Ectopic fat in skeletal muscle and liver is associated with shorter survival in patients with colorectal liver metastases

Abstract

Introduction: Whereas high adipose tissue mass is associated with longer survival in patients with cancer (cachexia), ectopic fat in muscle and liver appears to be related to poor survival. Using multiple computed tomography scans (CT-scans) over time and liver biopsies, we assessed the relationship between survival and liver steatosis as well as preoperative changes in muscle fat content and body composition in patients with colorectal liver metastases. Methods: Patients with two preoperative CT-scans were selected from a cohort of 289 patients with colorectal liver metastases undergoing partial hepatectomy. Scans were analysed using a single CT-slice at the L3 level to assess adipose tissue and skeletal muscle mass. Muscle fat content was assessed by calculating average Hounsfield units of muscle tissue (radiation attenuation). Liver biopsies were histologically scored for steatosis using the SAF-score. Results: 137 patients had two available preoperative CT-scans with a mean interval of 3.2 months. In multivariate cox-regression analysis, reduction in muscle radiation attenuation, reflecting fat accumulation, was associated with shorter disease-free survival (HR 1.98, 95%-CI:1.20-3.28;p< 0.01) and shorter overall survival (HR 1.79, 95%-CI:1.12-2.86;p=0.01). Liver steatosis was also associated with shorter overall survival (HR 1.77, 95%-CI:1.07-2.90;p=0.03). In contrast, high baseline total adipose tissue mass was related to increased disease-free survival (HR 0.60, 95%-CI:0.45-0.80;p< 0.01) and overall survival (HR 0.75, 95%-CI:0.58-0.98;p=0.03). Changes in skeletal muscle mass were not associated with survival. Conclusion: Ectopic fat in muscle and liver may be an important marker of tumour progression since it was associated with shorter disease-free survival and overall survival.