Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy

Skeletal muscle wasting is considered the central feature of cachexia, but the potential for skeletal muscle anabolism in patients with advanced cancer is unproven. We investigated the clinical course of skeletal muscle wasting in advanced cancer and the window of possible muscle anabolism. We conducted a quantitative analysis of computed tomography (CT) images for the loss and gain of muscle in population-based cohorts of advanced cancer patients (lung, colorectal, and pancreas cancer and cholangiocarcinoma) in a longitudinal observational study. Advanced-cancer patients (n = 368; median survival: 196 d) had a total of 1279 CT images over the course of their disease. With consideration of all time points, muscle loss occurred in 39% of intervals between any 2 scans. However, the overall frequency of muscle gain was 15.4%, and muscle was stable in 45.6% of intervals between any 2 scans, which made the maintenance or gain of muscle the predominant behavior. Multinomial logistic regression revealed that being within 90 d (compared with >90 d) from death was the principal risk factor for muscle loss (OR: 2.67; 95% CI: 1.45, 4.94; P = 0.002), and muscle gain was correspondingly less likely (OR: 0.37; 95% CI: 0.20, 0.69; P = 0.002) at this time. Sex, age, BMI, and tumor group were not significant predictors of muscle loss or gain. A window of anabolic potential exists at defined early phases of the disease trajectory (>90 d survival), creating an opportunity for nutritional intervention to stop or reverse cachexia. Cancer patients within 90 d of death have a low likelihood of anabolic potential.

Cancer cachexia-associated weight loss is poorly understood; energetically demanding tissues (eg, organ and tumor mass) and resting energy expenditure (REE) are reported to increase with advanced cancer. The objective was to quantify the potential contribution of increasing masses of energetically demanding tissues to REE with colorectal cancer cachexia progression. A longitudinal computed tomography (CT) image review was performed to quantify organ size (liver, including metastases, and spleen) and peripheral tissues (skeletal muscle and adipose tissue) during colorectal cancer cachexia progression (n = 34). Body composition was prospectively evaluated by CT and dual-energy X-ray absorptiometry, and REE was determined by indirect calorimetry in advanced colorectal cancer patients (n = 18). Eleven months from death, the liver (2.3 +/- 0.7 kg) and spleen (0.32 +/- 0.2 kg) were larger than reference values. One month from death, liver weight increased to 3.0 +/- 1.5 kg (P = 0.010), spleen showed a trend to increase (P = 0.077), and concurrent losses of muscle (4.2 kg) and fat (3.5 kg) (P < 0.05) were observed. The estimated percentage of fat-free mass (FFM) occupied by the liver increased from 4.5% to 7.0% (P < 0.001). The most rapid loss of peripheral tissues and liver and metastases gain occurred within 3 mo of death. A positive linear relation existed between liver mass and measured whole-body REE (r(2) = 0.35, P = 0.010); because liver accounted for a larger percentage of FFM, measured REE . kg FFM(-1) . d(-1) increased (r(2) = 0.35, P = 0.010). Increases in mass and in the proportion of high metabolic rate tissues, including liver and tumor, represented a cumulative incremental REE of approximately 17,700 kcal during the last 3 mo of life and may contribute substantially to cachexia-associated weight loss.