title: Genomic mapping and survival prediction in glioblastoma: molecular subclassification strengthened by hemodynamic imaging biomarkers.
abstract: OBJECTIVE
  To correlate tumor blood volume, measured by using dynamic susceptibility contrast material-enhanced T2*-weighted magnetic resonance (MR) perfusion studies, with patient survival and determine its association with molecular subclasses of glioblastoma (GBM).
  
  
  METHODS
  This HIPAA-compliant retrospective study was approved by institutional review board. Fifty patients underwent dynamic susceptibility contrast-enhanced T2*-weighted MR perfusion studies and had gene expression data available from the Cancer Genome Atlas. Relative cerebral blood volume (rCBV) (maximum rCBV [rCBV(max)] and mean rCBV [rCBV(mean)]) of the contrast-enhanced lesion as well as rCBV of the nonenhanced lesion (rCBV(NEL)) were measured. Patients were subclassified according to the Verhaak and Phillips classification schemas, which are based on similarity to defined genomic expression signature. We correlated rCBV measures with the molecular subclasses as well as with patient overall survival by using Cox regression analysis.
  
  
  RESULTS
  No statistically significant differences were noted for rCBV(max), rCBV(mean) of contrast-enhanced lesion or rCBV(NEL) between the four Verhaak classes or the three Phillips classes. However, increased rCBV measures are associated with poor overall survival in GBM. The rCBV(max) (P = .0131) is the strongest predictor of overall survival regardless of potential confounders or molecular classification. Interestingly, including the Verhaak molecular GBM classification in the survival model clarifies the association of rCBV(mean) with patient overall survival (hazard ratio: 1.46, P = .0212) compared with rCBV(mean) alone (hazard ratio: 1.25, P = .1918). Phillips subclasses are not predictive of overall survival nor do they affect the predictive ability of rCBV measures on overall survival.
  
  
  CONCLUSIONS
  The rCBV(max) measurements could be used to predict patient overall survival independent of the molecular subclasses of GBM; however, Verhaak classifiers provided additional information, suggesting that molecular markers could be used in combination with hemodynamic imaging biomarkers in the future.
authors.affiliation: Division of Neuroradiology, Department of Radiology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202, USA. rajanj@rad.hfh.edu
authors.forename: Rajan
authors.initials: R
authors.lastname: Jain
authors.forename: Laila
authors.initials: L
authors.lastname: Poisson
authors.forename: Jayant
authors.initials: J
authors.lastname: Narang
authors.forename: David
authors.initials: D
authors.lastname: Gutman
authors.forename: Lisa
authors.initials: L
authors.lastname: Scarpace
authors.forename: Scott N
authors.initials: SN
authors.lastname: Hwang
authors.forename: Chad
authors.initials: C
authors.lastname: Holder
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
authors.forename: Rivka R
authors.initials: RR
authors.lastname: Colen
authors.forename: Justin
authors.initials: J
authors.lastname: Kirby
authors.forename: John
authors.initials: J
authors.lastname: Freymann
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Carl
authors.initials: C
authors.lastname: Jaffe
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D002560:Cerebrovascular Circulation; D003287:Contrast Media; D019786:Gadolinium DTPA; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D019786:Gadolinium DTPA