Edema Progression during MRI-Guided Glioblastoma Radiotherapy

Abstract

There are limited studies evaluating brain changes on MRI during the standard six weeks of concurrent chemotherapy and radiotherapy (RT) for glioma. Existing studies suggest that MRI during chemoRT could be useful to determine response to treatment. At our institution, we have been treating select gliomas with one of the first commercially available 0.35T MRI-RT systems. The system includes one clinically useable pulse sequence called balanced steady state free precession (bSSFP), which produces a highly T2-weighted 3D image of the brain. The bSSFP MRIs are obtained daily for treatment setup and have demonstrated changes occurring in and around gliomas during patients’ chemoradiotherapy course. Our objective is to quantify the frequency, magnitude, and time course of these changes. Under a prospective registry protocol, we reviewed 14 patients at our institution who were treated for high grade glioma with chemoradiation, 60 Gy in 30 fractions plus temozolomide, on our institution’s MRI-RT system. We contoured the T2-weighted hyper-intense volumes from the MRI-RT set-up scans for all 30 fractions of treatment for each patient and then calculated the contoured MRI volumes. MRI-RT set-up scans during the last week of treatment were compared to the patients’ diagnostic MRIs obtained 3-4 weeks post-treatment completion to determine whether there were similar findings. 5 of 14 (36%) patients demonstrated greater than a 10% increase in T2-weighted MRI volume during the course of their treatment. Alternatively, 3 of 14 (21%) patients demonstrated greater than a 10% decrease in T2-weighted MRI volume during treatment. In 3 of the patients with volume growth, changes predominantly were observed during weeks 5 and 6 of treatment. The bSSFP images obtained during the last week of treatment demonstrated similar abnormalities compared to the diagnostic FLAIR MRIs obtained 3-4 weeks post-treatment. Patients who had volume expansion during treatment that resolved on serial follow-up MRIs were counted as pseudoprogressors. The time to true progression in the cohort was 19 months. Median follow-up was 14.7 months. 36% of high-grade glioma patients had growth of T2-weighted MRI volume during chemoradiotherapy, and these changes were similar to those observed on post-treatment diagnostic scans. Tumor volume expansion could be due to pseudoprogression, true progression, or changes in edema. Our future work aims to differentiate these possibilities with additional patients, follow-up, and MRI pulse sequences on the MRI-RT system. Groups using limited CTV margins for treatment planning should be aware that MRI volumes could significantly change during radiotherapy. Patients demonstrated T2-weighted MRI volume increase during weeks 5-6 of treatment, suggesting that studies using diagnostic MRI scans mid-treatment (week 3-4) may not fully capture the extent of progression.