Prospective randomized phase 2 trial of hypofractionated stereotactic radiotherapy in the re-irradiation of recurrent glioblastoma

Full text: Introduction: Recurrent Glioblastoma (GBM) remains a challenging disease with poor outcomes. Reirradiation is an option for selected cases of focal recurrent GBM with good performance. Hypofractionated Stereotactic Radiotherapy (HSRT) has been shown to potentially improve local control, preserve quality of life, and reduce treatment-related toxicity, but the optimal treatment regimen remains unclear. To the best of our knowledge, no prospective randomized trial investigated the ideal reirradiation dose fractionation for recurrent GBM. Purpose: To investigate if reirradiation of recurrent GBM with HSRT alone 35 Gy in 5 fractions (35Gy/5fx) compared to 25 Gy in 5 fractions (25Gy/5fx) improves outcomes while maintaining acceptable toxicity. Methods: We conducted a randomized prospective phase 2 trial involving patients with recurrent GBM. A minimum interval from first radiotherapy of 5 months and gross tumor volume of 150cc were required. Patients were randomized 1:1 to receive HSRT alone 25Gy/5fx or 35Gy/5fx. The primary endpoint was progression-free survival. Secondary end-points were overall survival (OS), toxicity and quality of life as reported by the FACT-Br questionnaire. This trial is registered at ClinicalTrials. gov NCT01464177. Results: From 2011 to 2019, 40 patients were randomized and received HSRT, 20 in each group. The median age was 50 years (IQR, 42 to 57). The median PFS in the 25Gy/5fx group was 4.9 months vs.5.3 months in the 35Gy/5fx group (p=0.23). The median OS in the 25Gy/5fx group was 9.2 months vs. 10 months in the 35Gy/5fx group. Treatment-related necrosis was numerically higher in the 35Gy/5fx group (4 (21%) vs. 2 (10%)), but without statistical significance (p=0.339). In an exploratory analysis, the median OS of patients that developed radiation necrosis was 14.1 months vs. 8.8 months in patients that did not (p=0.07). We did not detect a difference in quality of life between groups. Conclusions: In this prospective phase 2 trial, HSRT with 35Gy/5fx was not superior to 25Gy/5fx in terms of PFS or OS. Due to a potential increase in the rate of radiation necrosis, we suggest 25Gy/5fx as the standard dose in HSRT alone. (author)