Hypofractionated Proton Reirradiation for Recurrent Glioblastoma: Clinical and Dosimetric Outcomes from a Large Single Institution Series.

Abstract

Management of recurrent glioblastoma remains a major challenge, with no treatment shown to meaningfully prolong survival. Reirradiation may offer local control but is often constrained by concerns regarding dose to critical normal tissues. We evaluated clinical outcomes, toxicity, and cumulative dosimetric parameters in patients with recurrent glioblastoma treated with hypofractionated proton reirradiation. We retrospectively identified patients with recurrent glioblastoma treated with hypofractionated reirradiation courses of 35 Gy in 10 fractions. Cumulative composite dosimetry was calculated using EQD2 (α/β = 2) for organs at risk (OARs). Overall survival (OS) was estimated using Kaplan Meier methods. Cox proportional hazards modeling was performed to identify factors associated with OS. A contemporaneous cohort treated with hypofractionated photon reirradiation was identified for comparison. A total of 89 patients were treated with hypofractionated proton reirradiation for recurrent glioblastoma between 2015 and 2025 with median follow up of 7.2 months. Median age was 58 years (IQR 48-68), and 48% underwent reresection prior to reirradiation. Composite dosimetry demonstrated that the initial radiation course accounted for the majority of cumulative OAR dose, with proton reirradiation contributing limited additional exposure. Median OS from reirradiation in the proton cohort was 8.3 months (95% CI 6.27-9.47), with 6 and 12 month OS of 62.6% and 24.9%, respectively. On multivariable analysis, increasing age was independently associated with worse OS. A comparator cohort of 49 patients treated with photon reirradiation was identified. OS did not differ between proton and photon reirradiation cohorts. 8 (5.8%) patients experienced Grade 3 or 4 radiation necrosis. No Grade > 4 toxicities were observed. Hypofractionated proton reirradiation was feasible and associated with favorable toxicity outcomes, supporting its use as a retreatment option. Prospective studies are needed to further define optimal patient selection.