Large volume reirradiation as salvage therapy for glioblastoma after progression on bevacizumab.

Outcomes after bevacizumab failure for recurrent glioblastoma (GBM) are poor. Our analysis of 16 phase II trials (n = 995) revealed a median overall survival (OS) of 3.8 months (±1.0 month SD) after bevacizumab failure with no discernible activity of salvage chemotherapy. Thus, the optimal treatment for disease progression after bevacizumab has yet to be elucidated. This study evaluated the efficacy of reirradiation for patients with GBM after progression on bevacizumab. An IRB approved retrospective (2/2008-5/2013) analysis was performed of 23 patients with recurrent GBM (after standard radiotherapy/temozolomide) treated with bevacizumab (10 mg/kg) every 2 weeks until progression (median age 53 years; median KPS 80; median progression free survival on bevacizumab 3.7 months). Within 7-14 days of progression on bevacizumab, patients initiated reirradiation to a dose of 54 Gy in 27 fractions using pulsed-reduced dose rate (PRDR) radiotherapy. The median planning target volume was 424 cm(3). At the start of reirradiation, bevacizumab (10 mg/kg) was given every 4 weeks for two additional cycles. The median OS and 6 month OS after bevacizumab failure was 6.9 months and 65 %, respectively. Reirradiation was well tolerated with no symptomatic grade 3-4 toxicities. Favorable outcomes of reirradiation after bevacizumab failure in patients with recurrent GBM suggest its role as a treatment option for large volume recurrences not amenable to stereotactic radiosurgery. As PRDR is easily accomplished from a technological standpoint, we are in the process of expanding this approach to a multi-institutional cooperative group trial.