Age, Obesity, Sarcopenia, and Proximity to Death Explain Reduced Mean Muscle Attenuation in Patients with Advanced Cancer.

BACKGROUND: Cancer cachexia is characterized by skeletal muscle loss. A feature of muscle wasting, reduction in the mean muscle attenuation from computed tomography images is believed to reflect pathological infiltration of fat into muscle. It is a reported prognostic indicator in cancer patients. OBJECTIVES: To develop an explanatory multivariate model of muscle attenuation of cancer patients incorporating age, sex, disease characteristics, body composition. Time to death ≤92 days was included in the model as the demarcation of end-stage disease. DESIGN: Multivariate general linear model regression analysis of total mean muscle attenuation and change in muscle attenuation. SETTING: Regional cancer center (Alberta, Canada). PARTICIPANTS: Patients with gastrointestinal and respiratory tract cancers (mean age 64±11 years, 44% female). MEASUREMENTS: Total adipose tissue and skeletal muscle cross sectional area, and mean muscle attenuation at the 3rd lumbar vertebra were assessed from baseline computed tomography (n=1719), and a subset with repeated measures (n=246 patients with a total of 871 images). RESULTS: At baseline, muscle attenuation associated with total skeletal muscle (ß 0.09; 95% CI 0.07 to 0.11; p<0.001) and adipose tissue (ß -0.032; 95% CI -0.035 to -0.029; p<0.001) cross sectional areas, age (ß -0.28; 95% CI -0.32 to -0.24; p<0.001), time to death ≤92 days (ß -1.9; 95% CI -3.1 to -0.7; p=0.003) and male sex (ß -2.3; 95% CI -3.5 to -1.1; p<0.001). Change in muscle attenuation over time associated with total adipose tissue cross sectional area (ß -0.008; 95% CI -0.012 to -0.004; p<0.001) and time to death ≤92 days (ß -1.6; 95% CI -3.0 to -0.2; p=0.03). CONCLUSIONS: The radiation attenuation of skeletal muscle is lowest in individuals who are older, less muscular, have a higher fat mass and are within 92 days of death. Men had lower muscle attenuation than women when controlled for other variables.

Sarcopenic obesity: A Critical appraisal of the current evidence.

Sarcopenic obesity (SO) is assuming a prominent role as a risk factor because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). The increase in obesity prevalence rates in older subjects is of concern given the associated disease risks and more limited therapeutic options available in this age group. This review has two main objectives. The primary objective is to collate results from studies investigating the effects of SO on physical and cardio-metabolic functions. The secondary objective is to evaluate published studies for consistency in methodology, diagnostic criteria, exposure and outcome selection. Large between-study heterogeneity was observed in the application of diagnostic criteria and choice of body composition components for the assessment of SO, which contributes to the inconsistent associations of SO with cardio-metabolic outcomes. We propose a metabolic load:capacity model of SO given by the ratio between fat mass and fat free mass, and discuss how this could be operationalised. The concept of regional fat distribution could be incorporated into the model and tested in future studies to advance our understanding of SO as a predictor of risk for cardio-metabolic diseases and physical disability.

Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.

BACKGROUND: Cancer cachexia is characterised by skeletal muscle wasting; however, potential for muscle anabolism in patients with advanced cancer is unproven. METHODS: Quantitative analysis of computed tomography images for loss/gain of muscle in cholangiocarcinoma patients receiving selumetinib (AZD6244; ARRY-142886) in a Phase II study, compared with a separate standard therapy group. Selumetinib is an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase and of interleukin-6 secretion, a putative mediator of muscle wasting. RESULTS: Overall, 84.2% of patients gained muscle after initiating selumetinib; mean overall gain of total lumbar muscle cross-sectional area was 13.6 cm(2)/100 days (∼2.3 kg on a whole-body basis). Cholangiocarcinoma patients who began standard treatment were markedly catabolic, with overall muscle loss of -7.3 cm(2)/100 days (∼1.2 kg) and by contrast only 16.7% of these patients gained muscle. CONCLUSION: Our findings suggest that selumetinib promotes muscle gain in patients with cholangiocarcinoma. Specific mechanisms and relevance for cachexia therapy remain to be investigated.