MRI-based adaptive radiotherapy is changing the way we treat brain cancer

As we wrapped up the month of May and Brain Tumor Awareness month, we are taking time to focus and honor those affected by brain tumors, acknowledge the challenges they face, and reaffirm our commitment to advancing treatment and care. As we reflect on this important time, it is vital to highlight the complexity of treating gliomas and to reaffirm Elekta’s commitment to advancing therapies that improve both survival and quality of life (QoL) for those affected.

Among gliomas, glioblastomas (GBMs) are the most aggressive and difficult to treat. These fast-growing tumors infiltrate healthy brain tissue, making it especially challenging to delineate tumor boundaries and deliver effective treatment without harming critical brain structures. This complexity underscores the urgent need for more precise, adaptive approaches to radiation therapy.

A key challenge in using radiation therapy to treat gliomas is balancing the need to eradicate as many tumor cells as possible while protecting healthy brain tissue. To maximize cancer cell killing, radiation is delivered to the tumor (which is localized using imaging studies) as well as an area surrounding the tumor that includes tumor cells that may not appear on imaging and an additional area (known as a margin), which is intended to account for potential variations in radiation delivery during treatment. While this approach reduces the risk of missing tumor cells, it increases the potential to damage healthy tissue, leading to short-term adverse events that can negatively impact patients’ QoL and ability to continue treatment as well as significant long-term consequences. Another challenge is that gliomas move and change shape over the course of treatment, which can lead to misalignment between the treatment plan at the start of radiotherapy and the actual area of the tumor over the treatment period.

As a result, current approaches to ensure complete targeting of brain tumors comes at the expense of unnecessarily dosing healthy tissue in the brain, an organ in which all tissue is considered critical for function. Damaging healthy brain tissue can negatively impact patients’ cognitive and physical function in both the near and long term, which makes preserving healthy tissue an important treatment goal.

Advances in magnetic resonance imaging (MRI)-based adaptive radiotherapy (ART), such as Elekta’s groundbreaking Unity system now make it possible to precisely tune the delivery of radiation during each treatment session to optimize the balance between tumor control and protecting healthy brain tissue. In standard radiation therapy, a treatment plan is developed prior to treatment based on tumor size and location and the desired radiation dose and fractionation schedule. This plan is then administered for the specified number of fractions. In contrast, ART utilizes images taken during the course of treatment to modify and adapt the plan, enabling highly tailored, patient-specific regimens. For patients whose tumors shrink during the treatment period, margin reduction can further protect healthy tissue; for patients with tumor growth and/or migration during treatment, margin adaptation can ensure effective tumor targeting. ART can be offline (i.e. utilizing images taken when the patient is not actively undergoing treatment) or online, in which images are captured during the treatment session.

Data presented at the American Society for Radiation Oncology 2024 Annual Meeting1, and reviewed at the Radiosurgery Society Annual Meeting in 2025 demonstrate the potential for MRI-based ART with Unity to spare healthy brain tissue without compromising progression-free survival (PFS) or overall survival (OS). The presented data were from the UNITED (UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma) study, a 98-patient, single-arm Phase 2 study designed to assess the safety and feasibility of adaptive radiotherapy using a reduced margin (5 mm) compared to standard margin (15 mm) for patients with high-grade gliomas, specifically GBMs, who are receiving concurrent chemotherapy.

In this study, online contrast-enhanced MR images were obtained at the first and fifth fraction (treatment session), and the images were used to adapt the radiation treatment plan. For the remaining fractions (25 or 10, depending on long- or short-course treatment arm), non-enhanced online MR images were obtained and used to adapt to positional shifts. The goal of the study was to demonstrate non-inferiority of the reduced 5 mm CTV compared with a standard 15 mm CTV. Based on historical data, non-inferiority would be achieved if there were 13 or fewer marginal failure events (tumor growth or recurrence at the edge of the treatment area) among the 98 study participants.

Results at median follow-up of 23.3 months found marginal failure events in 4 patients, demonstrating non-inferiority of the adaptive plan compared with the standard approach (p<0.001). Median PFS was 11.6 months and 6.8 months for the long- and short-course arms, respectively; median OS was 18.5 and 10.6 months.

While additional studies are needed to evaluate the impact of MRI-based ART on cognitive and quality of life endpoints for patients with glioma, the UNITED study data add to the growing body of evidence suggesting that the approach may allow us to achieve the holy grail of radiation oncology: reducing margins and de-escalating treatment without compromising PFS and OS. To learn more about the UNITED trial, hear firsthand from Dr. Arjun Sahgal, an international clinical and research leader in the field of high-precision stereotactic radiation to the brain and spine for both metastases and primary tumors, as well as oligometastases and the chief of radiation oncology at Sunnybrook Health Sciences Centre’s Odette Cancer Centre, in a recent episode of Spilling the RT.

As we have come to the end of Brain Tumor Awareness Month, all of us at Elekta remain committed to innovating new technologies that give patients with brain cancer hope for a new beginning.

1 Detsky J, Chan AW, Palhares DM, et al. MR-linac on-line weekly adaptive radiotherapy for high grade glioma (HGG): Results from the UNITED single arm Phase II trial. Int J Rad Onc Biol Phys. 2024;120(2):S4.