Neuro-Oncology 14:i22 i25, 2012. doi:10.

1093/neuonc/nos097

NEURO-ONCOLOGY

Abstracts
CRANIOPHARYNGIOMA
CR-01. DEMOGRAPHICS AND PRACTICE PATTERNS IN CRANIOPHARYNGIOMA FROM THE SEER (SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS) DATABASE Todd Hankinson1, Emma Fields2, Michael Handler1, Nicholas Foreman1, and Arthur Liu2; 1Childrens Hospital Colorado, Aurora, CO, USA; 2 University of Colorado Denver, Aurora, CO, USA INTRODUCTION: Craniopharyngioma is histologically benign but associated with poor quality of life outcomes. The US NCIs Surveillance, Epidemiology and End Results (SEER) Program began collecting data regarding craniopharyngioma in 2004. METHODS: Using SEER-STAT, we identied all patients with ICD-O-3 codes for craniopharyngioma. Age was divided into 3 groups. Surgical intervention was divided into 3 groups: none, subtotal, and gross total/radical resection. Demographic, follow-up and treatment data were collected. RESULTS: Among 662 patients: 30.7% were , 19 years of age; 13.6% were 20-34 years and 55.7% were . 35 years. Age-adjusted incidence per 1,000,000 population was 1.7, 1.1, and 1.9, respectively. Ages with highest incidence were 65-69 and 70-74 years (2.6/million) followed by 5-9 and 60-64 years (2.5/ million). Radiation data was documented in 649 (98.0%) patients. Of these, 22.0% were treated. Radiation rates were 25.6%, 14.6%, and 21.9% in the three age groups. Surgery was documented in 579 (87.5%) patients. Of these, 81.2% underwent surgery. Among patients , 19 years: 17.3% had no surgery, 27.7% had STR and 54.9% had Radical/GTR. Among those 20-34 years, 11.3% had no surgery, 35.0% had STR and 53.8% had Radical/GTR. Among those . 35 years, 21.5% had no surgery, 23.0% had STR and 55.5% had Radical/GTR. Radiation rates were 21.1%, 17.8% and 22.9% in the three surgical groups. Follow-up was available for 6/662 patients (0.91%). CONCLUSIONS: Craniopharyngioma is rare. The bimodal incidence shows a larger peak during the 7-8th decades of life than during the 2nd decade. 18.8% of patients underwent no surgical intervention, conicting with most reports. Radiation treatment correlated with neither extent of resection nor age. Possible explanations include variability in treatment strategies, incomplete data, and the inclusion of patients with non-surgical lesions other than craniopharyngioma. Regarding craniopharyngioma, data regarding morbidity, longer follow-up, and comparative analyses with patient level datasets will maximize SEERs value in this population.

were categorized as small (1 pt/6 yrs), middle (2-5 pts /6yrs) or large-sized centres ( . 5 pts /6yrs). BMI SDS at diagnosis was similar in patients with or without hypothalamic involvement. Surgical lesions of anterior and posterior hypothalamic areas were associated with higher increases in BMI SDS during 36 mo post-diagnosis compared to patients without or only anterior lesion ( + 1.8BMISD,p 0.033; + 2.1BMISD,p 0.011), negatively impacting QoL in patients with posterior hypothalamic lesions. Surgical strategies varied between the 50 neurosurgical centres (3 large, 24 middle, 23 small centres). Patients treated in small centres presented with a higher rate of hypothalamic involvement compared to middle and large-sized centres. Treatment in large centres was less radical, the rates of complete resection and hypothalamic surgical lesions lower than those of middle-sized and small centres. However, multivariable analysis showed that preoperative hypothalamic involvement was the only independent risk factor for severe obesity (p 0.002). Radical strategies leading to posterior hypothalamic lesions are not recommended due to potential to exacerbate hypothalamic obesity and impaired QoL. Because our results show that initial hypothalamic involvement has an apriori effect on the clinical course, our recommendations are based on recognizing CP as a chronic disease.

