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ESMO E-Learning: Pathophysiology and Management of Cancer Cachexia: an Update


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This content is for ESMO members only.



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Learning objectives

  1. To provide the definition of cancer cachexia and an update on underlining pathophysiology mechanisms 
  2. To provide an update on staging of cancer cachexia and the approach to its diagnosis
  3. To provide a practical approach on interventions to be considered in patients with cancer cachexia and under what circumstances


Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. Anorexia, increased resting energy expenditure, presence of systemic inflammation, activation of unprofitable biochemical circles, insulin resistance, are all important features of the syndrome resulting in increased lipolysis and muscle wasting. 

Cachexia is present in 80% of cancer patients at the end-stage of the disease. It is also a major cause of death in that setting. Frequency at diagnosis depends on the primary site of tumour with the highest presence among patients with pancreatic, head and neck, and lung cancers. Anorexia - reduced desire for food affects approximately 50% of cancer patients at diagnosis.

Muscular depletion under a certain cut-off is called sarcopenia and is related to significant increase of morbidity and mortality, as well as decreased tolerance to therapy and quality of life. Normal ageing and other chronic conditions, diseases and medications may additionally contribute to sarcopenia. Obese patients may also be sarcopenic.

Timely diagnosis is important and should be based on nutritional screening questionnaires and body composition analysis. The treatment of cancer cachexia should correct all reversible causes of reduced food intake, provide timely nutritional consultation/intervention, suggest maintenance or increased level of physical activity, appreciate the fact that there is no standard drug therapy and motivate patients to entry into clinical trials.

The medical professionals should appreciate a multidisciplinary approach in patients with cancer cachexia and understand that, to patients under active antineoplastic treatment (pre-/cachectic stage) dietary counselling (with food and with or without oral nutritional supplements) and parenteral nutritional support should be offered, while nutritional support is ineffective in end-stage cancer (refractory cachectic stage).

This E-Learning module is an excellent update of a frequently neglected aspect of malignant diseases and provides an overview of the magnitude of the problem and a multimodal approach; which steps have to be considered in the diagnosis, an understanding of pathophysiology mechanisms, the current evidence for treatment of cancer cachexia, including nutritional support, exercise, pharmaconutrients, as well as the drugs used in common practice despite lack of standard therapy.

The Module also provides an excellent overview of novel drugs against cachexia and their mechanism of action and physiological effects. Special consideration is given to enrollment in cancer cachexia clinical trials, including eligibility criteria, intervention, endpoints and study interpretations. In addition, the author challenges end-of-life care in terms of an important question, i.e. when to stop nutritional support.

Declaration of interest

Ioannis Gioulbasanis has reported:
Financial interests:
Danone – Nutricia, Merck, Bristol Meyers Squibb: Invited Speaker, Personal.
Baxter, Roche, Genesis Pharma: Advisory Board, Personal.
Galenica, Expert Testimony, Personal.
Angelini – Demo, Invited Speaker, Personal.

Last update: 09 Jun 2022

This E-Learning module was published in 2016. The CME test expired in 2019. The author provided a module update as PDF presentation in 2022.

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