title: 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.
authors.affiliation: Centre for Imaging Sciences, University of Manchester, Manchester, United Kingdom. james.o'connor@manchester.ac.uk
authors.forename: James P B
authors.initials: JP
authors.lastname: O'Connor
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Jayson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A