Multiple interventions for reversing lost lean body mass and body composition in cancer patients: a systematic review and network meta-analysis

Severe loss of lean body mass is widely considered a harbinger of poor prognosis among cancer patients, especially when protein breakdown exceeds protein synthesis. Various interventions have been employed to reverse lean body mass loss. However, it is currently unclear which intervention is best at reversing lean body mass loss for patients with cancer. A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted to identify eligible English-language studies that evaluated the effectiveness of interventions for reversing lean body mass loss in cancer patients. Our search considered studies with a sample size of 40 or more participants, covering the period from the inception of each database to December 19, 2024. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool. Meta-analysis was performed using Stata version 14.0. The study was registered with PROSPERO (CRD42024518277). A total of 26 randomized controlled trials (RCTs), comprising 4487 cancer patients were included in the network meta-analysis. 11 of these studies were included from the previous review. The following six types of interventions were identified: nutrition intervention alone (n = 13), diet alone (n = 2), exercise (n = 7), drug (n = 12), combined exercise and nutrition (n = 1), and combined drug with nutrition (n = 5) intervention. Pairwise meta-analyses showed that exercise-nutrition and drug-nutrition interventions were more efficacious than control groups in reversing lean body mass loss. With regard to increasing body weight, interventions based on diet, nutrition, drug, as well as combined exercise with nutrition were effective. Network meta-analysis showed that drug-nutrition yielded the highest probability of being the most effective intervention for reversing lean body mass loss, as assessed by dual-energy X-ray absorptiometry (DEXA), with a surface under the cumulative ranking curve (SUCRA) value of 100. Drug intervention demonstrated a SUCRA value of 87.3, as assessed by bioimpedance analysis (BIA). Exercise intervention exhibited the highest probability of increasing body weight, with a SUCRA value of 94.7. Funnel plots and the Egger’s test confirmed the absence of publication bias for all endpoints. The results of this network meta-analysis suggest that drug-nutrition interventions may have certain potential advantages in reversing lean body mass loss in cancer patients under DEXA assessment, while single-drug interventions perform best via BIA. However, due to methodological heterogeneity across the included studies, these findings remain exploratory observations and should not be interpreted as clinical recommendations. Body weight may only serve as a reference indicator for assessing the improvement of lean body mass loss due to its inherent limitation. Future research should be tailored to patient cohorts and study aims.