Rapid Depletions of Subcutaneous Fat Mass and Skeletal Muscle Mass Predict Worse Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib

Abstract

The aim of this study was to investigate whether rapid depletions of fat mass and skeletal muscle mass predict mortality in hepatocellular carcinoma (HCC) patients treated with sorafenib. This retrospective study evaluated 61 HCC patients. The cross-sectional areas of visceral and subcutaneous fat mass and skeletal muscle mass were measured by computed tomography, from which the visceral fat mass index (VFMI), subcutaneous fat mass index (SFMI), and skeletal muscle index (L3SMI) were obtained. The relative changes in these indices per 120 days (ΔVFMI, ΔSFMI, and ΔL3SMI) before and after sorafenib treatment were calculated in each patient. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion (RD) group. Kaplan-Meier analysis revealed that with respect to ΔL3SMI (p = 0.0101) and ΔSFMI (p = 0.0027), the RD group had a significantly poorer survival. Multivariate analysis using the Cox proportional-hazards model also demonstrated that ΔL3SMI (≤-5.73 vs. >-5.73; hazard ratio [HR]: 4.010, 95% confidence interval [CI]: 1.799-8.938, p = < 0.001) and ΔSFMI (≤-5.33 vs. >-5.33; HR: 4.109, 95% CI: 1.967-8.584, p = < 0.001) were independent predictors. Rapid depletions of subcutaneous fat mass and skeletal muscle mass after the introduction of sorafenib indicate a poor prognosis.

Keywords: cancer cachexia; hepatocellular carcinoma; sarcopenia; skeletal muscle; sorafenib; subcutaneous fat.

Figure 1

Kaplan–Meier curves for overall survival time divided into the presence or absence of sarcopenia (a) and rapid depletion (RD) or non-rapid depletion (non-RD) groups in ΔL3SMI (≤−5.73 and >−5.73 cm²/m²/120 days) (b), ΔSFMI (≤−5.33 and >−5.33 cm²/m²/120days) (c), and ΔVFMI (≤−3.95 and >−3.95 cm²/m²/120 days) (d).

Figure 2

Kaplan–Meier curves for overall survival time divided into four groups according to the cutoffs for ΔL3SMI (−5.73 cm²/m²/120 days) and ΔSFMI (−5.33 cm²/m²/120 days).

Figure 3

Patient flow in this study.

Figure 4

Outline and formula for ΔL3SMI, ΔSFMI, and ΔVFMI. L3 skeletal muscle index (L3SMI) was the cross-sectional area of the muscle (cm²) at the L3 level of the computed tomography (CT) image normalized by the square of the height (m²). Subcutaneous fat mass index (SFMI) and visceral fat mass index (VFMI) were the cross-sectional areas of the subcutaneous and visceral fat (cm²), respectively, at the umbilical point normalized by the square of the height (m²).