title: Evaluation of dynamic contrast-enhanced MRI derived microvascular permeability in recurrent glioblastoma treated with bevacizumab.
abstract: 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. Follow-up 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 ρ = -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.
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany, philipp.kickingereder@gmail.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kickingereder
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wiestler
authors.forename: Markus
authors.initials: M
authors.lastname: Graf
authors.forename: Sabine
authors.initials: S
authors.lastname: Heiland
authors.forename: Heinz Peter
authors.initials: HP
authors.lastname: Schlemmer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Antje
authors.initials: A
authors.lastname: Wick
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.forename: Alexander
authors.initials: A
authors.lastname: Radbruch
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab