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Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study

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 refra...

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Autores principales: Yoon, Jun Sik, Sinn, Dong Hyun, Lee, Jeong-Hoon, Kim, Hwi Young, Lee, Cheol-Hyung, Kim, Sun Woong, Lee, Hyo Young, Nam, Joon Yeul, Chang, Young, Lee, Yun Bin, Cho, Eun Ju, Yu, Su Jong, Kim, Hyo-Cheol, Chung, Jin Wook, Kim, Yoon Jun, Yoon, Jung-Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896068/
https://www.ncbi.nlm.nih.gov/pubmed/31689972
http://dx.doi.org/10.3390/cancers11111721
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author Yoon, Jun Sik
Sinn, Dong Hyun
Lee, Jeong-Hoon
Kim, Hwi Young
Lee, Cheol-Hyung
Kim, Sun Woong
Lee, Hyo Young
Nam, Joon Yeul
Chang, Young
Lee, Yun Bin
Cho, Eun Ju
Yu, Su Jong
Kim, Hyo-Cheol
Chung, Jin Wook
Kim, Yoon Jun
Yoon, Jung-Hwan
author_facet Yoon, Jun Sik
Sinn, Dong Hyun
Lee, Jeong-Hoon
Kim, Hwi Young
Lee, Cheol-Hyung
Kim, Sun Woong
Lee, Hyo Young
Nam, Joon Yeul
Chang, Young
Lee, Yun Bin
Cho, Eun Ju
Yu, Su Jong
Kim, Hyo-Cheol
Chung, Jin Wook
Kim, Yoon Jun
Yoon, Jung-Hwan
author_sort Yoon, Jun Sik
collection PubMed
description 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.
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spelling pubmed-68960682019-12-23 Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study Yoon, Jun Sik Sinn, Dong Hyun Lee, Jeong-Hoon Kim, Hwi Young Lee, Cheol-Hyung Kim, Sun Woong Lee, Hyo Young Nam, Joon Yeul Chang, Young Lee, Yun Bin Cho, Eun Ju Yu, Su Jong Kim, Hyo-Cheol Chung, Jin Wook Kim, Yoon Jun Yoon, Jung-Hwan Cancers (Basel) Article 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. MDPI 2019-11-04 /pmc/articles/PMC6896068/ /pubmed/31689972 http://dx.doi.org/10.3390/cancers11111721 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoon, Jun Sik
Sinn, Dong Hyun
Lee, Jeong-Hoon
Kim, Hwi Young
Lee, Cheol-Hyung
Kim, Sun Woong
Lee, Hyo Young
Nam, Joon Yeul
Chang, Young
Lee, Yun Bin
Cho, Eun Ju
Yu, Su Jong
Kim, Hyo-Cheol
Chung, Jin Wook
Kim, Yoon Jun
Yoon, Jung-Hwan
Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
title Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
title_full Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
title_fullStr Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
title_full_unstemmed Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
title_short Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
title_sort tumor marker-based definition of the transarterial chemoembolization-refractoriness in intermediate-stage hepatocellular carcinoma: a multi-cohort study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896068/
https://www.ncbi.nlm.nih.gov/pubmed/31689972
http://dx.doi.org/10.3390/cancers11111721
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