Effects of cediranib (VEGF signaling inhibitor) on edema in newly diagnosed glioblastoma patients during initial chemoradiation.

Abstract

2012 Background: A significant benefit of antiangiogenic therapy is control of brain edema. We evaluated the impact of adding cediranib to standard chemoradiation (CRT) on peritumoral edema in patients with newly diagnosed glioblastoma(GBM) during the initial 6 weeks of CRT. Methods: Two cohorts of patients were enrolled in two clinical trials. The control group (N=13) received radiation for 6 weeks plus temozolomide. The cediranib (CED) group received standard CRT plus daily cediranib (N=34). MRIs were performed at baseline and weekly during CRT. Volumes of interest (VOIs) were drawn outlining the enhancing tumor on T1-weighted post contrast images and the abnormal FLAIR hyperintensity. ADC (apparent diffusion coefficient) maps were calculated from diffusion-weighted images and histograms of the distribution of ADC values created for each visit using the baseline FLAIR VOI to characterize the peritumoraledema. Patients were on stable or decreasing doses of steroids. Results: In the CED group, T1 and FLAIR VOI decreased during CRT vs controls where T1 VOI did not change and FLAIR VOI increased. By the end of CRT, the mode of the ADC histogram in the CED group shifted to the left while the mode of the controls shifted to the right. The skewness, a measure of asymmetry of the distribution, increased in the CED group and decreased in controls. Conclusions: In patients with newly diagnosed GBM treated with CRT and cediranib, tumor volume decreased on T1 and FLAIR images whereas the FLAIR volume significantly increased in the control group suggesting increased edema. The shift of mode to the right and decreasing skewness in controls (indicating an increase in the proportion of very high ADC values) suggests that adding cediranibprevented the development of edema and contributed to the resolution of existing edema. Preventing the edema by adding anti-VEGF treatment may improve the tolerability of CRT for GBM patients. [Table: see text]