MRI-Guided Adaptive Radiotherapy Enables Margin Reduction in Adult Patients With Glioblastoma

Clinical Summary:

• Design/Population: This single-arm phase 2 trial evaluated MRI-guided adaptive radiotherapy with reduced treatment margins in newly diagnosed adult patients with glioblastoma receiving concurrent chemoradiotherapy.
• Key Outcomes: MRI-guided adaptive radiotherapy resulted in a low rate of marginal failure with an acceptable safety profile despite reduced clinical target volume margins. 
• Clinical Relevance: These findings support further investigation of MRI-guided adaptive radiotherapy as a strategy to reduce radiation exposure to normal brain tissue while maintaining tumor control.

Results from the phase 2 UNITED trial demonstrated that MRI-guided adaptive radiotherapy with reduced treatment margins was associated with a low rate of marginal failure among adult patients with glioblastoma.

“Radiotherapy volumes for patients with glioblastoma have remained unchanged for decades and result in large volumes of irradiated brain,” stated Jay Detsky, MD PhD, Odette Cancer Centre, Toronto, Canada, and coauthors. “We aimed to show the safety of a small-margin, MRI-guided adaptive radiotherapy approach for glioblastoma.”

In this single-arm trial, 98 adult patients with newly diagnosed glioblastoma received MRI-guided radiotherapy using a 1.5-T MRI-linear accelerator. Patients underwent either long-course (60 Gy in 30 fractions; n = 59) or short-course (40 Gy in 15 fractions; n = 39) chemoradiotherapy. A personalized 5-mm clinical target volume margin was used, with inclusion of fluid-attenuated inversion recovery hyperintense regions at the treating physician's discretion. Weekly gadolinium-enhanced online adaptive planning was incorporated throughout treatment. The primary end point was the risk of marginal failure.

At a median follow-up of 14.2 months, the observed risk of marginal failure was 4%, meeting the prespecified noninferiority objective compared with historical controls.

The most common grade 3/4 adverse events included lymphopenia (11%) and thrombocytopenia (4%). There was 1 serious incidence of febrile neutropenia, and no treatment-related deaths were reported.

“MRI-guided adaptation for glioblastoma enables margin de-escalation and resulted in a low rate of marginal failure,” concluded Dr Detsky et al. “A randomized trial comparing this technique to a standard large-margin radiotherapy approach will establish whether toxicity and quality-of-life improvements can be realized.” 

Source:

Detsky JS, Chan AW, Moore-Palhares D, et al. MRI-guided adaptive radiotherapy for high grade glioma (UNITED): A single-centre, single-arm, non-inferiority, phase 2 trial. Lancet Oncol. Published online: May 14, 2026. doi:10.1016/s1470-2045(26)00088-4