. The cut-off value was represented by
P2.01-031 CCL CHEMOKINES MAY PLAY AN IMPORTANT ROLE IN the median of anti-RPL29 levels. Results: The patients consisted of 60 males
CISPLATIN RESISTANCE and 32 females, and their average age was 68.7 years (range: 44-87 years).
Sarah-Louise Ryan1, Peter Godwin2, Susan Heavey2, Kazuo Umezawa3, Martin Adenocarcinoma was the most common subtype (n = 69), which was followed
Barr2, Steven Gray2, Bryan Stanfill4, Anthony Davies1, Sinead Cuffe5, Stephen by squamous cell carcinoma (n = 13), adenosquamous cell carcinoma (n = 4),
Finn6, Derek Richard7, Kathy Gately2, Kenneth O’Byrne8, Anne-Marie Baird9 pleomorphic carcinoma (n =4), and large cell carcinoma (n = 2). Postoperative
1 pathological stage consisted of stage IA (n = 28), IB (n = 28), IIA (n = 11), IIB (n
Translational Cell Imaging Queensland, Queensland University of Technology,
Brisbane/QLD/Australia, 2Thoracic Oncology Research Group, Trinity College = 2), and IIIA (n = 23). EGFR activating mutations were found in 35 patients
Dublin/st. James’ Hospital, Dublin/Ireland, 3Dept. of Molecular Target Medicine (32 adenocarcinomas, 2 adenosquamous cell carcinomas, and 1 pleomorphic
Screening, Aichi Medical University, Aichi/Japan, 4 Csiro, Brisbane/ACT/Australia, carcinoma). The median of anti-RPL29 levels in 92 cases was 0.351. Three-
5
Dept of Medical Oncology, St James’ Hospital, Dublin/Ireland, 6Dept of year and five-year overall survival rate was 62.7% and 56.6%, respectively,
Histopathology, St James’ Hospital, Dublin/Ireland, 7Cancer Ageing and Research in the patients whose serum anti-RPL29 level was less than the median, and
Program, Queensland University of Technology, Brisbane/Australia, 8 Cancer and 90.0% and 83.7%, respectively, in the patients with the median or more of
Ageing Research Program, Princess Alexandra Hospital and Queensland University
anti-RPL29 levels (P = 0.005). In the multivariate Cox proportional hazard
of Technology, Brisbane/Australia, 9St. James’ Hospital & Queensland University of
model, anti-RPL29 level being the median or more and pathological stage IA
Technology, Dublin/Ireland
were identified as independent prognostic factors (P = 0.013 and P = 0.017,
Background: In the absence of a targetable mutation, cisplatin based respectively). Conclusion: Serum anti-RPL29 levels may be a novel prognostic
chemotherapy is the backbone of NSCLC treatment. However, a diverse marker for non-small cell lung cancer.
patient population combined with complex tumour heterogeneity is
Keywords: non-small cell lung cancer, serum, anti-RPL29, Prognosis
hampering its’ clinical utility. Although intrinsic and acquired resistance to
cisplatin is common, the mechanisms have not yet been fully elucidated.
However, some studies have suggested that inflammatory pathways may
play a key role in chemo-resistance. The aim of this project is to increase our
understanding of inflammatory mediated cisplatin resistance in NSCLC. POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
Methods: A number of isogenic cell line models of NSCLC (adenocarcinoma, PROTEINS IN LUNG CANCER AND PROTEOMICS –
squamous cell carcinoma, large cell carcinoma) cisplatin resistance were TUESDAY, DECEMBER 6, 2016
utilised to assess the role of inflammation in chemo-resistance. These
included a sensitive parental cell line (PT) and a matched resistant subtype P2.01-033 EXOSOMAL PROTEOMICS ANALYSIS REVEAL NEW
(CisR). The cell lines were screened for NFKB and a number of inflammatory
TARGETS FOR RADIATION-INDUCED LUNG TOXICITY DIAGNOSIS
mediators including chemokines and TLRs at the mRNA (RT-PCR/qPCR)
and protein level (Western Blot/ELISA). A specific NFKB inhibitor, DHMEQ, Xiance Jin, Congying Xie
and recombinant chemokines were employed to further characterise Radiotherapy and Chemotherapy, The 1St Affiliated Hospital of Wenzhou Medical
inflammatory pathways in PT and CisR cells in terms of cisplatin sensitivity, University, Wenzhou/China
proliferation (BrdU ELISA), cellular viability (Cytell Cell Imaging System) and
Background: radiation-induced lung toxicity (RILT) are observed today in
DNA damage response (Comet). An in vivo study was also completed using
patients who have undergone thoracic irradiation for the treatment of lung
DHMEQ alone and in combination with cisplatin. Results: A number of NFKB
malignancy. Radiation-induced damage to normal lung parenchyma remains
targets and responsive pathways are deregulated in CisR cells compared
the dose-limiting factor in chest radiotherapy. However, the radiative dosage
with their matched sensitive PT cell line. Amongst others, CCL2 and CCL5
is not effective for most of patients because of avoiding RILT. Therefore, novel
were altered across all NSCLC subtypes. Preliminary data suggests that
diagnosis methods reveal individual potential RILT are required. For now,
DHMEQ enhances cisplatin sensitivity in both PT and CisR cells, conversely
increasing evidence illustrates that exosomes in circulating fluids provide a
recombinant chemokines elicit a protective effect. Additionally, DHMEQ
promising way as biomarkers for noninvasive disease diagnosis. Exosomes
treatment resulted in opposite affects on CCL2 and CCL5 mRNA levels in
are 30–150 nm particles which are released from cells into the extracellular
the PT and CisR cell lines. This may reflect an alternative pathway hierarchy
environment and thousands of proteins have been identified in plasma
within the cells. Further characterisation is ongoing assessing chemokine
exosomes. Whether exosomal proteomics analysis could benefit lung cancer
specific inhibitors. Although, in vivo data suggests a trend of decreased
patients with appropriate radiative dosage and prevent RILT remains to be
tumour growth in the DHMEQ cohorts compared with vehicle control, the
studied. Methods: Plasma samples were collected from RILT patients with
data was not significant. However, tumour samples appeared more necrotic
grade I and II, and no RILT individuals matched with age, gender and blood
with DHMEQ and are currently being characterised using IHC for necrosis and
collection time after 10 to 30Gy radiation within 6 months. Plasma exosomes
proliferation. Conclusion: Targeting chemokines downstream of NFKB may
were accessed by 110,000×g ultracentrifugation and visualized by NS300
provide a means to overcome inflammatory mediated acquired and intrinsic
equipment. The raw data of exosomal proteomics profiles of RILT patients and
NSCLC chemo-resistance. Given the increased significance of immuno-
no-RILT individuals were generated by LC-MS and its expression were verified
oncology agents to harness the body’s own immune system in the fight
by western blot. Results: In the present study, we revealed 17 exosomal
against cancer, these agents may also prove fruitful in re-sensitising patients
protein participated in wounding response and two of them were correlated
to chemotherapy.
with RILT clinic stage. A2M (Alpha-2-macroglobulin) was decreased in RILT
Keywords: non-small cell lung cancer, inflammation, Chemokines, Cisplatin patients and FGB (Fibrinogen beta chain) was increased in RILT patients.
resistance Furthermore, A2M was decreasing from no radiative damage patients
to that of RILT grade I to II, and the FGB expression in exosomes showed
positive correlation with RILT from low to high level. The patients with low
FGB expression in plasma exosomes could tolerate higher radiative dosage
until the FGB was upregulated in plasma. Conclusion: LC-MS is an efficient
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY method for exosomal proteomics analysis and we reveal two stable targets
PROTEINS IN LUNG CANCER AND PROTEOMICS – A2M and FGB, which could indicate the potential of patients suffering RILT
after radiotherapy. The two novel targets could serve as promising diagnosis
biomarkers for avoiding RILT.
P2.01-032 IMPACT OF PREOPERATIVE SERUM ANTI-60S
Keywords: radiation-induced lung toxicity, Exosomal proteomics
RIBOSOMAL PROTEIN L29 LEVELS ON PROGNOSIS IN PATIENTS
WHO UNDERWENT SURGERY FOR NON-SMALL CELL LUNG CANCER
Hiromasa Yamamoto 1, Akinobu Takaki2, Tatsuro Hayashi3, Masashi
Furukawa3, Hiroyuki Tao3, Kazuhiko Shien1, Junichi Soh1, Kazunori Okabe3,
Shinichiro Miyoshi1, Shinichi Toyooka1 POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
1 PROTEINS IN LUNG CANCER AND PROTEOMICS –
Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate TUESDAY, DECEMBER 6, 2016
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan,
2
Gastroenterology and Hepatology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan, 3Thoracic P2.01-034 THE PREGNANCY ASSOCIATED ENDOMETRIAL PROTEIN
GLYCODELIN AS A BIOMARKER FOR MALIGNANT PLEURAL were similar between low and high-grade NEC, but those were different
MESOTHELIOMA compared to others (P<0.05). Indeed, EGFR, EBB2, P53 and BRAF IHC
expression were significantly lower in NEC group compared to other subtypes
Marc Schneider 1, Arne Warth2, Thomas Muley1, Michael Thomas3, Felix Jf
(P<0.05). Overall, LCC have lower protein expression than ADC and SCC,
Herth3, Hendrik Dienemann4, Michael Meister 1
1
specially P53 and VEFG. We detected several drivers mutation including EGFR
Translational Research Unit (Stf), Translational Lung Research Center Heidelberg
22%(19/80), ERBB2 2%(5/80), immune regulated genes CD276 6.8%(17/80)
(TLRC), Member of the German Center for Lung Research (DZL), Thoraxklinik at
Heidelberg University Hospital, Heidelberg/Germany, 2Institute of Pathology, and CTLA 15.4%(39/80). We observed also EMT gene mutations as CD44
Heidelberg University Hospital, Heidelberg/Germany, 3Department of Thoracic 30.7%(78/80), MMP2 2.8%(7/80), VGFA 2%(5/80), CDH1 2.4%(6/80), SNAI
Oncology, Translational Lung Research Center Heidelberg (TLRC), Member of the 2.8%(7/80), VIM 1.2%(3/80), and ZEB1 4%(12/80). Interestingly, a significant
German Center for Lung Research (DZL), Thoraxklinik at Heidelberg University higher AXL and CD44 gene expression was found in ADC and SCC specimens
Hospital, Heidelberg/Germany, 4Department of Thoracic Surgery, Translational compared to NEC(P=0.001 and P=0.04,respectively) Similar to the protein
Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung expression in overall low gene expressions was also observed in LCC compared
Research (DZL), Thoraxklinik at Heidelberg University Hospital, Heidelberg/ to others. Conclusion: We detected different patterns of protein and gene
Germany
alteration in LC with predominant low expression in NEC. Furthermore, the
Background: Malignant pleural mesothelioma (MPM) is a rare and high expression of EMT genes as AXL and CD44 observed among ADC and SCC
aggressive tumor with a short survival time arising from the mesothelial can be a evidence that those genes might be a distinctive RTK in these tumor
cells of the pleura. MPM is mainly associated with asbestos exposure and a than in NEC tumor suggesting that targeting these genes will be benefit as
strong inflammatory reaction. The common treatment of MPM combines anti-cancer treatment.
macroscopic complete resection and adjuvant or neoadjuvant chemotherapy,
Keywords: Immunohistochemistry, next generation sequencing, epithelial–
respectively. Soluble mesothelin and osteopontin are current available
mesenchymal transition, non small cell lung cancer
biomarker for malignant mesothelioma with moderate sensitivity and
specificity. Glycodelin is an immune system modulator well described during
pregnancy. It is involved in invasion of the trophoblast and in regulation of
the immunotolerance between the maternal immune system and the fetus.
Methods: With a commercial ELISA, we measured the glycodelin serum POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
concentrations of patients with MPM. In addition, we analyzed the glycodelin PROTEINS IN LUNG CANCER AND PROTEOMICS –
gene expression using quantitative PCR and stained glycodelin in formalin-
fixed paraffin embedded tissue slides. Results: We found high glycodelin
concentrations in the serum of patients with MPM compared to benign lung P2.01-036 IDENTIFICATION OF A NOVEL ONCOGENIC UBIQUITIN
diseases. Patients with high glycodelin serum concentrations exhibited a LIGASE FROM A LUNG CANCER EPIGENOME-WIDE ASSOCIATION
worse overall survival. Moreover, glycodelin serum levels correlated with
STUDY (EWAS)
tumor response to treatment. A comparison of soluble mesothelin-related
proteins (SMRP) and glycodelin in the serum of a large patient cohort Christian Faltus 1, Yassen Assenov2, Myrto Barrdahl3, Marina Laplana2, Olga
demonstrated that the detection of both soluble factors can increase Bogatyrova2, Anika Hüsing 3, Theron Johnson3, Michael Meister4, Thomas
the reliable diagnostic of MPM. Glycodelin mRNA and protein was highly Muley4, Arne Warth5, Christoph Plass6, Rudolf Kaaks7, Angela Risch8
1
expressed in MPM tumors compared to normal lung tissue. Conclusion: In this Epigenomics and Cancer Risk Factors, Division of Epigenomics and Cancer Risk
study, we first described the expression of glycodelin in MPM. Altogether, Factors, DKFZ - German Cancer Resarch Center, Heidelberg/germany; University
of Salzburg, Department of Molecular Biology, Salzburg/Austria, 2Epigenomics
glycodelin seems to be a new potential serum biomarker for the aggressive
and Cancer Risk Factors, Division of Epigenomics and Cancer Risk Factors, DKFZ
malignant pleural mesothelioma. - German Cancer Resarch Center, Heidelberg/Germany, 3Cancer Epidemiology,
Division of Cancer Epidemiology, DKFZ - German Cancer Resarch Center,
Keywords: malignant pleural mesothelioma, biomarker, Glycodelin Heidelberg/Germany, 4 Molecular Biology Laboratory, Translational Research
Unit, Thoraxklinik-Heidelberg GmbH, University of Heidelberg; Translational Lung
Research Center Heidelberg (TLRC-H), Member of the German Center for Lung
Research (DZL), Heidelberg/Germany, 5Tissue Bank of the National Center for Tumor
Diseases (NCT) Heidelberg; Institute of Pathology, Heidelberg University Hospital;
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY Translational Lung Research Center Heidelberg (TLRC-H), Member of the German
PROTEINS IN LUNG CANCER AND PROTEOMICS – Center for Lung Research (DZL), Heidelberg/Germany, 6Epigenomics and Cancer
Risk Factors, Division of Epigenomics and Cancer Risk Factors, DKFZ - German
Cancer Resarch Center Heidelberg, Germany; Translational Lung Research Center
Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),
P2.01-035 PROTEIN AND MOLECULAR ALTERATIONS IN EMT
Heidelberg/Germany, 7Cancer Epidemiology, Division of Cancer Epidemiology,
PATHWAYS OF LUNG CANCER: A COMPARATIVE ANALYSIS DKFZ - German Cancer Resarch Center, Heidelberg, Germany; Translational Lung
BETWEEN NSCLCS Research Center Heidelberg (TLRC-H), Member of the German Center for Lung
Juliana Machado1, Daniel Ascheri1, Patrícia Leao2, Priscila Milsoni1, Rogerio Research (DZL), Heidelberg/Germany, 8 Molecular Biology - Cancer Genetics and
Epigenetics, Division of Cancer Research and Epigenetics, University of Salzburg;
Oliveira3, Edwin Parra4, Vanessa Sá1, Cecília Farhat1, Alexandre Ab´saber 1,
Cancer Cluster Salzburg, Salzburg, Austria; Division of Epigenomics and Cancer
Maria Nagai5, Teresa Takagaki6, Alexandre Fabro2, Vera Capelozzi1 Risk Factors, DKFZ-German Cancer Resarch Center; TLRC-H,member of the German
1
Pathology, Faculty of Medicine, University of São Paulo, São Paulo/Brazil, Center for Lung Research (DZL), Heidelberg/Germany
2
Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão
Preto/Brazil, 3Bioestatistics, Biosciences Institue, São Paulo State University, Background: Lung cancer (LC) is the leading cancer-related cause of death
Botucatu/Brazil, 4Transelational Molecular Pathology, MD Anderson Cancer Center, worldwide with a 5-year survival rate of only 8%. Smoking is the main
Houston/TX/United States of America, 5Oncology, Faculty of Medicine, University risk factor for lung malignancies, but not every smoker develops LC. DNA
of São Paulo, São Paulo/Brazil, 6Pulmonary Division of Heart Institute, Faculty of
methylation alterations in tumor tissue lead to genome instability and thus
Medicine, University of São Paulo, São Paulo/Brazil
can contribute to malignant cell transformation. Smoking-associated blood
Background: The adoption of next-generation sequencing (NGS) may help to DNA methylation changes have been shown to indicate LC risk. We aimed to
identify single nucleotide variants (SNVs), small insertions–deletions (indels), investigate differential blood DNA methylation in healthy smokers for the
and larger structural variations including chromosomal rearrangements. identification of novel oncogenes. Methods: We performed Illumina 450K
Many molecular alterations have protein-level associations that can be epigenome-wide DNA methylation arrays for 66 smoking prediagnostic lung
questioned using immunohistochemistry (IHC). The goal of our work was cancer case-control pairs. The blood DNA samples for this nested case-control
investigated molecular patterns of predictive biomarkers and new genes design came from the European Prospective Investigation into Cancer and
involved as potential therapeutic targets with an emphasis on protein IHC Nutrition (EPIC) Heidelberg cohort. Differentially methylated candidate CpGs
and their translational promise. Methods: We studied 212 formalin fixed and were then tested in lung tumor versus adjacent normal tissue for differential
paraffin embedded tissues: 8 high-grade and 20 low-grade neuroendocrine methylation in multiple patient sample sets. Additionally, we tested whether
carcinomas(NEC), 102 adenocarcinomas(ADC), 65 squamous cell carcinomas differential methylation leads to differential gene expression in lung tumor
(SCC) and 17 large cell carcinomas(LCC), placed in tissue microarrays(TMAs). versus adjacent normal tissue. The top candidate CpG proximal gene was
EGFR,P53,KRAS,ALK,ERBB2,PTEN,BRAF,VEGF,CD24 and CD44 were examined evaluated in functional LC cell based assays to investigate the consequences
using IHC and Aperio system. DNA extracted(QIAmp) from a subset was used of its elevated expression in LC. Results: The top differentially methylated
to analyze several variants including EGFR, ERBB2, PIK3CA, MMP2, SNAI, candidate CpGs from EPIC were also found differentially methylated in
VGFA, VIM, ZEB1, AXL, CD44, CD276, and CDH1, using the TruSeq Custom lung tumor versus adjacent normal tissue. The two top hypermethylated
Amplicon assay on the Illumina MiSeq System, resulting data set for 80 LC CpGs were located within differentially methylated regions (DMRs) and the
were analyzed using the Variant-Studio software and correlated them with proximal or associated genes were differentially expressed in lung tumors.
the clinocopathological data. Results: The median age of the patients was The top DMR revealed the regulation of gene expression by DNA methylation
64 yrs (minimum-maximum, 24-88yrs). The population included 98(44.5%) of a downstream ubiquitin E3 ligase. Deregulated expression of that gene
women; 32(14,5%) never smokers and 100(45,5%) former smokers; only 2(1%) was associated with LC cell proliferation, migration and glucose uptake in
Asians. Our image analysis showed that the median IHC protein expressions vitro. The gene was found to be involved in the activation of AKT by mTORC2.

When the gene was knocked down, apoptotic genes which are suppressed Background: Non-diagnostic bronchoscopic or image guided biopsies of
by activated AKT in LC cells were re-expressed. Expression of a cell cycle small, solitary pulmonary nodules are a common and frustrating clinical
promoting regulator stimulated by activated AKT was found repressed in LC conundrum which can cause thoracic oncologists and patients to opt for
knock down cells. Conclusion: We identified differential DNA methylation in radical therapy without a pathological diagnosis. As a result, some patients
blood from healthy smokers who later developed LC. The top differentially with benign conditions have unnecessarily undergone radical treatment.
methylated CpGs were also differentially methylated in lung tumor versus This study sought to determine if metabolomics profiling of plasma could
adjacent normal tissue samples. The top DMR lead to expression of a proximal be used to distinguish early stage NSCLC cases from cancer-free controls.
ubiquitin E3 ligase. We showed, that this gene is crucial for the mTORC2- Furthermore, we sought to determine if phenotypic subtypes of NSCLC
mediated activation of AKT. This ubiquitin E3 ligase has not previously been could be distinguished from one another using metabolomics profiling.
associated with cancer but our findings identify it as a novel epigenetically Methods: Frozen preoperative plasma samples from a cohort of 48 early stage
deregulated LC oncogene. NSCLC patients (24 Adenocarcinomas, 24 Squamous Cell Carcinomas) and
24 cancer-free controls obtained prior to surgical resection were randomly
Keywords: DNA methylation, Epigenome-wide association study, lung cancer selected from a provincial lung cancer biorepository for metabolomics
analysis. Plasma samples were uniformly thawed, extracted, and analyzed
in triplicate by blinded personnel using ultra high performance liquid
chromatography/quadrupole time of flight mass spectrometry (UHPLC-
QTOF-MS). After data mining, metabolomics profiles were quantified and
PROTEINS IN LUNG CANCER AND PROTEOMICS – normalized using Mass Profiler Professional (Agilent Technologies, CA,
TUESDAY, DECEMBER 6, 2016 USA) and individual metabolites were identified using the Metlin Database.
Partial least square discrimination (PLSD) was used as a prediction model
to identify metabolomics profiles which effectively clustered NSCLC cases
P2.01-037 MOLECULAR BIOLOGY UNDERLYING COPD AND LUNG
from Controls and Adenocarcinomas from Squamous Cell Carcinomas.
CANCER CONVERGE ON FOXM1 NETWORK Results: More than 17,500 entities were detected using the UHPLC-QTOF-MS
Victor Martinez 1, Emily Vucic1, Kelsie Thu1, Erin Marshall1, Katey Enfield1, technique of which 250 potential metabolomics biomarkers were present
Brenda Minatel1, Sara Rahmati2, Tomas Tokar2, Mark Abovsky2, Chiara in all 72 samples. The PLSD analysis using all detected entities effectively
Pastrello2, Igor Jurisica2, Calum Macaulay1, Stephen Lam1, Wan Lam1 distinguished NSCLC cases from controls with 97% overall accuracy.
1
Integrative Oncology, British Columbia Cancer Research Centre, Vancouver/BC/ Several endogenous metabolites were statistically significantly affected in
Canada, 2Princess Margaret Cancer Centre, Toronto/ON/Canada Adenocarcinoma and Squamous Cell Carcinomas cases compared to control
samples. Some of the identified compounds include biliverdin IX, serotonin,
Background: Chronic obstructive pulmonary disease (COPD) is a progressive,
PE(15:0/20:2) and 3-ketosphingasine. In addition, 3-acetamidopropanal,
inflammatory lung disease associated with an up to 10-fold increased risk
9,10-dihydroxy-hexadecanoic acid and anandamide (20:5, n-3) were found
of lung cancer (LC). COPD and LC share common etiologies including genetic
in high concentrations in Adenocarcinoma cases compared to Squamous
susceptibilities and risk factors, such as smoking. This study systematically
Cell Carcinomas. Conclusion: Differences in the metabolomics profiles were
characterizes the molecular overlap between COPD and LC. Methods: Small
apparent and demonstrated the preliminary feasibility of distinguishing early
airway gene expression data was obtained from subjects with spirometry
stage NSCLC cases from controls and adenocarcinomas from squamous cell
measures (n=267) (GSE37147). Genome-wide, multi-omics data for lung
carcinomas using metabolomics techniques. Validation of this methodology
adenocarcinoma (LUAD) tumor and non-malignant lung tissues from two
on a larger, prospectively accrued, cohort is planned in order to optimize
cohorts (TCGA, n=515; BCCA, n=90) was analyzed. Weighted correlation
model fit and to assess the diagnostic and NSCLC subtype discriminatory
network analysis (WGCNA) was applied to identify clusters (modules) of
performance in the clinical setting.
highly correlated genes across airway expression profiles. Combined module
expression (eigengene scores) were used to: 1) identify modules negatively Keywords: NSCLC subtype differentiation, non-small cell lung cancer,
associated with FEV 1 and 2) calculate module preservation in lung tumors. metabolomics, lung cancer diagnosis
Signaling network, pathway and gene ontology analyses were performed
using IID, pathDIP, ClueGo and PARADIGM. Known and predicted protein-
protein physical interactions (PPIs) were obtained from IID. Network analysis
and visualization was performed in NAViGaTOR. Results: A module of 31 genes
significantly co-expressed across small airways was negatively associated POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
with FEV 1 and preserved in LUAD tumors. Genes in this module were enriched TUESDAY, DECEMBER 6, 2016
in functions associated with cell cycle progression, and known and/or
predicted to physically interact in the protein complex critical to mediating
G2/M progression. The forkhead transcription factor FOXM1 network was the P2.01-039 PROGNOSTIC SIGNIFICANCE OF CLAUDIN PROTEIN
most highly perturbed entity across 515 LUAD tumors. FOXM1 is an essential EXPRESSION IN HISTOLOGICAL SUBTYPES OF NON-SMALL CELL
mitotic protein, known to regulate expression of genes involved in cell cycle LUNG CANCER
progression, as well as stress response to ROS and DNA damage, angiogenesis Judit Moldvay 1, Katalin Fabian2, Márta Jäckel3, Zsuzsanna Németh4, Krisztina
and metastasis. COPD-related airway mRNA changes and genes highly altered Bogos1, József Furák5, László Tiszlavicz6, János Fillinger 7, Zsuzsa Schaff8,
at the DNA and mRNA level in LUAD tumors directly converge on the FOXM1 Balazs Dome1
regulated mitotic complex proteins and/or FOXM1 transcription factor 1
National Korányi Institute of Pulmonology, Budapest/Hungary, 2 Semmelweis
network. Conclusion: FOXM1 is overexpressed in multiple cancer types where University, Department of Pulmonology, Budapest/Hungary, 3Department of
it is correlated with poor prognosis and oncogenic transformation of epithelia Pathology, Medical Centre, Human Defense Forces, Budapest/Hungary, 4 Centre for
through induction of genomic instability. The convergence of COPD and LUAD Cancer Research and Cell Biology, Queen’s University, Belfast/Ireland, 5University
changes on this network may underlie increased LC risk in COPD patients, of Szeged, Department of Surgery, Szeged/Hungary, 6University of Szeged,
warranting further exploration as a target for COPD treatment and/or LC Department of Pathology, Szeged/Hungary, 7National Institute of Oncology,
prevention or treatment. Department of Pathology, Budapest/Hungary, 8Semmelweis University, 2nd
Department of Pathology, Budapest/Hungary
Keywords: copd, FOXM1, lung cancer, gene network
Background: We have investigated the correlation between claudin (CLDN)
protein expression and clinicopathological parameters as well as survival in
histological subtypes of non-small cell lung cancer. Methods: 137 pathologic
stage I primary bronchial cancers including 49 adenocarcinomas of non-
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42
PROTEINS IN LUNG CANCER AND PROTEOMICS – squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC)
using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative
estimation (IHC scores 0-5) were performed on archived surgical resection
P2.01-038 DISCRIMINATION OF NSCLC CASES FROM CANCER-FREE specimens. Results: Claudin IHC scores of L-ADC differed significantly from
CONTROLS AND ADENOCARCINOMA FROM SQUAMOUS CELL ADC (CLDN1: p=0.009, CLDN2: p=0.005, CLDN3: p=0.004, CLDN4: p=0.001,
CARCINOMA USING PLASMA METABOLOMICS PROFILES CLDN7: p<0.001, respectively) and SCC (CLDN1: p<0.001, CLDN3: p<0.001,
CLDN7: p<0.001, respectively). Highly significant CLDN3-CLDN4 parallel
Julian Kim1, Michael Abdalmassih1, David Dawe2, Gefei Qing 3, Shantanu
expression could be demonstrated in ADC and L-ADC (p<0.001 in both), which
Banerji4, Michel Aliani5
1
was not observed in SCC (p=0.131). ADC and SCC showed no correlation with
Radiation Oncology, University of Manitoba, Winnipeg/MB/Canada, 2Internal smoking, whereas in case of L-ADC heavier smoking correlated with higher
Medicine, University of Manitoba, Winnipeg/MB/Canada, 3 Anatomic and
CLDN3 expression (p=0.020). Regarding claudin expression and survival,
Pulmonary Pathology, University of Manitoba, Winnipeg/AB/Canada, 4 Medical
Oncology, Cancercare Manitoba, Winnipeg/MB/Canada, 5Human Nutrition and in SCC significant correlation could be demonstrated between CLDN1 IHC
Food Sciences, University of Manitoba, Winnipeg/AB/Canada positivity and better survival (p=0.038). In NSCLC as a whole, high CLDN2
expression proved to be a better prognostic factor when compared with cases
4
where CLDN2 IHC score was 0-1 vs. 2-5 (p=0.009), however, when analyzed Genetics, Center for Cancer Research, NCI, NIH, Bethesda/MD/United States of
separately, none of the histological subgroups showed correlation between America, 5Pathology, Center for Cancer Research, NCI, NIH, Bethesda/MD/United
CLDN2 expression and overall survival. Conclusion: Our results demonstrated States of America, 6Oncology, Lombardi Cancer Center, Georgetown University,
Washington/DC/United States of America
significant claudin expression differences not only between the SCC–ADC
and SCC–L-ADC but also between the L-ADC and ADC histological subgroups, Background: Tumor heterogeneity is a major impediment to targeted
which strongly underlines that L-ADC represents a distinct entity within the treatment response in a variety of cancers, including lung cancer, the
ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but commonest cause of cancer death. However, the extent of heterogeneity at
only in the SCC subgroup. the genomic and proteomic level along with its effects on treatment response
Keywords: Immunohistochemistry, lung cancer may be patient-specific. Methods: We undertook comprehensive whole
genome, exome or targeted sequencing, together with mass spectrometry-
based proteomics analyses on twelve sequentially procured lung and lymph
node metastatic sites and normal blood from an African American never-
smoker lung adenocarcinoma patient who had survived with metastatic
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY disease for over seven years while being treated with single or combination
PROTEINS IN LUNG CANCER AND PROTEOMICS – ERBB2-directed therapies. Results: Surprisingly, only 1% of somatic variants
were common between the two sites, as revealed by WGS. Interestingly,
one novel somatic translocation, PLAG1-ACTA2 was identified in both sites
P2.01-040 CXC CHEMOKINE RECEPTOR 3 AND ELR MOTIF resulting in overexpression of ACTA2 that may have been the driver of early
NEGATIVE CXC CHEMOKINE LIGAND AXIS IN NON-SMALL CELL metastasis in this patient. The likely predominant driver of proliferation,
LUNG CANCER ERBB2, was focally amplified along with CDK12, greater in the lung compared
to the lymph nodes. However, an ERBB2 L869R mutation was specific to the
Artjoms Spaks 1, Donats Breiva1, Ilmars Tracums1, Anastasija Bistrova1, Krista
lymph node. We also discovered a novel CDK12 G879V mutation that was
Grigorovica1, Irina Spaka2, Inta Jaunalksne3, Jurijs Nazarovs4
specific to the lung. Isogenic MCF10A cells expressing ERBB2 L869R were
1
Thoracic Surgery, Pauls Stradins Clinical University Hospital, Riga/Latvia, 2Riga more proliferative than those expressing wild type ERBB2. Cells expressing
Stradins University, Riga/Latvia, 3Clinical Immunology, Pauls Stradins Clinical
ERBB2 L869R that developed lapatinib resistance showed a mesenchymal
University Hospital, Riga/Latvia, 4Pathology, Pauls Stradins Clinical University
Hospital, Riga/Latvia
phenotype, increased migration, and produced significantly more lung
metastases than lapatinib-sensitive ERBB2 wild-type cells in a tail-vein
Background: CXC group chemokine receptors and ligands are well known injection assay, implicating this mutation in repeated progression of lymph
for their role in immune response, regulation of angiogenesis, tumour node metastases. The CDK12 mutation is expected to have resulted in a
development and growth. Understanding of lung cancer pathogenesis non-functional kinase, lower expression of DNA damage response genes,
requires comprehensive analysis of cell interaction in tumour greater instability of the lung tumor genome, and increased sensitivity
microenvironment formed by malignant cells, stromal cells and immune to chemotherapy. Accordingly, there was no metastatic sites evident at
cell infiltrate. CXC chemokine receptor 3 (CXCR3) and ELR motif negative autopsy in the lung, suggesting the lung metastatic sites were essentially
CXC chemokine ligands 4, 9, 10 and 11 (CXCL4, CXCL9, CXCL10 and CXCL11) cured. We further sought to correlate the genomic heterogeneity with
form an axis which is part of complex tumorigenesis process. Methods: alterations in the proteome and phosphoproteome using high-resolution
The study recruited 38 patients with NSCLC ranging from stage IA to IIA mass spectrometry. For this purpose, we first assembled patient-specific
undergoing anatomical pulmonary resection between January 2011 and database including all somatic variants, as revealed by WGS, from the lung
January 2012. Patients were followed to assess relapse rate and survival. and lymph node to interrogate the mass spectrometry data. Several aspects
CXCR3 expression and tumour infiltrating immune cells (neutrophils, T helper of the genomic heterogeneity were evident at the protein-level. These
cells - CD4, cytotoxic T lymphocytes - CD8, B cells - CD20, macrophages - CD68 include the identification of the mutant CDK12 G879V peptide and higher
and plasma cells - CD138) were evaluated in resected tumour specimens by expression of ERBB2 in the lung. Conclusion: The integrated proteo-genomics
immunohistochemistry. For CXCR3 basic annotation parameters included analyses reveal unprecedented tumor heterogeneity in a patient with lung
an evaluation of staining intensity (negative, weak, moderate or strong) and adenocarcinoma. However, similarities in key tumor driver pathways remain.
fraction of stained cells (rare, <25%, 25-75% or >75%). Blood samples from
peripheral vein and from pulmonary vein draining tumour vascular bed were Keywords: Proteo-genomics, Tumor heterogeneity, lung adenocarcinoma
collected at the time of surgery. Levels of CXCL4, CXCL9, CXCL10 and CXCL11
were measured using ELISA and CXCL gradient was calculated. Pearson
test was used to assess statistical relationship between CXCL levels, CXCR
expression and immune cell infiltrate. Results: Majority of tumour specimens POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
despite heterogeneity showed strong CXCR3 expression which was equally IMMUNE MECHANISMS IN THORACIC CANCER AND TARGETED THERAPY –
intense in tumour cells and stroma. Correlation between tumoral and stromal TUESDAY, DECEMBER 6, 2016
expression was very strong (r = 0.86, p < 0.001). Tumoral expression of CXCR3
correlated with total number of tumour infiltrating immune cells (r = -0.58, p < P2.01-042 T CELLS SUBSETS WITH INF-GAMMA, TNF-ALPHA AND
0.01), number of T helper cells (r = -0.5, p = 0.01) and T cytotoxic cells (r = -0.4, p <
ADA IN DISTINGUISHING TUBERCULOUS FROM MALIGNANT
0.05). Stromal CXCR3 expression had similar correlation with aforementioned
parameters but also included correlation with number of B cells in infiltrate (r
PLEURAL EFFUSIONS
= -0.45, p = 0.01). CXCL10 and CXCL11 gradients correlated with stromal CXCR3 Abdellah Ali
expression (r = 0.42, p < 0.05 and r = -0.42, p < 0.05). Moderate statistically Chest, Sohag University, Sohag/Egypt
significant correlation was found between CXCL4 and CXCL10 gradients and
relapse (r=0.39, r=0.35, p<0.05). Conclusion: CXCR3 and ELR motif negative Background: The differential diagnosis of tuberculous and malignant pleural
CXC chemokine axis plays role in lung cancer pathogenesis and needs further effusion (PE) is extremely difficult and continues to pose clinical challenges.
evaluation for better understanding of tumour immunology. we aimed to evaluate the utility of pleural fluid Interferon gamma (IFN- γ),
Adenosine deaminase (ADA), Tumar necrosis factor-alpha (TNF-a) levels with
Keywords: CXC chemokines, CXCR3, Tumour immunology T cells subsets in differential diagnosis of malignant (MPE) and tuberculous
pleural effusions (TPE). Methods: Forty patients with pleural effusion (20
tuberculous and 20 malignant) were included in the study. The percentages
of CD3 lymphocyte, CD4 lymphocyte and Treg (CD4 CD25) T cells in pleural
effusion from patients with tuberculous and malignant pleurisy were
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY determined by flow cytometry. The concentrations of TNF-a, IFN-γ and
TUESDAY, DECEMBER 6, 2016 ADA were simultaneously determined in pleural fluids by enzyme linked
immunosorbent assay and colorimetric method. Results: The ADA activity,
TNF-a and IFN-g concentration were significantly higher in tuberculous than
P2.01-041 INTEGRATED PROTEO-GENOMICS ANALYSES REVEAL MPE (84.22±41.47 vs. 23.19±17.93 U/l : P<0.0001, 122.45±47.69 vs. 35.03±31.88
EXTENSIVE TUMOR HETEROGENEITY AND NOVEL SOMATIC pg/ml : P < 0.0001 and 2.26±1.62 vs. 0.3±0.20 IU/ml : P<0.0001 respectively
VARIANTS IN LUNG ADENOCARCINOMA ). T-cells subsets (CD3 T-cells, CD4 T-cells and T reg cells) were significantly
Romi Biswas1, Shaojian Gao1, Contance Cultraro1, Xu Zhang1, Tapan Maity1, higher in TPE than MPE (76.46% vs. 65.29%; P 0.004, 51.21% vs. 43.50%; P
Corey Carter2, Anish Thomas1, Arun Rajan1, Ken-Ichi Hanada3, Young Song4, 0.044 and 14.60% vs. 12.43%; P 0.032 respectively). CD3 plus CD4 as well as
Zied Abdullaev5, Paul Meltzer4, James Yang 3, Svetlana Pack5, Giuseppe CD3 plus CD4 plus T reg combinations were all 100% specific for discriminating
Giaccone6, Javed Khan4, Udayan Guha1 TPE from MPE. TNF-α plus IFN-γ, TNF-α plus ADA, as well as TNF-α plus IFN-γ
1
Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, NCI,
plus ADA, were 100% specific for discriminating TPE from MPE. Furthermore,
NIH, Bethesda/MD/United States of America, 2Medical Oncology, Walter Reed the specificity of combined-diagnostic value of TNF-α, IFN-γ, ADA with T cells
National Military Medical Center, Bethesda/AL/United States of America, 3Surgery, subsets was > 95 %. Conclusion: The combinations of pleural fluid IFN- γ, ADA,
Center for Cancer Research, NCI, NIH, Bethesda/MD/United States of America, TNF-a levels and T cells subsets could effectively address the challenge of

distinguishing tuberculous pleural effusion from malignant pleural effusion. Background: Nivolumab is the first checkpoint inhibitor approved for the
treatment of Squamous (Sq) and non-Squamous (non-Sq) metastatic NSCLC in
Keywords: PLeural effusion, lung cancer, T cells second-line setting, showing a survival benefit in randomized phase III trials.
The aim of this study is to investigate the potential role of baseline peripheral
blood cells in relation to clinical outcomes following nivolumab treatment.
Methods: From November 2015 to to June 2016, we evaluated 45 patients
with Sq (n = 10) and non-Sq (n = 35) NSCLC, previously treated with first-line
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY platinum-based chemotherapy, that received nivolumab 3 mg/kg IV on day
Immune Mechanisms in Thoracic Cancer and Targeted 1 of each 2 week treatment cycle. Clinical characteristics (T-Stage, lymph
Therapy – nodes involvement, M-Stage) were assessed. Total numbers of leukocytes,
myeloid-derived suppressor cells (MDSCs), including both monocytic (Mo-
TUESDAY, DECEMBER 6, 2016 MDSC) and granulocytic (Gr-MDSC) type, regulatory T cells (T-regs), and serum
lactate dehydrogenase (LDH) were assessed. Endpoints were correlation
with objective response (OR), progression-free survival (PFS, categorized
P2.01-043 PATHOLOGIST AGREEMENT RATES OF PD-L1 TUMOR AND as ≤ 3 or > 3 months) and overall survival (OS). Tumor response was assessed
IMMUNE CELL QUANTITATION USING DIGITAL READ, FIELD-OF- using RECIST criteria, version 1.1, at week 9 and every 6 weeks thereafter until
VIEW, AND WHOLE TUMOR IMAGE ANALYSIS disease progression. Statistical methods were based on univariate analyses
Michael Barnes1, Isaac Bai2, Kien Nguyen1, Joerg Bredno1, Bharathi (Wilcoxon rank test). Results: The median PFS of the overall study population
Vennapusa2, Rachel Fonstad2, Suresh Agarwal1, Suhas Patil1, Elizabeth Little1, was 3 months. Data about Gr-MDSCs (identified by flow cytometry as Lin-
Hartmut Koeppen3, Christoph Guetter 1 CD15+CD14-CD11b+HLA-DRlow/-), Mo-MDSCs (Lin-CD14-CD11b+HLA-DRlow/-)
1 and absolute eosinophil counts (AEC) were available in 37/45 patients (82%)
Roche Diagnostics, Mountain View/CA/United States of America, 2Roche
Diagnostics, Tucson/AZ/United States of America, 3Genentech, South San of treated patients. Baseline absolute numbers of Gr-MDSCs, Mo-MDSCs
Francisco/CA/United States of America and AEC were greater in patients with good prognosis (PFS > 3 months) and
better outcomes. In particular among patients with shorter PFS, the median
Background: PD-L1 agents have shown clinical efficacy. Recent reports numbers of Gr-MDSCs, Mo-MDSCs and AEC were significantly lower than
have demonstrated the predictive value of PD-L1 immunohistochemistry those detected in patients with longer PFS (4 vs 13 cell/µl, p=0.01; 4 vs 21 cell/
(IHC) assessment from immune (IC) and tumor cells (TC) in non-small cell µl, p=0.06; 55 vs 155 cell/µl; p=0.02, respectively). No correlation was observed
lung carcinoma (NSCLC). While assessing percent staining of TC is a task between T-regs, LDH, absolute neutrophil, monocyte, lymphocyte counts and
familiar to pathologists, assessment of IC is novel and possibly challenging. clinical outcomes. Conclusion: A baseline blood signature characterized by
As noted in other studies, digital pathology (DP) with image analysis (IA) low levels of Gr-MDSCs, Mo-MDSCs and AEC is associated with poor outcome
has the potential to reduce inter-reader (IR) variation in specific situations. (median PFS ≤ of 3 months) in 67.6% of patients treated with nivolumab. In
However, the impact of DP IA on IR variation in the setting of PD-L1 IHC contrast, patients (32.4%) with high levels of these three biomarkers showed
scoring is unknown as are the effects of different IA approaches (field-of-view a median PFS significant longer than 3 months. Overall survival analysis is
[FOV] vs whole tumor [WT]). Methods: A cohort of 60 NSCLC formalin-fixed ongoing.
paraffin-embedded tissue samples was stained with PD-L1 IHC (SP142).
Three pathologists underwent training for IHC-based manual assay and DP Keywords: NSCLC, Nivolumab, biomarker, Immunotherapy
IA interpretation. Three scorers independently and blindly scored each case
using digital read (DR, no IA but digital assessment on computer monitor),
FOV IA, and WT IA. Data was analyzed using pair-wise overall percent
agreement rates (OPA) derived from assay threshold categorical bins. Results:
For IC scoring, WT IA significantly improved IR agreement and reproducibility IMMUNE MECHANISMS IN THORACIC CANCER AND TARGETED THERAPY –
rates as compared to DR and FOV-based approaches (table 1). TC WT IA also TUESDAY, DECEMBER 6, 2016
showed similar improvements.
P2.01-045 NINTEDANIB IMPROVES ANTI-TUMOR EFFICACY IN
TC-DR TC-FOV TC-WTA IC-DR IC-FOV
IC-WTA (%) COMBINATION WITH ANTI PD-1 IN SYNGENEIC TUMOR MODELS
(%) (%) (%) (%) (%)
SENSITIVE AND REFRACTORY TO IO INHIBITION
83.1 89.8 89.1 91.5
98.3 (91.0- 100.0 (93.9- Frank Hilberg, Markus Reschke, Marco Hofmann, Norbert Kraut
R1-R2 (71.5- (79.5- (77.0- (81.6-
99.7) 100.0) Parmacology, Boehringer Ingelheim Rcv, Wien/Austria
90.5) 95.3) 95.3) 96.3)
94.5 87.3 100.0 76.7 88.4 Background: Nintedanib, an oral triple-angiokinase inhibitor, has
100.0 (93.5-
R2-R3 (85.1- (76.0- (93.5- (62.3- (75.5- received regulatory approval in combination with docetaxel based on the
100.0)
98.1) 93.7) 100.0) 86.8) 94.9) demonstrated efficacy as a 2nd line treatment for NSCLC patients. Two
82.1 85.7 98.2 83.9 95.5 recently approved immune checkpoint PD1 antagonists have shaken up the
100.0 (93.6-
R1-R3 (70.2- (74.3- (90.6- (72.2- (84.9- established lines of NSCLC therapy. In order to explore the combination
100.0)
90.0) 92.6) 99.7) 91.3) 98.7) potential of Nintedanib with PD1 antagonists, we performed in vivo
combination experiments in two syngeneic murine tumor models. Methods:
Table 1: NSCLC IR OPA rates. PD-L1 IHC scoring threshold 1% (TC1/IC1), R = The murine tumor cell lines CT-26 and 4T1 were injected subcutaneously
Reader (95% confidence interval) Conclusion: Compared to DR and FOV IA, WT into female BALB/c mice. Established tumors around of 50-100mm³ were
IA significantly improved pathologists’ PD-L1 IR rates for TC and IC scoring in randomized into the different treatment groups and treated with vehicle,
NSCLC samples. Further studies regarding accuracy and reproducibility are RMP1-14 (murine anti PD-1, 10mg/kg, i.p., q3or4d), Nintedanib (50mg/kg,
being performed in a larger cohort. p.o., qd) and RMP1-14 plus Nintedanib. Anti tumor efficacy was determined
after 3 weeks of treatment. In a separate pharmacodynamic approach larger
Keywords: Digital Pathology, Immune and tumor cell scoring, PD-L1, Inter-
tumors of~300mm³ were treated for 10 days followed by FACS analyses of
pathologist reproducibility
the dissociated tumors for various myeloid cell subsets including monocytes/
macrophages and granulocytes (Markers: CD11c, CD11b, Ly6C, Ly6G, PD-L1,
F4/80), T cells/activation (Markers: CD3, CD4, CD8, CD25, FoxP3, IFN-gamma,
PD-1) and NK cells (Markers: CD335/Nkp46). Results: Single agent treatment
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY of CT-26 subcutaneous tumors with RMP1-14 and Nintedanib resulted in anti-
IMMUNE MECHANISMS IN THORACIC CANCER AND TARGETED THERAPY – tumor effect with T/C values of 45% and 63%, respectively. The combination
treatment group after 24 days showed a T/C value of 34%. In the RMP1-14
refractory tumor model 4T1 neither anti-PD1 treatment nor nintedanib
P2.01-044 BASELINE PERIPHERAL BLOOD CELL SUBSETS showed benefit (T/C=88% and 82%). The combination treatment after 26
ASSOCIATED WITH SURVIVAL OUTCOMES IN ADVANCED NSCLC days resulted in a T/C value of 38%. The particular immune cell infiltrate
TREATED WITH NIVOLUMAB IN SECOND-LINE SETTING composition and activation state in the different treatment groups will be
reported. Conclusion: The combination of angiogenic and immune checkpoint
Antonio Passaro 1, Patrizia Mancuso2, Valentina Labanca2, Gianluca Spitaleri1,
inhibition is an attractive opportunity to improve overall response rates
Elena Guerini-Rocco3, Massimo Barberis3, Sara Gandini4, Cristina Noberasco1,
and efficacy based on the dual roles of angiogenic factors in blood vessel
Ester Del Signore1, Chiara Catania1, Alessia Pochesci1, Francesco Bertolini2,
formation and immune regulation. In the CT-26 model improved additive
Filippo De Marinis1
efficacy could be demonstrated by combining Nintedanib with anti PD-1. More
1
Division of Thoracic Oncology, European Institute of Oncology, Milano/Italy, interestingly, the addition of Nintedanib in the anti PD-1 refractory model 4T1
2
Laboratory of Haemato-Oncology, European Institute of Oncology, Milan/Italy,
3 showed a synergistic combinatorial anti-tumor effect. These data fit well with
Pathology, European Institute of Oncology, Milan/Italy, 4Division of Epidemiology
the hypothesis that interfering with tumor angiogenesis in combination with
and Biostatistics, European Institute of Oncology, Milan/Italy
immune checkpoint inhibition will result in additive and synergistic effects by
positively regulating immune cell function and infiltration. reproducibility of scoring PD-L1 staining by evaluating intra- and inter-
observer reproducibility for the assessment of PD-L1 expression in NSCLC. The
Keywords: angiogenesis inhibition, immune checkpoint inhibition, secondary objective was to assess the impact of training on reproducibility.
combination angiogenesis inhibition and IO Methods: The study was a blinded, pathologist reproducibility study of
scoring PD-L1 expression in NSCLC cases stained with PD-L1 22C3 pharmDx™
kit using the Dako Automated Link 48 Platform. Two pathologists previously
trained and certified by Dako scored 789 specimens to form the gold
standard. From these specimens 60 were randomly selected to evaluate a
IMMUNE MECHANISMS IN THORACIC CANCER AND TARGETED THERAPY – 1% cut-point and 60 for a 50% cut-point. Both sample sets were designed to
TUESDAY, DECEMBER 6, 2016 include 50% positive/negative specimens and 20-30 close to each cut-point.
Ten pathologists were randomly assigned to two subgroups. Subgroup 1
analyzed all samples on two consecutive days. Subgroup 2 performed the
P2.01-046 QUANTITATIVE MEASUREMENT OF B7-H3 PROTEIN
same assessments, except they received a one hour training session prior to
EXPRESSION AND ITS ASSOCIATION WITH B7-H4, PD-L1 AND TILS the second assessment. Results: The overall percent agreement (OPA) for the
IN NSCLC analysis of the intra-observer reproducibility was 89.7% (95% CI: 85.7; 92.6)
Mehmet Altan1, Vasiliki Pelekanou2, Kurt Schalper2, Maria Toki2, Roy Herbst1, for the 1% cut-point sample set and 91.3% (95% CI: 87.6; 94.0) for the 50% cut-
David Rimm2 point. The OPAs for inter-observer reproducibility of all ten pathologists were
1
Thoracic Oncology, Yale Cancer Center, New Haven/United States of America, 2Yale 84.2% (95% CI: 82.8; 85.5) and 81.9% (95% CI: 80.4; 83.3) for the 1% and 50%
Cancer Center, New Haven/CT/United States of America cut-point sample sets, respectively. There was substantial agreement at both
the 1% cut-point (prevalence-adjusted bias-adjusted kappa 0.68 (95% CI: 0.65;
Background: B7-H3 (CD276) is a type I transmembrane protein that belongs to 0.71)) and the 50% cut-point (prevalence-adjusted bias-adjusted kappa 0.64
the B7 immunoregulatory family including PD-L1 (B7-H1) and is upregulated in (95% CI: 0.61; 0.67)).
multiple malignancies including Non-Small Cell Lung Cancer (NSCLC). Clinical
activity of monoclonal B7-H3 blocking antibodies such as Enoblituzumab Training was found to have no or very little impact on the inter- or intra-
are under investigation. In this study we measured the levels of B7-H3 observer reproducibility in subgroup 2. The OPAs for the inter-observer
protein in NSCLC and studied its association with major tumor infiltrating reproducibility assessments were 82.0% and 82.3% for the first and second
lymphocyte (TIL) subsets, levels of PD-L1, B7-H4 and clinico-pathological assessments of the 1% cut-point sample set, respectively, and 78.3% and
characterist

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Volume 12, Issue S1, January 2017

WCLC 2016 Abstracts

IASLC 17 TH WORLD CONFERENCE

OPDIVO is the only PD-1 inhibitor that delivered superior

OPDIVO is indicated for the treatment of locally advanced or metastatic

OS – overall survival; PD-1 – programmed death-1; PD-L1 – programmed death-ligand 1

1506AT16PR11523-04 10/16 © 2016 Bristol-Myers Squibb Company

105795 WCLC Vienna JTO Advert_OPDIVO v2.0 2016.10.06.indd 1 06/10/2016 14:40

BOOK OF ABSTRACTS INDEX

Invited Speaker Sessions Mini Oral Abstract Sessions

Plenary Sessions S2 Monday, December 5, 2016 S174

Education Sessions S9 Tuesday, December 6, 2016 S191

Scientific Sessions S36 Wednesday, December 7, 2016 S219

Meet the Expert Sessions S77

Pro-Con Sessions S95

Interactive Sessions S98 Poster Sessions

Nurses Session S100 Poster Session 1

Publish Only S760

Monday, December 5, 2016 S125

Tuesday, December 6, 2016 S141

Author Index S862

on June 1, 2013, banning smoking in airports, train stations, stadiums, schools,

S2 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

PL03.07 FIRST-LINE CERITINIB VERSUS CHEMOTHERAPY IN

This abstract is under embargo until December 6, 2016 at 07:00 CET.

SESSION PL04a: IMMUNE CHECKPOINT INHIBITORS IN

S4 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

PL05: CLOSING PLENARY SESSION: A LIFE IN THORACIC ONCOLOGY - REFLECTIONS FROM

PL05.04 TRANSLATIONAL LUNG CANCER RESEARCH

S6 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

identified and subsequently ROS-1. Molecular targeted agents demonstrated

S8 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

S10 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

World Health Organization. Cancer country profiles in Iran 2014. Geneva:

Heydari H. Home-based Palliative Care: A Strategy for Keeping Intensive Care

Keywords: Palliative medicine, cancer, Iran

SESSION ED03: GLOBAL TOBACCO CONTROL POLICIES:

ED03.01 TOBACCO CONTROL IN THE MIDDLE EAST

Despite many countries signing and ratifying the Framework Convention on

S12 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

Keywords: Prognosis, TNM classification, Staging, lung cancer

ED05: THE 8TH EDITION OF THE TNM STAGING SYSTEM

ED05.02 UPDATE ON THE MESOTHELIOMA STAGING SYSTEM

The initial TNM staging classification for malignant pleural mesothelioma

S14 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

ED05: THE 8TH EDITION OF THE TNM STAGING SYSTEM

ED05.04 WHAT’S NEW IN ESOPHAGEAL CANCER STAGING?

What’s New in Esophageal Cancer Staging? Thomas W. Rice, MD The 8th

S16 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

Keywords: pain- pathophysiology and management, pathophysiology of pain,

ED06.03 PAIN MANAGEMENT ED06.04 BIOLOGY AND MANAGEMENT OF TUMOR CACHEXIA

Moreover, it can help us address potential interventions that may be of sedation.

(See Figure next page)

S18 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

S20 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017

compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity

study. J Thorac Cardiovasc Surg 2013;146:358-64. 4. Zhao X, Qian L, Luo Q, et al.

Working Group 10. Mahmood S, Bilal H, Faivre-Finn C, Shah R. Is stereotactic

ED08: EARLY-STAGE NSCLC: STATE-OF-THE-ART TREATMENT AND PERSPECTIVES

ED08.02 THE ROLE OF RADIOTHERAPY IN EARLY-STAGE NSCLC