title: Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas.
abstract: OBJECTIVE
  Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes.
  
  
  METHODS
  Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions.
  
  
  RESULTS
  Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies.
  
  
  CONCLUSIONS
  Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.
authors.affiliation: From the Stanford Center for Biomedical Informatics Research and Biomedical Informatics Training Program (T.T.L., D.L.R.) Department of Radiology (T.T.L., L.A.M., W.A.D., K.W.Y., D.L.R.).
authors.forename: T T
authors.identifier: http://orcid.org/0000-0002-7450-9059
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Stanford Institute for Neuro-Innovation and Translational Neurosciences (A.S.A.) Institute for Stem Cell Biology and Regenerative Medicine (A.S.A.) Department of Neurosurgery (A.S.A., J.J.L., S.A.R., E.M.W., S.D.C., G.R.H.), Stanford University School of Medicine, Stanford, California.
authors.forename: A S
authors.identifier: http://orcid.org/0000-0002-6319-4565
authors.initials: AS
authors.lastname: Achrol
authors.affiliation: Department of Radiology (T.T.L., L.A.M., W.A.D., K.W.Y., D.L.R.).
authors.forename: L A
authors.identifier: http://orcid.org/0000-0002-7523-9003
authors.initials: LA
authors.lastname: Mitchell
authors.affiliation: Department of Radiology (T.T.L., L.A.M., W.A.D., K.W.Y., D.L.R.).
authors.forename: W A
authors.identifier: http://orcid.org/0000-0001-7626-991X
authors.initials: WA
authors.lastname: Du
authors.affiliation: Department of Neurosurgery (A.S.A., J.J.L., S.A.R., E.M.W., S.D.C., G.R.H.), Stanford University School of Medicine, Stanford, California.
authors.forename: J J
authors.identifier: http://orcid.org/0000-0002-0852-0014
authors.initials: JJ
authors.lastname: Loya
authors.affiliation: Department of Neurosurgery (A.S.A., J.J.L., S.A.R., E.M.W., S.D.C., G.R.H.), Stanford University School of Medicine, Stanford, California.
authors.forename: S A
authors.identifier: http://orcid.org/0000-0001-6061-0837
authors.initials: SA
authors.lastname: Rodriguez
authors.affiliation: Department of Neurological Surgery (A.F.), University of Washington School of Medicine, Seattle, Washington.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-7761-6765
authors.initials: A
authors.lastname: Feroze
authors.affiliation: Department of Neurosurgery (A.S.A., J.J.L., S.A.R., E.M.W., S.D.C., G.R.H.), Stanford University School of Medicine, Stanford, California.
authors.forename: E M
authors.identifier: http://orcid.org/0000-0003-4400-5076
authors.initials: EM
authors.lastname: Westbroek
authors.affiliation: Department of Radiology (T.T.L., L.A.M., W.A.D., K.W.Y., D.L.R.).
authors.forename: K W
authors.identifier: http://orcid.org/0000-0001-9860-3368
authors.initials: KW
authors.lastname: Yeom
authors.affiliation: Biomolecular Engineering (J.M.S.), University of California Santa Cruz, Santa Cruz, California.
authors.forename: J M
authors.identifier: http://orcid.org/0000-0002-2171-565X
authors.initials: JM
authors.lastname: Stuart
authors.affiliation: Department of Neurosurgery (A.S.A., J.J.L., S.A.R., E.M.W., S.D.C., G.R.H.), Stanford University School of Medicine, Stanford, California.
authors.forename: S D
authors.initials: SD
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery (A.S.A., J.J.L., S.A.R., E.M.W., S.D.C., G.R.H.), Stanford University School of Medicine, Stanford, California.
authors.forename: G R
authors.identifier: http://orcid.org/0000-0002-0233-7817
authors.initials: GR
authors.lastname: Harsh
authors.affiliation: From the Stanford Center for Biomedical Informatics Research and Biomedical Informatics Training Program (T.T.L., D.L.R.) Department of Radiology (T.T.L., L.A.M., W.A.D., K.W.Y., D.L.R.) dlrubin@stanford.edu.
authors.forename: D L
authors.identifier: http://orcid.org/0000-0001-5057-4369
authors.initials: DL
authors.lastname: Rubin
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis