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

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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 (Ktrans)—an estimate related to microvascular permeability—at baseline and voxel-wise-reduction (VWR) in Ktrans 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 Ktrans ranged from 0.050 to 0.205 min−1 (median, 0.109 min−1). The VWR in Ktrans ranged from 19.9 to 97.2 % (median, 89.4 %). Patients with lower baseline Ktrans and higher VWR in Ktrans showed significantly longer PFS and OS. Given the strong correlation of VWR in Ktrans and CET-volume changes (Spearman’s ρ = −0.73, p < 0.01) both variables were included in a multivariate model. Thereby, neither VWR in Ktrans nor CET-volume changes retained independent significance for PFS or OS. Pre-treatment Ktrans stratifies PFS and OS in patients with bevacizumab-treated rGB. Although early pharmacodynamics changes in Ktrans were not assessed, the VWR in Ktrans 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 Ktrans as a predictive and/or prognostic biomarker.

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Acknowledgments

This study was supported by a Grant of the DKFZ—German Cancer Research Center (“Intramurales Förderprogramm”).

Conflict of interest

Philipp Kickingereder: none; Benedikt Wiestler: none; Markus Graf: none; Sabine Heiland: none; Heinz-Peter Schlemmer—UNRELATED: Consultancy: Siemens, Grants/Grants Pending: Siemens, Payment for Lectures (including service on Speakers Bureaus): Siemens, Curagita, Covidien, Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: Siemens; Wolfgang Wick—UNRELATED: Consultancy: Roche, MSD, Payment for Lectures (including service on Speakers Bureaus): Roche, Prime Oncology, Research support: Apogenix, Boehringer Ingelheim, MSD and Roche. Member of the Steering Committee of the AVAglio trial. Patents (planned, pending or issued): IDH diagnostic antibody; Antje Wick: none Martin Bendszus—UNRELATED: Board Membership: Vascular Dynamics, Payment for Lectures (including service on Speakers Bureaus): Novartis, Roche, Codman, Guerbet; Alexander Radbruch: none.

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Authors and Affiliations

  1. Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany

    Philipp Kickingereder, Sabine Heiland, Martin Bendszus & Alexander Radbruch

  2. Department of Neurology, University of Heidelberg Medical Center, Heidelberg, Germany

    Benedikt Wiestler, Wolfgang Wick & Antje Wick

  3. German Cancer Consortium (DKTK), Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Benedikt Wiestler, Wolfgang Wick & Antje Wick

  4. Department of Radiology, DKFZ, Heidelberg, Germany

    Markus Graf, Heinz Peter Schlemmer & Alexander Radbruch

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  1. Philipp Kickingereder
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Correspondence to Philipp Kickingereder.

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11060_2014_1644_MOESM1_ESM.tif

Supplementary Fig. 1. Corresponding concentration–time curves of patients shown in Fig. 1 [x axis relative enhancement, y axis time (s)]

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Kickingereder, P., Wiestler, B., Graf, M. et al. Evaluation of dynamic contrast-enhanced MRI derived microvascular permeability in recurrent glioblastoma treated with bevacizumab. J Neurooncol 121, 373–380 (2015). https://doi.org/10.1007/s11060-014-1644-6

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  • DOI: https://doi.org/10.1007/s11060-014-1644-6

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