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

Abstract

Background: Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib. Methods: We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the third lumbar vertebra and umbilical level, respectively. Muscle depletion was defined as an SMI value < 42 cm²/m² in men and < 38 cm²/m² in women. High VFA (H-VFA) was defined as a value ≥100 cm². In addition to SMI and VFA, we also analyzed various clinical parameters as potential prognostic factors. Results: Multivariate analysis showed that having a tumor number < 7 (hazard ratio [HR] = 0.409, p < 0.001), absence of extrahepatic spread (EHS) (HR = 0.562, p < 0.001), absence of muscle depletion (HR = 0.498, p = 0.006), and H-VFA (HR = 0.556, p = 0.031) were significant factors for long-term survival. Therefore, we evaluated the prognosis of those with no muscle depletion with H-VFA. The no muscle depletion with H-VFA group showed significantly longer survival than the other group (median survival time 15.6 vs. 11.0 months, p = 0.003). Multivariate analysis showed that having a tumor number < 7 (HR = 0.454, p = 0.001), absence of EHS (HR = 0.511, p = 0.008), and no muscle depletion with H-VFA (HR = 0.454, p = 0.002) were significant predictors of survival. Conclusions: We identified no muscle depletion with H-VFA as a novel biomarker for advanced HCC patients treated with sorafenib.

Impact of cancer rehabilitation on the prognosis of patients with hepatocellular carcinoma

“…Patients who agreed to exercise were classified into the CR group (n=85), and those who did not agree to exercise were classified into the control group (n=67). We classified enrolled patients into the High SMI or Low SMI group according to the JSH criteria for sarcopenia (7), and the High VFA or Low VFA group as previously described (25). We also divided the patients into the High or Low LDH group and the High total protein group or Low total protein group based on the reference values of serum LDH and total protein levels, respectively.…”

“…A static stretching was conducted for 3-5 min, targeting the quadriceps femoris muscles, hamstrings, hip adductor muscles, and gastrocnemius. The static stretch was held to each muscle for 10-20 seconds at the point of feeling tightness (16,25). Strength training was conducted for 10 min, targeting the quadriceps femoris muscles, gastrocnemius, and tibialis anterior muscles.…”

“…Gastrocnemius and tibialis anterior muscles were conducted trained by the patient's weight. One set contained of 10 repetitions, and a maximum of 3 sets were performed (16,25). Balance training contain the patients practicing a one-leg stance and tandem stance for 5-10 min.…”

“…Balance training contain the patients practicing a one-leg stance and tandem stance for 5-10 min. The patient stood on a straight line and maintain posture in tandem stance training (16,25). Endurance training contained either ergometer or walking for 10-15 min.…”

“…Endurance training contained either ergometer or walking for 10-15 min. The intensity of endurance training was 11-13 points on the Borg scale, and the target heart rate was set by using the Karvonen Formula (16,25).…”