1. Hypofractionated vs. Standard Radiotherapy with or without Temozolomide for Older Patients with Glioblastoma Shyam K. Tanguturi MD, Ayal A. Aizer MD MHS, Patrick Y. Wen MD, David A. Reardon MD, Eudocia Q. Lee MD MPH, Lakshmi Nayak MD, Laura W. Christianson BA, Margaret C. Horvath BS, Ian F. Dunn MD, Alexandra J. Golby MD, Mark D. Johnson MD PhD, Elizabeth B. Claus MD PhD, Ennio A. Chiocca MD PhD, Keith L. Ligon MD PhD, Brian M. Alexander MD MPH, Nils D. Arvold MD

2. Background and Methods Glioblastoma (GBM) has poor prognosis among older patients, and shorter treatment duration has not been compared to standard therapy We examined 135 consecutive patients ≥ 65 y.o. with GBM treated at BWH/DFCI from 1994-2013 who received either: Hypofractionated radiotherapy (HRT) over 3 weeks +/- concurrent TMZ Standard fractionated radiotherapy (SRT) over 6-6.5 weeks +/- concurrent TMZ

3. Baseline Characteristics HRT (n = 9) HRT+TMZ (n = 34) SRT (n = 35) SRT+TMZ (n = 57) P Age, yrs (median)79787068<.001 KPS (median)507080 <.001 Year of diagnosis (median) 2009 20002011<.001 Tumor size, cm (median)5.14.444.3.33 Gross total resection33%24%31%25%.80 MGMT methylated10%29%0%23%.55 EGFR amplified44%24%11%23%.08 Significantly older age, lower KPS, and earlier year of diagnosis among HRT±TMZ patients, compared to SRT±TMZ

4. Overall Survival HRTHRT+TMZSRTSRT+TMZ Median OS (mo)4.19.69.511.1 MVA No significant OS difference between HRT+TMZ and SRT+TMZ (HRT+TMZ: HR 0.83; 95% CI, 0.45-1.55; P =.56) Older age, lower KPS, tumor multifocality, HRT alone, and SRT alone significantly associated with lower OS Propensity Score (PS) Analysis: TMZ Arms Only PS based on age, extent of resection, and KPS No significant OS difference between HRT+TMZ and SRT+TMZ (HRT+TMZ: HR 1.59; 95% CI, 0.59-4.26; P =.78)

5. Conclusions HRT+TMZ and SRT+TMZ had similar OS after adjusting for prognostic factors Suggests that with TMZ, the RT duration may be reduced by half (3 weeks) with no OS decrement, among older GBM patients Should be explored in randomized setting