In a single-center Canadian phase II trial (UNITED) reported in The Lancet Oncology, Detsky et al found that magnetic resonance imaging (MRI)-guided adaptation of radiotherapy allowed margin de-escalation and resulted in a low rate of marginal failure in patients with high-grade glioma.
Study Details
In the study, 98 patients enrolled at Sunnybrook Health Sciences Centre, Toronto, between April 2021 and May 2023 were planned for concurrent daily chemoradiotherapy up to 60 Gy in 30 daily fractions over 6 weeks (long course) or 40 Gy in 15 daily fractions over 3 weeks (short course). A 5-mm clinical target volume was used, with the allowance for associated T2-weighted fluid-attenuated inversion recovery hyperintense regions in an individualized manner at the discretion of the treating physician. All patients received 1.5 T MRI-guided linear accelerator (MR-Linac), incorporating weekly gadolinium-enhanced online adaptive fractions. The primary outcome of the study was the risk of marginal failure, with a noninferiority margin of 10% based on historical controls.
Key Findings
A total of 59 patients (60%) received long-course radiotherapy and 39 (40%) received short-course radiotherapy.
After a median follow-up of 14.2 months (interquartile range = 8.9–19.7 months), the incidence of marginal failure was 4% (95% confidence interval = 0%–8%). Of the four patients with marginal failure, three (5%) had received long-course radiotherapy and one (3%) had received short-course radiotherapy.
The most common grade 3 or 4 adverse events were lymphopenia (observed in 11% of 72 patients without baseline lymphopenia) and thrombocytopenia (occurring in 4% of 98 patients). Serious adverse events occurred in one patient (1%; febrile neutropenia). No treatment-related deaths were reported.
The investigators concluded: “MRI-guided adaptation for glioblastoma enables margin de-escalation and resulted in a low rate of marginal failure. 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.”
Jay Detsky, MD, PhD, of the Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The investigators reported that there was no external funding for the study. For full disclosures of the study authors, visit thelancet.com.
