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 (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.

Identification of Novel Tumor Microenvironment-Related Long Noncoding RNAs to Determine the Prognosis and Response to Immunotherapy of Hepatocellular Carcinoma Patients

“…Liver cancer is a common malignant tumor globally (Yoon et al, 2019). More than 800,000 new individuals are diagnosed with liver cancer annually, and the number of liver cancer-related deaths has reached approximately 780,000.…”

Survival of Patients with Hepatocellular Carcinoma in Renal Insufficiency: Prognostic Role of Albumin-Bilirubin Grade

“…Radiofrequency ablation was indicated in patients who had small HCC but unsuitable for surgical resection [24]. The criteria for transarterial chemoembolization (TACE) were unresectable HCC with adequate liver functional reserve and no main portal vein thrombosis [25]. Patients with advanced stage HCC were treated with targeted therapy [4].…”

Identification of an Epithelial-Mesenchymal Transition-Related Long Non-coding RNA Prognostic Signature to Determine the Prognosis and Drug Treatment of Hepatocellular Carcinoma Patients

“…Hepatocellular carcinoma (HCC) is one of the most common aggressive tumors that ranks as the fourth leading cause of cancer-related mortality worldwide ( 1 ). Despite the proven efficacies of several treatment methods, such as surgical resection, liver transplantation, ablation therapy, radiotherapy, targeted therapy, systemic chemotherapy, and immunotherapy, the prognosis remains unsatisfactory.…”