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August 25, 2015; 85 (8) Article

Standard chemoradiation for glioblastoma results in progressive brain volume loss

Morgan J. Prust, Kourosh Jafari-Khouzani, Jayashree Kalpathy-Cramer, Pavlina Polaskova, Tracy T. Batchelor, Elizabeth R. Gerstner, Jorg Dietrich
First published July 24, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001861
Morgan J. Prust
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.
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Kourosh Jafari-Khouzani
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.
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Jayashree Kalpathy-Cramer
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.
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Pavlina Polaskova
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.
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Tracy T. Batchelor
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.
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Elizabeth R. Gerstner
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.
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Jorg Dietrich
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.
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Citation
Standard chemoradiation for glioblastoma results in progressive brain volume loss
Morgan J. Prust, Kourosh Jafari-Khouzani, Jayashree Kalpathy-Cramer, Pavlina Polaskova, Tracy T. Batchelor, Elizabeth R. Gerstner, Jorg Dietrich
Neurology Aug 2015, 85 (8) 683-691; DOI: 10.1212/WNL.0000000000001861

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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.

GLOSSARY

ADC=
apparent diffusion coefficient;
DTI=
diffusion tensor imaging;
FA=
fractional anisotropy;
FLAIR=
fluid-attenuated inversion recovery;
FSL=
FMRIB's Software Library;
GM=
gray matter;
MEMPRAGE=
multiecho magnetization-prepared rapid-acquisition gradient echo;
NPC=
neural progenitor cell;
ROI=
region of interest;
RT=
radiation therapy;
SVZ=
subventricular zone;
VBM=
voxel-based morphometry;
WM=
white matter

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received December 2, 2014.
  • Accepted in final form April 3, 2015.
  • © 2015 American Academy of Neurology
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Letters: Rapid online correspondence

  • Re: Neurotoxicity of glioma-directed treatment: Expected and currently not preventable.
    • Jorg Dietrich, Physician, Clinical Director, Massachusetts General HospitalDietrich.Jorg@mgh.harvard.edu
    • Morgan Prust, Boston, MA
    Submitted December 10, 2015
  • Neurotoxicity of glioma-directed treatment: Expected and currently not preventable.
    • Marc C. Chamberlain, Physician, University of Washington Department of Neurology and Neurological Surgery Division of Neuro-Oncologychambemc@seattlecca.org
    Submitted September 22, 2015
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