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

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.

SUBMITTER: Yoon JS

PROVIDER: S-EPMC6896068 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Yoon Jun Sik JS Sinn Dong Hyun DH Lee Jeong-Hoon JH Kim Hwi Young HY Lee Cheol-Hyung CH Kim Sun Woong SW Lee Hyo Young HY Nam Joon Yeul JY Chang Young Y Lee Yun Bin YB Cho Eun Ju EJ Yu Su Jong SJ Kim Hyo-Cheol HC Chung Jin Wook JW Kim Yoon Jun YJ Yoon Jung-Hwan JH

Cancers 20191104 11

<h4>Background</h4>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.<h4>Methods</h4>This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We der ...[more]

PMID: 31689972

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Project description:BACKGROUND:Liver cancer is the fifth most common cancer and the second cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the best treatment of intermediate hepatocellular carcinoma (HCC). Doxorubicin is the most commonly used drug despite a low level of evidence. AIM:To compare the objective response rate of idarubicin-based TACE (Ida-TACE) against doxorubicin-based TACE (Dox-TACE) in intermediate stage HCC. METHODS:Between January 2012 and December 2014, all patients treated with TACE at our academic hospital were screened. Inclusion criteria were patients with Child-Pugh score A or B, a performance status below or equal to 1, and no prior TACE. Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin. Each patient treated with idarubicin was matched with two doxorubicin-treated patients. The TACE response was assessed by independent radiologists according to the mRECIST criteria. RESULTS:Sixty patients were treated with doxorubicin and thirty with idarubicin. There were 93% and 87% of cirrhotic patients and 87% and 70% of Child-Pugh A in the doxorubicin and idarubicin groups, respectively. The median number of HCC per patient was two in both groups with 31% and 26% of single nodules in doxorubicin and idarubicin groups, respectively. Objective response rate after first TACE was 76.7% and 73.3% (P = 0.797) with 41.7% and 40.0% complete response in doxorubicin and idarubicin groups, respectively. Progression-free survival was 7.7 mo in both groups, and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups, respectively. Safety profiles were similar in both groups, with grade 3-4 adverse events in 35% of Dox-TACE and 43% of Ida-TACEs. CONCLUSION:Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety. Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.

Dataset Information

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

Publications

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

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