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

Abstract

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. 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. 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 3months. We found that recurrent GB with a high percentage of neovascularization and active tumor before bevacizumab onset showed a poor or no treatment response. TME mapping might be useful to develop strategies for patient stratification and response prediction before bevacizumab onset.