SCLC

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
Small Cell Lung

Cancer
Version 1.2018 — September 18, 2017
NCCN.org
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Version 1.2018, 09/18/17 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®
Printed by Mario Gorrieri on 1/11/2018 7:37:20 AM. For personal use only. Not approved for distribution. Copyright © 2018 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines Version 1.2018 Panel Members NCCN Guidelines Index

Table of Contents
Small Cell Lung Cancer Discussion
* Gregory P. Kalemkerian, MD/Chair † Apar Kishor P. Ganti, MD † Julian Molina, MD, PhD ‡ Þ
Fred & Pamela Buffett Cancer Center
University of Michigan Mayo Clinic Cancer Center
Comprehensive Cancer Center John C. Grecula, MD § Cesar A. Moran, MD ≠
* Billy W. Loo, Jr., MD, PhD/Vice Chair § The Ohio State University Comprehensive The University of Texas
Cancer Center - James Cancer Hospital
Stanford Cancer Institute MD Anderson Cancer Center
and Solove Research Institute
Wallace Akerley, MD † Daniel Morgensztern, MD †
Matthew A. Gubens, MD, MS †
Huntsman Cancer Institute Siteman Cancer Center at Barnes-
UCSF Helen Diller Family
at the University of Utah Jewish Hospital and Washington
Comprehensive Cancer Center University School of Medicine
Albert Attia, MD § Christine L. Hann, MD, PhD †
Vanderbilt-Ingram Cancer Center Saraswati Pokharel, MD ≠
The Sidney Kimmel Comprehensive Roswell Park Cancer Institute
Cancer Center at Johns Hopkins
Michael Bassetti, MD §
University of Wisconsin David C. Portnoy, MD ‡ †
James A. Hayman, MD, MBA §
Carbone Cancer Center The University of Tennessee
University of Michigan Health Science Center
Comprehensive Cancer Center
Yanis Boumber, MD, PhD †
Fox Chase Cancer Center Deborah Rhodes, MD Þ
Rebecca Suk Heist, MD, MPH † Mayo Clinic Cancer Center
Massachusetts General Hospital
Roy Decker, MD, PhD § Cancer Center
Yale Cancer Center/Smilow Cancer Hospital Chad Rusthoven, MD §
University of Colorado Cancer Center
Marianna Koczywas, MD † ‡ Þ
M. Chris Dobelbower, MD, PhD § City of Hope Comprehensive
University of Alabama at Birmingham Rafael Santana-Davila, MD †
Cancer Center
Comprehensive Cancer Center Fred Hutchinson Cancer Research Center/
Seattle Cancer Care Alliance
Robert E. Merritt, MD ¶
Afshin Dowlati, MD † The Ohio State University Comprehensive
Case Comprehensive Cancer Center/ Charles C. Williams, Jr., MD †
Cancer Center - James Cancer Hospital
University Hospitals Seidman Cancer Moffitt Cancer Center
and Solove Research Institute
Center and Cleveland Clinic Taussig
Cancer Institute Nisha Mohindra, MD † NCCN
Robert H. Lurie Comprehensive Cancer Karin G. Hoffmann, RN, CCM
Robert J. Downey, MD ¶ Center of Northwestern University Miranda Hughes, PhD
Memorial Sloan Kettering Cancer Center
Charles Florsheim † Medical oncology

Patient Advocate ¶ Surgery/Surgical oncology
§ Radiation oncology
Continue ‡ Hematology/Hematology oncology
Þ Internal medicine
≠ Pathology
NCCN Guidelines Panel Disclosures *Discussion Section Writing Committee
NCCN Guidelines Version 1.2018 Table of Contents NCCN Guidelines Index

Table of Contents
NCCN Small Cell Lung Cancer Panel Members

Summary of the Guidelines Updates
Clinical Trials: NCCN believes that
the best management for any patient
Small Cell Lung Cancer: with cancer is in a clinical trial.
• Initial Evaluation and Staging (SCL-1) Participation in clinical trials is
• Limited Stage, Workup and Treatment (SCL-2) especially encouraged.
• Extensive Stage, Initial Treatment (SCL-4) To find clinical trials online at NCCN
• Response Assessment Following Initial Therapy (SCL-5) Member Institutions, click here:
• Surveillance (SCL-5) nccn.org/clinical_trials/physician.html.
• Progressive Disease: Subsequent Therapy and Palliative Therapy (SCL-6) NCCN Categories of Evidence and
Consensus: All recommendations
• Signs and Symptoms of Small Cell Lung Cancer (SCL-A) are category 2A unless otherwise
• Principles of Pathologic Review (SCL-B) indicated.
• Principles of Surgical Resection (SCL-C) See NCCN Categories of Evidence
• Principles of Supportive Care (SCL-D) and Consensus.
• Principles of Systemic Therapy (SCL-E)
• Principles of Radiation Therapy (SCL-F)
Staging (ST-1)
Lung Neuroendocrine Tumors – See the NCCN Guidelines for Neuroendocrine Tumors
The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical
circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or
warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2017.
NCCN Guidelines Version 1.2018 Updates NCCN Guidelines Index

Table of Contents
Updates in Version 1.2018 of the NCCN Guidelines for Small Cell Lung Cancer from Version 3.2017 include:
General
For consistency in imaging, statement was revised: “CT Chest/liver/adrenal abdomen CT with contrast” as appropriate throughout the
guideline.
SCL-1
• Initial Evaluation
Bullet 4 modified: “Electrolytes, liver function tests (LFTs), Ca LDH BUN, creatinine”
Bullet 7 modified: “PET/CT scan (skull base to mid-thigh), (if limited stage is suspected)”
Footnote “b” for H & P was added: “See Signs and Symptoms of Small Cell Lung Cancer (SCL-A)” (Also for SCL-5)
Footnote “c” for pathology review was added: “See Principles of Pathologic Review (SCL-B).”
SCL-2
• Additional Workup
Bullet 2 modified: “Pulmonary function tests (PFTs) during evaluation for surgery (if clinically indicated)”
Bullet 3 modified: “Bone imaging (radiographs or MRI) as appropriate if PET/CT equivocal (Consider biopsy if bone imaging is equivocal)”
SCL-3
• Adjuvant Treatment
Clinical stage N+ separated into N1 and N2.
◊◊N1 adjuvant treatment option added: “Systemic therapy ± mediastinal RT (sequential or concurrent)”
◊◊N2 adjuvant treatment option added: “Systemic therapy + mediastinal RT (sequential or concurrent)”
• Footnote “o” was modified: “For patients receiving adjuvant therapy, response assessment should occur only after completion of initial
adjuvant therapy (SCL-5); do not repeat scans to assess response during adjuvant treatment.”
SCL-4
• Initial Treatment of asymptomatic brain metastases
Statement was modified: “May administer systemic therapy first, with whole-brain RT after completion of systemic therapy”
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SCL-5
• Response Assessment Following Initial Therapy
Bullet 5 was modified: “Electrolytes, LFTs, Ca, BUN, creatinine”
• Adjuvant Treatment; Extensive disease: “PCI ± thoracic RT” revised to “Consider PCI ± thoracic RT.”
• Surveillance
Footnote “s” was added to heading: “See NCCN Guidelines for Survivorship”
• Complete response or partial response
Limited stage
◊◊Statement was revised: “After completion of initial recovery from primary therapy:”
◊ Bullet 1 was revised: “Oncology follow-up visits every 3–4 mo during y 1–2, every 6 mo during y 3–5, then annually”
◊◊Bullet 1 revised: “At every visit: H&P, CT Chest/abdomen; liver/adrenal with contrast, bloodwork only as clinically indicated”
◊◊Bullet 2 was added: “If PCI not given, then MRI (preferred) or CT brain with contrast every 3–4 mo during y 1–2”
Extensive stage
◊◊Statement was added: “After completion of initial or subsequent therapy”
◊ Bullet 1 was added: “Oncology follow-up visits every 2 mo during y 1, every 3–4 mo during y 2–3, then every 6 mo during years 4–5,
then annually”
◊◊Bullet 1 revised: “At every visit: H&P, CT Chest/abdomen; liver/adrenal with contrast, bloodwork only as clinically indicated”
◊◊Bullet 2 was added: “If PCI not given, then MRI (preferred) or CT brain with contrast every 3–4 mo during y 1–2”
◊◊Footnote “u” for thoracic RT was revised: “Sequential radiotherapy to thorax in selected patients, especially with residual thoracic
disease and low-bulk extrathoracic metastatic disease and complete response that has responded to systemic therapy.”
• Stable disease
Limited stage and Extensive stage
◊◊Statement was revised: “After completion of initial recovery from primary therapy:”
◊ Bullet 1 was revised: “Oncology follow-up visits every 3–4 mo during y 1–2, every 6 mo during y 3–5, then annually”
◊ Statement was added: “After completion of initial or subsequent therapy”
◊ Bullet 1 was added: “Oncology follow-up visits every 2 mo during y 1, every 3–4 mo during y 2–3, then every 6 mo during years 4–5,
then annually”
SCL-6
• Footnote “k,” “See Principles of Supportive Care (SCL-D)” was added after all “Palliative symptom management” statements.
• Footnote “v,” “See Principles of Palliative Care (PAL-1)” was added after all “Palliative symptom management” statements.
• For “PS 0-2,” “or” was removed from between “Consider subsequent systemic therapy” and “Palliative symptom management, including
localized RT to symptomatic sites.”
(SCL-A) Signs and Symptoms of Small Cell Lung Cancer
• A new section was added: “Signs and Symptoms of Small Cell Lung Cancer”
(SCL-B) Principles of Pathologic Review
• A new section was added: “Principles of Pathologic Review”
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(SCL-C) Principles of Surgical Resection
• A footnote was removed: “Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer.
N Engl J Med 2007;357:664-672.”
(SCL-D) Principles of Supportive Care
• Syndrome of inappropriate antidiuretic hormone
Sub-bullet 5 was revised: “Vasopressin receptor inhibitors (conivaptan, tolvaptan) for refractory hyponatremia”
(SCL-E) Principles of Systemic Therapy (1 of 3)
• Extensive stage (maximum of 4–6 cycles)
Bullet 7 was revised: “Cisplatin 30 mg/m2 days 1, 8 and irinotecan 65 mg/m2 days 1, 8”
Footnote “†” was added: “If not used as original regimen, may be used as therapy for primary progressive disease.”
• Subsequent systemic therapy
Footnote “‡” was added: “Subsequent systemic therapy refers to second-line and beyond therapy.”
• Relapse ≤6 mo, PS 0-2: nivolumab ± ipilimumab
Reference “22” was added: “Hellmann MD, Ott PA, Zugazagoitia J, et al. First report of a randomized expansion cohort from CheckMate 032
[abstract]. J Clin Oncol 2017;35: Abstract 8503.”
(SCL-E) Principles of Systemic Therapy (2 of 3)
• Limited-stage
Sub-bullet 1 was revised: “For patients receiving initial adjuvant therapy, response assessment should occur only after completion of initial
adjuvant therapy; do not repeat scans to assess response during adjuvant treatment.”
(SCL-F) Principles of Radiation Therapy (1 of 3)
• General Principles
Bullet 4 was revised: “Use of more advanced technologies is appropriate when needed to deliver adequate tumor doses while respecting
normal tissue dose constraints. Such technologies include (but are not limited to) 4D-CT and/or PET/CT simulation, IMRT/VMAT, IGRT, and
motion management strategies. IMRT is preferred over 3D conformal external-beam RT (CRT) on the basis of reduced toxicity in the setting
of concurrent
chemotherapy/RT. Quality assurance measures are essential and are covered in the NSCLC guidelines (see NSCL‑C).”
Reference “1” was added: “Chun SG, Hu C, Choy H, et al. Impact of intensity-modulated radiation therapy technique for locally advanced
non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. J Clin Oncol 2017;35:56-62.”
• Limited Stage
Bullet 5 was revised: “Dose and schedule: For limited‑stage SCLC, the optimal dose and schedule of RT have not been established; 45 Gy
in 3 weeks (1.5 Gy twice daily [BID]) is superior (category 1) to 45 Gy in 5 weeks (1.8 Gy daily). When BID fractionation is used, there should
be at least a 6‑hour inter‑fraction interval to allow for repair of normal tissue. If using once-daily RT, higher doses of 60–70 Gy should be
used. The current randomized trial CALGB 30610/RTOG 0538 is comparing the standard arm of 45 Gy (BID) in 3 weeks to 70 Gy in 7 weeks;
accrual to an experimental concomitant boost arm has closed. The European CONVERT trial demonstrated comparable overall survival and
toxicity between 45 Gy (BID) and 66 Gy (daily).”
Reference 20 was added: “Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients
with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol 2017;18:1116-
1125.”
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(SCL-F) Principles of Radiation Therapy (2 of 3)
• Extensive stage
Bullet 1 modified: “Consolidative thoracic RT is beneficial for selected patients with extensive‑stage SCLC that responds with CR or
good response to systemic therapy. Studies have demonstrated that consolidative thoracic RT up to definitive doses is well tolerated,
results in fewer symptomatic chest recurrences, and improves long‑term survival in some patients. The Dutch CREST randomized trial of
modest-dose thoracic RT (30 Gy in 10 fractions), in patients with extensive stage SCLC that responded to systemic therapy demonstrated
significantly improved 2-year overall survival and six-month PFS, although the protocol-defined primary endpoint of one-year overall
survival was not significantly improved. Subsequent exploratory analysis found the benefit of consolidative thoracic RT is limited to the
majority of patients who had residual thoracic disease after systemic therapy.”
Bullet 2 was added: “Dosing and fractionation of consolidative thoracic RT should be individualized within the range of 30 Gy in 10 daily
fractions to 60 Gy in 30 daily fractions, or equivalent regimens in this range.”
Reference 24 was added: “Slotman BJ, van Tinteren H, Praag JO, et al. Radiotherapy for extensive stage small-cell lung cancer– Authors
reply. Lancet 2015;385:1292-1293.”
• Prophylactic Cranial Irradiation (PCI)
Bullet 1 modified: “In patients with limited-stage SCLC who have a good response to initial therapy, PCI decreases brain metastases and
increases overall survival (category 1). In patients with extensive-stage SCLC that has responded to systemic therapy, PCI decreases
brain metastases. A randomized trial conducted by the EORTC found improved overall survival with PCI. However, while a Japanese
randomized trial conducted by the EORTC found that in patients who had no brain metastases on baseline MRI, improved overall survival
with PCI did not improve overall survival compared with routine surveillance MRI and treatment of asymptomatic brain metastases upon
detection.results from a Japanese randomized trial found no improved overall survival in patients who had MRI to confirm absence of brain
metastases at baseline. In patients not receiving PCI, surveillance for metastases by brain imaging should be considered performed.”
Bullet 5 was added: “When administering PCI, consider adding memantine during and after RT, which has been shown to decrease
neurocognitive impairment following whole brain radiation therapy (WBRT) for brain metastases.”
Reference 28 was updated: “Takahashi T, Yamanaka T,Takashi S et al. Prophylactic cranial irradiation versus observation in patients with
extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2017;18:663-671.”
Reference 31 was added: “Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving
whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol 2013;10:1429-1437.”
• Brain Metastases
Bullet 1 modified: “Brain metastases should be treated with WBRT rather than stereotactic radiotherapy/radiosurgery (SRT/SRS) alone,
because these patients tend to develop multiple CNS metastases. In patients who develop brain metastases after PCI, repeat WBRT may
be considered in carefully selected patients. SRS may also be considered, is preferred if feasible, especially if there has been a long-time
interval from initial diagnosis to occurrence of brain metastases and there is no uncontrolled extracranial disease.”
UPDATES
Version 1.2018, 09/18/17 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® 4 OF 4
NCCN Guidelines Version 1.2018 NCCN Guidelines Index

