Tumor marker-based definition of the transarterial chemoembolization-refractoriness in intermediate-stage hepatocellular carcinoma: A multi-cohort study

Jun Sik Yoon, Dong Hyun Sinn, Jeong Hoon Lee, Hwi Young Kim, Cheol Hyung Lee, Sun Woong Kim, Hyo Young Lee, Joon Yeul Nam, Young Chang, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Hyo Cheol Kim, Jin Wook Chung, Yoon Jun Kim, Jung Hwan Yoon

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2 Scopus citations

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 (∆MoRAL) 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 ∆MoRAL 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 ∆MoRAL 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.

Original languageEnglish
Article number1721
JournalCancers
Volume11
Issue number11
DOIs
StatePublished - Nov 2019

Keywords

  • Alpha-fetoprotein
  • Hepatocellular carcinoma
  • Protein induced by vitamin K absence-II
  • Tumor biology
  • Tumor marker

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