Prognostic significance of early changes in the apparent diffusion coefficient that occurs after treatment of patients with glioblastoma multiforme with bevacizumab

2058 Background: To determine the prognostic significance of changes in parameters derived from diffusion tensor imaging (DTI) that occur in response to combination chemotherapy with the antiangiogenesis agent bevacizumab (BEV) in patients with recurrent glioblastoma multiforme (GBM). Methods: 16 patients (10 men, 6 women; age range 38–62 years) with recurrent GBM underwent serial 1.5T MR imaging. Axial single-shot echo planar DTI (TR/TE 6000/100; flip angle 90 degrees; voxel: 1.72 x 1.72 x 5mm; b value of 1000 sec/mm2; 12 directions) was obtained on scans performed 3 days and 1 day prior to and 1 day after initiation of therapy with BEV and irinotecan (CPT-11). Clinical follow-up and survival status was documented up to 20 months after the date of initial MR imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were aligned to whole brain contrast-enhanced 3D FLASH and 3D FLAIR image volumes (1 mm isotropic voxels) using a rigid body normalized mutual information algorithm. Based on two pre-treatment scans, the 95% confidence limits for change (95%CL) in ADC and FA were calculated in volumes of tumor-related contrast-enhancement (TRE) and FLAIR signal abnormality (FSA). A patient was considered to have a change in FA or ADC after therapy if the difference between the pre- and post-treatment values was greater than the 95% CL for that parameter. Progression was defined on contrast-enhanced MRI using MacDonald criteria by neuro-oncologists blinded to the DTI findings. Survival was compared using the log rank test. Results: DTI detected a change in ADC within FSA after therapy in three patients (2 increased, 1 decreased). Patients with a change in ADC within FSA had significantly shorter overall (p < 0.0012) and progression free (p < 0.015) survival than those with no change. Median survival in the patient group with a change in ADC was 24.7 (95% CI [17.3, 39.4]) weeks and 56.4 (95% CI [41.7, 96]) weeks in those patients with no change. Conclusions: In patients with GBM treated with BEV and CPT-11, a change in ADC after therapy in areas of FSA is associated with decreased survival. Parameters derived from DTI may, therefore, potentially serve as early markers of treatment failure in patients with GBM. [Table: see text]