Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

Abstract

Abstract. The present study aimed to examine the impact of sarcopenia, defined as low muscle mass on computed tomography (CT), prior to sorafenib therapy on the clinical outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib therapy. In total, 232 patients with unresectable HCC (median age, 72 years) were analyzed, and the extent of sarcopenia was assessed using CT. Cross-sectional areas (cm 2 ) of the skeletal muscles at the third lumbar vertebra level were determined by manual outlining on the CT images. The cross-sectional areas were normalized for height [skeletal rates, progression-free survival (PFS) rates and best treatment response of the sarcopenia group were retrospectively compared with those of the non-sarcopenia group, and the factors associated with OS and PFS were examined. Sarcopenia was observed in 151 patients (65.1%). There were 165 patients with Child-Pugh A and 67 with Child-Pugh B cirrhosis. In the sarcopenia group, the median treatment duration was 66 days, whereas in the non-sarcopenia group it was 103 days (P=0.001). The median OS time was 174 days in the sarcopenia group and 454 days in the non-sarcopenia group (P<0.0001). The median PFS was 77 days in the sarcopenia group and 106 days in the non-sarcopenia group (P=0.0131). Multivariate analysis identified sarcopenia to be an independent predictor of OS (hazard ratio, 0.365; P<0.0001). The objective response rate and disease control rate in the sarcopenia group were significantly lower, compared with those in the non-sarcopenia group (P=0.0146 and P=0.0151, respectively). In conclusion, sarcopenia may be an indicator of poor clinical course in patients with HCC receiving sorafenib. IntroductionHepatocellular carcinoma (HCC) is one of the major causes of cancer-associated mortality worldwide, accounting for 5.7% of all newly diagnosed malignancies (1-5). The annual incidence rates of HCC are the highest in East Asia and Sub-Saharan Africa, where >80% of all known cases develop (1-5). Advances in treatments for HCC during the last few decades markedly improved the prognosis of the disease (1,2,4,5). However, a curative therapy such as surgical resection may be applied to a limited number (<20%) of patients with HCC (5,6). Sorafenib is a multi-kinase inhibitor that suppresses cancer growth and cell proliferation (7,8). Two pivotal randomized phase III studies, namely the Sorafenib HCC Assessment Randomized Protocol study (7)

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma

“…However, we found no significant differences regarding the reasons for sorafenib withdrawal such as adverse events, deterioration of liver function, and disease progression between the no muscle depletion with H-VFA group and the other groups (data not shown). Similar results have been found in other studies [16, 18]. …”

“…Although sarcopenia has been reported to be an independent predictor of survival in patients with various cancers including HCC [11-15], there have been only three studies on HCC patients treated with sorafenib [16-18]. However, there have been no studies focusing on both skeletal muscle and visceral fat in HCC patients treated with sorafenib.…”

“…In particular, sarcopenia has been reported to be an independent predictor of survival in patients with lung, gastrointestinal, pancreatic, and colorectal cancer as well as HCC [11-15]. For HCC patients receiving sorafenib therapy, it has been reported that skeletal muscle depletion is an independent prognostic factor [16-18]. However, visceral fat area (VFA) is a controversial topic regarding its effects on survival of patients with HCC [15, 19-21].…”

Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

“…We further excluded 5 studies: 1 investigated muscle depletion in patients on the waiting list for liver transplantation but excluded those with HCC [15], 1 was the subgroup analysis of a published cohort study [16], 1 presented with a result inconsistent with its statistical analysis [17], and 2 lacked available data to estimate HRs of the association between sarcopenia and our desired outcomes [18,19]. The final meta-analysis included 13 studies, comprising 3,111 patients ( Fig.…”

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment

“…[11][12][13][14][15] Its presence has also been associated with increased toxicity in patients with HCC treated with sorafenib 16 and reduced survival, but the few data available come mainly from oriental series, where ethnic and anthropometric differences limit reproducibility in a Western setting. [17][18][19] Only one Western study is available, with a limited number of patients treated with various tyrosine kinase inhibitors. 20 The aim of the present study was to identify the prevalence and influence of sarcopenia in a homogeneous population of European Caucasian patients with advanced HCC undergoing sorafenib therapy.…”