RTRB-03SHORT DELAY IN INITIATION OF RADIOTHERAPY WITH CONCURRENT CHEMOTHERAPY FOR GLIOBLASTOMA: A SECONDARY ANALYSIS OF NRG ONCOLOGY/RTOG 0525 AND 0825

INTRODUCTION: We previously reported the unexpected finding that survival was significantly improved in patients with newly-diagnosed GBM when radiation was initiated later (>4 weeks post-op) compared to earlier (≤2 weeks post-op). That analysis included 2855 patients from 16 RTOG trials conducted prior to the era of concurrent temozolomide (TMZ) with RT. We now report on 1127 patients from two studies involving newly-diagnosed GBM, treated with RT + TMZ followed by adjuvant TMZ. Our hypothesis was that concurrent TMZ has a synergistic/radiosensitizing mechanism, making RT timing less significant. METHODS: Data from patients on both arms of RTOG 0525 and the placebo arm of RTOG 0825 were investigated. An analysis comparable to our prior study was performed to determine whether there was still an impact on survival by delaying RT in the RT + TMZ era. Overall survival was investigated using Cox proportional hazard model. Progression from diagnosis to 30 days after RT completion was analyzed using Chi-square test. RESULTS: 94.9% of the patients started RT 2-5 weeks post-op. Given the small number of patients who started RT early, comparisons were made between >4 and ≤4 weeks delay of radiation. There was no statistically significant difference for overall survival (p-value = 0.29; HR = 0.93; 95% CI: 0.80-1.07) after adjusting for RPA and MGMT methylation status. Similarly, the rate of early progression did not differ significantly (p-value = 0.59). CONCLUSIONS: We did not see a significant prognostic influence of delaying radiation within the range of 2-5 weeks post-op when given concurrently with TMZ for newly-diagnosed GBM. TMZ may "level the playing field" for patients treated with chemoradiation and offset the effect of RT delay that was seen when RT was given alone; however, the effects of early initiation of radiation tested previously could not be replicated. Supported by National Cancer Institute grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422, Merck & Co. and Genentech.