Dynamic Muscle Atrophy Predicts Outcomes in Patients with Unresectable Hepatocellular Carcinoma Treated with First-Line Lenvatinib: A Retrospective Study in Taiwan.

Background/aims: Muscle volume loss (MVL) is associated with poor outcomes in patients with hepatocellular carcinoma (HCC). However, dynamic muscle atrophy during HCC treatment is also a critical concern. This study aimed to determine the clinical significance of MVL and severe muscle atrophy following lenvatinib treatment among patients with unresectable HCC.

Methods: This study included 302 patients with unresectable HCC who received first-line lenvatinib between July 2019 and December 2022. MVL was defined using the psoas muscle index, while severe muscle atrophy was classified as a ≥1.5% decrease in the psoas muscle index per month after lenvatinib initiation. To reduce the risk of selection bias, propensity score matching was performed.

Results: After propensity score matching, 168 patients were included, comprising 112 non-MVL and 56 MVL patients. The MVL group had significantly worse overall survival (9.9 months vs 15.0 months, p=0.021) and a higher incidence of treatment-related adverse events (82.8% vs 66.6%, p=0.03) than the non-MVL group. Among 128 patients with dynamic imaging assessments, those with severe muscle atrophy (n=76) had significantly shorter progression-free survival (4.1 months vs 10.9 months, p<0.001) and overall survival (11.1 months vs 25.9 months, p<0.001) than patients with mild atrophy. Multivariate analysis revealed that severe muscle atrophy was an independent risk factor for progression-free survival (hazard ratio [HR], 2.388; 95% confidence interval [CI], 1.519 to 3.756; p<0.001) and overall survival (HR, 2.130; 95% CI, 1.152 to 3.939; p=0.016), while MVL was not.

Conclusions: In real-world clinical practice, severe muscle atrophy is a stronger prognostic indicator than MVL among patients with unresectable HCC treated with first-line lenvatinib.