Cancer cachexia: A systematic literature review of items and domains associated with involuntary weight loss in cancer

Abstract

Background

The concept of cancer-related anorexia/cachexia is evolving as its mechanisms are better understood. To support consensus processes towards an updated definition and classification system, we systematically reviewed the literature for items and domains associated with involuntary weight loss in cancer.

Methods

Two search strings (cachexia, cancer) explored five databases from 1976 to 2007. Citations, abstracts and papers were included if they were original work, in English/German language, and explored an item to distinguish advanced cancer patients with variable degrees of involuntary weight loss. The items were grouped into the 5 domains proposed by formal expert meetings.

Results

: Of 14,344 citations, 1275 abstracts and 585 papers reviewed, 71 papers were included (6325 patients; 40–50% gastrointestinal, 10–20% lung cancer). No single domain or item could consistently distinguish cancer patients with or without weight loss or having various degrees of weight loss. Anorexia and decreased nutritional intake were unexpectedly weakly related with weight loss. Explanations for this could be the imprecise measurement methods for nutritional intake, symptom interactions, and the importance of systemic inflammation as a catabolic drive. Data on muscle mass and strength is scarce and the impact of cachexia on physical and psychosocial function has not been widely assessed.

Conclusions

Current data support a modular concept of cancer cachexia with a variable combination of reduced nutritional intake and catabolic/hyper-metabolic changes. The heterogeneity in the literature revealed by this review underlines the importance of an agreed definition and classification of cancer cachexia.

Introduction

A majority of patients with advanced cancer experience involuntary loss of weight [1]. A main cause for involuntary weight loss (WL) is cancer cachexia; a metabolic, paraneoplastic syndrome, often accompanied by anorexia, which leads to decreased physical function and psychological distress, affecting also patients’ loved ones [3]. The causes of cancer cachexia are complex and are triggered by tumor products and pro-inflammatory cytokines [4].

The historic, common definition of cancer cachexia is limited to WL and anorexia [5]. Although it has face-validity as an approach to screening, this minimalistic approach seems inadequate to guide clinical care decisions [6].

A generic definition for cachexia/wasting disease associated with any form of chronic illness was recently composed in a consensus meeting [8], and the SCRINIO Working Group [1], [96] recently proposed a cancer cachexia classification after examining a database of 1307 cancer outpatients.

The European Palliative Care Research Collaborative, funded by the European Union's 6th framework in 2006 [7] is developing classification systems for pain, depression and cachexia in patients with advanced cancer. Candidate items for cachexia classification include subjective assessments, blood tests, images, and other measurements [8].

Cancer cachexia is invariably described as being multifactorial, with many axes of complexity. Weight loss may be composed of lean or adipose tissues in different degree, with varying functional consequences. Weight loss is understood to be driven in a varying degree by low food intake, which in turn may be the result of a wide variety of symptoms directly (e.g., anorexia, dysphagia, dysgeusia) or indirectly (e.g., pain, fatigue) limiting oral intake. A variety of metabolic and endocrine changes and activation of catabolic pathways, accounts for some of the weight loss, which is typically greater than would be expected for the prevailing level of intake [9], [10], [11], [12], [13], [14], [15]. Functional deficits associated with cachexia may be physical, immune, metabolic or psychosocial. Cancer cachexia definition, classification and diagnostic criteria must integrate all of these facets in a relevant way, and this remains a considerable challenge. A consensus of the various attempts to define cachexia has recently been published [102].

Our aim was to perform a systematic literature review using bibliographic databases to identify relevant articles for critical evaluation of items associated with involuntary WL in cancer patients.