Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Sorafenib

Abstract

The aim of this study was to determine whether skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma (HCC) that is being treated with sorafenib. We evaluated 40 consecutive HCC patients who received sorafenib treatment. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the L3 skeletal muscle index (L3 SMI) was obtained. The factors contributing to overall survival, sorafenib dose reduction, and discontinuation of sorafenib were analyzed using the Cox proportional hazards model. L3 SMI (p = 0.020) and log (α-fetoprotein (AFP)) (p = 0.010) were identified as independent prognostic factors in HCC patients treated with sorafenib. The initial dose of sorafenib (p = 0.008) was an independent risk factor for sorafenib dose reduction, and log (AFP) (p = 0.008) was the only significant risk factor for the discontinuation of this drug. L3 SMI was not a risk factor for either dose reduction (p = 0.423) or the discontinuation (p = 0.132) of sorafenib. A multiple linear regression analysis determined the following relationship between skeletal muscle mass (assessed as L3 SMI) and the explanatory factors: L3 SMI = −0.1896 × (Age) − 10.3441 × (Child-Pugh score) − 9.3922 × (log (AFP)) + 1.6139 × (log (AFP)) × (Child-Pugh score) + 112.9166. Skeletal muscle depletion is inversely associated with age, Child-Pugh score, and log (AFP). Moreover, it is an independent prognostic factor for HCC patients treated with sorafenib.

Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib

“…This result indicated that these malnutritional factors were important for the survival of patients with HCC treated with sorafenib. Several recent reports indicated that decreased skeletal muscle mass was an important prognostic factor in patients with chronic liver disease and HCC (2,3,5,6). These results suggested that preventing reductions in skeletal muscle thickness may improve the OS of patients treated with sorafenib.…”

“…Recently, an increasing number of studies have demonstrated that sarcopenia may affect the clinical state of patients with liver disease (1)(2)(3). Moreover, skeletal muscle wasting assessed by CT has been reported to be a prognostic marker for patients with hepatocellular carcinoma (HCC) treated with sorafenib (5,6). In those reports, skeletal muscle mass was usually measured by imaging modalities, such as CT and magnetic resonance imaging.…”

Skeletal muscle mass is associated with toxicity, treatment tolerability, and additional or subsequent therapies in patients with hepatocellular carcinoma receiving sorafenib treatment

“…Previous studies have reported that the duration of sorafenib treatment is significantly shorter in patients with LSMM than in non‐LSMM patients . In contrast, others did not investigate the therapy duration . These findings indicate that patients with LSMM are more likely to have a shorter duration of sorafenib treatment than non‐LSMM patients; however, previous studies have indicated that LSMM was associated with survival without analyzing the duration of sorafenib treatment with Cox regression analysis.…”

“…Body mass index (BMI) is usually used as a simple index of obesity that can be easily calculated using a patient's height and weight; however, body composition such as skeletal muscle mass and adipose tissue mass is not exactly reflected by BMI. In terms of prognosis, the effects of BMI are controversial in patients with HCC receiving sorafenib treatment . Sarcopenia, which is defined as both loss of skeletal muscle mass and function, is classified as primary sarcopenia (age‐related) and secondary sarcopenia (activity‐, disease‐, or nutrition‐related) by the European Working Group on Sarcopenia in Older People (EWGSOP) .…”

“…In addition to skeletal muscle mass loss, intramuscular fat and visceral adiposity independently predicted mortality in patients with various stages of HCC in Japan . Several reports have recently demonstrated that skeletal muscle loss is associated with prognosis in patients with unresectable HCC receiving sorafenib treatment . However, only one report indicated that high visceral fat area (VFA) predicted survival in patients with HCC treated with tyrosine kinase inhibitors .…”