Prognostic impact of sarcopenia in patients with hepatocellular carcinoma treated with PD-1 inhibitor

Abstract

Background: Sarcopenia is a progressive generalized loss of skeletal muscle mass commonly observed in advanced stages of cancer. Objective: To assess the relationship between sarcopenia and the prognosis of patients with hepatocellular carcinoma (HCC) treated with a programmed cell death 1 (PD-1) inhibitor. Design: This is a retrospective study. Methods: This study included patients with HCC treated with camrelizumab between 1 March 2020 and 1 December 2021. The skeletal muscle area at the L3 vertebra middle level was used to calculate the skeletal muscle index. Propensity score matching (PSM) analysis was used to balance the variables between the two groups. Results: In all, 97 patients with HCC were included in the study, with 46 and 51 patients in the sarcopenia group and the non-sarcopenia group, respectively. The baseline characteristics of albumin, Child-Pugh class, albumin–bilirubin score, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were significantly different between the two groups. In total, 26 patients from each group ( n = 52) were selected after the PSM analysis. The progression-free survival (PFS) in the non-sarcopenia group was significantly longer than that in the sarcopenia group before and after PSM analysis (6.5 versus 4.8 months, p = 0.038). In addition, the disease control rate was similar before and after PSM analysis (57.7% versus 69.2%, p = 0.388). The objective response rate in the non-sarcopenia group tended to be higher than that in the sarcopenia group (11.5% versus 30.8%, p = 0.090, after PSM), but no statistically significant difference was found. The median overall survival (OS) in the non-sarcopenia group tended to longer than it in the sarcopenia group before PSM without significant differences (16.3 versus 11.3 months, p = 0.090) and the median OS was similar between the two groups after PSM (16.3 versus 16.8 months, p = 0.735). Conclusions: HCC patients with sarcopenia tended to have higher levels of inflammation and lower levels of albumin than patients without sarcopenia. Sarcopenia is associated with a shorter PFS in HCC patients treated with PD-1 inhibitor.

Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis

“…The meta-analysis included 20 retrospective studies involving a total of 2377 patients with HCC who received systemic therapy [11,12,[14][15][16][17][19][20][21][22][23][24][25][26][31][32][33][34][35][36]. One study reported the prevalence of LSMM and survival analysis results separately for lenvatinib and immunotherapy [20], while another conducted survival analysis separately for males and females [16].…”

“…Earlier studies investigated the effect of LSMM on survival in patients undergoing HCC treatment. Among patients receiving immunotherapy [11,[19][20][21][22][23], most studies report no significant association between LSMM and survival [20,24,25], with the exception of two studies [19,26]. Therefore, an updated review and meta-analysis of this topic is needed to gain a better understanding of the relationship between LSMM and the outcomes of HCC patient undergoing a variety of systemic therapy regimes.…”

Prognostic Effect of Sarcopenia in Hepatocellular Carcinoma Patients Targeted with Interventional Therapy Combined with Immunotherapy and Targeted Therapy

“…Regarding the correlation between immunotherapy or immune-targeted combination therapy and sarcopenia, multiple studies have presented varying perspectives. [29][30][31][32] Kuo et al 19 conducted a meta-analysis on the 184 aforementioned studies, ultimately indicating the widespread presence of low skeletal muscle mass in HCC patients undergoing different systemic treatment types, significantly correlating with adverse prognosis. Compared to our study, despite differences in the cut-off values used in various studies, the majority utilized L3-SMI to assess muscle mass, consistent with our research methodology.…”

The Negative Impact of Sarcopenia on Hepatocellular Carcinoma Treatment Outcomes

“…On the other hand, in camrelizumab-treated patients, sarcopenia was related to lower PFS but not to a lower OS, even if a trend toward lower OS in sarcopenic individuals was observed [125]. The presence of sarcopenia was related to higher inflammatory markers and lower levels of albumin, another marker of both malnutrition and reduced liver function [125].…”

“…A European study conducted on patients treated with various anti-PDL1 regimens confirmed that sarcopenia negatively affected OS, especially in patients with higher systemic inflammation activation [124]. On the other hand, in camrelizumab-treated patients, sarcopenia was related to lower PFS but not to a lower OS, even if a trend toward lower OS in sarcopenic individuals was observed [125]. The presence of sarcopenia was related to higher inflammatory markers and lower levels of albumin, another marker of both malnutrition and reduced liver function [125].…”