Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib

To evaluate the role of apparent diffusion coefficient (ADC) imaging in assessing tumor cell infiltration after treatment with the antivascular endothelial growth factor (anti-VEGF) agent, cediranib, we prospectively analyzed diffusion MRI scans from 30 patients participating in a Phase II trial of cediranib for recurrent glioblastoma. A patient-specific threshold was selected below which ADC values were determined to be abnormally low and suggestive of tumor. We determined the percent of low ADC in the FLAIR hyperintensity surrounding the enhancing tumor and then visualized the location of these low ADC voxels. The percent volume of the FLAIR hyperintensity comprised by low ADC increased significantly from baseline (2.3%) to day 28 (2.9%), day 56 (5.0%), and day 112 (6.3%) of treatment with cediranib suggesting increasing infiltrative tumor in some patients. Visualization of the location of the low ADC voxels suggested regions of tumor growth that were not visible on contrast-enhanced MRI. ADC maps can be used to suggest regions of infiltrative tumor cells with anti-VEGF therapy and should be validated in future studies.