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DIAGNOSIS INITIAL EVALUATIONa STAGE
• H&Pb
• Pathology reviewc
• CBC Limited stage
See Additional
• Electrolytes, liver function tests (See ST-1 for TNM
Small cell or Workup (SCL-2)
(LFTs), BUN, creatinine Classification)
combined small
• Chest/abdomen CT with contrast
cell/non-small cell
• Brain MRIa,d (preferred) or CT with
lung cancer on
contrast
biopsy or cytology
• PET/CT scan (skull base to
of primary or Extensive stage
mid-thigh), (if limited stage is See Initial
metastatic site (See ST-1 for TNM
suspected)a,e Treatment (SCL-4)
Classification)
• Smoking cessation counseling
and intervention. See the NCCN
Guidelines for Smoking Cessation
aIf extensive stage is established, further staging evaluation is optional. However, brain imaging, MRI (preferred), or CT with contrast should be obtained in all patients.
bSee Signs and Symptoms of Small Cell Lung Cancer (SCL-A).
cSee Principles of Pathologic Review (SCL-B).
dBrain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.
eIf PET/CT is not available, bone scan may be used to identify metastases. Pathologic confirmation is recommended for lesions detected by PET/CT that alter stage.
Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
SCL-1

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STAGE ADDITIONAL WORKUP
• If pleural effusion is present,

thoracentesis is Clinical stage Pathologic mediastinal See Initial
recommended; if T1-2, N0 stagingh,i,j Treatment (SCL-3)
thoracentesis inconclusive,
consider thoracoscopyf
• Pulmonary function tests
(PFTs) during evaluation for
Limited stage
surgery Limited stage in See Initial
(See ST-1 for TNM
• Bone imaging (radiographs excess of T1-T2, N0 Treatment (SCL-3)
Classification)
or MRI) as appropriate if
PET/CT equivocal (Consider
biopsy if bone imaging is
equivocal) Bone marrow biopsy, See
• Unilateral marrow thoracentesis, or bone studies Extensive-Stage
aspiration/biopsy in select consistent with malignancy Disease (SCL-4)
patientsg
fWhile most pleural effusions in patients with lung cancer are due to tumor, there are a few patients in whom multiple cytopathologic examinations of pleural fluid are
negative for tumor and fluid is non-bloody and not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the
effusion should be excluded as a staging element. Pericardial effusion is classified using the same criteria.
gSelection criteria include: nucleated red blood cells (RBCs) on peripheral blood smear, neutropenia, or thrombocytopenia suggestive of bone marrow infiltration.
hSee Principles of Surgical Resection (SCL-C).
iMediastinal staging procedures include mediastinoscopy, mediastinotomy, endobronchial or esophageal ultrasound-guided biopsy, and video-assisted thoracoscopy.
If endoscopic lymph node biopsy is positive, additional mediastinal staging is not required.
jPathologic mediastinal staging is not required if the patient is not a candidate for surgical resection or if non-surgical treatment is pursued.

SCL-2

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TESTING RESULTS INITIAL TREATMENTj ADJUVANT TREATMENT
N0 Systemic therapym
Lobectomyh,l Systemic therapym See Response

(preferred) and ± mediastinal RTl
Pathologic mediastinal Assessment +
mediastinal lymph N1 (sequential or
stagingh,i negative Adjuvant Treatment
node dissection concurrent) (SCL-5)o
Clinical stage or sampling
Pathologic
T1-2, N0
mediastinal stagingh,i
Systemic therapym
positive or medically
N2 + mediastinal RTn
inoperable or decision
(sequential or
made not to pursue
concurrent)
surgical resection
Systemic therapym + See Response

Good PS (0-2)
concurrent RTl (category 1) Assessment +
Adjuvant Treatment
Limited stage in Poor PS (3-4) Systemic therapym ± RTn (SCL-5)p
excess of T1-2, N0 due to SCLC (concurrent or sequential)
Poor PS (3-4) not Individualized treatment
due to SCLC including supportive carek
hSee Principles of Surgical Resection (SCL-C).

iMediastinal staging procedures include mediastinoscopy, mediastinotomy, endobronchial or esophageal ultrasound-guided biopsy, and video-assisted thoracoscopy. If endoscopic lymph
node biopsy is positive, additional mediastinal staging is not required.
kSee Principles of Supportive Care (SCL-D).
lSelect patients may be treated with systemic therapy/RT as an alternative to surgical resection.
mSee Principles of Systemic Therapy (SCL-E).
nSee Principles of Radiation Therapy (SCL-F).
oFor patients receiving adjuvant therapy, response assessment should occur only after completion of adjuvant therapy (SCL-5); do not repeat scans to assess response during adjuvant
treatment.
pFor patients receiving systemic therapy + concurrent RT, response assessment should occur only after completion of initial therapy (SCL-5); do not repeat scans to assess response
during initial treatment. For patients receiving systemic therapy alone or sequential systemic therapy followed by RT, response assessment by Chest/abdomen CT with contrast should
occur after every 2 cycles of systemic therapy and at completion of therapy (SCL-5).

SCL-3

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STAGE INITIAL TREATMENTk

• Good PS (0-2)
Combination systemic therapym including
• Poor PS (3-4)
Extensive stage supportive carek
due to SCLC
without localized See NCCN Guidelines for Palliative Care
symptomatic sites
or brain metastases • Poor PS (3-4) Individualized therapy including
not due to supportive carek
SCLC See NCCN Guidelines for Palliative Care
Systemic therapym ± RTn to
symptomatic sites
• SVC syndrome
If high risk of fracture due to osseous
• Lobar obstruction
structural impairment, consider See Response
• Bone metastases
Extensive stage Extensive stage + orthopedic stabilization and Assessment +
(See ST-1 for TNM localized palliative external-beam RTn Adjuvant Treatment
Classification) symptomatic sites RTn to symptomatic sites before (SCL-5)r
systemic therapy unless immediate
Spinal cord
systemic therapy is required.
compression
See NCCN Guidelines for Central
Nervous System Cancers
May administer systemic therapy first,

Asymptomatic with whole-brain RTn after completion of
Extensive stage with systemic therapym,q
brain metastases
Whole-brain RTn before systemic
Symptomatic therapy,m unless immediate systemic
therapy is indicated

qFor patients with asymptomatic brain metastases receiving systemic therapy before whole-brain RT, brain MRI (preferred) or CT with contrast should be repeated after
every 2 cycles of systemic therapy and at completion of therapy (SCL-5).
rDuring systemic therapy, response assessment by chest/abdomen CT with contrast should occur after every 2–3 cycles of systemic therapy and at completion of
therapy (SCL-5).
SCL-4

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RESPONSE ASSESSMENT FOLLOWING ADJUVANT SURVEILLANCEs

INITIAL THERAPY TREATMENT After completion of initial
therapy:
Limited • Oncology follow-up
PCIn,t (category 1) visits every 3 mo during
stage y 1–2, every 6 mo during
• Chest x-ray y 3, then annually
Complete • At every visit: H&Pb,
(optional)
response CT Chest/abdomen;
• Chest/
or partial bloodwork only as
abdomen CT After completion of initial clinically indicated
response or subsequent therapy:
with contrast • If PCI not given, then
• Brain MRId • Oncology follow-up MRId (preferred) or CT
Extensive Consider PCIn,t visits every 2 mo during brain with contrast For
(preferred) y 1, every 3–4 mo during
stage ± thoracic RTn,u every 3–4 mo during y Relapse,
or CT with y 2–3, then every 6 mo 1–2
contrast, if during years 4–5, then • New pulmonary nodule see
prophylactic annually should initiate workup Subsequent
cranial for potential new Therapy
After completion of initial therapy: primary (SCL-6)
irradiation Limited • Smoking cessation
• Oncology follow-up visits every 3 mo during y
(PCI) to be stage intervention, see the
1–2, every 6 mo during y 3, then annually NCCN Guidelines for
given
Stable Smoking Cessation
• CBC
disease • PET/CT is not
• Electrolytes, After completion of initial or subsequent therapy: recommended for
Extensive • Oncology follow-up visits every 2 mo during y
LFTs, BUN, routine follow-up
stage 1, every 3–4 mo during y 2–3, then every 6 mo
creatinine during years 4–5, then annually
Primary progressive disease See Subsequent Therapy/Palliative Therapy SCL-6)
bSee Signs and Symptoms of Small Cell Lung Cancer (SCL-A).

dBrain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.
sSee NCCN Guidelines for Survivorship.
tNot recommended in patients with poor performance status or impaired neurocognitive function.
uSequential radiotherapy to thorax in selected patients, especially with residual thoracic disease and low-bulk extrathoracic metastatic disease that has responded to
systemic therapy.
SCL-5

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PROGRESSIVE DISEASE SUBSEQUENT THERAPY/PALLIATIVE THERAPY
• Consider
subsequent
systemic
therapym,w
Continue until two • Palliative

PS 0-2 symptom
cycles beyond Progression
best response management,k,v
or including
Subsequent Response localized RTn
Progression or
systemic therapym,w development of to symptomatic
or unacceptable sites
Palliative symptom toxicity
PS 0-2 managementk,v
including localized Palliative
RTn to symptomatic symptom
sites No management,k,v
Relapse PS 3-4
or primary response or including
progressive unacceptable localized RTn to
disease toxicity symptomatic sites
Palliative symptom
management,k,v including
PS 3-4
localized RTl to symptomatic
sites

vSee Principles of Palliative Care (PAL-1).
wResponse assessment by chest/abdomen CT with contrast should occur after every 2–3 cycles of systemic therapy.
SCL-6

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SIGNS AND SYMPTOMS OF SMALL CELL LUNG CANCER (1 of 2)

Signs and symptoms due to local primary tumor growth
• Cough–endobronchial irritation, bronchial compression
• Hemoptysis–usually central or cavitary lesion
• Wheezing–partially obstructing endobronchial lesion
• Fever–post-obstructive pneumonia
• Dyspnea–bronchial obstruction, pneumonia, pleural effusion
Signs and symptoms due to primary tumor invasion or regional lymphatic metastases
• Hoarseness–left vocal cord paralysis due to tumor invasion or lymphadenopathy in the aorto-pulmonary window
• Hemidiaphragm elevation–due to phrenic nerve compression
• Dysphagia–due to esophageal compression
• Chest pain–involvement of pleura or chest wall, often dull and non-localized
• Superior vena cava syndrome–due to local invasion into mediastinum or lymphadenopathy in right paratracheal region
• Pericardial effusion and tamponade
• Cervical or supraclavicular lymph node enlargement
Signs and symptoms due to extrathoracic (hematogenous) metastases

• Brain metastases:
Headache, focal weakness or numbness, confusion, slurred speech, gait instability, incoordination
• Leptomeningeal carcinomatosis:
Headache, confusion, cranial nerve palsy, diplopia, slurred speech, radicular back pain, spinal cord compression
• Adrenal metastases:
Mid-back or flank pain, costovertebral angle tenderness
Adrenal insufficiency due to tumor involvement is rare
• Liver metastases:
Right upper quadrant pain or tenderness, jaundice, fatigue, fever, hepatomegaly
• Bone metastases:
Bone pain
Spinal cord compression–back pain, muscle weakness, numbness, paresthesia, loss of bowel and bladder control
• Constitutional:
Anorexia/cachexia–weight loss
Fatigue

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. SCL-A
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SIGNS AND SYMPTOMS OF SMALL CELL LUNG CANCER (2 of 2)

Signs and symptoms of paraneoplastic syndromes:
• Presence does not imply metastases or incurability
• Endocrine:
Due to ectopic peptide hormone production
Usually reversible with successful anti-tumor therapy
SIADH:
◊◊Ectopic vasopressin (ADH) secretion
◊◊Clinically significant hyponatremia in 5%–10% of SCLC
◊◊Malaise, weakness, confusion, obtundation, volume depletion, nausea
◊◊Hyponatremia, euvolemia, low serum osmolality, inappropriately concentrated urine osmolality, normal thyroid and adrenal function
Cushing’s syndrome:
◊◊Ectopic ACTH secretion
◊◊Weight gain, moon facies, hypertension, hyperglycemia, generalized weakness
◊◊High serum cortisol and ACTH, hypernatremia, hypokalemia, alkalosis
• Neurologic: All specific syndromes are rare

Subacute cerebellar degeneration [anti-Yo antibody]–ataxia, dysarthria
Encephalomyelitis [ANNA-1 (anti-Hu) antibody]–confusion, obtundation, dementia
Sensory neuropathy [anti-dorsal root ganglion antibody]–pain, sensory loss
Eaton-Lambert syndrome [anti-voltage-gated calcium channel antibody]–weakness, autonomic dysfunction
Cancer-associated retinopathy [anti-recoverin antibody]–visual loss, photosensitivity
• Hematologic:
Anemia of chronic disease
Leukemoid reaction–leukocytosis
Trousseau’s syndrome–migratory thrombophlebitis

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PRINCIPLES OF PATHOLOGIC REVIEW (1 of 2)
Pathologic Evaluation
• Pathologic evaluation is performed to determine the histologic classification of lung tumors and relevant staging parameters.
• The World Health Organization (WHO) tumor classification system provides the foundation for the classification of lung tumors, including
histologic subtype, staging factors, clinical features, molecular characteristics, genetics, and epidemiology.1-3
• Small cell lung cancer (SCLC) is a poorly differentiated neuroendocrine tumor. Distinguishing SCLC from other neuroendocrine
tumors, particularly typical and atypical carcinoids, is important due to significant differences in epidemiology, genetics, treatment, and
prognosis.4-6
• SCLC can be diagnosed on good-quality histologic samples via high-quality hematoxylin and eosin (H&E)–stained sections or on well-
preserved cytologic samples.
SCLC is characterized by small blue cells with scant cytoplasm, high nuclear-to-cytoplasmic ratio, granular chromatin, and absent or
inconspicuous nucleoli.
SCLC cells are round, oval, or spindle-shaped with molding and high mitotic counts.7-9
The most useful characteristics for distinguishing SCLC from large-cell neuroendocrine carcinoma (LCNEC) are the high nuclear-to-
cytoplasmic ratio and paucity of nucleoli in SCLC.
• Careful counting of mitoses is essential, because it is the most important histologic criterion for distinguishing SCLC from typical and
atypical carcinoids.
SCLC (>10 mitoses/2 mm2 field); atypical carcinoid (2–10 mitoses/2 mm2 field); typical carcinoid (0–1 mitoses/2 mm2 field)
Mitoses should be counted in the areas of highest activity and per 2 mm2 field, rather than per 10 high-power fields.
In tumors that are near the defined cutoffs of 2 or 10 mitoses per 2 mm2, at least three 2-mm2 fields should be counted and the calculated
mean (rather than the single highest mitotic count) should be used to determine the overall mitotic rate.1,2
Immunohistochemical Staining
• Immunohistochemistry can be very helpful in diagnosing SCLC in limited samples.5,7
Nearly all SCLCs are positive for cytokeratin antibody mixtures with broad reactivity, such as AE1/AE3 and CAM5.2.1,10
The majority of SCLCs are reactive to markers of neuroendocrine differentiation, including CD56/NCAM, synaptophysin, and
chromogranin A. Fewer than 10% of SCLCs are negative for all neuroendocrine markers.
Thyroid transcription factor-1 (TTF1) is positive in 85% to 90% of SCLCs.11-14
• Ki-67 immunostaining can be very helpful in distinguishing SCLC from carcinoid tumors, especially in small biopsy samples with crushed
or necrotic tumor cells in which counting mitotic figures is difficult.4,5
The Ki-67 proliferative index in SCLC is typically 50% to 100%.1

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PRINCIPLES OF PATHOLOGIC REVIEW (2 of 2) - References
1Travis WD, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press.
2015.
2Travis WD, Brambilla E, Burke AP, et al. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura,
Thymus, and Heart. J Thorac Oncol 2015;10:1240-1242.
3Travis WD, Brambilla E, Nicholson AG, et al and WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of
Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol 2015;10:1243-1260.
4Pelosi G, Rindi G, Travis WD, Papotti M. Ki-67 antigen in lung neuroendocrine tumors: unraveling a role in clinical practice. J Thorac Oncol
2014;9:273-284.
5Pelosi G, Rodriguez J, Viale G, Rosai J. Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy
specimens: a major pitfall in the management of lung cancer patients. Am J Surg Pathol 2005;29:179-187.
6Rindi G, Klersy C, Inzani F, et al. Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocr Relat Cancer
2014;21:1-16.
7Travis WD. Advances in neuroendocrine lung tumors. Ann Oncol 2010;21:vii65-71.
8Zakowski MF. Pathology of small cell carcinoma of the lung. Semin Oncol 2003;30:3-8.
9Nicholson SA, Beasley MB, Brambilla E, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical
specimens. Am J Surg Pathol 2002;26:1184-1197.
10Masai K, Tsuta K, Kawago M, et al. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary
neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol 2013;21:292-2977.
11Ordonez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell
carcinomas. Am J Surg Pathol 2000;24:1217-1223.
12Kaufmann O, Dietel M. Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other
neuroendocrine carcinomas of various primary sites. Histopathology 2000;36:415-420.
13Lantuejoul S, Moro D, Michalides RJ, et al. Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung
tumors. Am J Surg Pathol 1998;22:1267-1276.
14Wick MR. Immunohistology of neuroendocrine and neuroectodermal tumors. Semin Diagn Pathol 2000;17:194-203.

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PRINCIPLES OF SURGICAL RESECTION
• Stage I SCLC is diagnosed in less than 5% of patients with SCLC.

• Patients with disease in excess of T1-2, N0 do not benefit from surgery.1
• Patients with SCLC that is clinical stage I (T1-2, N0) after standard staging evaluation (including CT of the chest and upper abdomen, brain
imaging, and PET/CT imaging) may be considered for surgical resection.
Prior to resection, all patients should undergo mediastinoscopy or other surgical mediastinal staging to rule out occult nodal disease. This
may also include an endoscopic staging procedure.
Patients who undergo complete resection (preferably by a lobectomy with either mediastinal nodal dissection or sampling) should be
treated with postoperative systemic therapy.2 Patients without nodal metastases should be treated with systemic therapy alone. Patients
with nodal metastases should be treated with postoperative concurrent systemic therapy and mediastinal radiation therapy (RT).
• Because PCI can improve both disease-free and overall survival in patients with SCLC who have complete or partial response, PCI is
recommended after adjuvant systemic therapy in patients who have undergone a complete resection.3 PCI is not recommended in patients
with poor performance status or impaired neurocognitive functioning.4
1Lad T, Piantadosi S, Thomas P, et al. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell
lung cancer to combination chemotherapy. Chest 1994;106:320S-3S.
2Yang CE, Chan DY, Speicher PJ, et al. Role of adjuvant therapy in a population based cohort of patients with early-stage small-cell lung cancer. J Clin Oncol
2016;34:1057-1064.
3Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell cancer in complete remission. Prophylactic Cranial Irradiation
Overview Collaborative Group. N Engl J Med 1999;341:476-84.
4Le Péchoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in
complete remission after chemotherapy and thoracic radiotherapy. Lancet Oncol 2009;10(5):467-474.
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PRINCIPLES OF SUPPORTIVE CARE

• Smoking cessation advice, counseling, and pharmacotherapy
Use the 5 A’s Framework: Ask, Advise, Assess, Assist, Arrange (http://www.ahrq.gov/clinic/tobacco/5steps.htm)
See NCCN Guidelines for Smoking Cessation
• Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is not recommended during
concurrent systemic therapy plus radiotherapy (category 1 for not using GM-CSF).1
• Syndrome of inappropriate antidiuretic hormone

Fluid restriction
Saline infusion for symptomatic patients
Antineoplastic therapy
Demeclocycline
Vasopressin receptor inhibitors (conivaptan, tolvaptan) for refractory hyponatremia
• Cushing’s syndrome
Consider ketoconazole. If not effective, consider metyrapone.
Try to control before initiation of antineoplastic therapy
• Leptomeningeal disease: See NCCN Guidelines for Carcinomatous/Lymphomatous Meningitis
• Pain management: See NCCN Guidelines for Adult Cancer Pain
• Nausea/vomiting: See NCCN Guidelines for Antiemesis
• Psychosocial distress: See NCCN Guidelines for Distress Management
• See NCCN Guidelines for Palliative Care as indicated
1Bunn PA, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell
lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 1995;13:1632-1641.

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PRINCIPLES OF SYSTEMIC THERAPY* (1 of 3)
Systemic therapy as primary or adjuvant therapy: Subsequent systemic therapy:‡

• Limited stage (maximum of 4–6 cycles): • Clinical trial preferred.
Cisplatin 60 mg/m2 day 1 and etoposide 120 mg/m2 days 1, 2, 31
Cisplatin 80 mg/m2 day 1 and etoposide 100 mg/m2 days 1, 2, 32 • Relapse ≤6 mo, PS 0-2:
Carboplatin AUC 5–6 day 1 and etoposide 100 mg/m2 days 1, 2, 33 Topotecan PO or IV12-14
During systemic therapy + RT, cisplatin/etoposide is recommended Irinotecan15
(category 1). Paclitaxel16,17
The use of myeloid growth factors is not recommended during Docetaxel18
concurrent systemic therapy plus radiotherapy (category 1 for not Temozolomide19,20
using GM-CSF).4 Nivolumab ± ipilimumab21,22
Vinorelbine23,24
• Extensive stage (maximum of 4–6 cycles):† Oral etoposide25,26
Carboplatin AUC 5–6 day 1 and etoposide 100 mg/m2 days 1, 2, 35 Gemcitabine27,28
Cisplatin 75 mg/m2 day 1 and etoposide 100 mg/m2 days 1, 2, 36 Cyclophosphamide/doxorubicin/vincristine (CAV)12
Cisplatin 80 mg/m2 day 1 and etoposide 80 mg/m2 days 1, 2, 37 Bendamustine (category 2B)29
Cisplatin 25 mg/m2 days 1, 2, 3 and etoposide 100 mg/m2 days 1, 2, 38
Carboplatin AUC 5 day 1 and irinotecan 50 mg/m2 days 1, 8, 159 • Relapse >6 mo: original regimen30,31
Cisplatin 60 mg/m2 day 1 and irinotecan 60 mg/m2 days 1, 8, 1510
Cisplatin 30 mg/m2 days 1, 8 and irinotecan 65 mg/m2 days 1, 811 Consider dose reduction or growth factor support for patients
with PS 2
Response Assessment SCL-E 2 of 3
References on SCL-E 3 of 3
*The regimens included are representative of the more commonly used regimens for small cell lung cancer. Other regimens may be acceptable.
†If not used as original regimen, may be used as therapy for primary progressive disease.
‡Subsequent systemic therapy refers to second-line and beyond therapy.

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PRINCIPLES OF SYSTEMIC THERAPY (2 of 3)

Response assessment
• Limited-stage
For patients receiving adjuvant therapy, response assessment should occur only after completion of adjuvant therapy; do not repeat scans
to assess response during adjuvant treatment.
For patients receiving systemic therapy + concurrent RT, response assessment should occur only after completion of initial therapy; do not
repeat scans to assess response during initial treatment.
For patients receiving systemic therapy alone or sequential systemic therapy followed by RT, response assessment by chest/abdomen CT
with contrast should occur after every 2 cycles of systemic therapy and at completion of therapy.
• Extensive-stage
During systemic therapy, response assessment by chest/abdomen CT with contrast should occur after every 2–3 cycles of systemic
therapy and at completion of therapy.
For patients with asymptomatic brain metastases receiving systemic therapy before whole-brain RT, brain MRI (preferred) or CT with
contrast should be repeated after every 2 cycles of systemic therapy and at completion of therapy.
• Subsequent systemic therapy

Response assessment by chest/abdomen CT with contrast should occur after every 2–3 cycles of systemic therapy.

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PRINCIPLES OF SYSTEMIC THERAPY (3 of 3)

References
1Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic 16Smit EF, Fokkema E, Biesma B, et al. A phase II study of paclitaxel in heavily
radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and pretreated patients with small-cell lung cancer. Br J Cancer 1998; 77:347-351.
etoposide. N Engl J Med 1999;340(4):265-271. 17Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for
2Saito H, Takada Y, Ichinose Y, et al. Phase II study of etoposide and cisplatin with relapsed and refractory small cell lung cancer. Anticancer Res 2006; 26:777-781.
concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in 18Smyth JF, Smith IE, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung
patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology cancer. Eur J Cancer 1994; 30A:1058-1060.
Group 9902. J Clin Oncol 2006;24(33):5247-5252. 19Pietanza MC, Kadota K, Huberman K, et al. Phase II trial of temozolomide with
3Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus relapsed sensitive or refractory small cell lung cancer, with assessment of
late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res
disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative 2012;18:1138-1145.
20
Oncology Group (HeCOG). Ann Oncol 2001;12(9):1231-1238. Zauderer MG, Drilon A, Kadota K, et al. Trial of a 5-day dosing regimen of temozolomide
4Bunn PA, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte- in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA
macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung methyltransferase. Lung Cancer 2014;86:237-240.
21
cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus
Oncol 1995;13:1632-1641 ipilimumab in recurrent small-cell lung cancer (Checkmate 032): a multicentre, open-label
5Okamoto H, Watanabe K, Nishiwaki Y, et al. Phase II study of area under the plasma- phase 1/2 trial. Lancet Oncol 2016;17:883-895.
concentration-versus-time curve-based carboplatin plus standard-dose intravenous 22Hellmann MD, Ott PA, Zugazagoitia J, et al. First report of a randomized expansion cohort
etoposide in elderly patients with small cell lung cancer. J Clin Oncol 1999;17(11):3540- from CheckMate 032 [abstract]. J Clin Oncol 2017;35: Abstract 8503.
3545. 23Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, et al. Phase II study of
6Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients.
bevacizumab in combination with chemotherapy in previously untreated extensive-stage Eur J Cancer 1993; 29A:1720-1722.
small-cell lung cancer: results from the SALUTE trial. J Clin Oncol 2011;29:2215-2222. 24Furuse K, Kuboa K, Kawahara M, et al. Phase II study of vinorelbine in heavily previously
7Niell HB, Herndon JE, Miller AA, et al. Randomized phase III Intergroup trial of etoposide treated small cell lung cancer. Oncology 1996;53:169-172.
and cisplatin with or without paclitaxel and granulocyte-colony stimulating factor in patients 25Einhorn LH, Pennington K, McClean J. Phase II trial of daily oral VP-16 in refractory small
with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B trial 9732. J cell lung cancer. Semin Oncol 1990;17:32-35.
Clin Oncol 2005;23:3752-3759. 26Johnson DH, Greco FA, Strupp J, et al. Prolonged administration of oral etoposide in
8Evans WK, Shepherd FA, Feld R, et al. VP-16 and cisplatin as first-line therapy for patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol
small-cell lung cancer. J Clin Oncol 1985;3(11):1471-1477. 1990; 8:1613-1617.
9Schmittel A, Fischer von Weikersthal L, Sebastian M, et al. A randomized phase II trial 27Van der Lee I, Smit EF, van Putten JW, et al. Single-agent gemcitabine in patients with
of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients resistant small-cell lung cancer. An Oncol 2001;12:557-561.
with extended disease small-cell lung cancer. Ann Oncol 2006;17:663-667. 28Masters GA, Declerck L, Blanke C, et al. Phase II trial of gemcitabine in refractory or
10Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with relapsed small-cell lung cancer. J Clin Oncol 2003;21:1550-1555.
29
etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002;346(2): Lammers PE, Shyr Y, Li CI, et al. Phase II study of bendamustine in relapsed
85-91. chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol 2014;9:559-
11Hanna N, Bunn Jr. PA, Langer C, et al. Randomized phase III trial comparing 562.
irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated 30Postmus PE, Berendsen HH, van Zandwijk N, et al. Retreatment with the induction
extensive-stage disease small-cell lung cancer. J Clin Oncol 2006;24(13):2038-2043. regimen in small cell lung cancer relapsing after an initial response to short term
12von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, chemotherapy. Eur J Cancer Clin Oncol 1987;23:1409-1411.
doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. 31Giaccone G, Ferrati P, Donadio M, et al. Reinduction chemotherapy in small cell lung
J Clin Oncol 1999;17(2):658-667. cancer. Eur J Cancer Clin Oncol 1987;23:1697-1699.
13O’Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care
alone with supportive care with oral topotecan in patients with relapsed small-cell lung
cancer. J Clin Oncol 2006;24(34):5441-5447.
14Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with
intravenous topotecan as second-line therapy in small-cell lung cancer.
J Clin Oncol 2007;25(15):2086-2092.
15Masuda N, Fukuoka M, Kusunoki Y, et al. CPT-11: a new derivative of camptothecin for
the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 1992; 10:1225-
1229.
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PRINCIPLES OF RADIATION THERAPY

