Impact of Low Skeletal Muscle Mass on Long-Term Outcomes in Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization: A Retrospective Multi-Center Study

SIMPLE SUMMARY: Trans-arterial radioembolization (TARE) can effectively treat patients with locally advanced hepatocellular carcinoma (HCC). However, TARE is not widely used in clinical practice due to the lack of consensus on how to select the best candidates for this therapy. Therefore, it is crucial to find predictive biomarkers or clinical parameters that can differentiate the patients who will respond well to TARE and improve their outcomes. Low skeletal muscle mass (LSMM) is one of the factors that affects the prognosis of HCC patients and has been extensively studied in relation to different treatments. We used a semi-automated program that has been validated and proven to be reliable for assessing LSMM. In this study, we aimed to identify prognostic factors, including pre-treatment LSMM, for survival outcomes in patients with HCC undergoing TARE. ABSTRACT: Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90-loaded microspheres. This was a multi-center retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm(2)) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT), and 126 (36.3%) were classified as LSMM. The median overall survival (OS) was 28.1 months (95% CI, 24.8–35.7), and median progression-free survival was 8.0 months (95% CI, 6.4–9.4). Multivariate Cox regression analysis revealed that LSMM (hazard ratio [HR], 1.36; 95% CI, 1.00–1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33–2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04–1.92, p = 0.03), and albumin–bilirubin grade (2–3) (HR 1.74; 95% CI, 1.24–2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment LSMM independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.