1016TiP LEAP-012 trial in progress: Pembrolizumab plus lenvatinib and transarterial chemoembolization (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC) not amenable to curative treatment

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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The Combination Strategy of Transarterial Chemoembolization and Radiofrequency Ablation or Microwave Ablation against Hepatocellular Carcinoma

Analytical Cellular Pathology ◽

10.1155/2019/8619096 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Zhentian Xu ◽

Haiyang Xie ◽

Lin Zhou ◽

Xinhua Chen ◽

Shusen Zheng

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Clinical Data ◽

Transarterial Chemoembolization ◽

Microwave Ablation ◽

Great Majority ◽

Intermediate Stage ◽

Combination Strategy ◽

Term Outcome ◽

Long Term Outcome

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hepatectomy and liver transplantation (LT) are regarded as the radical treatment, but great majority of patients are already in advanced stage on the first diagnosis and lose the surgery opportunity. Multifarious image-guided interventional therapies, termed as locoregional ablations, are recommended by various HCC guidelines for the clinical practice. Transarterial chemoembolization (TACE) is firstly recommended for intermediate-stage (Barcelona Clinic Liver Cancer (BCLC) B class) HCC but has lower necrosis rates. Radiofrequency ablation (RFA) is effective in treating HCCs smaller than 3 cm in size. Microwave ablation (MWA) can ablate larger tumor within a shorter time. Combination of TACE with RFA or MWA is effective and promising in treating larger HCC lesions but needs more clinical data to confirm its long-term outcome. The combination of TACE and RFA or MWA against hepatocellular carcinoma needs more clinical data for a better strategy. The characters and advantages of TACE, RFA, MWA, and TACE combined with RFA or MWA are reviewed to provide physician a better background on decision.

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