Introduction

A revolutionary approach to treating high-grade glioma has emerged, and the results are nothing short of promising! The phase 2 UNITED trial (NCT04726397), recently presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, demonstrated that weekly online MR-Linac (MRL) adaptive radiotherapy, combined with the chemotherapy drug temozolomide (Temodar), is both safe and feasible. Most importantly, it significantly minimizes the exposure of normal brain tissue while reducing the clinical target volume (CTV) margins—a major breakthrough in the fight against this aggressive form of brain cancer.

Study Overview

The study involved a cohort of 108 patients who gave their consent, with 98 completing the treatment protocol. Conducted between April 2021 and May 2023, all participants were diagnosed with IDH-wildtype glioma, a common subtype of high-grade glioma. Notably, participants were divided into two treatment groups: 59 patients undergoing long-course radiotherapy at 60 Gy in 30 fractions, and 39 patients receiving short-course radiotherapy at 40 Gy in 15 fractions. The results revealed a diverse group of patients, where 52 had MGMT methylated disease, 41 had MGMT unmethylated disease, and 5 had indeterminate MGMT status.

Results and Findings

After an average follow-up of at least one year, the trial reported a marginal failure rate of just 4% among the patients, indicating a strong efficacy compared to historical data (P < .001). Alarmingly, 81% of those who experienced radiographic failure also had central failure components, highlighting the need for improved strategies.

Furthermore, the adaptive radiotherapy approach led to an extraordinary 40% reduction in treated CTV margins compared to traditional methods. When compared to the European Organisation for Research and Treatment of Cancer (EORTC) protocol, which typically uses a 15 mm margin, this represents a significant advancement in optimizing treatment delivery.

Survival Rates

For those receiving long-course radiotherapy, the median progression-free survival (PFS) recorded in the UNITED trial was 11.6 months, compared to 9.2 months in a contemporary phase 3 study (NCT01507506). Overall survival (OS) rates were similar, with 18.5 months in the UNITED trial versus 20.5 months in the comparison study (P = .53). For short-course patients, median PFS was recorded at 6.8 months—slightly improved from the 5.3 months seen in another historical cohort.

Expert Commentary

Dr. Jay Detsky, associate director of Medical Residency at Odette Cancer Centre, expressed optimism about the initial findings. "This is the first trial to probe MR-guided adaptive online radiation coupled with margin reduction. We’ve shown that it is not only safe but effective, with relatively low rates of marginal failures. One of our key questions moving forward will be whether this approach will improve quality of life and reduce treatment-related toxicity," Detsky commented.

Future Directions

In the pursuit of standardizing treatment, ongoing investigations are looking into tumor dynamics and advanced imaging biomarkers to enhance future protocols further. The study utilized cutting-edge technology, employing a 1.5 Tesla integrated MR-Linac device for precise imaging and treatment planning.

Conclusion

As research continues, this innovative adaptive radiotherapy modality could very well transform the landscape of high-grade glioma treatment, shedding light and hope for patients battling this formidable cancer. Excitingly, with more trials on the horizon, we may soon uncover more about this promising direction in cancer care!