Single-center phase 2 trial of MRI-guided adaptive radiotherapy for high-grade glioma

Radiotherapy volumes for patients with glioblastoma (GBM) have remained unchanged for decades and result in large volumes of irradiated brain. The phase 2 UNITED trial, at Sunnybrook Health Sciences Centre (Toronto, ON, Canada) evaluated the safety of a small-margin, MRI-guided adaptive radiotherapy approach for GBM. The trial included adult patients (ECOG performance status ≤ 2; life expectancy > 12 weeks) who were planned for concurrent daily chemoradiotherapy up to 60 Gy in 30 daily fractions over 6 weeks (long course; n=59) of 40 Gy in 15 daily fractions over 3 weeks (short course; n=39). A 5 mm clinical target volume was applied, with the allowance or associated T2-weighted fluid-attenuated inversion recovery hyperintense regions in a personalized way at the discretion of the treating physician. The patients were treated with 1.5 T MRI-guided linear accelerator incorporating weekly gadolinium-enhanced online adaptive fractions. The primary outcome was the risk of marginal failure powered for non-inferiority with a margin of 10% compared with a historical control. Median follow-up was 14.2 months. The observed risk of marginal failure was 4% (95% CI 0-8). The most common grade 3-4 adverse events were lymphopenia (11% in patients without baseline lymphopenia) and thrombocytopenia (4%). Serious adverse events occurred in one patient due to febrile neutropenia; there were no treatment-related deaths. The authors conclude that MRI-guided adaptation for GBM enabled margin de-escalation and resulted in a low rate of marginal failure.