General Principles:
• General principles of RT for lung cancer—including commonly used abbreviations; standards for clinical and technologic expertise and
quality assurance; and principles of RT simulation, planning, and delivery—are provided in the NCCN Guidelines for Non-Small Cell Lung
Cancer (see NSCL‑C) and are applicable to RT for SCLC.
• RT has a potential role in all stages of SCLC, as part of either definitive or palliative therapy. Radiation oncology input, as part of a
multidisciplinary evaluation or discussion, should be provided for all patients early in the determination of the treatment strategy.
• To maximize tumor control and to minimize treatment toxicity, critical components of modern RT include appropriate simulation, accurate
target definition, conformal RT planning, and ensuring accurate delivery of the planned treatment. A minimum standard is CT‑planned 3D
conformal RT. Multiple fields should be used, with all fields treated each day.
• Use of more advanced technologies is appropriate when needed to deliver adequate tumor doses while respecting normal tissue dose
constraints. Such technologies include (but are not limited to) 4D-CT and/or PET/CT simulation, IMRT/VMAT, IGRT, and motion management
strategies. IMRT is preferred over 3D conformal external-beam RT (CRT) on the basis of reduced toxicity in the setting of concurrent
chemotherapy/RT.1 Quality assurance measures are essential and are covered in the NSCLC guidelines (see NSCL‑C).
• Useful references include the ACR Appropriateness Criteria at: http://www.acr.org/quality-safety/appropriateness-criteria
Limited Stage:
• Timing: RT concurrent with systemic therapy is standard and preferred to sequential chemo/RT.2 RT should start early, with cycle 1 or 2 of
systemic therapy (category 1).3 A shorter time from the start of any therapy to the end of RT (SER) is significantly associated with improved
survival.4
• Target definition: RT target volumes should be defined based on the pretreatment PET scan and CT scan obtained at the time of radiotherapy
planning. PET/CT should be obtained, preferably within 4 weeks and no more than 8 weeks, before treatment. Ideally, PET/CT should be
obtained in the treatment position.
• Historically, clinically uninvolved mediastinal nodes have been included in the RT target volume, whereas uninvolved supraclavicular nodes
generally have not been included. Consensus on elective nodal irradiation (ENI) is evolving.5 Several more modern series, both retrospective
and prospective, suggest that omission of ENI results in low rates of isolated nodal recurrences (0%–11%, most <5%), particularly when
incorporating PET staging/target definition (1.7%–3%).6-11 ENI has been omitted in current prospective clinical trials (including CALGB
30610/RTOG 0538 and the EORTC 08072 [CONVERT] trial).
• In patients who start systemic therapy before RT, the gross tumor volume (GTV) can be limited to the post‑induction systemic therapy
volume to avoid excessive toxicity. Initially involved nodal regions (but not their entire pre‑systemic therapy volume) should be covered.8,12
• Dose and schedule: For limited‑stage SCLC, the optimal dose and schedule of RT have not been established; 45 Gy in 3 weeks (1.5 Gy
twice daily [BID]) is superior (category 1) to 45 Gy in 5 weeks (1.8 Gy daily).13,14 When BID fractionation is used, there should be at least a
6‑hour inter‑fraction interval to allow for repair of normal tissue. If using once-daily RT, higher doses of 60–70 Gy should be used.15-18 The
current randomized trial CALGB 30610/RTOG 0538 is comparing the standard arm of 45 Gy (BID) in 3 weeks to 70 Gy in 7 weeks; accrual to
an experimental concomitant boost arm19 has closed. The European CONVERT trial demonstrated comparable overall survival and toxicity
between 45 Gy (BID) and 66 Gy (daily).20
See Extensive Stage, Normal Tissue Dose Constraints, Prophylactic Cranial Irradiation, Brain Metastases on SCL-F 2 of 3

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. SCL-F
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Extensive Stage:
• Consolidative thoracic RT is beneficial for selected patients with extensive‑stage SCLC with CR or good response to systemic therapy.
Studies have demonstrated that consolidative thoracic RT up to definitive doses is well tolerated, results in fewer symptomatic chest
recurrences, and improves long‑term survival in some patients.21,22 The Dutch CREST randomized trial of modest-dose thoracic RT (30
Gy in 10 fractions) in patients with extensive stage SCLC that responded to systemic therapy demonstrated significantly improved 2-year
overall survival and 6-month PFS, although the protocol-defined primary endpoint of 1-year overall survival was not significantly improved.23
Subsequent exploratory analysis found the benefit of consolidative thoracic RT is limited to the majority of patients who had residual
thoracic disease after systemic therapy.24
• Dosing and fractionation of consolidative thoracic RT should be individualized within the range of 30 Gy in 10 daily fractions to 60 Gy in 30
daily fractions, or equivalent regimens in this range.
Normal Tissue Dose Constraints:
• Normal tissue dose constraints depend on tumor size and location. For similar RT prescription doses, the normal tissue constraints used for
NSCLC are appropriate (see NSCL‑C).
• When administering accelerated RT schedules (eg, BID) or lower total RT doses (eg, 45 Gy), more conservative constraints should be used.
When using accelerated schedules (eg, 3–5 weeks), the spinal cord constraints from the CALGB 30610/RTOG 0538 protocol should be used
as a guide: ie, the maximum spinal cord dose should be limited to ≤41 Gy (including scatter irradiation) for a prescription of 45 Gy BID in 3
weeks and limited to ≤50 Gy for more protracted schedules.
Prophylactic Cranial Irradiation (PCI):
• In patients with limited-stage SCLC who have a good response to initial therapy, PCI decreases brain metastases and increases overall
survival (category 1).25,26 In patients with extensive-stage SCLC that has responded to systemic therapy, PCI decreases brain metastases.
A randomized trial conducted by the EORTC found improved overall survival with PCI. However, a Japanese randomized trial found that in
patients who had no brain metastases on baseline MRI, PCI27 did not improve overall survival compared with routine surveillance MRI and
treatment of asymptomatic brain metastases upon detection.28 In patients not receiving PCI, surveillance for metastases by brain imaging
should be performed.
• The preferred dose for PCI to the whole brain is 25 Gy in 10 daily fractions. A shorter course (eg, 20 Gy in 5 fractions) may be appropriate
in selected patients with extensive-stage disease. In a large randomized trial (PCI 99-01), patients receiving a dose of 36 Gy had higher
mortality and higher chronic neurotoxicity compared to patients treated with 25 Gy.29,30
• Neurocognitive Function: Increasing age and higher doses are the most predictive factors for development of chronic neurotoxicity. In trial
RTOG 0212, 83% of patients older than 60 years of age experienced chronic neurotoxicity 12 months after PCI versus 56% of patients
younger than 60 years of age (P = .009).30 Concurrent systemic therapy and high total RT dose (>30 Gy) should be avoided in patients
receiving PCI.
• Administer PCI after resolution of acute toxicities of initial therapy. PCI is not recommended in patients with poor performance status or
impaired neurocognitive functioning.
• When administering PCI, consider adding memantine during and after RT, which has been shown to decrease neurocognitive impairment
following whole brain radiation therapy (WBRT) for brain metastases.31
Brain Metastases:
• Brain metastases should be treated with WBRT rather than stereotactic radiotherapy/radiosurgery (SRT/SRS) alone, because these patients
tend to develop multiple CNS metastases. In patients who develop brain metastases after PCI, repeat WBRT may be considered in carefully
selected patients.32,33 SRS is preferred if feasible, especially if there has been a long-time interval from initial diagnosis to occurrence of
brain metastases and there is no uncontrolled extracranial disease.34,35
• Recommended dose for WBRT is 30 Gy in 10 daily fractions.
See General Principles, Limited Stage (SCL-F 1 of 3) References on
Note: All recommendations are category 2A unless otherwise indicated. SCL-F 3 of 3
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References
1Chun SG, Hu C, Choy H, et al. Impact of intensity-modulated radiation therapy technique for locally chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B
advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 study 39808. Int J Radiat Oncol Biol Phys 2004;59:460-468.
19Komaki R, Paulus R, Ettinger DS, et al. Phase II study of accelerated high-dose radiotherapy with
randomized clinical trial. J Clin Oncol 2017;35:56-62.
2Takada M, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic concurrent chemotherapy for patients with limited small-cell lung cancer: Radiation Therapy Oncology
radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: Group protocol 0239. Int J Radiat Oncol Biol Phys 2012;83:e531-6.
20Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy
results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 2002;20:3054-3060.
3Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised,
therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol superiority trial. Lancet Oncol 2017;18:1116-1125.
21Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment
2004;22:4837-4845.
4De Ruysscher D, Pijls-Johannesma M, Bentzen SM, et al. Time between the first day of of patients with extensive disease small-cell lung cancer: A randomized study. J Clin Oncol 1999;17:
chemotherapy and the last day of chest radiation is the most important predictor of survival in 2092-2099.
22Yee D, Butts C, Reiman A, et al. Clinical trial of post-chemotherapy consolidation thoracic radiotherapy
limited-disease small-cell lung cancer. J Clin Oncol 2006;24:1057-1063.
5Videtic GMM, Belderbos JSA, Kong F-MS, et al. Report from the International Atomic Energy for extensive-stage small cell lung cancer. Radiother Oncol 2012;102:234-238.
23Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-
Agency (IAEA) consultants’ meeting on elective nodal irradiation in lung cancer: small-cell
lung cancer (SCLC). Int J Radiat Oncol Biol Phys 2008;72:327-334. cell lung cancer: a phase 3 randomised controlled trial. Lancet 2015;385:36-42.
6De Ruysscher D, Bremer R-H, Koppe F, et al. Omission of elective node irradiation on basis of 24Slotman BJ, van Tinteren H, Praag JO, et al. Radiotherapy for extensive stage small-cell lung cancer-
CT-scans in patients with limited disease small cell lung cancer: a phase II trial. Radiother Oncol Authors’ reply. Lancet 2015;385:1292-1293.
25Arriagada R, Le Chevalier T, Rivière A, et al. Patterns of failure after prophylactic cranial irradiation in
2006;80:307-312.
7van Loon J, De Ruysscher D, Wanders R, et al. Selective nodal irradiation on basis of (18)FDG-PET small-cell lung cancer: analysis of 505 randomized patients. Ann Oncol 2002;13:748-754.
26Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell
scans in limited-disease small-cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys
2010;77:329-336. lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group.
8Hu X, Bao Y, Zhang L, et al. Omitting elective nodal irradiation and irradiating postinduction versus N Engl J Med 1999;341:476-484.
27Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung
preinduction chemotherapy tumor extent for limited-stage small cell lung cancer: interim analysis of
a prospective randomized noninferiority trial. Cancer 2012;118:278-287. cancer. N Engl J Med 2007;357:664-672.
9Shirvani SM, Komaki R, Heymach JV, et al. Positron emission tomography/computed tomography- 28Takahashi T, Yamanaka T, Seto T et al. Prophylactic cranial irradiation versus observation in patients
guided intensity-modulated radiotherapy for limited-stage small-cell lung cancer. Int J Radiat Oncol with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial.
Biol Phys 2012;82:e91-97. Lancet Oncol 2017;18:663-671.
10Xia B, Chen G-Y, Cai X-W, et al. Is involved-field radiotherapy based on CT safe for patients with 29Le Péchoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial
limited-stage small-cell lung cancer? Radiother Oncol 2012;102:258-262. irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after
11Colaco R, Sheikh H, Lorigan P, et al. Omitting elective nodal irradiation during thoracic irradiation in chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT
limited-stage small cell lung cancer - Evidence from a phase II trial. Lung Cancer 2012;76:72-77. 99-01): a randomised clinical trial. Lancet Oncol 2009;10:467-474.
12Liengswangwong V, Bonner JA, Shaw EG, et al. Limited-stage small-cell lung cancer: patterns of 30Wolfson AH, Bae K, Komaki R, et al. Primary analysis of a phase II randomized trial Radiation
intrathoracic recurrence and the implications for thoracic radiotherapy. J Clin Oncol 1994;12:496-502. Therapy Oncology Group (RTOG) 0212: Impact of different total doses and schedules of prophylactic
13Turrisi AT, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease small-cell
limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med lung cancer. Int J Radiat Oncol Biol Phys 2011;81:77-84.
31Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients
1999;340:265-271.
14Schild SE, Bonner JA, Shanahan TG, et al. Long-term results of a phase III trial comparing once-daily receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol
radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol 2013;10:1429-1437.
32Sadikov E, Bezjak A, Yi Q-L, et al. Value of whole brain re-irradiation for brain metastases--single centre
Biol Phys 2004;59:943-951.
15Choi NC, Herndon JE, Rosenman J, et al. Phase I study to determine the maximum-tolerated dose experience. Clinical oncology (Royal College of Radiologists (Great Britain)) 2007;19:532-538.
33Son CH, Jimenez R, Niemierko A, et al. Outcomes after whole brain reirradiation in patients with brain
of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with
concurrent chemotherapy for limited-stage small-cell lung cancer. J Clin Oncol 1998;16:3528-3536. metastases. Int J Radiat Oncol Biol Phys 2012;82:e167-172.
16Miller KL, Marks LB, Sibley GS, et al. Routine use of approximately 60 Gy once-daily thoracic 34Harris S, Chan MD, Lovato JF, et al. Gamma knife stereotactic radiosurgery as salvage therapy after
irradiation for patients with limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys failure of whole-brain radiotherapy in patients with small-cell lung cancer. Int J Radiat Oncol Biol Phys
2003;56:355-359. 2012;83:e53-59.
17Roof KS, Fidias P, Lynch TJ, et al. Radiation dose escalation in limited-stage small-cell lung cancer. 35Wegner RE, Olson AC, Kondziolka D, et al. Stereotactic radiosurgery for patients with brain metastases
Int J Radiat Oncol Biol Phys 2003;57:701-708. from small cell lung cancer. Int J Radiat Oncol Biol Phys 2011;81:e21-27.
18Bogart JA, Herndon JE, Lyss AP, et al. 70 Gy thoracic radiotherapy is feasible concurrent with

