Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin.

ABSTRACT

Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan-Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBVload by 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.