Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial

United European Gastroenterol J. 2024 Oct;12(8):1016-1027. doi: 10.1002/ueg2.12627. Epub 2024 Jul 15.

Abstract

Background and aims: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC.

Methods: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis.

Results: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04.

Conclusions: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS.

Impact and implications: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

Keywords: HCC; MASH; MASLD; albumin; alcoholic liver disease; hepatocellular cancer; myosteatosis; survival; target therapy; viral.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Body Mass Index
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / mortality
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Male
  • Middle Aged
  • Muscle, Skeletal* / pathology
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use
  • Serum Albumin / analysis
  • Serum Albumin / metabolism
  • Sorafenib* / therapeutic use

Substances

  • Sorafenib
  • Antineoplastic Agents
  • Phenylurea Compounds
  • Serum Albumin
  • Niacinamide