Abstract
Background: For patients with hepatocellular carcinoma (HCC), the definition of refractoriness to transarterial chemoembolization (TACE), which might make them a candidate for systemic therapy, is still controversial. We aimed to derive and validate a tumor marker-based algorithm to define the refractoriness to TACE in patients with intermediate-stage HCC. Methods: This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We derived a prediction model for overall survival (OS) using the pre- and post-TACE model to predict tumor recurrence after living donor liver transplantation (MoRAL) (i.e., MoRAL score = 11×√protein induced by vitamin K absence-II + 2×√alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193). These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149). Results: The changes in MoRAL score (ΔMoRAL) after initial TACE was an independent predictor of OS (MoRAL-increase vs. MoRAL-non-increase: adjusted hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.37–3.46, p = 0.001; median OS = 18.8 vs. 37.8 months). In a subgroup of patients with a high baseline MoRAL score (≥89.5, 25th percentile and higher), the prognostic impact of ΔMoRAL was more pronounced (MoRAL-increase vs. MoRAL-non-increase: HR = 3.68, 95% CI = 1.54–8.76, p < 0.001; median OS = 9.9 vs. 37.4 months). These results were reproduced in the external validation cohorts. Conclusion: The ΔMoRAL after the first TACE, a simple and objective index, provides refined prognostication for patients with intermediate-stage HCC. Proceeding to a second TACE may not provide additional survival benefits in cases of a MoRAL-increase after the first TACE in patients with a high baseline MoRAL score (≥89.5), who might be candidates for systemic therapy.
Highlights
Hepatocellular carcinoma (HCC) is an aggressive tumor that is the fourth leading cause of cancer-related mortality worldwide [1]
Assessment for Retreatment with transarterial chemoembolization (TACE) (ART) score [7] and the ABCR (standing for alpha-fetoprotein (AFP), BCLC, Child-Pugh, and Response) score [8], which have been controversial in their efficacy in retrospective validation studies [9,10,11,12]
Among the 745 patients who were admitted to SNUH with treatment-naïve intermediate-stage hepatocellular carcinoma (HCC), 290 patients were eligible for this study and 97 patients were excluded according to exclusion criteria (Supplementary Figure S1A)
Summary
Hepatocellular carcinoma (HCC) is an aggressive tumor that is the fourth leading cause of cancer-related mortality worldwide [1]. There have been several decision-making models developed for TACE retreatment, such as the Assessment for Retreatment with TACE (ART) score [7] and the ABCR (standing for alpha-fetoprotein (AFP), BCLC, Child-Pugh, and Response) score [8], which have been controversial in their efficacy in retrospective validation studies [9,10,11,12] Such scoring systems for TACE retreatment were not adopted in the most recent practice guidelines [13,14]. (i.e., MoRAL score = 11× protein induced by vitamin K absence-II + 2× alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193) These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
