Comparing cerebral blood volume and vascular permeability measurements with tumor volume measurements following anti-angiogenesis therapy in recurrent gliomas

Abstract

2030 Background: Dynamic susceptibility contrast-enhanced MRI (DSC MRI) is emerging as an important adjunctive biomarker to assess the effectiveness of anti-angiogenic therapies in the treatment of brain tumors. The purpose of our study is to compare changes in relative cerebral blood volume (rCBV) and in perfusion-permeability index (KTrans) with those of tumor volume measurements (T1c, T2/Flair) in predicting tumor therapeutic response in recurrent high-grade gliomas treated with bevacizumab, an anti-VEGF monoclonal antibody. Methods: 11 patients were treated with one to four cycles of bevacizumab and CPT-11. Their histological diagnoses were: glioblastoma multiforme (n=7), anaplastic astrocytoma (n=2), anaplastic oligodendroglioma (n=1), and diffuse pontine glioma (n=1). All patients had baseline DSC MRI scans prior to the administration of bevacizumab and were followed clinically and radiographically with both conventional and DSC MRI. Mixed model regression was used to compare the pre-treatment and post-treatment levels of each response measure. Results: There were statistically significant reductions in both actual rCBV measurements and T1c enhancement following treatment with bevacizumab and CPT-11. The pretreatment rCBV and T1c rates of change (as determined per 100 days) correlated significantly with time (p values are 0.0229 and 0.0014, respectively), while only the post treatment rCBV demonstrated significant rate of change (p value = 0.0001), suggesting that rCBV may reflect the effects of bevacizumab better than tumor volume. However, when the changes in rate from pre- to post-treatment status were considered, both rCBV and T1c demonstrated significance (p= 0.0001, 0.0157, respectively). There was a trend towards females having higher mean levels of KTrans than males at the same time point relative to treatment onset, but the result was not statistically significant (p=0.072). Conclusions: rCBV as measured from DSC MRI can be used as a surrogate biomarker to determine therapeutic response to bevacizumab. This may influence the neurosurgical risk/benefit equation as well as alter the aggressiveness of the post-operative adjuvant therapy in patients with recurrent gliomas. No significant financial relationships to disclose.