CR-03. NO LONG-TERM WEIGHT REDUCTION AFTER GASTRIC BANDING (LAGB) IN OBESE PATIENTS WITH CRANIOPHARYNGIOMA INVOLVING HYPOTHALAMIC STRUCTURES - EXPERIENCES FROM KRANIOPHARYNGEOM 2000 Hermann L. Mu rn Maroske2, and Ernst Hanisch3; ller1, Ursel Gebhardt1, Jo 1 Dep. of Pediatrics, Klinikum Oldenburg, Oldenburg, Germany; 2Dep. of Surgery, Verbundklinikum Rothenburg o.d.T., Rothenburg, Germany; 3 Dep. of General, Visceral, and Endocdrine Surgery, Asklepios Klinik, Langen, Germany BACKGROUND: Craniopharyngiomas are embryogenic malformations which lead to eating disorders and morbid obesity due to hypothalamic involvement. The experience with laparoscopic adjustable gastric banding (LAGB) in obese craniopharyngioma patients is limited especially in regard to long-term effects and tolerability. PATIENTS AND METHODS: We are reporting on four patients with childhood craniopharyngioma diagnosed at age 2, 13, 12, and 20 years. RESULTS: Body mass index (BMI-SDS) at diagnosis was -0.9, + 4.5, + 4.7 and + 0.23 SD. All patients developed morbid obesity (BMI-SDS: + 10,87, + 10.36, + 11.4, + 6,2) so that 11, 5, 9 and 3 years after diagnosis LAGB were performed. LAGB were well tolerated. During long-term follow-up, the nadir BMI SDS ( + 6.9, + 9.5, + 7.8, + 4.9) were reached 2.0, 0.5, 1.0, 0.8 years after LAGB. At last evaluation 9.1, 5.3, 7.1, 7.1 years after LAGB, the patients BMI (BMI SDS at last evaluation: + 10.2, + 13.9, + 10.2, + 6.3) had increased again but remained at a constant level comparable with baseline BMI SDS at the time of LABG. Quality of life was not decreased due to LAGB and tolerability was sufcient. CONCLUSIONS: We conclude that LAGB is feasible and could have clinical relevant effects on long-term weight stabilization of obese craniopharyngioma patients with hypothalamic syndrome. However, a signicant weight reduction was not achieved after LAGB in patients with childhood craniopharyngioma. Non-reversible bariatric procedures such as gastric bypass are not recommended for treatment of obese children and adolescents with craniopharyngioma due to ethical considerations. Supproted by the German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung, Bonn, Germany).

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CR-02. INITIAL HYPOTHALAMIC INVOLVEMENT IS THE MAJOR RISK FACTOR FOR IMPAIRED PROGNOSIS AND QUALITY OF LIFE IN CHILDHOOD CRANIOPHARYNGIOMA REGARDLESS OF CHOSEN TREATMENT STRATEGIES RESULTS OF KRANIOPHARYNGEOM 2000 Hermann L. Mu ller1, Ursel Gebhardt1, Monika Warmuth-Metz2, Rolf-Dieter Kortmann3, Andreas Faldum4, Torsten Pietsch5, Niels So rensen6, and Gabriele Calaminus1; 1Dep. of Pediatrics, Klinikum Oldenburg, 2 Oldenburg, Germany; Dep. of Neuroradiology, University Hospital Wu rzburg, Wu rzburg, Germany; 3Dep. of Radiooncology, University Hospital Leipzig, Leipzig, Germany; 4Inst. for Medical Biometrics, Epidemiology and Informatics, University of Mainz, Mainz, Germany; 5Inst. for Neuropathology, University Hospital Bonn, Bonn, Germany; 6Dep. of Neurosurgery, Evangelisches Krankenhaus, Oldenburg, Germany; 7Dep. of Ped. Oncology, University Hospital Mu nster, Mu nster, Germany Hypothalamic obesity has major impact on prognosis and quality of life (QoL) in childhood craniopharyngioma (CP). The pathogenic relevance of initial hypothalamic involvement versus treatment-related hypothalamic lesions is a matter of controversy. 120 patients were recruited prospectively (2001-2007) and evaluated after 3 yrs of follow-up. Body mass index (BMI) and QoL at diagnosis and 36 mo after diagnosis were analyzed based on reference assessment of tumour localization and post-surgical hypothalamic lesions using a standardized grading system (no, anterior, posterior involvement/lesion). Treatment was analyzed regarding neurosurgical strategy of 50 participating neurosurgical centres and the centre sizes. Based on patient load during the 6-year recruitment period, participating centres

