The Review by Fearon and colleagues1
raises several semantic issues in their definition and diagnosis of cachexia
. Their definition covers several distinct conditions such as denutrition induced by starvation, physiological age-related sarcopenia, or cachexia. Patients with cancer might present with malnutrition (secondary to anorexia and starvation), cachexia, or both, which are two different processes. Both processes could affect muscle mass, functional status, perception of tiredness, and quality of life. Additionally, age is a major risk factor for cancer, and body composition changes with age, but the causes and consequences of these changes are only partly understood.2
focused attention on these changes in body composition by giving them a name, sarcopenia; this term translates loosely as “deficiency of muscle”, and is now used to refer specifically to the gradual loss of skeletal muscle mass and strength that occurs with advancing age.
Cachexia is widely recognised as severe muscle wasting that accompanies cancer or an immunodeficient state. Although there is no widely accepted definition, cachexia is most commonly viewed as the cytokine-associated wasting of protein and energy stores due to the effects of disease.4
Systemic inflammation mediated through cell injury or activation of the immune system triggers an acute inflammatory response. People with cachexia lose roughly equal amounts of fat and fat-free mass, while maintaining extracellular water and intracellular potassium. The loss of fat-free mass is mainly from skeletal muscle. By contrast, starvation results in a loss of body fat and non-fat mass due to inadequate intake of protein and energy and sarcopenia is associated with a reduction in muscle mass and strength occurring with normal ageing, which is related to a reduction in motor unit number and atrophy of muscle fibres—especially the type IIa fibres. Loss of lean tissue, especially skeletal muscle mass, is increasingly recognised to have important consequences in elderly patients (eg, functional disability and falls).
Factors that could accelerate sarcopenia include starvation and cachexia, both of which are common in patients with cancer. The key clinical question is whether these changes in body composition seen in these patients are distinct entities or represent an interdependent continuum. The importance of defining the distinction lies in development of a targeted therapeutic approach to loss of skeletal muscle and muscle strength in patients with cancer. Failure to distinguish the causes of skeletal muscle loss often results in frustration because of poor clinical responses to therapeutic interventions.
A therapeutic approach to loss of skeletal muscle mass and strength in patients with cancer depends on correct classification.5
The term sarcopenia should be reserved for age-related decline in muscle mass not attributable to the presence of pathologically induced proinflammatory cytokines. Cachexia might be a better term for a decline in muscle mass associated with known inflammatory disease. Although starvation due to protein energy undernutrition is widely regarded as the primary cause of loss of fat and fat-free mass, a failure to improve with nutritional replacement should trigger consideration of other causes.
Cachexia is sometimes a symptom in patients with cancer
The author declared no conflicts of interest.