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.

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

Fig. 1.

Kaplan-Meier plot for overall survival (OS) and progression-free survival (PFS) (A and B) for all patients stratified by treatment administered (bevacizumab [BEV] vs non-BEV chemotherapy), (C and D) for patients in the BEV cohort stratified by the median baseline relative cerebral blood volume (rCBV), and (E and F) for patients in the non-BEV cohort stratified by the median baseline rCBV.

Fig. 2.

Contrast-enhancing T1 (T1-C+) images, fluid-attenuated inversion recovery (FLAIR) images, and relative cerebral blood volume (rCBV) maps (window center/width of 3.5/7.0) superimposed on corresponding T1-C+ images of 4 representative patients with recurrent glioblastoma (A-D) at baseline prior to initiating bevacizumab (BEV) treatment (upper row) and at first follow-up (lower row). Patients were stratified as nonresponder (A and B): progression after 2.8 months (second follow-up) for A and 2.0 months (first follow-up) for B) and responder (C and D: progression after 12.3 for C and 13.8 months for D) on the basis of baseline rCBV analysis (rCBV values of 6.4 and 5.9 for A and B and 3.5 and 1.2 for C and D). Corresponding rCBV-values, T1-C+, and FLAIR tumor volumes at first follow-up changed by −48%,−26%, and −20% for A; −44%, +180%, +73% for B; −55%, −62%, and −43% for C; and −60%, −86%, and −70% for D.