ESTRO 36 Abstract Book

S331 ESTRO 36 _______________________________________________________________________________________________

and IORT, patients received standard adjuvant therapy, consisting of concomitant external-beam radiotherapy (EBRT; 60 Gy) and temozolomide followed by cycling maintenance temozolomide chemotherapy (5/28 schedule). The primary endpoint was safety as per the occurrence of dose-limiting toxicities (DLT) within 3 months after IORT. Secondary endpoints were progression- free survival (PFS) and overall survival (OS). In addition, we performed an exploratory analysis of the local PFS (defined as tumor recurrence within 1 cm of the resection cavity border). The trial is registered at ClinicalTrials.gov, number NCT02104882. Results Fifteen patients were treated (n=7 at 20 Gy, n=4 at 30 Gy, n=4 at 40 Gy) during surgery. The majority of patients (n=13) underwent incomplete resection. Six patients had unresected multifocal tumors and 3 did not receive per- protocol adjuvant treatment (PPT). Hypermethylation of the MGMT promoter was absent in 10 patients. The median follow-up was 13.8 months. The majority of grade 3-5 adverse events (23 of 27) were deemed related to EBRT, chemotherapy or tumor progression. No DLT occurred and thus the IORT dose was escalated to 40 Gy. Suspected or confirmed radionecrosis was detected in 5 patients of all 3 dose levels. The median PFS was 11.2 months (95%CI: 5.4-17.0) in all and 11.3 months (95%CI: 10.9-11.6) with PPT. The median local PFS was 14.3 m (95%CI: 8.4-20.2) in all and 17.8 m (95%CI: 9.7-25.9) with PPT. The median OS was 16.2 m (95%CI: 11.1-21.4) for all and 17.8 m (95%CI: 13.9-21.7) with PPT. One patient unexpectedly showed distant response of a satellite lesion that was initially not targeted with IORT. Conclusion IORT resulted in a highly relevant increase in PFS and exhibited a manageable safety profile in a cohort with mostly incompletely resected GBM and unfavorable prognostic factors. A multinational randomized phase III trial has been set up to test IORT plus standard of care versus standard of care alone (INTRAGO II; NCT02685605). PO-0633 Randomized study of adjuvant temozolomide (6 vs.12 cycle) in newly diagnosed glioblastoma multiforme A.K. Gandhi 1 , M. Bhandari 1 , D.N. Sharma 1 , P. Julka 1 , G.K. Rath 1 1 All India Institute of Medical Sciences, Radiation oncology, New Delhi, India Purpose or Objective The role of adjuvant temozolomide (TMZ) beyond 6 cycles in newly diagnosed glioblastoma multiforme (GBM) is not clear. We did this prospective randomized study with a hypothesis that E-TMZ for a total of 12 adjuvant cycles would improve survival of patients with newly diagnosed GBM as compared to conventional 6 cycles of TMZ (C- TMZ). Material and Methods Between January 2012 and July 2013, 40 post-operative patients of GBM between age 18-65 years and Karnofsky Performance Score (KPS) ≥ 70 were included. Patients were randomized to receive radiation (60 Gray in 30 fractions over 6 weeks) with concomitant TMZ (75 mg/m 2 /day) and adjuvant therapy with either 6 (C-TMZ arm) or 12 cycles (E-TMZ arm) of TMZ (150-200 mg/m 2 for 5 days, repeated 4 weekly). Toxicity was assessed using CTCAE (common terminology criteria for adverse events) version 3.0. Progression free survival (PFS) was calculated from the time of diagnosis to the time of progression or death. Overall survival (OS) was calculated from the time of diagnosis to the time of death from any cause. Kaplan Meier method was used for survival analysis. P value of < 0.05 was taken as significant and SPSS version 12.0 [SPSS Inc., Chicago, IL, USA] was used for all statistical analysis. All patients signed informed consent before entry into the

study and the study was approved by Institutional ethics committee (IESC/T-027/2011). Results 20 patients were treated in each arm. Median age was 49 years and 44 years and median KPS was 90 and 80 respectively in C-TMZ and E-TMZ arms. Gross total resection was possible in 60% and 55% patients and subtotal resection was done in 40% and 45% patients respectively in C-TMZ and E-TMZ arm. 10 and 9 patients respectively in C-TMZ and E-TMZ arm had grade 2 and no patient suffered from grade 3 non-hematological toxicities. 2 patients each had grade 2 hematological toxicity in C-TMZ (both thrombocytopenia) and E-TMZ arm (one neutropenia and one thrombocytopenia) and 1 patient in E-TMZ arm had grade 4 (neutropenia) hematological toxicity during concurrent radiotherapy. Overall, 0% and 5% respectively in C-TMZ and E-TMZ arm had hematological toxicity ≥ 3 in grade during concurrent phase. Median follow up in C-TMZ and E-TMZ arm were 14.65 and 19.85 months. Median PFS was 12.8 months and 16.8 months in C-TMZ and E-TMZ arm respectively (p=0.069). 2 year PFS was 16.4% vs. 18.7% in C-TMZ and E-TMZ arm respectively (Figure 1). Median OS was 15.4 months vs. 23.8 months in C-TMZ and E-TMZ arm respectively (p=0.044). 2-year OS was 12.9% vs. 35.5% respectively in C-TMZ and E-TMZ arm (Figure 2).

Conclusion The result of our study suggests that E-TMZ is safe, tolerable as well as confers significant survival advantage as compared to conventional duration of TMZ. Pending results from larger, phase III, multi-institutional studies, it appears prudent for us to suggest use of at least 12 cycles of adjuvant TMZ in patients with newly diagnosed GBM.