NIMG-57. SURVIVAL ANALYSIS OF GLIOBLASTOMA (GBM) PATIENTS RECEIVING NEURAL STEM CELL (NSC)-MEDIATED TREATMENT USING T1-WEIGHTED DYNAMIC CONTRAST ENHANCED (DCE) MRI

Abstract

The aim of this study was to investigate the effect of tissue perfusion on response to neural stem cell (NSC)-mediated enzyme/prodrug gene therapy and overall survival (OS) of patients with recurrent GBM. This retrospective study includes 12 GBM patients who received NSC-mediated tumor localized 5-Flurouracil chemotherapy production in a first-in-human trial. Perfusion parameters including plasma volume (Vp), permeability (Ktrans) and leakage (λtr) were extracted from DCE-MRIs at three time-points; MRI1-start of the treatment, MRI2-end of the treatment, MRI3-one month follow-up. Relative change in perfusion parameters between MRI2 and MRI3 was calculated by Δ=(MRI3–MRI2)/MRI2. Contrast-enhanced tumor volume was computed from T1-weighted post-contrast MRI at each time point. The effect of perfusion parameters on OS was evaluated with Cox regression. Imaging results were compared with histologic evaluation of surgical specimens. Higher ΔVp and Δλtr as continuous measures were associated with worse OS (p<0.01, log-rank). Additionally, the cut-point of ΔVp>1.4 was associated with a median OS of 2 months (95% CI 0.13-NR) versus 13.0 months for ΔVp≤1.4 (95% CI 9.0-NR, p<0.01, log-rank). Δλtr> 0.4 was associated with a median OS of 4.5 months (0.13-NR) versus 14.5 months (9-NR) otherwise (p<0.03). Volume of contrast enhancement did not show any significant correlation. Imaging findings of vessel and cell density agreed with qualitative assessments of surgical specimens. The positive correlation of leakage with OS at MRI2 could be explained by increased diffusion of the prodrug to the NSCs and thus the chemotherapy to the tumor cells. ΔVp and Δλtr effects on OS could be explained by a decrease in vessel density due to increased response to treatment resulting from improved penetration of the prodrug. Our results show the potential value of DCE-MRI parameters to predict survival and may be useful as a measure of treatment response following NSC-mediated therapy.