Standard chemoradiation for glioblastoma results in progressive brain volume loss

Objective: To investigate the effects of chemotherapy and cranial irradiation on normal brain tissue using in vivo neuroimaging in patients with glioblastoma. Methods: We used longitudinal MRI to monitor structural brain changes during standard treatment in patients newly diagnosed with glioblastoma. We assessed volumetric and diffusion tensor imaging measures in 14 patients receiving 6weeks of chemoradiation, followed by up to 6 months of temozolomide chemotherapy alone. We examined changes in whole brain, gray matter (GM), white matter (WM), anterior lateral ventricle, and hippocampal volumes. Normal-appearing GM, WM, and hippocampal analyses were conducted within the hemisphere of lowest/absent tumor burden. We examined diffusion tensor imaging measures within the subventricular zone. Results: Whole brain (F = 2.41; p = 0.016) and GM (F = 2.13; p = 0.036) volume decreased during treatment, without significant WM volume change. Anterior lateral ventricle volume increased significantly (F = 65.51; p <0.001). In participants analyzed beyond 23 weeks, mean ventricular volume increased by 42.2% (SE: 8.8%; t = 4.94; p <0.005). Apparent diffusion coefficient increased within the subventricular zone (F = 7.028; p <0.001). No significant changes were identified in hippocampal volume. Conclusions: We present evidence of significant and progressive treatment-associated structural brain changes in patients with glioblastoma treated with standard chemoradiation. Future studies using longitudinal neuropsychological evaluation are needed to characterize the functional consequences of these structural changes.