P16.06 * EARLY PERFUSION CHANGES IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS TREATED WITH BEVACIZUMAB: PRELIMINARY EVALUATION BY THE PARAMETRIC RESPONSE MAP DERIVED FROM DYNAMIC CONTRAST-ENHANCED MRI

Abstract

OBJECTIVE: To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by the Parametric Response Map derived from Dynamic Contrast-Enhanced MRI (DCE-MRI), may be a predictor of the response to treatment assessed through conventional MRI follow-up. METHODS: 20 patients have been enrolled in the present study. For each patient two DCE-MRI examinations, before and after the first dose of bevacizumab, were acquired. The region of interest was defined on the IAUGC (Initial Area Under Gadolinium Concentration) maps, using co-registered T1-weighted contrast-enhanced images as a guide to the tumour location. For both perfusion parameters, the parametric response map (PRM) (1) was calculated. The PRM is a voxel-wise analytic method allowing to identify and quantify the regions wherein the parameter value increased, decreased or remained stable, during or after therapy. The modifications of hyper and hypo-perfused sub-volumes, including tumour necrosis, was assessed within the lesion using a volumetric histogram analysis. The significance of changes in the different perfusion metrics, observed at baseline and during treatment, was established. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. On the same patients, serial evaluations of plasma and serum VEGF levels and Von Willebrand factor (vWF) antigen were performed at the same time points. RESULTS: Early significant reductions in both IAUGC and Ktrans values, after a single dose of bevacizumab, were observed. Both the PRMs and the histogram modifications indicated the normalizing effect of bevacizumab on tumour pathological vasculature. An improvement in hypoxia after a single dose of bevacizumab seems to be predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up and a better response to treatment. Circulating plasma levels of VEGF and vWF antigen significantly increased in all patients after a single dose of bevacizumab. Preliminary results showed a tendency to a significant relationship between changes in median IAUGC and in levels of vWF antigen, while no correlation was found between changes in tumour size and circulating parameters. CONCLUSIONS: Early monitoring of the modifications induced on perfusion maps, derived from DCE-MRI, as well as the variations of vWF antigen, may provide useful information to document and predict the effect of anti-angiogenic agents. REFERENCE: 1. Galbán, C.J. et al. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. CLIN CANCER RES. 2011 Jul 15;17(14):4751-4760.