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Predicting Glioblastoma Response to Bevacizumab Through MRI Biomarkers of the Tumor Microenvironment

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Abstract

Purpose

Glioblastoma (GB) is one of the most vascularized of all solid tumors and, therefore, represents an attractive target for antiangiogenic therapies. Many lesions, however, quickly develop escape mechanisms associated with changes in the tumor microenvironment (TME) resulting in rapid treatment failure. To prevent patients from adverse effects of ineffective therapy, there is a strong need to better predict and monitor antiangiogenic treatment response.

Procedures

We utilized a novel physiological magnetic resonance imaging (MRI) method combining the visualization of oxygen metabolism and neovascularization for classification of five different TME compartments: necrosis, hypoxia with/without neovascularization, oxidative phosphorylation, and aerobic glycolysis. This approach, termed TME mapping, was used to monitor changes in tumor biology and pathophysiology within the TME in response to bevacizumab treatment in 18 patients with recurrent GB.

Results

We detected dramatic changes in the TME by rearrangement of its compartments after the onset of bevacizumab treatment. All patients showed a decrease in active tumor volume and neovascularization as well as an increase in hypoxia and necrosis in the first follow-up after 3 months. We found that recurrent GB with a high percentage of neovascularization and active tumor before bevacizumab onset showed a poor or no treatment response.

Conclusions

TME mapping might be useful to develop strategies for patient stratification and response prediction before bevacizumab onset.

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Funding

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft—DFG; Grant Numbers STA 1331/3-1 and DO 721/9-1) and by the ELAN program (Erlanger Leistungsbezogene Anschubfinanzierung und Nachwuchsförderung; Grant Number 14-05-21-1-Stadlbauer).

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Authors and Affiliations

  1. Department of Neurosurgery, University of Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Andreas Stadlbauer, Karl Roessler, Max Zimmermann, Michael Buchfelder & Andrea Kleindienst

  2. Institute of Medical Radiology, University Clinic of St. Pölten, Dunant-Platz 1, 3100, St. Pölten, Austria

    Andreas Stadlbauer & Gertraud Heinz

  3. Department of Neuroradiology, University of Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Arnd Doerfler

  4. Department of Neurology, University Clinic of St. Pölten, Dunant-Platz 1, 3100, St. Pölten, Austria

    Stefan Oberndorfer

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  1. Andreas Stadlbauer
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  2. Karl Roessler
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  3. Max Zimmermann
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  4. Michael Buchfelder
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Correspondence to Andreas Stadlbauer.

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Stadlbauer, A., Roessler, K., Zimmermann, M. et al. Predicting Glioblastoma Response to Bevacizumab Through MRI Biomarkers of the Tumor Microenvironment. Mol Imaging Biol 21, 747–757 (2019). https://doi.org/10.1007/s11307-018-1289-5

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