Value of Dynamic Contrast Perfusion MRI to Predict Early Response to Bevacizumab in Newly Diagnosed Glioblastoma: Results from ACRIN 6686 Multi-Center Trial.

BACKGROUND 44 patients in RTOG 0825, a phase III trial of standard therapy with bevacizumab or without (placebo) in newly diagnosed glioblastoma, underwent dynamic contrast enhanced and/or dynamic susceptibility contrast MRI in ACRIN 6686. The association between early changes in relative cerebral blood volume (rCBV) and volume transfer constant (Ktrans) with overall survival (OS) was evaluated. METHODS MRI was performed at post-op baseline (S0), immediately before (S1), 1 day (S2), and 7 weeks after (S3) bevacizumab or placebo initiation. Mean normalized and standardized rCBV (nRCBV, sRCBV) and Ktrans were measured within contrast-enhancing lesion. Wilcoxon rank sum tests compared parameter changes from S1-S2 and S1-S3. Association with OS and progression-free survival were determined using Kaplan-Meier and log-rank tests. Treatment response for groups stratified by pretreatment nRCBV (S0, S1) was explored. The intraclass correlation coefficient and repeatability coefficient for the placebo arm (S1-S2) were used to assess repeatability. RESULTS 27-37 datasets were evaluable per time point. Significant differences between treatment arms were found for changes in nRCBV and sRCBV from S1-S2 and S1-S3, and in Ktrans for S1-S3. Improved progression-free survival (p=0.05) but not OS (p=0.46) was observed. High pretreatment rCBV predicted improved OS for bevacizumab-treated patients. Based on the intraclass correlation coefficient, sRCBV (0.92) was more repeatable than nRCBV (0.71) and Ktrans (0.75), consistent with repeatability coefficient values. CONCLUSIONS Bevacizumab significantly changes rCBV but not Ktrans as early as 1 day post-treatment in newly diagnosed glioblastoma unrelated to outcomes. Improvements in clinical trial design to maximize rCBV benefit are indicated.