CR-04. RANDOMIZED MULTICENTER TRIAL ON PATIENTS WITH CHILDHOOD CRANIOPHARYNGIOMA (KRANIOPHARYNGEOM 2007) - UPDATE AFTER 41 MONTHS OF RECRUITMENT Hermann L. Mu ller1, Ursel Gebhardt1, Fabian Pohl1, Rolf-Dieter Kortmann1, Andreas Faldum1, Monika Warmuth-Metz1, Torsten Pietsch1, Gabriele Calaminus1, and Niels So rensen1; 1Dep. of Pediatrcs, Klinikum Oldenburg, Oldenburg, Germany; 2Dep. of Radiooncology, University Hospital Regensburg, Regensburg, Germany; 3Dep. of Radiooncology, University Hospital Leipzig, Leipzig, Germany; 4Inst. for Medical Biometrics, Epidemiology and Informatics, University of Mainz, Mainz, Germany; 5Dep. of Neuroradiology, University Hospital Wu rzburg, Wu rzburg, Germany; 6 Inst. for Neuropathology, University Hospital Bonn, Bonn, Germany; 7Dep. of Ped. Oncology, University Hospital Mu nster, Mu nster, Germany; 8Dep. of Neurosurgery, Evangelisches Krankenhaus Oldenburg, Oldenburg, Germany Despite high survival rates (92%) in patients with childhood craniopharyngioma (CP), quality of life (QoL) is frequently impaired due to sequelae such as severe obesity resulting from hypothalamic involvement of CP. Based on the results of the multicenter prospective study

Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2012.

Abstracts

KRANIOPHARYNGEOM 2000 radical surgery is no appropriate treatment strategy in patients with hypothalamic involvement. Furthermore, tumour progression/relapses are frequent early events in CP patients. The analysis of event-free survival-rates (EFS) in 117 prospectively evaluated patients with CP showed a high rate of early events in terms of tumour progression after incomplete resection (EFS: 0.31 + 0.07) and relapses after complete resection (EFS: 0.63 + 0.09) during the rst three years of follow-up. Accordingly, in KRANIOPHARYNGEOM 2007 QoL, and survival rates in CP pts ( . 5yrs at diagnosis) are analyzed after randomization of the time point of irradiation (XRT) after incomplete resection (immediate XRT versus XRT at progression of residual tumour). Up to now (03/11) 78 pts with CP were recruited (42 pts in the randomization arm; 33 pts in the surveillance arm; 3 pts in the process of review of imaging). 13 of 42 pts were randomized. 29 pts could not be randomized due to parental decision (11 pts), late schedule (14 pts) and due to decision of the physician (4 pts). In conclusion, KRANIOPHARYNGEOM 2007 represents the rst randomized trial in CP and the rst study in pediatric neurooncology analyzing QoL as an endpoint. Aim of the study is to analyze the appropriate time point of XRT in order to improve QoL in patients with hypothalamic involvement. The recruiting compliance is high. However, the randomization compliance has to be improved in order to reach cohort sizes necessary for reliable statistical analysis and to answer the questions assessed by the randomized trial KRANIOPHARYNGEOM 2007. Supported by the German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung)

cases of craniopharyngiomas in patients under 18 years of age regarding clinical presentation, neuroimaging, recurrence, morbidity, and mortality, with particular attention to hypothalamic obesity. RESULTS: In general, our cohort conformed to published data in regard to neuroimaging characteristics and had similar clinical ndings in the areas of endocrine, visual, neurologic, neurobehavioral, and hypothalamic domains. At last follow-up, 54% of our patients were either overweight (8%) or obese (46%). Only 25% of our patients had a healthy body mass index (BMI), and 21% were considered underweight at last follow-up. Contrasting this data with BMIs at diagnosis where 21% were overweight and 17% were obese, there was a signicant trend towards obesity over time. Even patients who were underweight or at a healthy weight at diagnosis progressed to obesity (27%). A signicant portion of our mortality appeared to be related to complications of obesity, however one death did occur in a patient considered to be underweight. The native american population in Arizona appears to have a statistically higher incidence of obesity in childhood. In our study, 75% of our native americans were obese at last follow-up, and accounted for 50% of the mortality. We have found that risk factors for hypothalamic obesity include a history of pre-morbid obesity and involvement of the hypothalamic structures at diagnosis. CONCLUSION: Hypothalamic obesity is a signicant complication of craniopharyngiomas and is associated with increased mortality. There is limited genomic information regarding hypothalamic obesity with few therapeutic options. Therefore, practioners must have a heightened awareness, and provide early education and aggressive intervention stressing diet and exercise.

