The relationship between systemic therapies and low skeletal muscle mass in patients with intermediate and advanced hepatocellular carcinoma

Abstract

Background: Low skeletal muscle mass (LSMM) has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients receiving systemic therapy. However, its impact across different treatment regimens remains unclear. Methods: A retrospective study analyzed 714 patients with intermediate and advanced HCC, divided into immunotherapy (I, n=85), target-immunotherapy combination (I+T, n=545), and targeted therapy (T, n=84) groups based on treatment. Skeletal muscle was assessed via computed tomography (CT) at the third lumbar vertebral level (L3) before and after 3 months of treatment. LSMM was evaluated by the third lumbar skeletal muscle index (L3-SMI) using a predefined threshold. Patients were stratified by baseline values and treatment changes. Kaplan-Meier and Cox models were used to compare overall survival (OS) and progression-free survival (PFS). Results: There was no significant difference in the loss of muscle mass among the three groups of LSMM patients; whereas, non-LSMM(NLSMM) patients in group T lost more muscle mass than those in group I (P=0.040).In the I+T group, patients who achieved an objective response (ORR) had less muscle mass loss than those without (P=0.013), while the changes in muscle mass for patients in the I group and T group were unrelated to treatment response. Baseline or post-treatment LSMM was associated with poorer median OS, especially in the I+T group. Progressive LSMM was linked to shorter median PFS (4.9 vs 5.7 months) and OS (9.8 vs 16.5 months), with similar results in the I+T group (mPFS, 4.2 vs. 5.8 months; mOS, 9.7 vs 16.1 months). Patients with LSMM had a higher incidence of treatment-related SAEs, particularly ascites and fatigue. Conclusion: In patients with combined LSMM in hepatocellular carcinoma, muscle loss did not significantly differ between those treated with I, I+T, and T; however, T treatment contributed to muscle mass loss in NLSMM patients. Greater muscle loss correlated with poorer treatment outcomes and increased SAEs, and baseline, post-treatment, and progressive LSMM were linked to significantly worse prognoses, particularly with combined treatment regimens.