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February 19, 2013; 80 (8) Article

Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline

Ann M. Peiffer, C. Marc Leyrer, Dana M. Greene-Schloesser, Elaine Shing, William T. Kearns, William H. Hinson, Stephen B. Tatter, Edward H. Ip, Stephen R. Rapp, Mike E. Robbins, Edward G. Shaw, Michael D. Chan
First published February 6, 2013, DOI: https://doi.org/10.1212/WNL.0b013e318283bb0a
Ann M. Peiffer
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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C. Marc Leyrer
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Dana M. Greene-Schloesser
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Elaine Shing
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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William T. Kearns
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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William H. Hinson
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Stephen B. Tatter
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Edward H. Ip
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Stephen R. Rapp
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Mike E. Robbins
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Edward G. Shaw
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Michael D. Chan
From the Department of Radiation Oncology (A.M.P., C.M.L., D.M.G.-S., W.T.K., W.H.H., M.E.R., E.G.S., M.D.C.), Graduate Neuroscience Program (E.S.), Department of Neurosurgery (S.B.T.), Department of Psychiatry (S.R.R.), Department of Public Health Sciences–Biostatistics (S.R.R., E.H.I.), and Brain Tumor Center of Excellence (A.M.P., D.M.G.-S., S.B.T., S.R.R., M.E.R., E.G.S., M.D.C.), Wake Forest School of Medicine, Winston-Salem, NC.
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Citation
Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline
Ann M. Peiffer, C. Marc Leyrer, Dana M. Greene-Schloesser, Elaine Shing, William T. Kearns, William H. Hinson, Stephen B. Tatter, Edward H. Ip, Stephen R. Rapp, Mike E. Robbins, Edward G. Shaw, Michael D. Chan
Neurology Feb 2013, 80 (8) 747-753; DOI: 10.1212/WNL.0b013e318283bb0a

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Abstract

Objective: In a retrospective review to assess neuroanatomical targets of radiation-induced cognitive decline, dose volume histogram (DVH) analyses of specific brain regions of interest (ROI) are correlated to neurocognitive performance in 57 primary brain tumor survivors.

Methods: Neurocognitive assessment at baseline included Trail Making Tests A/B, a modified Rey-Osterreith Complex Figure, California or Hopkins Verbal Learning Test, Digit Span, and Controlled Oral Word Association. DVH analysis was performed for multiple neuroanatomical targets considered to be involved in cognition. The %v10 (percent of ROI receiving 10 Gy), %v40, and %v60 were calculated for each ROI. Factor analysis was used to estimate global cognition based on a summary of performance on individual cognitive tests. Stepwise regression was used to determine which dose volume predicted performance on global factors and individual neurocognitive tests for each ROI.

Results: Regions that predicted global cognitive outcomes at doses <60 Gy included the corpus callosum, left frontal white matter, right temporal lobe, bilateral hippocampi, subventricular zone, and cerebellum. Regions of adult neurogenesis primarily predicted cognition at %v40 except for the right hippocampus which predicted at %v10. Regions that did not predict global cognitive outcomes at any dose include total brain volume, frontal pole, anterior cingulate, right frontal white matter, and the right precentral gyrus.

Conclusions: Modeling of radiation-induced cognitive decline using neuroanatomical target theory appears to be feasible. A prospective trial is necessary to validate these data.

GLOSSARY

CCOP=
Community Clinical Oncology Program;
COWA=
Controlled Oral Word Association;
CVLT=
California Verbal Learning Test;
DVH=
dose volume histogram;
NCI=
National Cancer Institute;
NTCP=
normal tissue complication probability;
ROI=
region of interest;
RTOG=
Radiation Therapy Oncology Group;
ROCF=
Rey-Osterrieth Complex Figure;
RT=
radiotherapy;
SVZ=
subventricular zone;
WBI=
whole-brain irradiation

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 www.neurology.org

  • Received June 25, 2012.
  • Accepted October 18, 2012.
  • © 2013 American Academy of Neurology
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