Elsevier

The Lancet Oncology

Volume 12, Issue 5, May 2011, Pages 489-495
The Lancet Oncology

Review
Definition and classification of cancer cachexia: an international consensus

https://doi.org/10.1016/S1470-2045(10)70218-7Get rights and content

Summary

To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined 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. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m2) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages—precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.

Introduction

Cachexia has been recognised for a long time as an adverse effect of cancer. It is associated with reduced physical function,1 reduced tolerance to anticancer therapy,2 and reduced survival.3, 4 Weight loss in patients with cancer is rarely recognised, assessed,5 or managed actively.6, 7 Thus, cachexia represents an important unmet need.

Patients with severe muscle wasting, ongoing catabolism, low performance status, and metastatic disease refractory to therapy are unlikely to have clinically important benefits from multimodal treatment intended to result in gain of lean tissue and function. At this stage, the goal of therapy is palliation of symptoms and reduction in distress for both patient and family.8 Against this spectrum, there would be merit in recognising the onset of cachexia so that interventions to reduce or delay its effect can be implemented.9 However, for this to happen, a definition of the condition and recognition of its diagnostic indicators would be needed.10

Clinical management of cachexia is currently both limited11, 12 and complex.9 Various different procachectic mechanisms can be involved,13, 14, 15 which ideally should be assessed and ranked according to importance and reversibility before a management plan is established.16 However, routine management has not achieved such a level of sophistication.17 Additionally, most randomised trials have investigated single agents in unselected patients presenting with weight loss of any aetiology.18 A more sophisticated characterisation would benefit individual patients and improve the robustness of conclusions drawn from trials.

Although our understanding of cachexia has progressed over the past decade,19 a lack of a definition, diagnostic criteria, and classification has impeded advancement in both clinical trials and clinical practice.20, 21, 22 A generic definition for all types of cachexia in both adults and children has been proposed,23 but the associated diagnostic criteria are not cancer specific and have not been validated.24 Two other definitions of cancer cachexia have also been proposed,4, 25 but both are based on single-centre experience and do not follow any formal consensus process.

The aim of this study was to develop a definition, diagnostic criteria, and classification system specific to cancer cachexia by use of a formal consensus process. The aim was not to agree on a definitive guideline, because precise cutoffs remain to be determined. The added value of the project derives from its cancer-specific focus linked to clinical management, trial design, education, and policy.

Section snippets

Methods

A Delphi process (brainstorming, narrowing down, and quantification) was applied,26 and it is presented in figure 1. Experts in clinical cancer cachexia research (medical and surgical oncologists, palliative medicine specialists, and nutritionists) were identified on the basis of leadership in publication, clinical cancer cachexia research or phase 3 clinical trials, and participation in clinical cancer cachexia peer review panels. Key individuals in assessment and classification of

Definition and diagnosis

Cancer cachexia is defined as 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. Consensus statements for diagnosis are presented in the panel.

Stage

Cancer cachexia

Conclusion

Cachexia remains a challenging clinical syndrome, the importance of which lies in its prevalence and profound adverse effect on patients' quality and length of life.1, 2, 3 The present consensus definition focuses on the complex interplay between reduced food intake and abnormal metabolism and identifies loss of skeletal muscle as key in patients' functional impairment. Such emphasis supports the concept that skeletal muscle mass can be both a marker for the syndrome and an important

Search strategy and selection criteria

This Review on items and domains associated with involuntary weight loss in cancer applied two search strings conceptualised around weight loss (including cachexia, anorexia, and wasting) and cancer. A search was done of the Medline, Cochrane, Embase, PsychINFO, and CINAHL databases for papers that included either a comparison of groups of patients with or without weight loss or patients with various degrees of weight loss. Only papers published between 1976, and 2007, in English or German were

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