Standard Chemoradiation for Glioblastoma Results in Progressive Brain Volume Loss

Abstract

Chemotherapy and radiation produce adverse neurologic side effects, such as progressive cognitive decline. Investigation into the effects of cancer therapies on normal brain tissue is needed to develop in vivo markers of neurotoxicity. We longitudinally assessed serial neuroimaging parameters in 14 glioblastoma patients receiving six weeks of standard chemoradiation, followed by up to six months of temozolomide chemotherapy alone. We examined changes in whole brain (WB), gray matter (GM), white matter (WM), anterior lateral ventricle and hippocampal volumes within each patient’s hemisphere of lowest/no tumor burden. We examined diffusion tensor imaging parameters within the subventricular zone (SVZ). WB (F = 2.41; p = 0.016) and GM volume (F = 2.13; p = 0.036) decreased during treatment, without significant WM volume change. Anterior lateral ventricle volume increased significantly (F = 65.51; p < 0.001). In subjects analyzed beyond 23 weeks, mean ventricular volume increased by 42.2% (SE: 8.8%; t = 4.94; p < 0.005). Apparent diffusion coefficient (ADC) increased within the SVZ (F = 7.028; p < 0.001). Hippocampal volume did not change significantly. We present evidence of treatment-associated brain changes during standard chemotherapy and radiation. Future studies employing serial neuropsychological measures are needed to characterize the functional consequences of these effects.