Management of Systemic Therapies and Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma Based on Sarcopenia Assessment

Abstract

<b><i>Background:</i></b> Sarcopenia, defined as the loss of skeletal muscle mass (MM), physical performance, and strength, has been associated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients treated with several therapies. As systemic therapies, including molecular targeted agents, have a strong impact on sarcopenia, we aimed to review the impact of sarcopenia in patients receiving systemic therapies, especially sorafenib and hepatic arterial infusion chemotherapy (HAIC). <b><i>Summary:</i></b> Several studies have demonstrated that sarcopenia is associated with poor clinical outcomes in patients receiving sorafenib or lenvatinib, while HAIC has no association with overall survival (OS) and sarcopenia. Furthermore, based on our previous study, we developed the management of sorafenib score (MS score) to stratify patients’ survival according to the positivity of three parameters (skeletal MM, disease control of sorafenib, and post-sorafenib therapy), ranging from 0 to 3. Patients with an MS score ≥2 (median survival time [MST], 16.4 months) showed significantly longer survival than those with an MS score ≤1 (MST, 8.4 months) (<i>p</i> < 0.001). This result indicates that patients need at least two positive parameters to prolong OS. Although performance status (PS) has been used in the Barcelona Clinic Liver Cancer staging system, we consider that the assessment of sarcopenia has the potential to replace PS. <b><i>Key Messages:</i></b> Sarcopenia is associated with poor clinical outcomes in patients of HCC receiving sorafenib or lenvatinib. The MS score, based on the positivity of three prognostic factors, including skeletal MM, in patients receiving sorafenib, can be a reliable indicator of prolonged survival.

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

“…The long-term prognosis for patients with HCC is heavily influenced by liver reserve, cancer staging, and patient performance [4,5]. Unfortunately, the current systems used for determining cancer stage and prognosis lack parameters that consider nutritional, functional, and performance status [5,6]. One such factor is sarcopenia, which independently predicts poor overall survival (OS) and progression-free survival (PFS) in HCC patients [7,8].…”

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

“…It has been reported that sarcopenia is associated with poor prognosis in HCC patients, including surgical treatment, molecular targeted therapy, and interventional therapy. [16][17][18]23,40,41 In this study, we found that there was a significant negative correlation between SMI and maximum tumor dimension, PLT, and ALP, and we speculated that SMI may be related to liver synthesis and catabolism and tumor characteristics. Although the underlying mechanism is not fully elucidated, protein catabolism in diseases such as cancer can lead to significant loss of muscle mass and can be seen in up to 40% of patients with liver cirrhosis.…”

“…Notably, although several academic organizations have published diagnostic criteria for sarcopenia, an agreement has not been reached. [20][21][22][23] In terms of previous studies, the cut-off point of SMI may be the median, the optimal cut-off value, or according to the recommendations of academic society groups, which may differ depending on the number of patients or by patient ethnicity. 23 In this study, to reduce the influence of factors other than SMI, we defined the median value of SMI as the cutoff value for sarcopenia.…”

“…[20][21][22][23] In terms of previous studies, the cut-off point of SMI may be the median, the optimal cut-off value, or according to the recommendations of academic society groups, which may differ depending on the number of patients or by patient ethnicity. 23 In this study, to reduce the influence of factors other than SMI, we defined the median value of SMI as the cutoff value for sarcopenia. Body mass index (BMI) was defined as weight (kg)/ height (m 2 ), and SMI was defined as the total cross-sectional skeletal muscle area in the L3 plane (cm 2 )/height (m 2 ).…”

Evaluation of Multiple Liver Cancer Scoring Systems

“…[ 62 ] A study based on the Japanese population found that the HKLC staging system was superior to the BCLC staging system in predicting the survival rate of liver cancer patients after radiofrequency ablation (RFA), and the HKLC staging system could better guide the indications and scope of RFA treatment. [ 63 ]…”