Quantitative Analysis of Signal Heterogeneity in the Hepatobiliary Phase of Pretreatment Gadoxetic Acid-Enhanced MRI as a Prognostic Imaging Biomarker in Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma

SIMPLE SUMMARY: Transarterial chemoembolization (TACE) is the recommended treatment for intermediate-stage hepatocellular carcinoma (HCC), and its role as a curative treatment is now greater than previously due to the introduction of targeted molecular and immunotherapies. An important current concern is patient selection in TACE for intermediate-stage HCC, which includes an extremely heterogeneous population. The hepatobiliary phase (HEB) in gadoxetic acid disodium-enhanced MRI (EOB-MRI) is related to β-catenin, so EOB-MRI could be a molecular imaging biomarker reflecting tumor biology. Although HCC with signal heterogeneity in the HBP of EOB-MRI showed malignant behavior, no previous study has evaluated prognosis after TACE based on signal heterogeneity quantified in the HBP of EOB-MRI. In this study, we showed a quantitative analysis of tumor signal heterogeneity in HBP on EOB-MRI was valuable in predicting the prognosis after TACE and suggested a treatment strategy for patients with intermediate-stage HCC based on this quantitative evaluation. ABSTRACT: Background: In the era of local and systemic therapies for intermediate-stage hepatocellular carcinoma (HCC), personalized therapy has become available. The aim of our study was to evaluate the usefulness of quantitative analysis of pretreatment gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis following transarterial chemoembolization (TACE). Methods: This retrospective study included patients with treatment-naïve intermediate-stage HCC who underwent EOB-MRI before the initial TACE and were treated by initial TACE between February 2007 and January 2016. Signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantitatively evaluated by the coefficient of variation (CV). The cutoff CV value was determined using the Classification and Regression Tree algorithm. Results: A total of 64 patients were enrolled. In multivariate analysis, High CV (≥0.16) was significantly associated with poor prognosis (p = 0.038). In a subgroup analysis of patients within up-to-7 criteria, MST was significantly shorter in the High CV group than in the Low CV group (37.7 vs. 82.9 months, p = 0.024). In patients beyond up-to-7 criteria, MST was 18.0 and 38.3 months in the High CV and Low CV groups, respectively (p = 0.182). In both groups scanned at 1.5 T or 3.0 T, High CV was significantly associated with poor prognosis (p = 0.001 and 0.003, respectively). Conclusion: CV of the tumor in the HBP of EOB-MRI is a valuable prognostic factor of TACE.