Body weight and composition endpoints in cancer cachexia clinical trials: Systematic Review 4 of the cachexia endpoints series

Abstract

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.

Keywords: body composition; cachexia; cancer cachexia; clinical trials.

Figure 1

PRISMA flow chart.

Figure 2

Geographical distribution of included cancer cachexia trials.

Figure 3

Temporal trends in relative use of body weight and body composition assessments. BIA, bioimpedance analysis; BMI, body mass index; CT, computed tomography; DEXA, dual‐energy X‐ray absorptiometry.

Figure 4

Summary of anthropometric measures of body composition by intervention modality. BMI, body mass index.

Figure 5

Summary of bioelectrical/radiological measures of body composition by intervention modality. BIA, bioimpedance analysis; CT, computed tomography; DEXA, dual‐energy X‐ray absorptiometry; LBM, lean body mass.

Figure 6

A network diagram illustrating combinations of reported bioelectrical/radiological endpoints. Endpoints pertaining to muscle are highlighted in green. Endpoints pertaining to fat are highlighted in orange. Green connecting lines highlight the use of two measures of muscle in the same trial. Similarly, orange lines highlight the use of two measures of fat, while grey lines indicate combinations of muscle and fat measures. The size of the nodes reflects the number of studies that have reported the endpoint. The thickness of the connecting line reflects the number of studies reporting each pair of measures. BIA, bioimpedance analysis; CT, computed tomography; DEXA, dual‐energy X‐ray absorptiometry; LBM, lean body mass.