Relative Cerebral Blood Volume Is a Potential Predictive Imaging Biomarker of Bevacizumab Efficacy in Recurrent Glioblastoma

Neuro Oncol. 2015 Aug;17(8):1139-47. doi: 10.1093/neuonc/nov028. Epub 2015 Mar 9.


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.

Keywords: bevacizumab; biomarker; cerebral blood volume; glioblastoma; rCBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Bevacizumab / therapeutic use*
  • Biomarkers, Tumor
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Cerebral Cortex / blood supply*
  • Contrast Media
  • Disease-Free Survival
  • Female
  • Glioblastoma / blood supply
  • Glioblastoma / diagnosis*
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Contrast Media
  • Bevacizumab