Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?

Abstract

The management of solid tumors has been transformed by the advent of VEGF pathway inhibitors. Early clinical evaluation of these drugs has used pharmacodynamic biomarkers derived from advanced imaging such as dynamic MRI, computed tomography (CT), and ultrasound to establish proof of principle. We have reviewed published studies that used these imaging techniques to determine whether the same biomarkers relate to survival in renal, hepatocellular, and brain tumors in patients treated with VEGF inhibitors. Data show that in renal cancer, pretreatment measurements of K trans and early pharmacodynamic reduction in tumor enhancement and density have prognostic significance in patients treated with VEGF inhibitors. A weaker, but significant, relationship is seen with subtle early size change (10% in one dimension) and survival. Data from high-grade glioma suggest that pretreatment fractional blood volume and K trans were prognostic of overall survival. However, lack of control data with other therapies prevents assessment of the predictive nature of these biomarkers, and such studies are urgently required.

Validation of Dynamic Contrast-Enhanced Ultrasound in Predicting Outcomes of Antiangiogenic Therapy for Solid Tumors

“…Until now, the majority of studies that used functional imaging as biomarkers26,27 were conducted on patients with RCC, HCC, and glioma.…”

Qualification of a Noninvasive Magnetic Resonance Imaging Biomarker to Assess Tumor Oxygenation

“…On the one hand, attempts are made to target the established tumor vasculature or neovasculature by the use of antivascular or antiangiogenic agents (2-6), whose effects are traditionally assessed noninvasively not only using dynamic contrast MRI (DCE-MRI) after administration of an exogenous paramagnetic contrast agent (7)(8)(9), but also possibly using endogenous hemodynamic markers, including BOLD-MRI (blood oxygen level dependent MRI; ref. 10).…”

Vascular Endothelial Growth Factor (VEGF), Mast Cells and Inflammation

“…The progressive destruction of cartilage and bone in RA is a result of elevated pro-inflammatory cytokine gene expression and synovial neovascularization due to the expression of VEGF which has been shown to be the critical angiogenesis factor responsible for vascular proliferation and blood vessel invasion of the synovial lining membrane (97)(98). The major mechanism of anti-inflammatory agents (NSAID) used in RA is a shared pathway dependent on the suppression of NF-kappaB activity, which may subsequently decrease transcription of growth factors such as VEGF.…”