Salvage Re-Irradiation for Recurrent High-Grade Glioma and Comparison to Bevacizumab Alone

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High-grade gliomas (HGGs) are the most common lethal primary brain tumor in adults and almost always recur after initial treatment. Despite this, there is little evidence arguing superiority of a single treatment strategy at time of recurrence, with options including supportive care, re-resection, systemic therapy, or re-irradiation. While bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is now commonly used for recurrent HGG, there has been longstanding interest in re-irradiation for patients with local-only recurrence. The purpose of this study is to examine outcomes of patients with recurrent HGG treated with re-irradiation. This is a retrospective analysis of patients with recurrent HGG who received salvage re-irradiation at a major academic institution from 2010-2014, as well as those who received bevacizumab alone. Progression-free survival (PFS) and overall survival (OS) were calculated from date of re-irradiation completion, or date of bevacizumab initiation in the bevaciumab alone cohort. Cox proportional hazards modeling was used to examine factors associated with OS. Propensity score modeling was used to compare survival after re-irradiation vs. bevacizumab alone. Sixty-seven patients received re-irradiation for recurrence, and 177 patients received bevacizumab alone. Among the re-irradiation cohort, 51% received concurrent bevacizumab. Median time in the re-irradiation cohort from initial diagnosis to re-irradiation was 31.4 months. The most common re-irradiation dose/fractionation regimens were 6 Gy x 5 (36%), 3.5 Gy x 10 (21%), 2.67 Gy x 15 (15%), and 18-20 Gy x 1 (15%). No early or late toxicities > grade 2 were observed. Median PFS and OS after re-irradiation were 4.8 months 10.7 months, respectively. Number of progressions prior to re-irradiation (adjusted hazard ratio [AHR], 1.6; 95% CI, 1.1-2.3; P = .007), and recurrence in a new brain location (vs. local-only; AHR, 7.4; 95% CI, 2.4-23.1; P < .001) were associated with OS; dose/fractionation regimen was not. Compared to bevacizumab alone, patients who received re-irradiation had a non-significant increase in OS (HR, 0.80; 95% CI, 0.53-1.23; P = .31). Among patients with local-only recurrence, there was a trend towards longer median OS after re-irradiation compared to bevacizumab alone (12.4 vs. 8.0 months; P = .12). Re-irradiation for recurrent HGG appears safe and was associated with reasonable PFS and OS even as many patients received bevacizumab and had >2 prior progressions. Number of progressions prior to re-irradiation and recurrence location were associated with OS, while dose/fractionation regimen was not. While re-irradiation was not associated with OS benefit in propensity score adjusted analysis compared with bevacizumab alone, there was a trend towards OS benefit in patients with local-only recurrence.