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Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.

Background Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results. Methods Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas. Results Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%. Conclusion The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).

INTRODUCTION The efficacy of chemotherapy in recurrent ependymoma is unclear. We present results from the German HIT-REZ-studies. METHODS 137 patients were analyzed regarding the treatment with chemotherapy at first recurrence, the time from first relapse to progression (PFS) and to either time-point of death or last follow-up (OS). Tumor response evaluation was based on MRI and clinically; molecular data was available in 80. RESULTS In our cohort, 96 patients (20 supratentorial, 73 infratentorial, 3 spinal) received chemotherapy during first recurrence: 49 (51.0%) temozolomide (TMZ) monotherapy, 12 (12.5%) HIT-SKK regime, 9 (9.4%) carboplatin/etoposide (CE) and 26 (27.1%) other combinations. In 19.8% (26.5% in TMZ), chemotherapy was administered prior to surgery (neoadjuvant), which resulted in tumor progression in 78% (85% in TMZ). Gross-total resection was achieved in 86% without neoadjuvant chemotherapy and in 74% (69% in TMZ) with neoadjuvant treatment. Switching to trofosfamide/etoposide (TE) after surgery and unresponsiveness to TMZ showed further progression in all cases of tumor-residuum after surgery. Regarding 1-year-PFS, treatment with HIT-SKK (50.0%±14.4%) or CE (55.6%±16.6%) was advantageous over TMZ (30.2%±6.7%). However, 5-y-OS was lower in CE (19.0% ±16.8%) than in TMZ (39.8%±7.7%) and HIT-SKK (42.9%±8.7%). Long-term control was seen in individual cases of TMZ, HIT-SKK and CE, with TMZ providing longest response of 72 months. CONCLUSION Neoadjuvant TMZ has no significant advantage regarding PFS. However, in few cases chemotherapy prevented progression after incomplete resection. Difficulties in response evaluation and variability in therapies hinder conclusions. Supported by the German Children’s Cancer Foundation

BACKGROUND: In pediatric patients with medulloblastoma (MB) the 5-year-OS rate dependent on risk group is 35% to 90%. In unresectable or metastatic recurrence longterm prognosis is poor. Aim of this study was to evaluate the role of irradiation in relapsed MB patients registered in the German studies HIT-MED, HIT-REZ-97/-2005 and HIT-REZ-Registry between July 1997 and December 2016. METHODS: Data analyzed at relapse were age, gender, stage, primary/relapse therapy, and follow-up. Kaplan-Meier analysis and log rank test were used to estimate the PFS/OS after 1(st) recurrence and (re)irradiation. RESULTS: 257 patients with recurrent/refractory MB [75 female/182 male, median age 11.0 years (0.8-37.9), median PFS after 1(st) diagnosis 24.8 months (2.6-270.2), 81% metastatic disease at relapse] were included in this analysis. Median PFS and OS after first relapse were 12.3 months (95%CI: 9.4;15.2) and 23.8 months (95%CI: 19.3-28.3), the 5-year-PFS and 5-year-OS rate were 6.8%±1.7% and 19.3%±2.7%, respectively. The PFS and OS differed significantly between 4 different cohorts: patients (A) with 1(st) irradiation at 1(st) relapse (n=29), (B) with re-irradiation (n=54), (C) without re-irradiation at 1(st) relapse (n=164), and (D) without irradiation at any time (10). The best 5-year-PFS and 5-year-OS rate were observed in cohort A with 20.1% ±7.8 and 34.2% ±9.3, respectively. Looking for different strata significant differences were seen in patients with metastatic disease. CONCLUSIONS: Radiotherapy at relapse can be used as salvage therapy in patients without primary irradiation. It can lead to prolonged PFS and OS especially in patients with metastatic disease. Supported by German Children’s Cancer Foundation.

RO-23. RECURRENT EPENDYMOMA A CHALLENGING THERAPY: RE-IRRADIATION PROLONGS SURVIVAL IN FAILURE OF RADICAL RESECTION Stephan Tippelt1,RuthMikasch1,Monika Warmuth-Metz5,Torsten Pietsch7, Robert Kwiechien3, Andreas Faldum3, Stefan Rutkowski2, Katja Von Hoff2, Martin Mynarek2, Udo Bode4, Nele Siegler1, Gudrun Fleischhack1, and Rolf-Dieter Kortmann6; University Hospital Essen, Pediatric Hematology and Oncology, Essen, Germany; University Hospital Hamburg, Pediatric Hematology and Oncology, Hamburg, Germany; University Munster, Institute of Biostatistics and Clinical Research, Munster, Germany; University of Bonn, Childrens Hospital, Pediatric Hematology and Oncology, Bonn, Germany; University of Wuerzburg, Neuroradiology, Wurzburg, Germany; University of Leipzig, Department of Radiotherapy and Radioonkology, Leipzig, Germany; University of Bonn, Medical Center, Institute of Neuropathology, Bonn, Germany INTRODUCTION: In pediatric patients with ependymoma the 10-year overall survival (OS) rate is 64% with poor 5-year OS rates of only 42-55% in infancy. Beside maximal radical resection local radiotherapy is standard of care; chemotherapy is controversially discussed. In recurrence treatment options are rare. Re-resection with maximal radical intense is indicated in local relapses. In unresectable or metastatic disease longterm prognosis is fatal. Merchant et al. and others showed prolonged OS rates after re-irradiation even in metastatic disease. PATIENTS AND METHODS: From 55 patients of the German HIT2000 and HIT-REZ study cohort with recurrent ependymomaswhoreceivedre-irradiationdataasage; stageofdisease; time and extent of surgery; time, dose and volume of radiotherapy; time and kind of chemotherapy at primary diagnosis and relapse; date and disease state at last follow up and causes of death were analyzed. OS time was estimated based on Kaplan–Meier-analysis and compared to a cohort of 40 patients without re-irradiation. RESULTS: The 55 patients (74% male) with a median age at primary diagnosis/first recurrence of 5.4/8.4 years showed metastatic disease at recurrence in 47% and a median time to first progression of 22 months. Median OS after first relapse was 31 (CI 21-41) months with 5-year-OS rate of 33%. In comparison to the cohort without re-irradiation significant better 5-year-OS rate was observed in patients with residual tumor at time of re-irradiation (40 vs. 8%). CONCLUSION: Re-irradiation can lead to prolonged survival if radical surgery is impossible and is highly recommended in these cases. Neuro-Oncology 18:iii159–iii164, 2016. doi:10.1093/neuonc/now082.23 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.