title: Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma.
abstract: BACKGROUND
  To analyze the relevance of dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) derived relative cerebral blood volume (rCBV) analysis for predicting response to bevacizumab (BEV) in patients with recurrent glioblastoma (rGB).
  
  
  METHODS
  A total of 127 patients diagnosed with rGB receiving either bevacizumab (71 patients, BEV cohort) or alkylating chemotherapy (56 patients, non-BEV cohort) underwent conventional anatomic MRI and DSC-MRI at baseline and at first follow-up after treatment initiation. The mean rCBV of the contrast-enhancing tumor (cT1) as well as cT1 and fluid-attenuated inversion recovery (FLAIR) volumes at both time points were correlated with progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models, logistic regression, and the log-rank test.
  
  
  RESULTS
  Baseline rCBV was associated with both PFS (hazard ratio [HR] = 1.3; P < .01) and OS (HR = 1.3; P < .01) in the BEV cohort and predicted 6-month PFS in 82% and 12-month OS in 79% of patients, whereas it was not associated with PFS (HR = 1.0; P = .70) or OS (HR = 1.0; P = .47) in the non-BEV cohort. Corresponding median OS and PFS rates in the BEV cohort for patients with rCBV-values less than 3.92 (optimal threshold from receiver operating characteristic [ROC] analysis of 12-month OS data) were 14.2 and 6.0 months, as compared to 6.6 and 2.8 months for patients with rCBV-values greater than 3.92 (P < .01, respectively). cT1 and FLAIR volumes at first follow-up were significant predictors of 6-month PFS and 12-month OS in the BEV cohort but not in the non-BEV cohort. Corresponding volumes at baseline were not significant in any cohort.
  
  
  CONCLUSIONS
  Pretreatment rCBV is a potential predictive imaging biomarker in BEV-treated rGB but not alkylating chemotherapy-treated rGB, which is superior to volumetric analysis of conventional anatomic MRI and predicts 6-month PFS and 12-month OS in 80% of BEV-treated patients.
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Philipp
authors.initials: P
authors.lastname: Kickingereder
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wiestler
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Sina
authors.initials: S
authors.lastname: Burth
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Antje
authors.initials: A
authors.lastname: Wick
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Martha
authors.initials: M
authors.lastname: Nowosielski
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Sabine
authors.initials: S
authors.lastname: Heiland
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schlemmer
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K., S.B., S.H., M.B., A.R.); Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany (B.W., A.W., W.W.); German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ, Heidelberg, Germany (B.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Department of Radiology, DKFZ, Heidelberg, Germany (H.-P.S., A.R.).
authors.forename: Alexander
authors.initials: A
authors.lastname: Radbruch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D002540:Cerebral Cortex / Q000098:blood supply*; D003287:Contrast Media; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D003287:Contrast Media; D000068258:Bevacizumab
keywords: bevacizumab; biomarker; cerebral blood volume; glioblastoma; rCBV