title: Dynamic-susceptibility contrast agent MRI measures of relative cerebral blood volume predict response to bevacizumab in recurrent high-grade glioma.
abstract: BACKGROUND
  The anti-VEGF antibody, bevacizumab, is standard treatment for patients with recurrent glioblastoma. In this setting, traditional anatomic MRI methods such as post-contrast T1-weighted and T2-weighted imaging are proving unreliable for monitoring response. Here we evaluate the prognostic significance of pre- and posttreatment relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast MRI to predict response to bevacizumab.
  
  
  METHODS
  Thirty-six participants with recurrent high-grade gliomas who underwent rCBV imaging 60 days before and 20-60 days after starting bevacizumab treatment were enrolled. Tumor regions of interest (ROIs) were determined from deltaT1 maps computed from the difference between standardized post and precontrast T1-weighted images. Both pre- and posttreatment rCBV maps were corrected for leakage and standardized (stdRCBV) to a consistent intensity scale. The Kaplan-Meier method was used to determine if either the pre- or post-bevacizumab stdRCBV within the tumor ROI was predictive of overall survival (OS) or progression free survival (PFS).
  
  
  RESULTS
  The OS was significantly longer if either the pre- (380d vs 175d; P=.0024) or posttreatment stdRCBV (340d vs 186d; P = .0065) was <4400. The posttreatment stdRCBV was also predictive of PFS (167d vs 78d; P = .0006). When the stdRCBV values were both above versus both below threshold, the OS was significantly worse (100.5d vs 395d; P < .0001). With a 32.5% decrease in stdRCBV, the risk of death was reduced by about 68% but increased by 140% with a 29% increase in stdRCBV.
  
  
  CONCLUSIONS
  Standardized rCBV is predictive of OS and PFS in patients with recurrent high-grade brain tumor treated with bevacizumab.
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Schmainda
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Melissa
authors.initials: M
authors.lastname: Prah
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Connelly
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rand
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Hoffman
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Wade
authors.initials: W
authors.lastname: Mueller
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., M.P., S.D.R.); Department of Biophysics, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S.); Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee Wisconsin (K.M.S., J.C., S.D.R., W.M., M.G.M.); Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., M.G.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.G.H); Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin (J.C., W.M., M.G.M.).
authors.forename: Mark G
authors.initials: MG
authors.lastname: Malkin
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000098:blood supply*; D003287:Contrast Media; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab
keywords: DSC; MRI; bevacizumab; brain tumor; perfusion; rCBV