Evaluation of dynamic contrast-enhanced MRI derived microvascular permeability in recurrent glioblastoma treated with bevacizumab

Bevacizumab, an antibody to vascular endothelial growth factor, is commonly used in the setting of recurrent glioblastoma (rGB). The aim of the present study was to evaluate whether dynamic-contrast-enhanced MRI (DCE-MRI) derived microvascular permeability is related to bevacizumab treatment outcome in rGB. Twenty-two patients with rGB underwent DCE-MRI at a median of 2.6 weeks prior initializing bevacizumab therapy. Followup MRI-scans (DCE-MRI available for 19/22 patients) were obtained after a median of 9.9 weeks. The volume transfer constant (K-trans)-an estimate related to microvascular permeability-at baseline and voxel-wise-reduction (VWR) in K-trans at first follow-up were measured from the entire contrast-enhancing tumor (CET) and correlated with progression-free and overall survival (PFS, OS) using uni-and multivariate cox-regression (significance-level p < 0.05). Baseline K-trans ranged from 0.050 to 0.205 min(-1) (median, 0.109 min(-1)). The VWR in K-trans ranged from 19.9 to 97.2% (median, 89.4%). Patients with lower baseline K-trans and higher VWR in K-trans showed significantly longer PFS and OS. Given the strong correlation of VWR in K-trans and CET-volume changes (Spearman's rho = -0.73, p < 0.01) both variables were included in a multivariate model. Thereby, neither VWR in K-trans nor CET-volume changes retained independent significance for PFS or OS. Pre-treatment K-trans stratifies PFS and OS in patients with bevacizumab-treated rGB. Although early pharmacodynamics changes in K-trans were not assessed, the VWR in K-trans at first follow-up had no additional benefit over assessment of CET-volume changes. Further prospective trials are needed to confirm these findings and to elucidate the potential role of pre-treatment K-trans as a predictive and/or prognostic biomarker.