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CR-05. CHANGES OF PERIPHERAL a LPHA-MELANOCORTIN STIMULATING HORMONE ( a -MSH) IN CHILDHOOD CRANIOPHARYNGIOMA PATIENTS IN COMPARISON WITH OTHER FORMS OF CHILDHOOD OBESITY Hermann L. Mu ller1, Pablo J. Enriori2, Ursel Gebhardt1, Anke Hinney3, Johannes Hebebrandt3, Thomas Reinehr4, Michael Cowley2, and Christian Roth5; 1Dep. of Pediatrics, Klinikum Oldenburg, Oldenburg, Germany; 2Div. of Neuropsciences, National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA; 3Dep.of Child and Adolescent Psychiatry, University of Duisburg-Esse, Essen, Germany; 4 Dep. of Paediatric Nutrition Medicine, Vestische Children Hospital, University Witten-Herdecke, Datteln, Germany; 5Seattle Childrens Hospital Research Insitute, Seattle, WA, USA OBJECTIVE: Relationships of blood circulating melanocortins to childhood obesity are not well established. We evaluated serum a-melanocyte stimulating hormone (a-MSH) in lean children and different study groups of childhood obesity. METHODS: We examined serum a-MSH in 52 otherwise healthy children with childhood obesity (Ob,mean age 11 years, 32 girls/20 boys), 27 normal-weight children of same age, 7 additional obese patients with reduced melanocortin-4 receptor function (MC4Rmut), and 22 patients with craniopharyngioma (CP). Fasting serum a-MSH and leptin were measured by RIA. Serum a-MSH was also evaluated one hour after 500 kcal liquid meal (CP and Ob) and at the end of one year lifestyle intervention in 24 Ob patients. RESULTS: a-MSH levels were similar in obese vs. lean children but signicantly lower in CP (p , 0.001) and signicantly higher (p , 0.05) in MC4Rmut patients compared to Ob. One hour after liquid meal, a-MSH increased in patients with SO but not with CP. After one year, a-MSH levels increased signicantly in the successful weight reduction Ob subgroup despite unchanged cortisol levels. a-MSH changes correlated to weight status changes (r 0.67; p 0.0003) but not to changes of cortisol, insulin or insulin resistance index HOMA. CONCLUSIONS: Persistently low a-MSH levels in CP patients are suspected to be due to pituitary or hypothalamic damage. High peripheral levels in MC4Rmut carriers indicate up-regulation of a-MSH. Changes of weight status are associated with changes of peripheral a-MSH. Synthetic a-MSH analogues might offer a promising therapeutic option for treatment of hypothalamic obesity in craniopharyngioma patients.

CR-07. PEGYLATED INTERFERON-ALFA-2B (PI) FOR RECURRENT CRANIOPHARYNGIOMAS Regina Jakacki, Jacky Yeung, Ashok Panigrahy, and Ian Pollack; Childrens Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA BACKGROUND: Previous studies of systemic and intra-lesional administration of non-pegylated interferon have shown efcacy against craniopharyngioma. Pegylating interferon prolongs the half-life, increases the area under the curve (AUC) and enhances efcacy. EXPERIMENTAL DESIGN: Since 2002, 5 children, ages 9-15 years old, with recurrent craniopharyngiomas were treated at the Childrens Hospital of Pittsburgh with subcutaneous injections of PI at a dose of 1-3 mcg/kg/week for up to 2 years. RESULTS: Patient #1 developed recurrent tumor s/p gross total resection (GTR). She initially showed an increase in the predominantly cystic tumor after 3 months of treatment with PI, followed by a complete response (CR) by the end of treatment. She remains without evidence of disease (NED) 8 years later. Patient #2 developed recurrent tumor 3.3 years s/p subtotal resection (STR) and radiation therapy. He had complete disappearance of the predominantly cystic component after 4 months of treatment with PI and remains with a small calcied residual 5 years later. Patient #3 developed recurrent tumor s/p GTR x 3. He had a CR after 7 months of treatment with PI and remains NED 13 months later. Patient #4 developed recurrent tumor s/p STR x 2. He had a minor response after 4 months of treatment with PI, which was maintained for 12 months until he developed a new third nerve palsy and increase in cyst size. Patient #5 developed recurrent tumor s/p GTR. Her cyst remains stable after 4 months of treatment with PI. CONCLUSIONS: Pegylated interferon can result in durable responses in patients with recurrent craniopharyngioma. Further evaluation in a multiinstitutional context is warranted.

