title: Standard chemoradiation for glioblastoma results in progressive brain volume loss.
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.
authors.affiliation: 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.
authors.forename: Morgan J
authors.initials: MJ
authors.lastname: Prust
authors.affiliation: 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.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Jafari-Khouzani
authors.affiliation: 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.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Kalpathy-Cramer
authors.affiliation: 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.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Polaskova
authors.affiliation: 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.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.affiliation: 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.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gerstner
authors.affiliation: 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.
authors.forename: Jorg
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D024221:Antineoplastic Protocols; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D059248:Chemoradiotherapy; D016371:Cranial Irradiation / Q000009:adverse effects*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D056324:Diffusion Tensor Imaging; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide