Definition and classification of cancer cachexia: heading for an international consensus?

KCH Fearon University of Edinburgh Scotland

What is the cancer cachexia phenotype?

Cachexia A clinical syndrome characterised by

. . .the shoulders, clavicles, chest and thighs melt away. This illness is fatal. . .

• anorexia • early satiety • weight loss • muscle wasting • anaemia

Hippocrates 460–370 BC

• oedema Calman KC 1982

Definition of cancer cachexia

Definition of cachexia

Cachexia = • Weight loss > 10% • CRP > 10 mg/L • Food intake < 1500 kcal

Evans WJ et al. Cachexia: a new definition. Clin Nutr, 2008

Problem: patient could have simple starvation

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Consensus definition of sarcopenia, cachexia and precachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics".

Definition of cancer cachexia

• The term cachexia is derived from the Greek words kakòs (bad) and héxis (condition). Cachexia may be defined as a multifactorial syndrome characterized by severe body weight, fat and muscle loss and increased protein catabolism due to underlying disease(s). Cachexia is clinically relevant since it increases patients’ morbidity and mortality. Contributory factors to the onset of cachexia are anorexia and metabolic alterations, i.e. increased inflammatory status, increased muscle proteolysis, impaired carbohydrate, protein and lipid metabolism.

Bozzetti F et al. A critical reappraisal of the definition of cancer cachexia and proposal for a staging system. Nutr Ther Metabol, 2008

Muscaritoli M et al Clin Nutr. 2010 Apr;29(2):154-9.

Definition and classification of cancer cachexia: an international consensus framework

What does a classification system need to do? Diagnostic

Staging

Criteria

Need to

Needs to

Bruera E, Fainsinger R L, Jatoi A, Loprinzi C,

Address:

Identify: Early phase

Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos V

EPCRC NCRI PCCSG ESPEN SIGCS

Management

Domains

Fearon KCH, Strasser F, Anker SD, Bosaeus I, MacDonald N, Mantovani G, Davis M,

Assessment

Mechanisms need to be: •Evaluated/ranked according to:

•obesity

(prophylaxis)

•aged

•Late phase

•importance

(symptomatic only)

•reversibility impact needs to be measured:

•routine clinical practice •research •clinical trials •Education/ policy

•mass/function Lancet Oncology 2011,12:489-95

•pyschosocial distress

Evolution of Classification System ****

Definition* Diagnosis Classification

Focus Groups & Evidence Base **

Assessment

Delphi Consensus

Framework***

Validation & Evolution

Process x2 (n=19 experts)

*Evans W et al

**Blum D et al

Clin Nutr 2008, 27,

Crit Rev. Oncol/Haem,

793-9

2011

***Fearon K et al

****Kaasa S et al

Lancet Oncol, 2011

JCO 2008, 23, 3867-73

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Definition • Cancer cachexia is 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. The pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism.

Diagnosis Involuntary weight loss >5% over last 6 months (in absence of simple starvation) OR

Definition of cachexia CACHEXIA DIAGNOSIS

Weight loss >2% with BMI 2% with an appendicular skeletal muscle index consistent with sarcopenia (males 5%

• Low performance score

• Metabolic/endocrine

Often reduced food

• Immunocompromised

change

Intake/Systemic

3 prescription drugs

Impact Mobility 0-2 Self-view of health and nutritional status Lives independently

The Missing Link

Definition Classification

Assessment Therapeutic Evidence Base

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Summary • New classification framework for cancer cachexia is evolving but needs further validation

RCTs

• The EBM treatment of cachexia should inform assessment • RCTs are required…….ENROL in MENAC!

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