Response of nonenhancing regions in glioblastoma to VEGF-signaling inhibitor cediranib correlates with tumor infiltration.

Abstract

3036 Background: Antiangiogenic therapy has limited direct antitumor effect in glioblastoma (GBM). Mainly its benefits may derive from anti-permeability and anti edema effects. In GBMs treated with cediranib we found that regions on MRI that are suggestive of being vasogenic edema, according to Diffusion Tensor Imaging (DTI) data, experience a greater decrease in volume than non-enhancing regions suggestive of being tumor infiltrated. Methods: Thirty-four newly diagnosed GBM patients were scanned on 3Tesla Siemens at two pre-therapy time points (2 days apart). Patients were treated with cediranib, standard radiation and temozolomide. Due to technical difficulties, 4 patients were left out of the analysis. Diffusion images were acquired with TR=7500ms, TE=84ms and b-values 0 and 700s/mm2 in 42 directions. A board certified radiologist determined the extent of abnormality on FLAIR and T1-weighted post contrast images. Non-enhancing regions (NER) were determined by subtracting the T1 enhancing area and any necrosis from the FLAIR abnormality. Volume of NERs was observed at baseline and day 47 of treatment. Mean Apparent Diffusion Coefficient (ADC) and mean Fractional Anisotropy (FA) of the NER were used to represent extent of tumor burden. Tumor Infiltration Index (TII), a measure based on comparing DTI metrics in metastatic tumors to GBM, was also derived. Twelve patients with metastatic cancer to the brain who underwent the same imaging and analysis pretreatment were used. High FA and low ADC and TII represent areas with more tumor burden. Results: There was a significant correlation between mean FA in the NERs at baseline and the percent volume reduction of the NER at day 47 (rho=0.45, p<0.02). Similarly, ADC and TII were correlated with percent volume reduction in the NER. Conclusions: DTI metrics have been used in GBMs to measure tumor infiltration. We found volume reduction of NERs to be inversely correlated to tumor burden. Thus, glioma patients with greater vasogenic edema may benefit from a different treatment paradigm than patients with lower vasogenic edema. [Table: see text]