Fractionated reirradiation of recurrent high-grade gliomas: Safety with higher reirradiation dose and larger targets.

Background: The optimal regimen, normal tissue tolerances, and appropriate indications for reirradiation for recurrent high-grade glioma (HGG) are uncertain. The aim of this study was to determine whether higher reirradiation dose was associated with toxicity or survival.

Methods: Patients with HGG treated with fractionated reirradiation at a single institution from 2007 to 2022 were retrospectively reviewed. Metrics evaluated included overall survival (OS), prognostic factors for survival, and treatment-related toxicity.

Results: Two hundred and thirty patients with recurrent HGG were reviewed. Median follow-up was 8.8 months. Median reirradiation dose was 41.4 Gy with 80.4% receiving concurrent systemic therapy. Median cumulative maximum doses to brainstem and optic structures were 77.9 Gy (range: 4.6-146.0 Gy) and 55.1 Gy (3.3-106.3 Gy), respectively. No injuries to these structures were identified. Radiation necrosis (RN) was identified in 9.4%. There were no significant associations between RN and target size, systemic therapy use, or reirradiation dose. Median OS was 10.2 months from reirradiation start. On multivariate analysis, improved OS was associated with better KPS, longer interval between radiotherapy sessions, reirradiation at first recurrence, and reirradiation dose ≥ 41.4 Gy. Median OS for those with IDH wildtype glioblastoma was 8.7 months. On multivariate analysis of an IDH wildtype disease subanalysis, improved OS was associated with longer interval between radiotherapy sessions and higher reirradiation dose.

Conclusions: These data support the safety and efficacy of fractionated reirradiation for recurrent HGG. They suggest higher reirradiation dose may be feasible, including for large treatment volumes and for tumors near the brainstem or optic structures.