CR-08. MANAGEMENT PATHWAY FOR CRANIOPHARYNGIOMA FOLLOWING CCLG GUIDELINES Conor Mallucci, Barry Pizer, Mohamed Didi, Jo Blair, Swathi Upadrasta, Arun Doss, Shivaram Avula, and Benedetta Pettorini; Alder Hey Childrens NHS Foundation Trust, Liverpool, UK INTRODUCTION: In 2005, the Childrens Cancer Leukaemia Group (CCLG) proposed a treatment strategy for craniopharyngioma. The proposal advocated limited surgery followed by upfront radiotherapy for large tumours with hypothalamic involvement, and radical resection only for tumours smaller than 2-4 cm without hypothalamic involvement. The aim of this study is to review our experience of management of craniopharyngioma after 2005. We have appraised risk factors for stratication and introduced re-stratication after endoscopic decompression. METHODS: All children diagnosed with craniopharyngioma from 2005 were included. Pre-operative and post-operative assessment included: MRI, full endocrine screening and full ophthalmologic assessment. Management was based on the presence of hypothalamic syndrome, hydrocephalus, tumour size and the radiological Paris grading system with respect to the involvement of the oor of the IIIrd ventricle. Endoscopic drainage and lavage of tumour cyst was performed prior to formalizing the risk grade and surgical strategy.

CR-06. A REVIEW A CHILDHOOD CRANIOPHARYNGIOMAS WITH PARTICULAR ATTENTION TO HYPOTHALAMIC OBESITY Amy Rosenfeld1, Daniel Arrington2, Michael Etzl1, Jeffrey Miller1, Annie Gieseking1, Igor Dvorchik1, and Allen Kaplan1; 1Phoenix Childrens Hospital, Phoenix, AZ, USA; 2Boston Childrens Hospital, Boston, MA, USA BACKGROUND: Although craniopharyngiomas are considered benign neoplasms by the World Health Organization (WHO) classication, these tumors have signicant morbidity and mortality. Hypothalamic obesity is a frequent complication of craniopharyngiomas, and one that has been refractory to current management. PATIENTS/METHODS: We reviewed 24

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Only after the drainage a denitive tumour assessment was achieved and denitive surgery was performed in 4-6 weeks time. We developed a new grading criteria to include recognized risk factors in the management of craniopharyngioma. RESULTS: Twenty patients were included in the study. Ten of them (50%) underwent endoscopic cyst drainage prior to denitive surgery. The results of the subsequent surgical excision were complete resection, near total resection or sub-total resection in 6 (30%), 5 (25%) and 9 (45%) patients respectively. There was no surgical related mortality and no new neurological decits. Nine patients (45%) underwent radiotherapy at some stage. CONCLUSIONS: In this study we tried to develop an advanced model for the management of paediatric craniopharyngioma. An improved risk grading system may have a direct impact in the surgical strategy and surgical outcome and could be able to improve morbidity related to surgical and adjuvant treatments.

CR-09. PROTONTHERAPY FOR CRANIOPHARYNGIOMA IN CHILDREN: UPDATE OF THE ORSAY PROTON CENTER EXPERIENCE Claire Alapetite1, Ste phanie Puget2, Amandine Rufer1, Jean-Louis Habrand3, Ste phanie Bolle3, Georges Noel4, Catherine Nauraye1, Ludovic De Marzy1, Nathalie Boddaert2, Herve Brisse1, Christian Sainte-Rose2, Michel Zerah2, Sergio Boetto6, Christelle Laffond5, Mathilde Chevignard5, Jacques Grill3, and 1 Franc ois Doz1; Institut Curie, Radiation Oncology Department & Proton Centre, Paris & Orsay, France; 2Hopital Necker Enfants Malades, Paris, France; 3Institut Gustave Roussy, Villejuif, France; 4Centre Paul Strauss, Strasbourg, France; 5Hopital National Saint Maurice, Saint Maurice, France; 6 Hopital Toulouse Purpan, Toulouse, France Craniopharyngioma is associated to severe morbidity including hypothalamic dysfunction related to tumour growth and/or post-operative damage. After incomplete resection, radiotherapy reduces recurrence rate although its place is debated especially in younger children. Improving dose-gradient to critical structures and reducing brain exposure, protontherapy (PT) offers reconsidering post-operative RT according to clinical presentation. From 1994-2009, 49 craniopharyngioma, median age 10[3.8-16.1], were irradiated; at relapse in 19 cases; and as part of a combined prospective approach following conservative subtotal resection in 30 patients with hypothalamic involvement (starting 2004). Two patients required general anaesthesia. Cystic monitoring led to; replanning of collimators/compensators in one case; treatment transient interruption for surgery in one case. Multidisciplinary follow-up includes serial imaging and neurocognitive evaluation in all recent cases. Median Total dose 54 CGE, conventionallyfractionated, was delivered using photon-proton approach in 10 early patients, and thereafter protontherapy only. Comparative dosimetry (3DCRT/IMRT/protons) in 2 cases, showed benet of proton-beams for; critical organs (non-abutting chiasma, brain-stem, cochlea); temporal lobes and whole brain exposure. At median FU 53mths [24-156], 4 in-eld relapses (3 cystic, 1 solid) required surgery at median 43mths [3-68]. One relapse occurred along surgical access-route after 56 mths. All but one children had hypopituitarism prior PT. No PT-related optic-neuropathy was observed. In children irradiated after several surgeries, neuro-psychological evaluation emphasised altered short-term memory and social and emotional functioning, and signicant school difculties. In children treated prospectively with conservative approach, results show reduced morbidity with lower rate of obesity and behavioural disorders when preserving hypothalamus. Preliminary results of combined approach with conservative surgery for craniopharyngioma with hypothalamic involvement suggests reduced morbidity without jeopardizing tumour control. Long term follow-up is required including longitudinal analysis of neurocognition and quality of life. With the potential to decrease risk of late-sequelae and second malignancies, protontherapy is a promising tool, especially for younger children.

