Glioblastoma, the most common primary brain cancer, is treated with surgical resection where possible followed by chemoradiotherapy. Researchers at the University of Miami’s Sylvester Comprehensive Cancer Center have now demonstrated that delivering the radiotherapy on an MRI-linac could provide an early warning of tumour growth, potentially enabling rapid adaptation during the course of treatment.
The Sylvester Comprehensive Cancer Center has been treating glioblastoma patients with MRI-guided radiotherapy since 2017. While standard clinical practice employs MRI scans before and after treatment (roughly three months apart) to monitor a patient’s response, the MRI-linac enables daily imaging. The research team, led by radiation oncologist Eric Mellon, proposed that such daily scans could reveal any changes in the tumour volume or resection cavity far earlier than the standard approach.
To investigate this idea, Mellon and colleagues studied 36 patients with glioblastoma undergoing chemoradiotherapy on a 0.35 T MRI-linac. During 30 radiotherapy fractions, delivered over six weeks, they imaged patients daily on the MRI-linac to assess the volumes of lesions and surgical resection cavities (the site where the tumour was removed).
The researchers then compared the non-contrast MRI-linac images to images recorded pre- (one week before) and post- (one month after) treatment using a standalone 3T MRI with gadolinium contrast. Detailing their findings in the International Journal of Radiation Oncology – Biology – Physics, they report that in general, lesion and cavity volumes seen on non-contrast MRI-linac scans correlated strongly with volumes measured using standalone contrast MRI.
Of the patients in this study, eight had a cavity in the brain, 12 had a lesion and 16 had both cavity and lesion. From pre- to post-radiotherapy, 18 patients exhibited lesion growth, while 11 had cavity shrinkage. In 74% of the cases, changes in lesion volume (growth, shrinkage or no change) assessed on the MR-linac matched those seen on contrast MRI.
“If MRI-linac lesion growth did occur, which was in 60% of our patients [with lesions], there is a 57% chance that it will correspond with tumour growth on standalone post-contrast imaging,” said first author Kaylie Cullison, who shared the study findings at the recent ASTRO Annual Meeting.
In the other 26% of cases, contrast MRI suggested lesion shrinkage while the MRI-linac scans showed lesion growth. Cullison suggested that this may be partly due to radiation-induced oedema, which is difficult to distinguish from tumour on the non-contrast MRI-linac images.
The significant anatomic changes seen during daily imaging of glioblastoma patients suggest that adaptation could play an important role in improving their treatment. In cases where lesions or surgical resection cavities shrink, for example, treatment margins could be reduced to spare normal brain tissue from irradiation. Conversely, for patients with growing lesions, radiotherapy margins could be expanded to ensure complete tumour coverage.
Importantly, there were no cases in this study where patients showed a decrease in their MRI-linac lesion volumes and an increase in their standalone MRI volumes from pre- to post-treatment. In other words, the MR-linac did not miss any cases of true tumour growth. “You can use the MRI-linac non-contrast imaging as an early warning system for potential tumour growth,” said Cullison.
Based on their findings, the researchers propose an adaptive workflow for glioblastoma radiotherapy. For resection cavities, which are clearly visible on non-contrast MRI-linac images, adaptation to shrinkage seen on weekly (standalone or MRI-linac) non-contrast MR images is feasible. Alongside, if an MRI-linac scan shows lesion progression during treatment, gadolinium contrast could be administered (for standalone MRI or MRI-linac scans) to confirm this growth and define adaptive target volumes.
Imaging on an MR-Linac identifies radiation-resistant brain tumours
An additional advantage of this workflow is it reduces the use of contrast. Glioblastoma evolution is typically evaluated using contrast-enhanced MRI. However, potential gadolinium deposition with repeated contrast scans is a concern among patients, and the US Food & Drug Administration advises that gadolinium contrast studies should be minimized where possible. This new adaptive approach meets this requirement by only requiring contrast when non-contrast MRI shows an increase in lesion size.
Cullison tells Physics World that the team will next conduct an adaptive radiation therapy trial using the proposed workflow, to determine whether it improves patient outcomes. “We also plan further exploration and analysis of our data, including multiparametric MRI from the MRI-linac, in a larger patient cohort to try to predict patient outcomes (tumour growth; true progression versus pseudo-progression; survival times, etc) earlier than current methods allow,” she explains.
