Morgan J Prust1, Kourosh Jafari-Khouzani1, Jayashree Kalpathy-Cramer1, Pavlina Polaskova1, Tracy T Batchelor1, Elizabeth R Gerstner1, Jorg Dietrich2. 1. From Harvard Medical School (M.J.P., J.D.), Boston; and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (M.J.P., K.J.-K., J.K.-C., P.P., E.R.G.), and Department of Neurology, Center for Neuro-Oncology (T.T.B., E.R.G., J.D.), Massachusetts General Hospital, Harvard Medical School, Boston, MA. 2. From Harvard Medical School (M.J.P., J.D.), Boston; and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (M.J.P., K.J.-K., J.K.-C., P.P., E.R.G.), and Department of Neurology, Center for Neuro-Oncology (T.T.B., E.R.G., J.D.), Massachusetts General Hospital, Harvard Medical School, Boston, MA. dietrich.jorg@mgh.harvard.edu.
Abstract
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 6 weeks 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.
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 6 weeks 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.
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