Edema Progression during MRI-Guided Glioblastoma Radiotherapy

Abstract

There are limited studies evaluating brain changes on MRI during the six weeks of concurrent chemotherapy and radiotherapy (RT) for glioma. Existing studies suggest that MRI during chemoradiotherapy could be useful to determine early response to treatment. At our center, we have been treating selected gliomas with one of the first commercially available 0.35T MRI-RT systems. The system includes one clinically useable pulse sequence, balanced steady state free precession (bSSFP), which obtains a 1.5 mm isotropic highly T2-weighted 3D image volume through the brain with minimal distortions. The bSSFP MRIs are obtained daily for treatment setup, and we have seen changes occurring in and around gliomas during chemoradiotherapy. 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 MRI-RT system. We contoured the T2-weighted hyperintense volumes from the MRI-RT bSSFP images for all 30 treatment fractions for each patient and measured the volumes of those MRIs. The MRIs from fraction 30 were compared to the diagnostic MRIs obtained 3-4 weeks post-treatment to determine whether there were similar findings. 5 of 14 (36%) patients demonstrated greater than a 10% increase in tumor volume during the course of their treatment. In 3 of these patients with growth, changes predominantly were observed during week 5 and 6 of treatment. One patient’s non-enhancing unresected tumor decreased 24% in volume during the course of treatment. The bSSFP images obtained at the end of treatment demonstrated similar FLAIR abnormalities compared to diagnostic MRIs 3-4 weeks post treatment completion. Patients who had volume expansion during treatment that resolved on serial follow-up MRIs were counted as pseudoprogression, and excluding pseudoprogressors, the progression free survival in the cohort was 19 months. Median follow-up was 14.7 months. 36% of high grade glioma patients had growth of T2-weighted 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 solely due to changes in edema. Our future work aims to differentiate these possibilities with additional patients and MRI pulse sequences. Changes were greatest during weeks 5-6 of the treatment course, suggesting that studies using diagnostic MRI scans during RT should be obtained late in the treatment course.