title: Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients.
abstract: OBJECTIVE
  The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type.
  
  
  METHODS
  The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients' clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis.
  
  
  RESULTS
  The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679±0.068, Akaike's information criterion 566.7, P<0.001).
  
  
  CONCLUSIONS
  A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM.
authors.affiliation: Division of Neuroradiology, University of Virginia Health System, Charlottesville, VA, United States.
authors.forename: Manal
authors.initials: M
authors.lastname: Nicolasjilwan
authors.affiliation: Center for Biomedical Informatics & Information Technology, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Center for Biomedical Informatics & Information Technology, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yan
authors.affiliation: Center for Biomedical Informatics & Information Technology, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Daoud
authors.initials: D
authors.lastname: Meerzaman
authors.affiliation: Department of Radiology and Imaging Sciences Division of Neuroradiology, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Holder
authors.affiliation: Department of Biomedical Informatics, Emory University, Atlanta, GA, United States.
authors.forename: David
authors.initials: D
authors.lastname: Gutman
authors.affiliation: Departments of Radiology and Neurosurgery, Henry Ford, Detroit, MI, United States.
authors.forename: Rajan
authors.initials: R
authors.lastname: Jain
authors.affiliation: Division of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Rivka
authors.initials: R
authors.lastname: Colen
authors.affiliation: Department of Radiology and Medicine (Biomedical Informatics Research), Stanford University, Stanford, CA, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Rubin
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Pascal O
authors.initials: PO
authors.lastname: Zinn
authors.affiliation: Neuroradiology Section, St. Jude Children's Research Hospital, Memphis, TN, United States.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Hwang
authors.affiliation: Division of Neuroradiology, University of Virginia Health System, Charlottesville, VA, United States.
authors.forename: Prashant
authors.initials: P
authors.lastname: Raghavan
authors.affiliation: Radiology and Imaging Sciences, National Institutes of Health, Clinical Center, Bethesda, MD, United States.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
authors.affiliation: Departments of Neurosurgery, Henry Ford, Detroit, MI, United States.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Scarpace
authors.affiliation: Departments of Neurosurgery, Henry Ford, Detroit, MI, United States.
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.affiliation: Division of Neuroradiology, University of California, San Diego, CA, United States.
authors.forename: James
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Cancer Systems Biology (CCSB) & Department of Radiology, Stanford University, Stanford, CA, United States.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gevaert
authors.affiliation: Arizona State University Life Science, Tempe, AZ, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Buetow
authors.affiliation: SAIC-Frederick, Inc., Frederick, MD, United States.
authors.forename: John
authors.initials: J
authors.lastname: Freymann
authors.affiliation: SAIC-Frederick, Inc., Frederick, MD, United States.
authors.forename: Justin
authors.initials: J
authors.lastname: Kirby
authors.affiliation: Division of Neuroradiology, Thomas Jefferson University Hospital, Philadelphia, PA, United States.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Flanders
authors.affiliation: Division of Neuroradiology, University of Virginia Health System, Charlottesville, VA, United States; CHU de Vaudois, Department of Radiology, Lausanne, Switzerland. Electronic address: max.wintermark@gmail.com.
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015995:Prevalence; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers
keywords: Genetics; Glioblastoma; Magnetic resonance imaging; Prognosis; Survival