The report is a product of the VA/HSR Evidence Synthesis Program.

Classification of Cancer Cachexia: A Systematic Review

Takeaway: Cachexia is a progressive wasting syndrome characterized by loss of weight and muscle mass, and changes in inflammatory and metabolic processes. ESP investigators identified 32 unique cancer cachexia algorithms that used more than 20 different components to assess cachexia. Most studies described algorithms with 2 classification categories, though some reported as many as 4 classification categories. Based on data from 49 studies with adjusted analyses, patients with cachexia had worse survival compared to patients without cachexia, and patients with more severe cachexia had worse survival outcomes compared to less severe cachexia. Few studies reported other outcomes of interest, including physical functioning, hospitalization, and cachexia symptom burden. Studies are needed to identify optimal cachexia algorithms and to better understand the relationship between cachexia severity and patient-important outcomes.

Cachexia is a progressive wasting syndrome characterized by loss of weight and muscle mass, and changes in inflammatory and metabolic processes. Cachexia in patients with cancer is associated with poor outcomes including mortality, reduced quality of life, decreased physical and psychological functioning, and increased hospital length of stay. There are a variety of proposed algorithms to “stage” or diagnose cancer cachexia. However, some include components that are not easily obtained in all settings, and some algorithms may not distinguish cachexia from other related conditions such as malnutrition. Although multiple cancer cachexia diagnostic and staging algorithms are available, the effect of these strategies on clinical and patient-important outcomes remains unclear.

In response to a request from the VHA Nutrition Field Advisory Board, HSR’s Evidence Synthesis Program (ESP) Center in Providence, RI, conducted a systematic review on the evidence of existing algorithms to classify cachexia and synthesize the association between cachexia and clinical and patient-important outcomes.

ESP investigators searched for peer-reviewed articles in Medline, Embase, Cochrane library, and ClinicalTrials.gov from inception to August 1, 2023. Eligible studies explicitly examined cachexia, included an algorithm with multiple components with the intent to identify or stage cachexia, and included patients >18 years of age with any cancer. The investigators identified 114 eligible studies that described 32 unique cancer cachexia algorithms. Most studies described algorithms with 2 classification categories, though some reported as many as 4 classification categories.

Summary of Findings

• Survival was the most commonly reported outcome; other outcomes included function, hospitalization, or cachexia-relevant burden, though there was sparse reporting of these outcomes.
• The Fearon 2011 algorithm, or a modification of it, was the most frequently reported algorithm (N = 68), followed by the Cachexia Index (CXI) (N = 16), the Evans 2008 algorithm (N = 8), and the Glasgow Prognostic Score or a modification of it (N = 6).
• Across all studies, the 32 unique algorithms used more than 20 different components. The most frequently used components included anorexia, appetite loss, or nutrition measures.
• The cutoffs for components and definitions of cachexia varied.
• Of the 32 algorithms, 22 were compared to clinical exam or to the Fearon 2011 algorithm.
• The majority of algorithms found worse survival outcomes for people with cachexia compared to those without cachexia.
• Worse overall mortality is predicted by the Evans 2008 algorithm, Fearon 2006 algorithm, or CXI compared to the Fearon 2011 algorithm.

Implications

Standardizing the identification of cancer cachexia can improve practice and support targeted interventions. Health systems aiming to implement an algorithm in routine practice should focus on feasibility and ease of use. Implementation of a standardized cachexia measure in VA would require leadership support, development of collection infrastructure, education of the oncology field, and monitoring/reinforcement of the importance of collection.

Limitations

This review included only studies that explicitly used the term “cachexia.” It is possible that studies that assessed cachexia but used a different term were excluded, or that studies that did not explicitly distinguish between cachexia and other related conditions were included.

Future Research

Studies are needed to identify optimal cachexia algorithms and to better understand the relationship between cachexia severity and patient-important outcomes.

Citation: Rieke K, Kanaan G, Mai JH, Caputo E, Rickard TR, Balk EM, Trikalinos TA, Leonard T, Rich S, Latourrette R, Rudolph JL, Jutkowitz E. Washington, DC: Evidence Synthesis Program, Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs. VA ESP Project 368; 2023.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/cachexia.cfm (intranet only).

An HSR Cyberseminar will be presented on this report January 30, 2025 at 2:00 p.m.

How can VA leadership work with the ESP? Nominations for systematic review topics may be submitted to the program at any time. When you submit a topic nomination form, ESP Coordinating Center staff will work with you to determine the appropriate research approach and ESP product to address your questions of interest. Topics are selected and assigned to an ESP Center based on program capacity and alignment with VA national goals

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers; and to disseminate these reports throughout VA.

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