3 OF 3
NCCN Guidelines Version 1.2018 Staging NCCN Guidelines Index

Table of Contents
American Joint Committee on Cancer (AJCC)- Definitions of TNM N Regional Lymph Nodes
T Primary Tumor NX Regional lymph nodes cannot be assessed
TX Primary tumor cannot be assessed, or tumor proven by the presence of N0 No regional lymph node metastasis
malignant cells in sputum or bronchial washings but not visualized by N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes,
imaging or bronchoscopy and intrapulmonary nodes including involvement by direct extension
T0 No evidence of primary tumor N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
Tis Carcinoma in situ: N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or
Tis (AIS): adenocarcinoma contralateral scalene, or supraclavicular lymph node(s)
Tis (SCIS): squamous cell carcinoma M Distant Metastasis
T1 Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral M0 No distant metastasis
pleura, without bronchoscopic evidence of invasion more proximal than the
M1 Distant metastasis
lobar bronchus (i.e., not in the main bronchus); the uncommon superficial
spreading tumor of any size with its invasive component limited to the M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural
bronchial wall, which may extend proximal to the main bronchus, is also nodules or malignant pleural or pericardial effusion; most pleural
classified as T1a (pericardial) effusions with lung cancer are due to tumor; in a few
T1mi Minimally invasive adenocarcinoma patients, however, multiple microscopic examinations of pleural
T1a Tumor 1 cm or less in greatest dimension (pericardial) fluid are negative for tumor, and the fluid is nonbloody
T1b Tumor more than 1 cm but not more than 2 cm in greatest dimension and is not an exudate; where these elements and clinical judgment
T1c Tumor more than 2 cm but not more than 3 cm in greatest dimension dictate that the effusion is not related to the tumor, the effusion
T2 Tumor more than 3 cm but not more than 5 cm; or tumor with any of the should be excluded as a staging descriptor
following features (T2 tumors with these features are classified T2a if 4 cm M1b Single extrathoracic metastasis in a single organ and involvement of
or less or if size cannot be determined and as T2b if greater than 4 cm but a single distant (nonregional) node
not larger than 5 cm): M1c Multiple extrathoracic metastases in one or several organs
• Involves main bronchus regardless of distance to the carina, but without
involving the carina
• Invades visceral pleura
• Associated with atelectasis or obstructive pneumonitis that extends to the
hilar region, either involving part of the lung or the entire lung
T2a Tumor more than 3 cm but not more than 4 cm in greatest dimension
T2b Tumor more than 4 cm but not more than 5 cm in greatest dimension
T3 Tumor more than 5 cm but not more than 7 cm in greatest dimension or one
that directly invades any of the following: parietal pleura (PL3), chest wall
(including superior sulcus tumors), phrenic nerve, parietal pericardium; or
associated separate tumor nodule(s) in the same lobe as the primary
T4 Tumors more than 7 cm or one that invades any of the following: diaphragm,
mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve,
esophagus, vertebral body, carina; separate tumor nodule(s) in a different
ipsilateral lobe to that of the primary
The AJCC 8th Edition Cancer Staging System will be implemented on January 1, 2018. For the AJCC 7th Edition Staging Manual, visit www.springer.com.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC
Cancer Staging Manual, Eighth Edition (2016) published by Springer Science+Business Media. (For complete information and data supporting the staging tables,
visit www.springer.com.) Any citation or quotation of this material must be credited to the AJCC as its primary source. The inclusion of this information herein does
not authorize any reuse or further distribution without the expressed, written permission of Springer SBM, on behalf of the AJCC.
ST-1
NCCN Guidelines Version 1.2018 Staging NCCN Guidelines Index

Table of Contents
Anatomic Stage/Prognostic Groups

Occult TX N0 M0
carcinoma
Stage 0 Tis N0 M0
Stage IA1 T1mi N0 M0
T1a N0 M0
Stage IA2 T1b N0 M0
Stage IA3 T1c N0 M0
Stage IB T2a N0 M0
Stage IIA T2b N0 M0
Stage IIB T1a,b,c N1 M0
T2a,b N1 M0
T3 N0 M0
Stage IIIA T1a,b,c N2 M0
T2a,b N2 M0
T3 N1 M0
T4 N0 M0
T4 N1 M0
Stage IIIB T1a,b,c N3 M0
T2a,b N3 M0
T3 N2 M0
T4 N2 M0
Stage IIIC T3 N3 M0
T4 N3 M0
Stage IVA Any T Any N M1a
Any T Any N M1b
Stage IVB Any T Any N M1c
The AJCC 8th Edition Cancer Staging System will be implemented on January 1, 2018. For the AJCC 7th Edition Staging Manual, visit www.springer.com.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC
Cancer Staging Manual, Eighth Edition (2016) published by Springer Science+Business Media. (For complete information and data supporting the staging tables,
visit www.springer.com.) Any citation or quotation of this material must be credited to the AJCC as its primary source. The inclusion of this information herein does
not authorize any reuse or further distribution without the expressed, written permission of Springer SBM, on behalf of the AJCC.
ST-2

Table of Contents
Discussion This discussion is being updated to correspond with the Treatment ................................................................................... MS-6
newly updated algorithm. Last updated 02/24/17
Systemic Therapy ........................................................................................... MS-6
NCCN Categories of Evidence and Consensus
Elderly Patients........................................................................................... MS-9
Category 1: Based upon high-level evidence, there is uniform
Second-Line and Beyond (Subsequent) Systemic Therapy ....................... MS-10
NCCN consensus that the intervention is appropriate.
Radiotherapy ................................................................................................ MS-11
Category 2A: Based upon lower-level evidence, there is uniform
Thoracic Radiotherapy .............................................................................. MS-11
NCCN consensus that the intervention is appropriate.
Prophylactic Cranial Irradiation ................................................................. MS-13
Category 2B: Based upon lower-level evidence, there is NCCN
consensus that the intervention is appropriate. Palliative Radiotherapy ............................................................................. MS-14
Category 3: Based upon any level of evidence, there is major Surgical Resection of Stage I SCLC .............................................................. MS-14
NCCN disagreement that the intervention is appropriate.
Surveillance ...............................................................................MS-15
All recommendations are category 2A unless otherwise
References ................................................................................MS-17
indicated.
Table of Contents
Overview ..................................................................................... MS-2
Literature Search Criteria and Guidelines Update Methodology .... MS-2
Diagnosis .................................................................................... MS-3

Screening ........................................................................................................ MS-3
Manifestations ................................................................................................. MS-3
Pathology ........................................................................................................ MS-4
Staging ........................................................................................ MS-4
Prognostic Factors....................................................................... MS-6
Version 1.2018, 09/18/17 © National Comprehensive Cancer Network, Inc. 2017, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-1

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Overview plus thoracic radiotherapy.8,9 In patients with extensive-stage disease,

Neuroendocrine tumors account for approximately 20% of lung cancers; chemotherapy alone can palliate symptoms and prolong survival in
most (approximately 14%) are small cell lung cancer (SCLC).1,2 In 2017, most patients; however, long-term survival is rare.10 Note that the
an estimated 31,000 new cases of SCLC will occur in the United definitions for limited-stage and extensive-stage SCLC incorporate TNM
States.3 Nearly all cases of SCLC are attributable to cigarette smoking.4 staging (see the NCCN Guidelines for SCLC and Staging in this
Although the incidence of SCLC has been decreasing, the incidence in Discussion). Surgery is only appropriate for a few patients (2%–5%)
women is increasing and the male-to-female incidence ratio is now 1:1.2 with surgically resectable stage I SCLC.11 Clinical trials generally
Management of SCLC and other lung neuroendocrine tumors (LNTs) is represent state-of-the-art treatment for patients with SCLC. Despite
described in the NCCN Clinical Practice Guidelines in Oncology (NCCN recent advances, the standard therapy for SCLC as outlined by these
Guidelines®) for SCLC and for LNTs, which include the algorithms and NCCN Guidelines still needs to be improved. Thus, participation in
this supporting Discussion text (see the NCCN Guidelines® for SCLC clinical trials should be strongly encouraged.
and Lung Neuroendocrine Tumors in the NCCN Guidelines for
Smoking cessation should be strongly promoted in patients with SCLC
Neuroendocrine Tumors, available at NCCN.org). The Summary of the
and other high-grade neuroendocrine carcinomas (see the NCCN
Guidelines Updates section in the algorithm describes the most recent
Guidelines for Smoking Cessation, available at NCCN.org).12 Former
revisions, which have been incorporated into this revised Discussion
smokers should be strongly encouraged to remain abstinent. Patients
(see the NCCN Guidelines for SCLC). For the 2017 update for SCLC,
with SCLC who continue to smoke have increased toxicity during
nivolumab and nivolumab with ipilimumab were added as new options
treatment and shorter survival.13 Programs using behavioral counseling
for second-line and beyond (ie, subsequent) systemic therapy;5 new
combined with FDA–approved medications that promote smoking
imaging guidelines for response assessment after systemic therapy
cessation can be very useful.
were also added in addition to other changes as outlined in the
summary updates. The NCCN Guidelines for SCLC were originally Literature Search Criteria and Guidelines Update
published 20 years ago and have been subsequently updated at least Methodology
once every year (see NCCN.org).6
Before the update of this version of the NCCN Guidelines for SCLC, an
SCLC is characterized by a rapid doubling time, high growth fraction, electronic search of the PubMed database was performed to obtain key
and early development of widespread metastases. Most patients with literature in SCLC—published between April 1, 2015 and May 1, 2016—
SCLC present with hematogenous metastases; approximately one third using the following search term: small cell lung cancer. The PubMed
present with limited disease confined to the chest. SCLC is highly database was chosen, because it is the most widely used resource for
sensitive to initial chemotherapy and radiotherapy; however, most medical literature and indexes only peer-reviewed biomedical literature.
patients eventually die of recurrent disease.7 In patients with The search results were narrowed by selecting studies in humans
limited-stage SCLC, the goal of treatment is cure using chemotherapy published in English. Results were confined to the following article
types: Clinical Trial, Phase 1; Clinical Trial, Phase 2; Clinical Trial,

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Phase 3; Clinical Trial, Phase 4; Guideline; Randomized Controlled Manifestations

Trial; Meta-Analysis; Systematic Reviews; and Validation Studies. SCLC typically presents as a large hilar mass and bulky mediastinal
lymphadenopathy that cause cough and dyspnea.17 Frequently, patients
The PubMed search resulted in 253 citations and their potential
present with symptoms of widespread metastatic disease, such as
relevance was examined. The data from key PubMed articles as well as
weight loss, debility, bone pain, and neurologic compromise. It is
articles from additional sources deemed as relevant to these NCCN
uncommon for patients to present with a solitary peripheral nodule
Guidelines and discussed by the panel have been included in this
without central adenopathy. In this situation, fine-needle aspiration
version of the Discussion section (eg, e-publications ahead of print,
(FNA) may not adequately differentiate small cell carcinoma (which is a
meeting abstracts). Recommendations for which high-level evidence is
high-grade neuroendocrine carcinoma) from low-grade (typical
lacking are based on the panel’s review of lower-level evidence and
carcinoid), intermediate-grade (atypical carcinoid), or large-cell
expert opinion. The complete details of the development and update of
neuroendocrine carcinoma (LCNEC) (which is also a high-grade
the NCCN Guidelines are available on the NCCN webpage.
neuroendocrine carcinoma) (see Lung Neuroendocrine Tumors in the
Diagnosis NCCN Guidelines for Neuroendocrine Tumors available at
NCCN.org).18,19
Screening
Ideally, a screening test should detect disease at an early stage when it Many neurologic and endocrine paraneoplastic syndromes are
is still curable. Currently, no effective screening test is available to associated with SCLC.20-22 Neurologic syndromes include
detect early-stage SCLC; the disease is typically diagnosed when Lambert-Eaton myasthenic syndrome, encephalomyelitis, and sensory
patients present with symptoms indicative of advanced-stage disease.14 neuropathy. Patients with the Lambert-Eaton syndrome present with
The National Lung Screening Trial (NLST) reported that screening with proximal leg weakness that is caused by antibodies directed against the
annual, low-dose, spiral CT scans decreased lung cancer–specific voltage-gated calcium channels.23,24 Paraneoplastic encephalomyelitis
mortality in asymptomatic high-risk individuals (see the NCCN and sensory neuropathy are caused by the production of an antibody
Guidelines for Lung Cancer Screening, available at NCCN.org).15 (anti-Hu) that cross-reacts with both small cell carcinoma antigens and
Although low-dose CT screening can detect early-stage non-small cell human neuronal RNA-binding proteins resulting in multiple neurologic
lung cancer (NSCLC), it does not seem to be useful for detecting deficits.25
early-stage SCLC.14-16 Low-dose CT screening is probably not useful
because of the aggressiveness of SCLC, which results in the SCLC cells sometimes produce polypeptide hormones, including
development of symptomatic disease between annual scans, thereby vasopressin (antidiuretic hormone [ADH]) and adrenocorticotropic
limiting the potential effect on mortality.14 hormone (ACTH), which cause hyponatremia of malignancy (ie,
syndrome of inappropriate ADH secretion [SIADH]) and Cushing
syndrome, respectively.26,27 In patients with SCLC, SIADH occurs more