lesions were solid-cystic (67%) with subtotal excision as the commonest surgery (77%). At a mean follow-up of 36 months (range 6-98 months), 63 patients were controlled with a 5-yr OS of 95.6% and 5-yr PFS of 92.3%. Pre-RT mean VQ, performance IQ (PQ) and FSIQ were 82.2, 83.5 and 79.6 respectively. Mean FSIQ of 91.4 was maintained at 4 years followup following RT. Superior neurocognitive outcomes were seen when , 13% volume of left temporal lobe received 43.2 Gy and if doses to hippocampus were restricted to V80 , 5.8% and V95 , 0.7%. Mean trait-anxiety score was poor at baseline (25) improving to 17 at 4-year follow-up. Mean BI score at baseline, 2 year and 4 year were 95.0, 100 and 100 respectively. Pre-RT BI score was signicantly lower in visually handicapped (p 0.007), low KPS score (0.004), poor neurological function status (NPS) (0.014) and in patients with severe hydrocephalus (p 0.031). LOTCA scores showed improvement in visuo-motor/thinking and maintained in orientation, spatial-perception, thinking and attention concentration domains. At baseline, 73% patients had hormone deciency in at least one axis. Growth hormone, corticosteroid and thyroid hormone axes impairment were present in 20%, 21% and 11% patients respectively. Pre-RT BI score was signicantly lower in visually handicapped (p 0.007), low KPS score, poor NPS and severe hydrocephalus. CONCLUSION: Craniopharyngioma patients have poor neuropsychological/endocrinal function even before starting RT. However, there is no further decline upto 4 years follow-up after high-precision RT.

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CR-12. NEURO-ENDOCRINE MORBIDITY IS REDUCED BY A UK (2005) CONSENSUS RISK-BASED CONSERVATIVE SURGICAL AND RADIATION MANAGEMENT STRATEGY IN CHILDHOOD CRANIOPHARYNGIOMA. (THE GREAT ORMOND STREET HOSPITAL SINGLE CENTRE SERIES) Esieza Clare Ikazoboh, Mehul Dattani, and Helen Spoudeas; Neuro-endocrine Division of the London Centre for Paediatric Endocrinology, University College (UCLH), and Great Ormond Street (GOSH) Hospitals, London, UK Craniopharyngiomas (CP), rare pituitary-related tumours, are difcult to excise without unacceptable life-limiting neuro-endocrine morbidity. We aimed to assess whether morbidity has reduced at our centre by a more conservative age- and risk-based surgical + /- radiation strategy adopted over 12-years since our previous 1996 (de Vile et al) series in line with later 2005 (Spoudeas et al) UK consensus guidance. METHOD: Retrospective case-note analysis of 40patients (18 males) diagnosed with CP between 01/01/1998 and 01/01/2010 at mean (95%CI) age 8.6(7.2-10.0) years and followed for 6.0(4.8-7.2)years. Patients underwent either complete (GpA N8), incomplete (GpB N15), or non-debulking (cystic aspiration) resection (GpC N16) + /- radiation. 24/40 received up-front focal adjuvant radiation for residual tumour and in one a watch and wait strategy was adopted. Neuro-endocrine outcomes were assessed with a morbidity score and compared to our previous primary surgical strategy series. RESULTS: 19(48.7%) patients recurred, (14/31 with and 5/8 without residual; 9/24 with and 10/15 without radiation). 5-year EFS was 45%. Patients were already heavy at diagnosis (mean BMI 0.86sds), but increased further (to 2.07sds) with time gaining 1.21sds (95%CI 0.72-1.69;p , 0.0005), equivalent to 0.2sds per year of follow-up, especially after multiple debulking surgeries ( p 0.157 for trend) or complete tumour resection (GpA;p 0.351). 9 patients were hyperphagic, 8 sleep-disordered, 3 had temperature dysregulation and 8 registered blind or partially-sighted. All 40(100%) had one or more endocrinopathies, most commonly GHD (97.5%) and least commonly DI (55.0%) and ACTH deciency (72.5%). 27.5% were receiving school support. Compared with our previous 1996 series, recurrence rates (49% vs. 41%) are similar with a signicant reduction in life-threatening DI (55% vs. 80%) and ACTH deciency (72% vs. 85%). Obesity however remains a problem, set at diagnosis. CONCLUSION: Our single centre series data support the UK 2005 consensus risk-based approach with early radiation to reduce unacceptable morbidity without compromising survival or its quality.

