Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma

摘要: Purpose To establish the maximum tolerated dose of a 3-fraction hypofractionated stereotactic reirradiation schedule when delivered with concomitant bevacizumab to treat recurrent high-grade gliomas. Methods and Materials Patients glioma Karnofsky performance status ≥60, history standard fractionated initial radiation, tumor volume at recurrence ≤40 cm 3 , absence brainstem or corpus callosum involvement were eligible. A 3+3 phase 1 escalation trial design was utilized, dose-limiting toxicities defined as any grade 5 possibly, probably, definitely related radiation. Bevacizumab given 10 mg/kg every 2 weeks. Hypofractionated initiated after 2 doses, in fractions other day, starting 9 Gy per fraction. Results total patients enrolled 9 Gy × 3 level cohort, 10 Gy × 3 7 11 Gy × 3 cohort. One toxicity fatigue cognitive deterioration possibly observed this declared combination bevacizumab. Although no symptomatic radionecrosis observed, substantial treatment-related effects necrosis resected specimens. The intent-to-treat median overall survival 13 months. Conclusions Reirradiation using support is feasible reasonably well tolerated. Dose-escalation possible up 11 Gy × 3, which achieves near doubling biological equivalent normal brain, comparison our previous 6 Gy × 5 schedule. Promising warrants further investigation.