Cancer Cachexia: Mechanisms and Clinical Implications

Cachexia is a multifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and carbohydrate). Whether it is primarily driven by the tumour or as a result of the host response to the tumour has yet to be fully elucidated. Cachexia is compounded by anorexia and the relationship between these two entities has not been clarified fully. Inconsistencies in the definition of cachexia have limited the epidemiological characterisation of the condition and there has been slow progress in identifying therapeutic agents and trialling them in the clinical setting. Understanding the complex interplay of tumour and host factors will uncover new therapeutic targets

Impact of musculoskeletal degradation on cancer outcomes and strategies for management in clinical practice

The prevalence of malnutrition in patients with cancer is one of the highest of all patient groups. Weight loss (WL) is a frequent manifestation of malnutrition in cancer and several large-scale studies have reported that involuntary WL affects 50–80% of patients with cancer, with the degree of WL dependent on tumour site, type and stage of disease. The study of body composition in oncology using computed tomography has unearthed the importance of both low muscle mass (sarcopenia) and low muscle attenuation as important prognostic indications of unfavourable outcomes including poorer tolerance to chemotherapy; significant deterioration in performance status and quality of life (QoL), poorer post-operative outcomes and shortened survival. While often hidden by excess fat and high BMI, muscle abnormalities are highly prevalent in patients with cancer (ranging from 10 to 90%). Early screening to identify individuals with sarcopenia and decreased muscle quality would allow for earlier multimodal interventions to attenuate adverse body compositional changes. Multimodal therapies (combining nutritional counselling, exercise and anti-inflammatory drugs) are currently the focus of randomised trials to examine if this approach can provide a sufficient stimulus to prevent or slow the cascade of tissue wasting and if this then impacts on outcomes in a positive manner. This review will focus on the aetiology of musculoskeletal degradation in cancer; the impact of sarcopenia on chemotherapy tolerance, post-operative complications, QoL and survival; and outline current strategies for attenuation of muscle loss in clinical practice

A window beneath the skin: how computed tomography assessment of body composition can assist in the identification of hidden wasting conditions in oncology that profoundly impact outcomes?

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise

Sarcopenia and cachexia in the era of obesity: Clinical and nutritional impact

Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population

Computed tomography diagnosed cachexia and sarcopenia in 725 oncology patients: is nutritional screening capturing hidden malnutrition?

Background: Nutrition screening on admission to hospital is mandated in many countries, but to date, there is no consensus on which tool is optimal in the oncology setting. Wasting conditions such as cancer cachexia (CC) and sarcopenia are common in cancer patients and negatively impact on outcomes; however, they are often masked by excessive adiposity. This study aimed to inform the application of screening in cancer populations by investigating whether commonly used nutritional screening tools are adequately capturing nutritionally vulnerable patients, including those with abnormal body composition phenotypes (CC, sarcopenia, and myosteatosis). Methods: A prospective study of ambulatory oncology outpatients presenting for chemotherapy was performed. A detailed survey incorporating clinical, nutritional, biochemical, and quality of life data was administered. Participants were screened for malnutrition using the Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), and the Nutritional Risk Index (NRI). Computed tomography (CT) assessment of body composition was performed to diagnose CC, sarcopenia, and myosteatosis according to consensus criteria. Results: A total of 725 patients (60% male, median age 64 years) with solid tumours participated (45% metastatic disease). The majority were overweight/obese (57%). However, 67% were losing weight, and CT analysis revealed CC in 42%, sarcopenia in 41%, and myosteatosis in 46%. Among patients with CT-identified CC, the MUST, MST, and NRI tools categorized 27%, 35%, and 7% of them as ‘low nutritional risk’, respectively. The percentage of patients with CT-identified sarcopenia and myosteatosis that were categorised as ‘low nutritional risk’ by MUST, MST and NRI were 55%, 61%, and 14% and 52%, 50%, and 11%, respectively. Among these tools, the NRI was most sensitive, with scores <97.5 detecting 85.8%, 88.6%, and 92.9% of sarcopenia, myosteatosis, and CC cases, respectively. Using multivariate Cox proportional hazards models, NRI score < 97.5 predicted greater mortality risk (hazard ratio 1.8, confidence interval: 1.2–2.8, P = 0.007). Conclusions: High numbers of nutritionally vulnerable patients, with demonstrated abnormal body composition phenotypes on CT analysis, were misclassified by MUST and MST. Caution should be exercised when categorizing the nutritional risk of oncology patients using these tools. NRI detected the majority of abnormal body composition phenotypes and independently predicted survival. Of the tools examined, the NRI yielded the most valuable information from screening and demonstrated usefulness as an initial nutritional risk grading system in ambulatory oncology patients

Quark-gluon plasma phenomenology from anisotropic lattice QCD

The FASTSUM collaboration has been carrying out simulations of N_f=2+1 QCD at nonzero temperature in the fixed-scale approach using anisotropic lattices. Here we present the status of these studies, including recent results for electrical conductivity and charge diffusion, and heavy quarkonium (charm and beauty) physics.Comment: Talk given at Quark Confinement and the Hadron Spectrum (Confinement XI), 8-12 September, St. Petersburg, Russia. 8 pages, 7 figure

Impact of weight loss and sarcopenia on response to chemotherapy, quality of life and survival.

The prevalence of malnutrition in patients with cancer has frequently been shown to be one of the highest of all hospital patient groups. Weight loss is a frequent manifestation of malnutrition in patients with cancer. Several large-scale studies over the last 35 years have reported that involuntary weight loss affects 50-80% of these patients with the degree of weight loss dependent on tumour site, type and stage of disease. This review will focus on the consequences of malnutrition, weight loss and muscle wasting in relation to chemotherapy tolerance, post-operative complications, quality of life and survival in oncology patients. The prognostic impact of weight loss on overall survival has long been recognised with recent data suggesting losses as little as 2.4% predicts survival independent of disease, site, stage or performance score. Recently the use of gold-standard methods of body composition assessment, including computed tomography, have led to an increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation, as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities are highly prevalent (ranging from 10-90%, depending on cancer site and the diagnostic criteria used). Both low muscle mass and low muscle attenuation have been associated with poorer tolerance to chemotherapy; increased risk of postoperative complications; significant deterioration in a patients' performance status, and poorer psychological well-being, overall quality of life, and survival