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frequently than Cushing syndrome. Cancer treatment and/or supportive chromogranin A, neuron-specific enolase, neural cell adhesion molecule
care may also cause hyponatremia (eg, cisplatin, opiates).28 Treatment (NCAM; CD56), and synaptophysin.18 However, these markers alone
for SIADH includes fluid restriction (which is difficult for patients cannot be used to distinguish SCLC from NSCLC, because
because of increased thirst), demeclocycline, or vasopressin receptor approximately 10% of NSCLCs will be immunoreactive for at least one
inhibitors (ie, conivaptan, tolvaptan) (see Principles of Supportive Care of these neuroendocrine markers.34
in the NCCN Guidelines for SCLC).28-30 ADH levels and hyponatremia
usually improve after successful treatment for SCLC. Staging
The NCCN Panel adopted a combined approach for staging SCLC
Pathology using both the AJCC TNM staging system and the older Veterans
SCLC is a malignant epithelial tumor consisting of small cells with scant Administration (VA) scheme for SCLC (see the following 2
cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, paragraphs).7,35 Historically, contralateral mediastinal and ipsilateral
and absent or inconspicuous nucleoli.18,31 The cells are round, oval, or supraclavicular lymphadenopathy were generally classified as
spindle-shaped; nuclear molding is prominent. The mitotic count is high. limited-stage disease, whereas the classification of contralateral hilar
The classic and distinctive histology on hematoxylin and eosin (H&E) and supraclavicular lymphadenopathy is more controversial and
may be sufficient for identifying SCLC; it is a poorly differentiated tumor treatment is individualized for the patients.7,35,36 Approximately 66% of
that is categorized as a high-grade neuroendocrine carcinoma.18 Up to patients present with overt hematogenous metastases, which commonly
30% of autopsies in patients with SCLC reveal areas of NSCLC involve the contralateral lung, liver, adrenal glands, brain, bones, and/or
differentiation; this finding is more commonly detected in specimens bone marrow. The AJCC is currently revising the TNM staging system
from previously treated patients and suggests that pulmonary for SCLC; new staging guidelines will be published in late 2016.37 The
carcinogenesis occurs in a pluripotent stem cell capable of SCLC panel will continue to use the combined VA/TNM system for
differentiation along divergent pathways. staging SCLC after publication of the 8th edition of the AJCC Cancer
Staging Manual.
Although 95% of small cell carcinomas originate in the lung, they can
also arise from extrapulmonary sites, including the nasopharynx, In 2010, the lung cancer TNM staging system was revised by the
gastrointestinal tract, and genitourinary tract.32,33 Both pulmonary and International Association for the Study of Lung Cancer (IASLC) and
extrapulmonary small cell carcinomas have a similar clinical and adopted by the AJCC (7th edition, 2010) (see Tables 2 and 3 in the
biologic behavior, leading to a high potential for widespread NCCN Guidelines for SCLC).38-41 This TNM staging system is applicable
metastases. to both NSCLC and SCLC based on studies that showed the prognostic
significance of the various stage designations in both diseases.38,40 In
Nearly all SCLCs are immunoreactive for keratin, epithelial membrane the combined approach for staging SCLC, limited-stage SCLC is
antigen, and thyroid transcription factor–1 (TTF-1).18 Most SCLCs also defined as stage I to III (T any, N any, M0) that can be safely treated
stain positively for markers of neuroendocrine differentiation, including

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with definitive radiation therapy, excluding T3–4 due to multiple lung except for brain imaging.7 Unilateral bone marrow aspirates and
nodules that are too extensive or have tumor/nodal volume that is too biopsies may be indicated in select patients with nucleated red blood
large to be encompassed in a tolerable radiation plan (see Table 1 in cells on peripheral blood smear, neutropenia, or thrombocytopenia
the NCCN Guidelines for SCLC). Extensive-stage SCLC is defined as suggestive of bone marrow infiltration and with no other evidence of
stage IV (T any, N any, M1a/b) or T3–4 due to multiple lung nodules metastatic disease. Bone marrow involvement as the only site of
that are too extensive or have tumor/nodal volume that is too large to be extensive-stage disease occurs in fewer than 5% of patients. If
encompassed in a tolerable radiation plan. limited-stage disease is suspected, a PET/CT scan can be performed to
assess for distant metastases.7,35 A bone scan can be performed if
The VA Lung Study Group’s 2-stage classification scheme is also used PET/CT is equivocal or not available.
to define the extent of disease in patients with SCLC: 1) limited-stage
disease is disease confined to the ipsilateral hemithorax, which can be PET scans can increase staging accuracy in patients with SCLC,
safely encompassed within a radiation field; and 2) extensive-stage because SCLC is a highly metabolic disease.43-45 PET/CT is superior to
disease is disease beyond the ipsilateral hemithorax, including PET alone.45 Approximately 19% of patients who undergo PET are
malignant pleural or pericardial effusion or hematogenous metastases.42 upstaged from limited- to extensive-stage disease, whereas only 8% are
Because most of the literature on SCLC classifies patients based on the downstaged from extensive- to limited-stage disease.36 For most
VA’s definitions of limited-stage or extensive-stage disease, these metastatic sites, PET/CT is superior to standard imaging; however,
definitions are often used for clinical decision making. However, the PET/CT is inferior to MRI or CT for the detection of brain metastases
TNM system is useful for selecting patients with T1-2, N0 disease who (see the NCCN Guidelines for Central Nervous System Cancers,
are eligible for surgery and for radiation treatment planning.35 Clinical available at NCCN.org).46 Changes in management based on PET
research studies should begin to use the TNM system, because it will staging were reported in approximately 27% of patients, mainly because
allow for more precise assessments of prognosis and specific therapy in of alterations in the planned radiation field as a result of improved
the future. detection of intrathoracic sites of disease.36,44,47 Although PET/CT seems
to improve staging accuracy in SCLC, pathologic confirmation is still
All patients with SCLC, even those with radiographically limited-stage required for PET/CT–detected lesions that result in upstaging.
disease (per the VA’s definition), require systemic therapy either as
primary or adjuvant therapy. Therefore, staging provides a therapeutic Before surgical resection, pathologic mediastinal staging is required to
guideline for thoracic radiotherapy, which is indicated primarily for confirm PET/CT scan results in patients who seem to have clinical
patients with limited-stage disease. Full staging includes a history and stage T1–2, N0 disease.7 However, mediastinal staging is not required if
physical examination; CT scan (with intravenous contrast) of the chest, the patient is not a candidate for surgical resection or if non-surgical
liver, and adrenal glands; and brain imaging using MRI (preferred) or treatment is planned. Invasive mediastinal staging can be performed
CT scan (with intravenous contrast).36 However, once a patient has either by conventional mediastinoscopy or by minimally invasive
been found to have extensive-stage disease, further staging is optional, techniques such as transesophageal endoscopic ultrasound–guided

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FNA (EUS-FNA), endobronchial ultrasound–guided transbronchial dehydrogenase [LDH]) are the most important adverse prognostic
needle aspiration (EBUS-TBNA), or video-assisted thoracoscopy factors. Female gender, age younger than 70 years, normal LDH, and
(VATS).48,49 stage I disease are associated with a more favorable prognosis in
patients with limited-stage disease. Younger age, good PS, normal
Thoracentesis with cytologic analysis is recommended if a pleural creatinine level, normal LDH, and a single metastatic site are favorable
effusion is large enough to be safely accessed via ultrasound guidance. prognostic factors in patients with extensive-stage disease.50,51
If thoracentesis does not show malignant cells, then thoracoscopy can
be considered to document pleural involvement, which would indicate Treatment
extensive-stage disease. The effusion should be excluded as a staging Systemic Therapy
element if: 1) multiple cytopathologic examinations of the pleural fluid
For all patients with SCLC, chemotherapy is an essential component of
are negative for cancer; 2) the fluid is not bloody and not an exudate;
appropriate treatment. Adjuvant chemotherapy is recommended for
and 3) clinical judgment suggests that the effusion is not directly related
those who have undergone surgical resection. For patients with
to the cancer. Pericardial effusions are classified using the same
limited-stage SCLC in excess of T1-2, N0 and good PS (0–2),
criteria.
recommended treatment consists of chemotherapy with concurrent
Staging should not focus only on sites of symptomatic disease or on thoracic radiotherapy (category 1).9,52,53 For patients with
sites suggested by laboratory tests. Bone scans are positive in up to extensive-stage disease, chemotherapy alone is the recommended
30% of patients without bone pain or an abnormal alkaline phosphatase treatment, although radiotherapy may be used in select patients for
level. Bone imaging with radiographs or MRI may be appropriate if palliation of symptoms (see Initial Treatment and Principles of Systemic
PET/CT is equivocal. Brain imaging (MRI preferred or CT scan) can Therapy in the NCCN Guidelines for SCLC). In patients with
identify central nervous system (CNS) metastases in 10% to 15% of extensive-stage and brain metastases, chemotherapy can be given
patients at diagnosis, of which approximately 30% are asymptomatic. either before or after whole-brain radiotherapy depending on whether
Early treatment of brain metastases results in less chronic neurologic the patient has neurologic symptoms (see Initial Treatment in the NCCN
morbidity, arguing for the usefulness of early diagnosis in asymptomatic Guidelines for SCLC).10,54
patients. Because of the aggressive nature of SCLC, staging should not
For the 2017 update, the NCCN Panel added new recommendations for
delay the onset of treatment for more than 1 week; otherwise, many
response assessment during and after therapy in patients with
patients may become more seriously ill in the interval, with a significant
limited-stage or extensive-stage SCLC. After adjuvant chemotherapy
decline in their performance status (PS).
alone or chemotherapy with concurrent RT for patients with
Prognostic Factors limited-stage disease, response assessment using CT with contrast of
the chest, liver, and adrenal gland should occur only after completion of
Poor PS (3–4), extensive-stage disease, weight loss, and markers
initial therapy; repeating scans during therapy is not recommended. For
associated with excessive bulk of disease (such as lactate

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systemic therapy alone or sequential systemic therapy followed by RT carboplatin in patients with SCLC as did a retrospective analysis in
in patients with limited-stage disease, response assessment using CT patients with extensive-stage disease.61,63,64 A meta-analysis of
with contrast of the chest, liver, and adrenal gland should occur after individual patient data from 4 randomized studies compared
every 2 cycles of systemic therapy and again at completion of therapy. cisplatin-based versus carboplatin-based regimens in patients with
During systemic therapy for patients with extensive-stage disease, SCLC.65 Of 663 patients included in this meta-analysis, 32% had
response assessment using CT with contrast of the chest, liver, and limited-stage disease and 68% had extensive-stage disease. No
adrenal gland should occur after every 2 to 3 cycles of chemotherapy significant difference was observed in response rate (67% vs. 66%),
and again at completion of therapy. Scanning for brain metastases is progression-free survival (5.5 vs. 5.3 months), or overall survival (9.6
also recommended in patients with extensive-stage disease who have vs. 9.4 months) in patients receiving cisplatin- versus
asymptomatic brain metastases and are receiving systemic therapy carboplatin-containing regimens, suggesting equivalent efficacy in
before whole-brain RT; brain MRI (preferred) or brain CT with contrast patients with SCLC.
should occur after every 2 cycles of chemotherapy and again at
completion of therapy. Many other combinations have been evaluated in patients with
extensive-stage disease, with little consistent evidence of benefit when
Single-agent and combination chemotherapy regimens have been compared with EP. The combination of irinotecan and a platinum agent
shown to be active in SCLC. Etoposide and cisplatin (EP) is the most initially appeared to be better than EP. A small phase 3 trial performed
commonly used initial combination chemotherapy regimen (see in Japan reported that patients with extensive-stage SCLC who were
Principles of Systemic Therapy in the NCCN Guidelines for SCLC).55 treated with irinotecan plus cisplatin experienced a median survival of
This combination replaced alkylator/anthracycline-based regimens 12.8 months compared with 9.4 months for patients treated with EP
based on its superiority in both efficacy and toxicity in the limited-stage (P=.002).66 In addition, the 2-year survival was 19.5% in the irinotecan
setting.56 EP plus concurrent thoracic radiotherapy is the recommended plus cisplatin group versus 5.2% in the EP group.66 However, 2
therapy for patients with limited-stage disease in excess of T1-2, N0 subsequent large phase 3 trials performed in the United States
(category 1).52,53,57,58 comparing irinotecan plus cisplatin with EP failed to show a significant
difference in response rate or overall survival between the regimens.67,68
In combination with thoracic radiotherapy, EP causes an increased risk
of esophagitis, pulmonary toxicity, and hematologic toxicity.59 The use of A phase 3 randomized trial (n = 220) found that median overall survival
myeloid growth factors is not recommended (category 1 for not using was slightly improved with irinotecan and carboplatin compared with
GM-CSF) in patients undergoing concurrent chemoradiation.60 In clinical carboplatin and oral etoposide (8.5 vs. 7.1 months, P = .04).69 Based on
practice, carboplatin is frequently substituted for cisplatin to reduce the these findings, the carboplatin and irinotecan regimen is an option in the
risk of emesis, neuropathy, and nephropathy.61 However, the use of NCCN Guidelines for patients with extensive-stage disease. A
carboplatin carries a greater risk of myelosuppression.62 Small meta-analysis suggests an improvement in PFS and overall survival
randomized trials have suggested similar efficacy of cisplatin and with irinotecan plus platinum regimens compared with etoposide plus

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platinum regimens.70 However, this meta-analysis was not performed did not improve survival and was associated with unacceptable toxicity
using data from individual patients. In addition, the relatively small in a subsequent phase 3 study.77 The use of maintenance or
absolute survival benefit needs to be balanced against the toxicity consolidation chemotherapy beyond 4 to 6 cycles of standard treatment
profile of irinotecan-based regimens. Therefore, the NCCN Panel produces a minor prolongation of duration of response without
continues to consider etoposide plus platinum as the standard regimen improving survival and carries a greater risk of cumulative toxicity.78 A
for patients with either limited-stage or extensive-stage SCLC. meta-analysis reported that maintenance chemotherapy did not prolong
overall survival.79
In patients with limited-stage disease, response rates of 70% to 90%
are expected after treatment with EP plus thoracic radiotherapy, The inability to destroy residual cells, despite the initial chemosensitivity
whereas in extensive-stage disease, response rates of 60% to 70% can of SCLC, suggests the existence of cancer stem cells that are relatively
be achieved with combination chemotherapy alone. Unfortunately, resistant to cytotoxic therapy. To overcome drug resistance, alternating
median survival rates are only 14 to 20 months and 9 to 11 months for or sequential combination therapies have been designed to expose the
patients with limited- and extensive-stage disease, respectively. After tumor to as many active cytotoxic agents as possible during initial
appropriate treatment, the 2-year survival rate is approximately 40% in treatment.80 However, randomized trials have failed to show improved
patients with limited-stage disease, but less than 5% in those with PFS or overall survival with this approach.81,82
extensive-stage disease.71 Thoracic radiotherapy improves local control
rates by 25% in patients with limited-stage disease and is associated Multidrug cyclic weekly therapy was designed to increase dose
with improved survival.52,53 Data suggest that chemoradiotherapy may intensity. Early phase 2 results of this approach were promising,
be indicated for patients with limited-stage disease who have although favorable patient selection was of some concern.83,84
cytologically negative or indeterminate pleural effusions, but not for Nevertheless, no survival benefits were documented in randomized
those with pericardial effusions.72,73 trials, and excessive treatment-related mortality was noted with
multidrug cyclic weekly regimens.85-88 The role of higher-dose therapy
Many strategies have been evaluated in an effort to improve on the for patients with SCLC remains controversial. Higher complete and
standard treatment for extensive-stage SCLC, including the addition of partial response rates, and modestly longer median survival times, have
a third agent to standard 2-drug regimens. In 2 trials, the addition of been observed in patients receiving high doses when compared with
ifosfamide (or cyclophosphamide plus an anthracycline) to EP showed a those given conventional doses of the same agents.89 In general,
modest survival advantage for patients with extensive-stage disease.74,75 however, randomized trials comparing conventional doses to an
However, these findings have not been uniformly observed, and the incrementally increased dose intensity up to 2 times the conventional
addition of an alkylating agent, with or without an anthracycline, dose have not consistently shown an increase in response rate or
significantly increases hematologic toxicity when compared to EP survival.90-93 In addition, a meta-analysis of trials that compared
alone.76 Similarly, the addition of paclitaxel to either cisplatin or standard versus dose-intense variations of the cyclophosphamide,
carboplatin plus etoposide yielded promising results in phase 2 trials but doxorubicin, and vincristine (CAV) and EP regimens found that

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increased relative dose intensity resulted in only a small, clinically with extensive-stage SCLC.104 Overall, attempts to improve long-term
insignificant enhancement of median survival in patients with survival rates in patients with SCLC through the addition of more agents
extensive-stage disease.94 or the use of dose-intense chemotherapy regimens, maintenance
therapy, or alternating non–cross-resistant chemotherapy regimens
Currently available cytokines (eg, granulocyte-macrophage have failed to yield significant advantages when compared to standard
colony-stimulating factor [GM-CSF], granulocyte colony-stimulating approaches.
factor) can ameliorate chemotherapy-induced myelosuppression and
reduce the incidence of febrile neutropenia, but cumulative Elderly Patients
thrombocytopenia remains dose limiting. Although trials involving The incidence of lung cancer increases with age. Although the median
patients with SCLC were instrumental in obtaining FDA approval for the age at diagnosis is 70 years, elderly patients are under-represented in
clinical use of cytokines,95 maintenance of dose intensity with growth clinical trials.105 Although advanced chronologic age adversely affects
factors does not prolong disease-free or overall survival.96,97 Thus, the tolerance to treatment, the functional status of an individual patient is
routine use of growth factors at the initiation of systemic therapy is not much more useful than age in guiding clinical decision making (see the
recommended. NCCN Guidelines for Senior Adult Oncology, available at NCCN.org).
Older patients who are functional in terms of the ability to perform
The benefits of antiangiogenic therapy are being evaluated in SCLC. In activities of daily living should be treated with standard combination
patients with limited-stage SCLC, a phase 2 study of irinotecan, chemotherapy (and radiotherapy, if indicated).106,107 However,
carboplatin, and bevacizumab with concurrent radiotherapy followed by myelosuppression, fatigue, and lower organ reserves are encountered
maintenance bevacizumab was terminated early because of an more frequently in elderly patients; therefore, they must be watched
unacceptable incidence of tracheoesophageal fistulae. In carefully during treatment to avoid excessive risk. Greater attention to
extensive-stage SCLC, phase 2 trials of platinum-based chemotherapy the needs and support systems of elderly patients is recommended to
plus bevacizumab have yielded promising response and survival provide optimal care. Overall, elderly patients have a similar prognosis
data.98-101 However, at least one randomized trial has demonstrated no as stage-matched younger patients.
survival benefit for the addition of bevacizumab to standard
chemotherapy.102 Other randomized phase 3 trials are ongoing in Randomized trials have indicated that less-intensive treatment (eg,
patients with extensive-stage SCLC.103 Currently, the NCCN Panel does single-agent etoposide) is inferior to combination chemotherapy (eg,
not recommend use of bevacizumab in patients with SCLC. platinum plus etoposide) in elderly patients with good PS (0–2).108,109 A
recent retrospective analysis in 8637 elderly patients with limited-stage
Although immune checkpoint inhibitors have demonstrated activity in a disease reported that chemoradiation increased survival when
variety of cancers, including SCLC, a recent phase 3 randomized trial compared with chemotherapy alone.106 Several other strategies have
reported that the addition of ipilimumab to etoposide with either cisplatin been evaluated in elderly patients with SCLC.64,110-112 The use of 4
or carboplatin did not improve either overall survival or PFS in patients cycles of carboplatin plus etoposide seems to yield favorable results,

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because the area-under-the-curve (AUC) dosing of carboplatin takes recommendation) (see Principles of Systemic Therapy in the NCCN
into account the declining renal function of the aging patient.112 Guidelines for SCLC).119-122 These agents are listed in order of
However, targeting carboplatin to an AUC of 5, rather than 6, is more preference in the NCCN Guidelines. Ifosfamide was deleted for the
reasonable in this population.113 The usefulness of short-course, 2017 update, because panel members no longer use this agent.
full-intensity chemotherapy has also been explored in elderly or infirm
patients, and the results with only 2 cycles of chemotherapy seem to be For the 2017 update, the NCCN Panel added recommendations for
acceptable, although this approach has not been directly compared with nivolumab and nivolumab plus ipilimumab (both are category 2A) as
standard therapy.114 options for subsequent therapy for patients who have relapsed 6
months or less after primary therapy. Nivolumab and ipilimumab are
Second-Line and Beyond (Subsequent) Systemic Therapy novel immunotherapeutic agents that stimulate the immune system and
Although SCLC is very responsive to initial treatment, most patients thus have different mechanisms of action when compared with standard
relapse with relatively resistant disease.115,116 These patients have a cytotoxic chemotherapy.123 These recommendations are based on a
median survival of only 4 to 5 months when treated with further recent phase 1/2 trial in which patients received either nivolumab alone
systemic therapy. Subsequent systemic therapy provides significant or various doses of nivolumab with ipilimumab for relapsed SCLC.5
palliation in many patients, although the likelihood of response is highly Response rates were 10% (10/98) for nivolumab 3 mg/kg, 23% (14/61)
dependent on the time from initial therapy to relapse.117 If this interval is for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 19% (10/54) for
less than 3 months (refractory or resistant disease), response to most nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. The responses did not
agents or regimens is poor (≤10%). If more than 3 months have elapsed correlate with PD-L1 expression; studies indicate the SCLC has a lower
(sensitive disease), expected response rates are approximately 25%. If rate of PD-L1 expression than NSCLC.5 Diarrhea was the most
patients relapse more than 6 months after first-line treatment, then common grade 3 or 4 treatment-related adverse event. The overall
treatment with their original regimen is recommended.7,117,118 Response frequency of grade 3 or 4 adverse events was about 20%, and fewer
assessment should occur after every 2 to 3 cycles of subsequent than 10% of patients discontinued treatment because of
systemic therapy using CT with contrast of the chest/liver/adrenal gland. treatment-related adverse events.
Dose reduction or growth factor support should be considered for
patients with PS 2 who are receiving subsequent systemic therapy. Preliminary data suggest that temozolomide may be useful for patients
with SCLC, especially those with brain metastases and methylated
Based on phase 2 trials, recommended subsequent systemic therapy O6-methylguanine-DNA methyltransferase (MGMT).120,124 A recent
agents for patients who have relapsed 6 months or less after primary phase 3 trial (JCOG0605) from Japan in patients with sensitive relapsed
therapy include topotecan, irinotecan, paclitaxel, docetaxel, SCLC reported that the combination of cisplatin, etoposide, and
temozolomide, nivolumab with or without ipilimumab, vinorelbine, oral irinotecan improved survival (median, 18.2 months; 95% CI, 15.7–20.6)
etoposide, gemcitabine, CAV, and bendamustine (category 2A for all when compared with topotecan (12.5 months, 10.8–14.9; hazard ratio
agents except for bendamustine, which is a category 2B [HR], 0.67; 90% CI, 0.51–0.88; P = .0079). However, the toxicity of this

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approach was significant, and it is not recommended as standard Radiotherapy

second-line therapy.125 The Principles of Radiation Therapy in the algorithm describe the
radiation doses, target volumes, and normal tissue dose volume
A randomized phase 3 trial compared single-agent intravenous
constraints for mainly limited-stage SCLC, and include references to
topotecan with the combination regimen CAV.126 Both arms had similar
support the recommendations; prophylactic cranial irradiation (PCI) and
response rates and survival, but intravenous topotecan caused less
treatment of brain metastases are also discussed (see the NCCN
toxicity. In another phase 3 trial, oral topotecan improved overall
Guidelines for SCLC). The American College of Radiology (ACR)
survival when compared with best supportive care (26 vs. 14 weeks).127
Appropriateness Criteria are a useful resource.139 The Principles of
Single-agent topotecan is approved by the FDA as subsequent therapy
Radiation Therapy in the NSCLC algorithm may also be useful (eg,
for patients with SCLC who relapse after initial response to
general principles of radiotherapy, palliative radiotherapy) (see the
chemotherapy. Either oral or intravenous topotecan may be used,
NCCN Guidelines for NSCLC, available at NCCN.org). This section
because efficacy and toxicity seem to be similar with either route.127,128
describes the studies supporting the NCCN recommendations for
Many practicing oncologists have noted excessive toxicity with the SCLC. A few reports have suggested that stereotactic ablative
standard regimen of 1.5 mg/m2 of intravenous topotecan for 5 days, and radiotherapy (SBRT) might be useful for select patients with
studies suggest that an attenuated dose may be equally efficacious with limited-stage SCLC; however, there are insufficient data to make a
lower toxicity.129 Published studies have yielded conflicting data recommendation.140,141
regarding the usefulness of weekly topotecan in patients with relapsed
Thoracic Radiotherapy
SCLC, and this approach remains under investigation.130,131 Amrubicin is
The addition of thoracic radiotherapy has improved survival for patients
an active drug in patients with relapsed or refractory SCLC.132-135
with limited-stage disease. Meta-analyses that included more than 2000
However, grade 3–4 toxicity, primarily neutropenia, is common.136,137 A
patients show that thoracic radiation for limited-stage disease yields a
phase 3 trial reported that amrubicin did not improve overall survival as
25% to 30% reduction in local failure, and a corresponding 5% to 7%
second-line treatment for SCLC when compared to topotecan, except in
improvement in 2-year survival when compared with chemotherapy
a subset of patients with refractory disease.138
alone.52,53 However, achieving long-term local control using conventional
The optimal duration of subsequent systemic therapy has not been fully chemoradiotherapy for patients with limited-stage SCLC remains a
explored, although its duration is usually short and the cumulative challenge.
toxicity is frequently limiting even in patients who experience response.
For these reasons, subsequent systemic therapy should be continued Timing of Radiation with Chemotherapy
until 2 cycles beyond best response, progression of disease, or The administration of thoracic radiotherapy requires the assessment of
development of unacceptable toxicity. Additional subsequent systemic several factors, including the timing of chemotherapy and radiotherapy
therapy (eg, third line) can be considered if patients are still PS 0-2. (concurrent vs. sequential), timing of radiotherapy (early vs. late),

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volume of the radiation port (original tumor volume vs. shrinking field as once a day over 5 weeks. The twice-daily schedule produced a survival
the tumor responds), dose of radiation, and fractionation of advantage, but a higher incidence of grade 3 to 4 esophagitis was seen
radiotherapy. Early concurrent chemoradiotherapy is recommended for when compared with the once-daily regimen. Median survivals were 23
patients with limited-stage SCLC based on randomized trials. A versus 19 months (P = .04), and 5-year survival rates were 26% versus
randomized phase 3 trial by the Japanese Cooperative Oncology Group 16% in the twice-daily and once-daily radiotherapy arms, respectively.147
assessed sequential versus concurrent thoracic radiotherapy combined A significant criticism of this trial is that the doses of radiation in the 2
with EP for patients with limited-stage disease. They reported that arms were not biologically equivalent. In light of this, ongoing trials are
patients treated with concurrent radiotherapy lived longer than those evaluating biologically equivalent doses of 45 Gy delivered twice daily
treated with sequential radiotherapy.59 versus 60 to 70 Gy delivered once daily.148 Another concern regarding
hyperfractionation is that twice-daily thoracic radiation is technically
Another randomized phase 3 trial (by the National Cancer Institute of challenging for patients with bilateral mediastinal adenopathy.
Canada)—comparing radiotherapy beginning with either cycle 2 or cycle
6 of chemotherapy—showed that early radiotherapy was associated Another randomized phase 3 trial showed no survival difference
with improved local and systemic control and with longer survival.142 between once-daily thoracic radiotherapy to 50.4 Gy with concurrent EP
Several systematic reviews and meta-analyses on the timing of thoracic and a split course of twice-daily thoracic radiotherapy to 48 Gy with
radiotherapy in limited-stage SCLC have reported that early concurrent concurrent EP.149 However, split-course radiotherapy may be less
radiotherapy results in a small, but significant improvement in overall efficacious because of interval tumor regrowth between courses.
survival when compared with late concurrent or sequential Overall, patients selected for combined modality treatment that
radiotherapy.143,144 Another meta-analysis in patients with limited-stage incorporates twice-daily radiotherapy must have an excellent PS and
SCLC showed that survival was improved with more rapid completion of good baseline pulmonary function.
the chemo/RT regimen (start of any chemotherapy until the end of
radiotherapy [SER]).145 A recent meta-analysis of individual patient data Radiation for Limited-Stage SCLC
from 12 trials (2,668 patients) reported that early concurrent chemo/RT For limited-stage disease in excess of T1-2, N0, the NCCN Guidelines
increased 5-year overall survival (HR, 0.79; 95% CI, 0.69–0.91), recommend that radiotherapy should be used concurrently with
although severe acute esophagitis was also increased, when compared chemotherapy and that radiotherapy should start with the first or second
with late concurrent therapy.146 cycle (category 1). The optimal dose and schedule of radiotherapy have
not been established. However, 45 Gy in 3 weeks (twice-daily regimen)
Radiation Fractionation is superior to 45 Gy once daily in 5 weeks.147 For twice-daily
The ECOG/Radiation Therapy Oncology Group compared once-daily to radiotherapy, the recommended schedule is 1.5 Gy twice daily to a total
twice-daily radiotherapy with EP.147 In this trial, 412 patients with dose of 45 Gy in 3 weeks (category 1). For once-daily radiotherapy, the
limited-stage SCLC were treated with concurrent chemoradiotherapy recommended schedule is 2.0 Gy once daily to a total dose of 60 to 70
using a total dose of 45 Gy delivered either twice a day over 3 weeks or Gy (see Principles of Radiation Therapy in the NCCN Guidelines for