CR-11. DETAILED NEUROPSYCHOLOGICAL, ACTIVITY OF DAILY LIVING AND ENDOCRINE FUNCTION ASSESSMENT IN CHILDREN WITH CRANIOPHARYNGIOMA TREATED WITH HIGH PRECISION FOCAL RADIOTHERAPY: DATA FROM A PROSPECTIVE TRIAL Rakesh Jalali1, Tejpal Gupta1, Savita Goswami1, Nalini Shah2, and Nayana Golambade1; 1Tata Memorial Centre (NeuroOncology), Mumbai, India; 2KEM Hospital (Endocrinology), Mumbai, India BACKGROUND: To report prospective detailed outcome data in young patients with residual/recurrent craniopharyngioma treated with highprecision focal radiotherapy (RT). METHODS: 71 patients (48 males, 23 females; median age-13 years) underwent prospective detailed serial evaluation of neurocognitive, modied Barthels index (BI), LOTCA and neuroendocrine function at baseline and follow-up after RT. RESULT: Majority

CR-13. PROTON RADIOTHERAPY FOR PEDIATRIC CRANIOPHARYNGIOMAS: INITIAL RESULTS Michael Confer1, Rene McNall-Knapp1, Sowmya Krishnan1, Naina Gross1, and Sameer Keole2; 1University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2ProCure Proton Therapy Center, Oklahoma City, OK, USA PURPOSE/OBJECTIVE(S): Craniopharyngiomas are benign, epithelial tumors arising from remnants of Rathkes pouch frequently treated successfully with limited surgery and post-operative radiation therapy. Despite the numerous documented dosimetric advantages of proton therapy for pediatric

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craniopharyngiomas, there remains a paucity of clinical data of patients treated with particle therapy. We report the preliminary clinical outcomes of pediatric patients treated with proton therapy at ProCure Proton Therapy Center in Oklahoma City. MATERIALS/METHODS: All pediatric patients with biopsy-conrmed craniopharyngioma treated at ProCure were identied and retrospectively reviewed. All patients had undergone either biopsy and decompression or subtotal resection prior to proton radiotherapy. Plans utilized 3-4 treatment ports, with a median of 2 elds treated daily. Surveillance imaging, typically weekly, was performed throughout radiotherapy to monitor potential cyst volume changes. Post-therapy MRIs were performed 4 weeks following the completion of proton radiotherapy and then quarterly. RESULTS: Thirteen pediatric patients (7 subtotal resection, 6 biopsy and decompression) received post-operative proton radiotherapy. Treatment was administered at 1.8 cobalt-Gray equivalents (CGE) per fraction to a median of 50.4 CGE (range 50.4-54). Two patients, one subtotal resection and one biopsy and decompression only, required replanning during treatment due to cyst expansion. Both patients, at median of 4.7 months post-radiotherapy, required cyst decompression for symptomatic growth. With median follow-up of 8.4 months, all patients are alive and 11 patients (85%) demonstrate no evidence of recurrence or cyst expansion. Treatment was well tolerated with no grade 3 toxicities and one grade 2 headache during treatment. No patient has developed new endocrinopathy post-radiotherapy. CONCLUSIONS: Proton radiotherapy is an effective post-operative treatment modality for pediatric patients with craniopharyngioma after limited surgery. Therapy is well tolerated with minimal acute side effects and no late toxicity to date. Patients with cyst growth during treatment appear to be at highest risk for post-treatment cyst expansion.

1998-2008 (p 0.004). There is a survival advantage for children who have had a total or near total ( . 90%) resection (p 0.047) and a nonsignicant trend towards improved survival in those receiving radiotherapy (p 0.178). CONCLUSION: Our study shows that patients with craniopharyngioma continue to present many challenges in relation to their survival outcomes, both in the short to medium term but also in the very long term. The role of chemotherapy in the setting of craniopharyngioma is worthy of wider discussion in both the national and international settings. Our 50-year experience treating children with craniopharyngioma in a population-based setting may have implications for the current treatment recommendations for craniopharyngioma in young children.

