A Phase 1 Dose-Escalation Trial of Reirradiation for Patients With Recurrent Glioblastoma

PURPOSE: A dose-escalation trial of reirradiation (reRT) was conducted in patients with a diagnosis of recurrent glioblastoma (rGBM) to increase the total overall dose given to the tumor without increasing toxicity. The primary objective of this study was to establish the maximum tolerated dose (MTD) for reRT in patients with rGBM. METHODS AND MATERIALS: A phase 1 dose-escalation study using a "3 plus 3" design aimed at identifying reRT MTD with secondary study endpoints of overall survival, progression-free survival, Health-Related Quality of Life, and neurocognitive outcomes. Patients with histologically proven rGBM, Karnofsky Performance Status ≥70, and >12 months since standard chemoradiation, were enrolled in the study. Patients received daily radiation therapy, 5 fractions per week, with dose levels (DLs) (total radiation dose [Gy]/number fractions): DL1 1(35/10), DL2 (42/12), and DL3 (49/14). Response and progression were defined as per Response Assessment in Neuro-Oncology criteria. Neurocognition and patient-reported outcomes were obtained before reRT, at completion of treatment and at follow-up intervals. RESULTS: Fourteen patients were enrolled (64% male, median Karnofsky Performance Status 80 [range, 70-90], median age 54 [range, 38-65]) in DL1(3), DL2(6), and DL3(5). The median time between upfront radiation therapy to completion of reRT was 47.2 months (range, 12.6-93.5 months) with patients enrolled from 2016 to 2022. Median progression-free survival was 5.09 months (3.5, 7.2, and 5.2 months for DL 1, 2, and 3, respectively). Overall survival was 10.3 months (6.1, 14.4, and 13.3 months for DL 1, 2, and 3, respectively). No treatment-related toxicity was observed for DLs 1 and 2. In DL3, 3 of 5 patients experienced neurologic decline without prior radiographic evidence of tumor and were therefore designated as grade 3 treatment-related toxicity. However, no dose-limiting toxicity was observed at any DL. CONCLUSIONS: Results of the trial reveal 4200 cGy in 12 fractions as the MTD for the group of patients with rGBM.