Carla M. Prado

Sarcopenia as a Determinant of Chemotherapy Toxicity and Time to Tumor Progression in Metastatic Breast Cancer Patients Receiving Capecitabine Treatment

Purpose: Body composition has emerged as an important prognostic factor in cancer patients. Severe depletion of skeletal muscle (sarcopenia) and, hence, of overall lean body mass may represent an occult condition in individuals with normal or even high body weight. Sarcopenia has been associated with poor performance status, 5-fluorouracil toxicity, and shortened survival in cancer patients. Here, we prospectively studied patients with metastatic breast cancer receiving capecitabine treatment in order to determine if sarcopenia was associated with a higher incidence of toxicity and a shorter time to tumor progression (TTP). Experimental Design: Fifty-five women with metastatic breast cancer resistant to anthracycline and/or taxane treatment were included. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment, and TTP was determined prospectively. Results: Approximately 25% of patients were classified as sarcopenic, and this feature was seen in normal weight, overweight, and obese individuals. Toxicity was present in 50% of sarcopenic patients, compared with only 20% of nonsarcopenic patients (P = 0.03), and TTP was shorter in sarcopenic patients (101.4 days; confidence interval, 59.8-142.9) versus nonsarcopenic patients (173.3 days; confidence interval, 126.1-220.5; P = 0.05). Conclusion: Sarcopenia is a significant predictor of toxicity and TTP in metastatic breast cancer patients treated with capecitabine. Our results raise the potential use of body composition assessment to predict toxicity and individualize chemotherapy dosing.

Body Composition as an Independent Determinant of 5-Fluorouracil–Based Chemotherapy Toxicity

Purpose: Evidence suggests that lean body mass (LBM) may be useful to normalize doses of chemotherapy. Data from a prospective study were used to determine if the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin. Experimental Design: Toxicity after cycle 1 was graded according to National Cancer Institute Common Toxicity Criteria, version 2.0. Muscle tissue was measured by computerized tomography. An extrapolation to the LBM compartment of the whole body was employed. Results: Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity (P = 0.005). This observation was pertinent to women (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low proportion of LBM relative to their body surface area. Conclusion: Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area. We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition.

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.

Lean Tissue Imaging A New Era for Nutritional Assessment and Intervention

Body composition refers to the amount of fat and lean tissues in our body; it is a science that looks beyond a unit of body weight, accounting for the proportion of different tissues and its relationship to health. Although body weight and body mass index are well-known indexes of health status, most researchers agree that they are rather inaccurate measures, especially for elderly individuals and those patients with specific clinical conditions. The emerging use of imaging techniques such as dual energy x-ray absorptiometry, computerized tomography, magnetic resonance imaging, and ultrasound imaging in the clinical setting have highlighted the importance of lean soft tissue (LST) as an independent predictor of morbidity and mortality. It is clear from emerging studies that body composition health will be vital in treatment decisions, prognostic outcomes, and quality of life in several nonclinical and clinical states. This review explores the methodologies and the emerging value of imaging techniques in the assessment of body composition, focusing on the value of LST to predict nutrition status.

The emerging role of computerized tomography in assessing cancer cachexia.

Purpose of reviewThe present review represents an overview of the potential opportunistic use of computerized tomography (CT) to enhance our understanding of abnormal body composition, specifically lean and adipose tissue changes in cancer cachexia. Recent findingsOne of the characteristics of cancer cachexia is the depletion of muscle with or without adipose tissue loss. Therefore, a body composition tool that specifically distinguishes between these tissues is essential in assessing this syndrome. Cancer patients are routinely evaluated by high resolution imaging such as CT for the purpose of diagnosis and follow-up. Recent work exploiting CT images for body composition analysis has revealed the natural history of cancer cachexia, including progressive alterations in skeletal muscle, adipose tissue, organs, and tumor mass. CT-based quantification of skeletal muscle has permitted identification of individuals with sarcopenia, and links between sarcopenia and functional status, chemotherapy toxicity, time to tumor progression, and mortality. SummaryCT images routinely acquired from health records of cancer patients can be used to quantify specific lean and adipose tissues, to interpret body composition in population-based studies, and to evaluate individual patients in a clinical and therapeutic decision-making setting.

Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential?

BACKGROUND Skeletal muscle wasting is considered the central feature of cachexia, but the potential for skeletal muscle anabolism in patients with advanced cancer is unproven. OBJECTIVE We investigated the clinical course of skeletal muscle wasting in advanced cancer and the window of possible muscle anabolism. DESIGN 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. RESULTS 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. CONCLUSIONS 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.

Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation: Sarcopenia After Liver Transplantation

Muscle depletion or sarcopenia is associated with increased mortality in patients with cirrhosis; how it affects mortality after liver transplantation requires further study. In this study, we aimed to establish whether sarcopenia predicts increased morbidity or mortality after liver transplantation. We analyzed 248 patients with cirrhosis who had a computed tomography (CT) scan including the third lumbar vertebra before liver transplantation. Data were recovered from medical charts, the skeletal muscle cross‐sectional area was measured with CT, and sarcopenia was defined with previously published sex‐ and body mass index–specific cutoffs. One hundred sixty‐nine patients (68%) were male, and the mean age at transplantation was 55 ± 1 years. The etiologies of cirrhosis were hepatitis C virus (51%), alcohol (19%), autoimmune liver diseases (15%), hepatitis B virus (8%), and other etiologies (7%). Sarcopenia was present in 112 patients (45%), and it was more frequent in males (P = 0.002), patients with ascites (P = 0.02), and patients with higher bilirubin levels (P = 0.05), creatinine levels (P = 0.02), international normalized ratios (P = 0.04), Child‐Pugh scores (P = 0.002), and Model for End‐Stage Liver Disease scores (P = 0.002). The median survival period after liver transplantation was 117 ± 17 months for sarcopenic patients and 146 ± 20 months for nonsarcopenic patients (P = 0.4). Sarcopenic patients had longer hospital stays (40 ± 4 versus 25 ± 3 days; P = 0.005) and a higher frequency of bacterial infections within the first 90 days after liver transplantation (26% versus 15%, P = 0.04) in comparison with nonsarcopenic patients. In conclusion, sarcopenia is one of the most common complications in patients with cirrhosis and is predictive of longer hospital stays and a higher risk of perioperative bacterial infections after liver transplantation, but it is not associated with increased mortality. Liver Transpl 20:640–648, 2014.

Osteosarcopenic obesity: the role of bone, muscle, and fat on health

Osteopenia/osteoporosis, sarcopenia, and obesity are commonly observed in the process of aging, and recent evidence suggests a potential interconnection of these syndromes with common pathophysiology. The term osteosarcopenic obesity has been coined to describe the concurrent appearance of obesity in individuals with low bone and muscle mass. Although our understanding of osteosarcopenic obesity’s etiology, prevalence, and consequences is extremely limited, it is reasonable to infer its negative impact in a population that is aging in an obesogenic environment. It is likely that these individuals will present with poorer clinical outcomes caused by the cascade of metabolic abnormalities associated with these changes in body composition. Clinical outcomes include but are not limited to increased risk of fractures, impaired functional status (including activities of daily living), physical disability, insulin resistance, increased risk of infections, increased length of hospital stay, and reduced survival. These health outcomes are likely to be worse when compared to individuals with obesity, sarcopenia, or osteopenia/osteoporosis alone. Interventions that utilize resistance training exercise in conjunction with increased protein intake appear to be promising in their ability to counteract osteosarcopenic obesity.

Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis

Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients.

Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity

Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat.