Pre-sarcopenia determines post-progression outcomes in advanced hepatocellular carcinoma after sorafenib failure

Abstract

Many second-line therapies are recently approved for patients with advanced hepatocellular carcinoma (HCC), in whom protein malnutrition is prevalent that would affect treatment outcomes. In this study, we aimed to investigate the role of pre-sarcopenia and muscle restoration in patients with sorafenib-failed advanced HCC. From August 2012 to March 2017, 385 patients who developed radiology-proven HCC progression after sorafenib treatment were enrolled in the study. Pre-sarcopenia is defined as transverse psoas muscle thickness per body height < 16.8 mm/m, which was prevalent (64.7%) in our patients. Age > 60 years, female gender, and body mass index < 22 kg/m2 were independent predictors to the development of pre-sarcopenia. Patients with muscle depletion had significantly worse post-progression survival (PPS) compared with their counterparts (median PPS: 3.8 vs. 5.8 months, p = 0.003), particularly in those with intermediate liver reserves (Child–Pugh class B or Albumin-bilirubin grade 2). Besides, pre-sarcopenia independently predicted post-progression mortality in sorafenib-failed HCC (hazard ratio: 1.340, p = 0.012). In patients who developed pre-sarcopenia before sorafenib treatment, muscle restoration was associated with a longer PPS compared with their counterparts (6.3 vs. 3.6 months, p = 0.043). In conclusion, pre-sarcopenia independently determined the outcomes of sorafenib-failed HCC. Nutrition support to restore muscle mass would prolong survival for higher-risk patients.

Prognostic value of low skeletal muscle mass in hepatocellular carcinoma patients treated with sorafenib or lenvatinib: A meta-analysis

“…After being excluded by titles and abstracts, 29 full-text articles were assessed for eligibility. 18 records didn't meet the inclusion criteria and were discarded: 2 involving other kinase inhibitors (Nault et al, 2013[ 28 ], 2015[ 29 ]), 9 with overlapped patient data (Antonelli et al, 2018[ 2 ]; Gigante et al, 2015[ 13 ]; Hoshino et al, 2015[ 16 ]; Imai et al, 2015[ 17 ], 2019[ 19 ]; Labeur et al, 2018[ 23 ][ 24 ]; Okada et al, 2019[ 33 ]; Saeki et al, 2019[ 34 ]), 5 lacking HR and 95 % CI (Mir et al, 2012[ 26 ]; Okada et al, 2020[ 32 ]; Saeki et al, 2018[ 35 ]; Uchikawa et al, 2020[ 39 ]; Ueki et al, 2016[ 40 ]), 1 without any interesting outcome (Cheng et al, 2019[ 7 ]) and 1 with low quality and faulty data (Nishikawa et al, 2017[ 30 ]). Thus, 11 retrospective studies (Antonelli et al, 2018[ 3 ]; Endo et al, 2020[ 10 ]; Hiraoka et al, 2017[ 15 ]; Imai et al, 2020[ 18 ]; Labeur et al, 2019[ 25 ]; Naganuma et al, 2017[ 27 ]; Sawada et al, 2019[ 36 ]; Takada et al, 2018[ 38 ]; Uojima et al, 2020[ 41 ]; Wu et al, 2021[ 43 ]; Yamashima et al, 2017[ 45 ]) were included in this meta-analysis, comprising 1148 patients.…”

Skeletal Muscle Volume Is an Independent Predictor of Survival after Sorafenib Treatment Failure for Hepatocellular Carcinoma

“…As skeletal muscle volume is not associated with time to progression [ 17 ], which is associated with PFS, it has been suggested that it is associated with PPS. However, there have been few studies on the relationship between skeletal muscle volume and PPS [ 33 ]. Although a recent report showed that PPS is significantly associated with pre-sarcopenia at the time of PD in HCC patients receiving sorafenib, the relationship between skeletal muscle volume before sorafenib treatment and PPS has not been established [ 33 ].…”

“…However, there have been few studies on the relationship between skeletal muscle volume and PPS [ 33 ]. Although a recent report showed that PPS is significantly associated with pre-sarcopenia at the time of PD in HCC patients receiving sorafenib, the relationship between skeletal muscle volume before sorafenib treatment and PPS has not been established [ 33 ]. This is the first study to demonstrate that skeletal muscle volume before sorafenib treatment is a significant predictor of PPS, but not PFS.…”

Sarcopenia in hepatocellular carcinoma: Current knowledge and future directions

“…Furthermore, methods to assess the prognosis of HCC patients during/after loco-regional (radiofrequency ablation, radioembolization, chemoembolization), liver transplantation, and systemic therapy (chemotherapy, immunotherapy) could have a long-lasting impact on these individuals. One such objective method is to use sarcopenia to assess the patient response and overall could assist in OS in HCC patients[ 14 , 22 - 34 ]. Therefore, this manuscript aims to describe the role of sarcopenia in the management and prognosis in HCC.…”