Purpose/Objective(s): Recurrent high-grade gliomas (HGG) have limited treatment options. Both re-irradiation (reRT) and bevacizumab have been used as salvage treatment with limited success. Our institutional practice is to reserve reRT for bevacizumab failure to minimize the risk of radiation toxicity. This report summarizes efficacy of reRT, post-bevacizumab salvage chemotherapy (PBSC) with or without subsequent reRT, or best supportive care (BSC) for high-grade gliomas that progressed on salvage bevacizumab. Materials/Methods: A total of 86 patients were treated for recurrent highgrade gliomas between 2012 and 2016. Patients with prior pathological diagnosis of glioma, prior course of RT, and pathological or radiographic evidence of progressive high-grade disease after salvage bevacizumab were included in this retrospective study. A total of 71 patients received a median of 2 (range 1-5) salvage systemic chemotherapy agents prior to bevacizumab. Prognostic factors and outcomes were abstracted from our institution's electronic medical record. Results: Initial histologic grade was II in 16 patients, III in 18 patients, and 4 in 52 patients. Median age at initial diagnosis was 55 years. Chemotherapeutic agents used prior to bevicizumab included temozolomide, procarbazine, carboplatin, lomustine, carmustine, PCV, and imatinib. Thirteen of 21 BSC patients received a median of 1 chemotherapy agent prior to bevacizumab (range 1-3). Twenty-nine of 36 PBSC patients received a median of 2 chemotherapy agents prior to bevacizumab (range 1-5). Twenty-seven of 28 reRT patients received a median of 2 chemotherapy agents prior to bevacizumab (range 1-4). Median PFS after bevacizumab failure was 2.6 months (1.5 months BSC, 3.0 months for those receiving PBSC with or without subsequent reRT, and 3.1 months for immediate post-bevacizumab reRT (pZ0.0001)). All PBSC patients went on to receive a median of 2 chemotherapy agents (range 1-3) after first progression. Eighteen of 36 also eventually received reRT after PBSC. After reRT, 27 of 28 patients received a median of 1 chemotherapy agent (range 1-2) and 4 patients were treated with an Optune device. Median overall survival from bevacizumab failure was 2.0 months BSC, 6.4 months PBSC, 8.6 months PBSC followed by reRT, and 5.7 months reRT (p<0.0001). Conclusion: Compared to reports in which reRT is used earlier in the course of disease progression, progression-free survival in this cohort of heavily pre-treated high-grade glioma patients is limited. However, reirradiation as well as post-bevacizumab salvage chemotherapy may be associated with improved patient survival when compared to best supportive care even late in the course of disease progression in high-grade glioma.
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