CR-15. DISEASE CONTROL FOR PEDIATRIC CRANIOPHARYNGIOMA: DOES SURGICAL APPROACH IMPACT OUTCOME? Erin Kiehna1, Edward Laws2, Edward Oldeld1, and John Jane, Jr1; 1 University of Virginia, Charlottesville, VA, USA; 2Brigham and Womens, Harvard, Boston, MA, USA OBJECTIVE: Although pediatric craniopharyngioma has traditionally been treated via transcranial approach, there is growing acceptance of transsphenoidal resection (TSR). While TSR for small craniopharyngiomas can reduce overall morbidity, it remains to be demonstrated whether this is an appropriate management strategy for giant craniopharyngiomas. This study reports outcomes of a consecutive series of pediatric craniopharyngioma patients treated via TSR at a single institution with the goal of dening a risk-based treatment algorithm. METHODS: Thirty pediatric patients (age , 21) with pathologically consistent craniopharyngioma underwent TSR at UVA between 1993-2011 (mean follow-up 40 months). Medical records and imaging were retrospectively reviewed. Tumors were stratied based on degree of hypothalamic involvement. Disease control and clinical outcomes were analyzed. RESULTS: Fifteen patients had pre and postoperative imaging available for retrospective review. Five patients had small tumors without hypothalamic involvement; four had gross total resections (GTR) with one recurrence treated with another TSR GTR; one underwent fenestration and radiosurgery with stable disease. 80% have panhypopituitarism. Five patients tumors displaced the hypothalamus without inltration, all underwent attempted GTR; three are disease free (one with adjuvant radiosurgery), one experienced disease progression, underwent a second TSR and is disease free, one has stable residual tumor. 80% have panhypopituitarism. Five patients tumors had hypothalamic involvement; two underwent GTR and remain disease free, two underwent near total resections followed by conformal radiation with stable disease, one underwent subtotal resection and proton beam radiation with stable disease. 80% have panhypopituitarism. Whether primary or recurrent disease, TSR resulted in disease control. CONCLUSIONS: The transsphenoidal approach for pediatric craniopharyngioma is an effective operative strategy with a high rate of gross total resection and visual improvement with a low risk of recurrence. The cost is overwhelming panhypopituitarism. The transsphenoidal approach should be considered in pediatric patients with craniopharyngioma, including large tumors with hypothalamic involvement.

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CR-14. OUTCOMES FOR CRANIOPHARYNGIOMAS DIAGNOSED IN THE NORTH WEST REGION OF THE UK DURING 1954-2008 Danielle Ormandy1, Robert Alston2, Ian Kamaly-Asl3, Rao Gattamaneni4, Jillian Birch2, and Edward Estlin4; 1University of Manchester Medical School, Manchester, Greater Manchester, UK; 2Cancer Research UK Paediatric and Familial Cancer Research Group, University of Manchester, Manchester, Greater Manchester, UK; 3Department of Paediatric Neurosurgery, Royal Manchester Childrens Hospital, Manchester, Greater Manchester, UK; 4Dept of Paediatric Oncology, Royal Manchester Childrens Hospital, Manchester, Greater Manchester, UK BACKGROUND: Craniopharyngioma constitutes approximately 3-4% of all CNS tumours. They are the most common non-glial tumour of childhood, accounting for 8-9% of paediatric CNS tumours. They present many challenges in terms of treatment and survivorship issues. This study was undertaken to provide further insight into the epidemiology, natural history, treatment and outcomes over the last 56 years in the northwest of England. METHOD: Data relating to presentation, management and survival for 82 patients diagnosed under 15 years of age with a craniopharyngioma between the years 1954-2008, was extracted from the records of Manchester Childrens Tumour Registry and local hospitals. RESULTS: The most common symptoms were headache (71%), visual disturbance (69%) and vomiting (51%). The overall ve-year survival (OS) was 82% (95% CI 73-91%), with event-free survival of 63% (95% CI 53-75%). The 10 year OS was 73% with OS at 20 and 40 years of 62% and 52% respectively. 20-year OS for males was 70% whilst for females it was 55% (p 0.002). Survival has improved over time with 57% ve-year OS for cases diagnosed 1954-1964 but 100% ve-year OS for those diagnosed

NEURO-ONCOLOGY

JUNE 2012

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