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.

Although several studies have established a link between obesity and colon cancer risk, little is known about the effect of obesity on outcomes after diagnosis. We investigated the association of body mass index (BMI) with outcomes after colon cancer in patients from cooperative group clinical trials. The study cohort consisted of 4288 patients with Dukes B and C colon cancer who were accrued from July 1989 to February 1994 to National Surgical Adjuvant Breast and Bowel Project randomized trials. Risk of recurrence, second primary cancer, and mortality (overall and by likely cause) were evaluated in relation to BMI at diagnosis using statistical modeling. Median follow-up time was 11.2 years. All statistical tests were two-sided. Very obese patients (BMI > or = 35 kg/m2) had greater risk of a colon cancer event (recurrence or secondary primary tumor; hazard ratio [HR] = 1.38, 95% confidence interval [CI] = 1.10 to 1.73) than normal weight patients (BMI = 18.5-24.9 kg/m2). Mortality was greater for very obese (HR = 1.28, 95% CI = 1.04 to 1.57) and underweight (BMI < 18.5 kg/m2) (HR = 1.49, 95% CI = 1.17 to 1.91) than for normal weight patients. The increased risk of mortality for underweight patients was dominated by non-colon cancer deaths (HR of such deaths compared with normal weight patients = 2.23, 95% CI = 1.50 to 3.31), whereas for the very obese, deaths likely due to colon cancer were increased (HR = 1.36, 95% CI = 1.06 to 1.73). Among colon cancer patients, a BMI greater than 35.0 kg/m2 at diagnosis was associated with an increased risk for recurrence of and death from colon cancer. Further studies are needed to determine pathways between obesity and recurrence risk and whether weight reduction or related interventions would improve prognosis.