Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil

Background & Aims: Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients. This study evaluated the correlation of vascular response measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the clinical outcome. Methods: DCE-MRI was performed in advanced HCC patients treated with sorafenib (800 mg/d) plus tegafur/uracil (250 mg/m(2)/d based on tegafur) at baseline and after 14 days of treatment. An operator-defined region of interest was placed in the most strongly enhanced area of the tumor to measure the pharmacokinetic parameter K-trans. Changes in K-trans after treatment were correlated with the best tumor response and survival. Results: Thirty-one patients were evaluable. There were one partial response (PR), 18 stable disease (SD), and 12 progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline K-trans was higher in patients with PR or SD (median 1215.2 x 10(-3)/min, range 582.5-4555.3 x 10(-3)/min) than patients with PD (median 702.0 x 10(-3)/min, range 375.2-1938.0 x 10(-3)/min, p = 0.008). After 14 days of study treatment, the median K-trans change was -47.1% (range -87.0 to -18.0%) in patients with PR or SD, and 9.6% (range -44.8 to +81%) in those with PD (p < 0.001). A vascular response, defined by a 40% or greater decrease in K-trans after 14 days of study treatment, correlated with longer progression-free survival (median 29.1 vs. 8.7 weeks, p = 0.033) and overall survival (median 53.0 vs. 14.9 weeks, p = 0.016). Percentage of K-trans change after treatment is an independent predictor of tumor response, progression-free survival, and overall survival. Conclusions: K-trans measured by DCE-MRI correlated well with tumor response and survival in HCC patients who received sorafenib plus metronomic tegafur/uracil therapy. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.