2090 Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma

INTRODUCTION: Recurrent glioblastomas can potentially be treated with hypofractionated stereotactic radiation therapy (HSRT). METHODS: A prospective randomized phase 2 trial involved patients with recurrent glioblastoma (per the 2007 and 2016 WHO classification). A minimum interval from the first radiation therapy of 5 months and a gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS) with a 2-sided ? of 0.15. RESULTS: From 2011 to 2019, 40 patients received HSRT, with 20 in each group. The median age was 50 years (range, 27-71); 75% underwent new resection before HSRT. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P=.23). Six-month PFS was similar at 40% for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P=.201). Grade = 3 necrosis was higher in the 35 Gy/5 fx group (16% vs 5%), but not statistically significant (P=.267). In an exploratory analysis, median OS of patients with treatment-related necrosis was 14.1 months, compared to 8.7 months for those without (P=.003). CONCLUSIONS: HSRT with 35 Gy/5 fx was not superior to 25 Gy/5 fx in PFS or OS. Due to a potential increase in treatment-related necrosis, 25 Gy/5 fx is suggested as the standard dose. Follow-up should differentiate tumor progression from manageable complications.