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SCLC).150-152 The minimum standard for thoracic irradiation is patients with extensive-stage SCLC who responded to chemotherapy, a
CT-planned 3-D conformal radiotherapy. More advanced technologies phase 3 trial by Slotman et al (Dutch CREST trial) reported that the
may also be used when needed (eg, 4D-CT) (see Principles of addition of sequential thoracic radiotherapy did not improve the primary
Radiation Therapy in the NCCN Guidelines for SCLC). The radiation endpoint of 1-year overall survival (33% vs. 28%, P = .066), but a
target volumes can be defined on the PET/CT scan obtained at the time secondary analysis did find improvement in 2-year overall survival (13%
of radiotherapy planning using definitions in reports 50 and 62 from the vs. 3%, P = .004) when compared with patients who did not receive
International Commission on Radiation Units & Measurement sequential thoracic radiotherapy.165
(ICRU).153,154 However, the pre-chemotherapy PET/CT scan should be
reviewed to include the originally involved lymph node regions in the Prophylactic Cranial Irradiation
treatment fields.152,155 Intracranial metastases occur in more than 50% of patients with SCLC.
Randomized studies have shown that PCI is effective in decreasing the
The normal tissue constraints used for NSCLC are appropriate for incidence of cerebral metastases, but most individual studies did not
SCLC when using similar radiotherapy doses (see the NCCN have sufficient power to show a meaningful survival advantage.166 A
Guidelines for NSCLC, available at NCCN.org). When using meta-analysis of all randomized PCI trials (using data from individual
accelerated schedules (eg, 3–5 weeks), the spinal cord constraints from patients) reported a 25% decrease in the 3-year incidence of brain
the CALCB 30610/RTOG 0538 protocol can be used as a guide (see metastases, from 58.6% in the control group to 33.3% in the
Principles of Radiation Therapy in the NCCN Guidelines for PCI-treated group.167 Thus, PCI seems to prevent (and not simply
SCLC).156-158 Intensity-modulated radiation therapy (IMRT) may be delay) the emergence of brain metastases. This meta-analysis also
considered in select patients (see Principles of Radiation Therapy in the reported a 5.4% increase in 3-year survival in patients treated with PCI,
NCCN Guidelines for SCLC and the NCCN Guidelines for NSCLC).159-163 from 15.3% in the control group to 20.7% in the PCI group.167 Although
the number of patients with extensive-stage disease was small in this
Thoracic Radiation for Extensive-Stage SCLC meta-analysis, the observed benefit was similar in patients with both
Based on the results of a randomized trial by Jeremic et al,164 the limited- and extensive-stage disease.
addition of sequential thoracic radiotherapy may be considered in select
patients with low-bulk metastatic extensive-stage disease who have a A retrospective study of patients with limited-stage disease also found
complete or near complete response after initial chemotherapy. In this that PCI increased survival at 2, 5, and 10 years compared with those
trial, patients experiencing a complete response at distant metastatic who did not receive PCI.168 A randomized trial from the EORTC
sites after 3 cycles of EP were randomized to receive either 1) further assessed PCI versus no PCI in 286 patients with extensive-stage SCLC
EP; or 2) accelerated hyperfractionated radiotherapy (ie, 54 Gy in 36 whose disease had responded to initial chemotherapy; PCI decreased
fractions over 18 treatment days) in combination with carboplatin plus symptomatic brain metastases (14.6% vs. 40.4%) and increased the
etoposide.164 The investigators found that the addition of radiotherapy 1-year survival rate (27.1% vs. 13.3%) compared with controls.169
resulted in improved median overall survival (17 vs. 11 months). In Preliminary data from a Japanese phase 3 trial suggest that PCI did not

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improve survival in patients with extensive-stage disease who had MRI Palliative Radiotherapy
to confirm that they did not have brain metastases.170 For patients with localized symptomatic sites of disease (ie, painful bony
lesions, spinal cord compression, obstructive atelectasis) or with brain
Late neurologic sequelae have been attributed to PCI, particularly in metastases, radiotherapy can provide excellent palliation (see Initial
studies using fractions greater than 3 Gy and/or administering PCI Treatment in the NCCN Guidelines for SCLC and the NCCN Guidelines
concurrently with chemotherapy.171,172 Thus, PCI is not recommended for NSCLC, available at NCCN.org).178-180 Orthopedic stabilization may
for patients with poor PS (3–4) or impaired neurocognitive function.173,174 be useful in patients at high risk for fracture because of osseous
Older age (>60 years) has also been associated with chronic structural impairment. Because patients with SCLC often have a short
neurotoxicity.175 When given after the completion of chemotherapy and life span, surgery is not usually recommended for spinal cord
at a low dose per fraction, PCI may cause less neurologic toxicity. compression.
Before the decision is made to administer PCI, a balanced discussion Whole-brain radiotherapy is recommended for brain metastases in
between the patient and physician is necessary.176 PCI is a category 1 patients with SCLC due to the frequent occurrence of multiple
recommendation for patients with limited-stage disease who attain a metastases (see Principles of Radiation Therapy in the NCCN
complete or partial response; PCI is a category 2A recommendation for Guidelines for SCLC and the NCCN Guidelines for Central Nervous
patients with extensive-stage disease.169,173 PCI is also recommended System Cancers, available at NCCN.org).181 Although late
for all patients who have had a complete resection (see Principles of complications, such as neurocognitive impairment, may occur with
Surgical Resection in the NCCN Guidelines for SCLC). The preferred whole-brain radiotherapy this is less of an issue in patients with SCLC
dose for PCI to the whole brain is 25 Gy in 10 daily fractions (2.5 because long-term survival is rare.171 The recommended dose for
Gy/fraction), (see Principles of Radiation Therapy in the NCCN whole-brain radiotherapy is 30 Gy in 10 daily fractions.181 In patients
Guidelines for SCLC).167,169,177 The NCCN Panel feels that a shorter who develop brain metastases after PCI, stereotactic radiosurgery may
course of PCI may be appropriate (eg, 20 Gy in 5 fractions) for selected be considered.182
patients with extensive-stage disease.169 Higher doses (eg, 36 Gy)
increased mortality and toxicity when compared with standard doses Surgical Resection of Stage I SCLC
(25 Gy).175,177 PCI should not be given concurrently with systemic The Principles of Surgical Resection for SCLC are described in the
therapy, and high total radiotherapy dose (>30 Gy) should be avoided NCCN algorithm; studies supporting these recommendations are
because of the increased risk of neurotoxicity.175 Fatigue, headache, described in this section. Briefly, the NCCN Guidelines state that
and nausea/vomiting are the most common acute toxic effects after surgery should only be considered for patients with stage I (T1–2, N0)
PCI.174,177 After the acute toxicities of initial therapy have resolved, PCI SCLC in whom mediastinal staging has confirmed that mediastinal
can be administered. For patients not receiving PCI, surveillance for lymph nodes are not involved.183 Data show that patients with clinically
metastases with brain imaging should be considered.

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staged disease in excess of T1–2,N0 do not benefit from surgery.184 In all patients with clinical stage I (T1–2, N0) SCLC who are being
Note that only 5% of patients with SCLC have true stage I SCLC.39 considered for surgical resection, occult nodal disease should be ruled
out through mediastinal staging before resection.191 If resection is
The Lung Cancer Study Group conducted the only prospective performed, the NCCN Panel favors lobectomy and does not feel that
randomized trial evaluating the role of surgery in SCLC.184 Patients with segmental or wedge resections are appropriate for patients with SCLC.
limited-stage disease, excluding those with solitary peripheral nodules, After complete resection, adjuvant chemotherapy or chemoradiation is
received 5 cycles of chemotherapy with CAV; those showing a recommended.173,187,192,193 Adjuvant chemotherapy alone is
response to chemotherapy were randomly assigned to undergo recommended for patients without nodal metastases, whereas
resection plus thoracic radiotherapy or thoracic radiotherapy alone. The concurrent chemotherapy and postoperative mediastinal radiotherapy
overall survival rates of patients on the 2 arms were equivalent, are recommended for patients with nodal metastases (see Adjuvant
suggesting no benefit to surgery in this setting. However, only 19% of Treatment in the NCCN Guidelines for SCLC). Although panel members
enrolled patients had clinical stage I (T1–2, N0, M0) disease. agree that postoperative mediastinal radiotherapy is recommended in
this setting, it should be based on the extent of nodal
Most data regarding the benefit of surgery are from retrospective
sampling/dissection and extent of nodal positivity; however, there are no
reviews.183,185-189 These studies report favorable 5-year survival rates of
data to support this recommendation.
40% to 60% in patients with stage I disease. In most series, survival
rates decline significantly in patients with more advanced disease, PCI should be considered after adjuvant therapy in select patients,
leading to the general recommendation that surgery should only be because it can improve survival (see Prophylactic Cranial Irradiation in
considered in those with stage I disease. Interpretation of these results this Discussion and Adjuvant Treatment in the NCCN Guidelines for
is limited by the selection bias inherent in retrospective reviews and by SCLC).167 For the 2017 update, the NCCN Panel added new
the variable use of chemotherapy and radiotherapy. recommendations for response assessment after adjuvant therapy.
Response assessment using CT with contrast of the chest, liver, and
Analyses of the SEER database also suggest that surgery may be
adrenal gland should occur only after completion of initial therapy for
appropriate for some patients with localized disease.11,190 However,
patients with limited-stage disease; repeating scans during therapy is
these studies are limited by the lack of information on chemotherapy
not recommended.
use in the database. In addition, comparison of the survival of surgical
patients to all those who did not undergo surgery is inherently flawed by Surveillance
selection bias. Ultimately, the role of surgery in SCLC will not be fully
The schedule for follow-up examinations is shown in the algorithm (see
defined until results are available from trials comparing surgery plus
Surveillance in the NCCN Guidelines for SCLC); the frequency of
adjuvant chemotherapy to concurrent chemoradiotherapy in patients
surveillance decreases during subsequent years because of the
who are rigorously staged.
declining risk of recurrence.194 PET/CT or brain MRI (or CT) is not

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recommended for routine follow-up. If a new pulmonary nodule

develops, it should prompt evaluation for a new primary lung cancer,
because second primary tumors are a frequent occurrence in patients
who are cured of SCLC.195,196 Smoking cessation should be encouraged
for all patients with SCLC, because second primary tumors occur less
commonly in patients who quit smoking (see the NCCN Guidelines for
Smoking Cessation, available at NCCN.org).197-199 Former smokers
should be encouraged to remain abstinent.

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Small Cell Lung

NCCN Guidelines Version 1.2018 Panel Members NCCN Guidelines Index

Charles Florsheim † Medical oncology

NCCN Guidelines Version 1.2018 Table of Contents NCCN Guidelines Index

NCCN Small Cell Lung Cancer Panel Members

NCCN Guidelines Version 1.2018 Updates NCCN Guidelines Index

NCCN Guidelines Version 1.2018 Updates NCCN Guidelines Index

NCCN Guidelines Version 1.2018 Updates NCCN Guidelines Index

NCCN Guidelines Version 1.2018 Updates NCCN Guidelines Index

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

DIAGNOSIS INITIAL EVALUATIONa STAGE

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

STAGE ADDITIONAL WORKUP

• If pleural effusion is present,

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

TESTING RESULTS INITIAL TREATMENTj ADJUVANT TREATMENT

Lobectomyh,l Systemic therapym See Response

Systemic therapym + See Response

hSee Principles of Surgical Resection (SCL-C).

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

STAGE INITIAL TREATMENTk

May administer systemic therapy first,

kSee Principles of Supportive Care (SCL-D).

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

RESPONSE ASSESSMENT FOLLOWING ADJUVANT SURVEILLANCEs

Primary progressive disease See Subsequent Therapy/Palliative Therapy SCL-6)

bSee Signs and Symptoms of Small Cell Lung Cancer (SCL-A).

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

PROGRESSIVE DISEASE SUBSEQUENT THERAPY/PALLIATIVE THERAPY

Continue until two • Palliative

kSee Principles of Supportive Care (SCL-D).

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

SIGNS AND SYMPTOMS OF SMALL CELL LUNG CANCER (1 of 2)

Signs and symptoms due to extrathoracic (hematogenous) metastases

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

SIGNS AND SYMPTOMS OF SMALL CELL LUNG CANCER (2 of 2)

• Neurologic: All specific syndromes are rare

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

PRINCIPLES OF PATHOLOGIC REVIEW (1 of 2)

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

PRINCIPLES OF PATHOLOGIC REVIEW (2 of 2) - References

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

PRINCIPLES OF SURGICAL RESECTION

• Stage I SCLC is diagnosed in less than 5% of patients with SCLC.

NCCN Guidelines Version 1.2018 NCCN Guidelines Index

PRINCIPLES OF SUPPORTIVE CARE

• Syndrome of inappropriate antidiuretic hormone

• Leptomeningeal disease: See NCCN Guidelines for Carcinomatous/Lymphomatous Meningitis

• Pain management: See NCCN Guidelines for Adult Cancer Pain

• Nausea/vomiting: See NCCN Guidelines for Antiemesis

• Psychosocial distress: See NCCN Guidelines for Distress Management