Introduction

In a groundbreaking development presented at the 2024 American Society for Radiation Oncology Annual Meeting (ASTRO), researchers revealed that online MR-Linac (MRL) adaptive radiotherapy combined with concurrent temozolomide (Temodar) is not only safe but also feasible for patients battling high-grade glioma. The phase 2 UNITED trial (NCT04726397) demonstrated that this innovative treatment approach significantly reduced clinical target volume (CTV) margins and minimized exposure of normal brain tissue, a crucial advantage emphasized by the study's findings.

Trial Overview

The trial enrolled 108 participants, with 98 patients adhering to the treatment protocols. Spanning from April 2021 to May 2023, all participants had IDH-wildtype glioma, a specific and aggressive type of brain tumor. Among this group, 59 patients underwent long-course radiotherapy at a cumulative dosage of 60 Gy in 30 fractions, while 39 others received a shorter regimen at 40 Gy in 15 fractions. Notably, most patients had MGMT methylated disease (52 patients), signaling a favorable response prognosis compared to MGMT unmethylated (41 patients) and indeterminate cases (5 patients).

Results

The study reported an impressively low marginal failure rate of only 4% (n = 4/98) after a minimum follow-up of one year, which indicates non-inferiority compared with historical failure rates (P < .001). Furthermore, the data revealed that among patients experiencing radiographic failure, a staggering 81% also had central failure components, underscoring the need for vigilant monitoring.

Adaptive Radiotherapy Impact

The transition to adaptive radiotherapy led to an astounding mean reduction of 40% in treated CTV margins compared to the European Organisation for Research and Treatment of Cancer (EORTC) standard of 15 mm. Even more compelling, the adaptive method reduced treatment volume by 71% versus the Radiation Therapy Oncology Group (RTOG) standard, which involves T2-weighted fluid-attenuated inversion recovery (FLAIR) plus an additional 2 cm. This substantial reduction could herald a new era of treatment protocols aimed at preserving healthy brain tissue.

Clinical Outcomes Comparison

When comparing clinical outcomes, patients receiving long-course radiation therapy exhibited a median progression-free survival (PFS) of 11.6 months—outshining previous cohorts such as the phase 3 SPECTRO GLIO study, which recorded a PFS of 9.2 months for patients treated under standard margins. The overall survival (OS) rates were similarly close but did not show statistically significant differences (18.5 months in the UNITED trial vs. 20.5 months in SPECTRO GLIO, P = .53). In the short-course radiation group, the median PFS was 6.8 months in the UNITED population, as opposed to 5.3 months from earlier studies. The OS median was reported at 10.6 months compared to 9.3 months in previous trials. While these findings are promising, they highlight the urgent need for further research on long-term outcomes and quality-of-life indices associated with this new treatment protocol.

Expert Commentary

Dr. Jay Detsky, a leading researcher on the trial and assistant professor in the Department of Radiation Oncology at the University of Toronto, emphasized the significance of these results. 'This is the first trial to investigate MR-guided adaptive online radiation with reduced margins. We have demonstrated that it is safe and feasible; however, the ultimate question remains whether these changes improve quality of life and decrease toxicity, something that a randomized trial will better clarify.'

Ongoing Research

In parallel with the trial, ongoing studies are focusing on standardizing FLAIR usage beyond 5 mm and are investigating tumor dynamics alongside advanced imaging biomarkers to enhance treatment personalization and effectiveness.

Conclusion

Utilizing a pre-planned reference alongside MR simulation, the patients in this trial were treated using a state-of-the-art 1.5 Tesla integrated MR-Linac device. The CTV considered the gross tumor volume (GTV), comprising the surgical cavity and any residual tumor, adjusted with a 5 mm margin, while anatomical barriers were also taken into account by radiation oncologists as necessary. As the cancer research community eagerly awaits further results, adaptive MR-guided radiotherapy is quickly emerging as a potential game-changer in the fight against high-grade gliomas. Could this innovative treatment redefine how we approach brain cancer? Stay tuned for updates as researchers continue their quest to improve patient outcomes!