Can Exercise Counteract Cancer Cachexia? A Systematic Literature Review and Meta-Analysis

Abstract

Background: Cancer-cachexia is associated with chronic inflammation, impaired muscle metabolism and body mass loss, all of which are classical targets of physical exercise.

Objectives: This systematic review and meta-analysis aimed to determine the effects of exercise on body and muscle mass in cachectic cancer hosts.

Data sources: PubMed/Medline, EMBASE, CINHAL, ISI Web of Science, and Cochrane Library were searched until July 2019.

Study selection: Trials had to be randomized controlled trials or controlled trials including cancer patients or animal models with cachexia-inducing tumors. Only sole exercise interventions over at least 7 days performed in a controlled environment were included.

Data extraction: Risk of bias was assessed and a random-effects model was used to pool effect sizes by standardized mean differences (SMD).

Results: All eligible 20 studies were performed in rodents. Studies prescribed aerobic (n = 15), strength (n = 3) or combined training (n = 2). No statistical differences were observed for body mass and muscle weight of the gastrocnemius, soleus, and tibialis muscles between the exercise and control conditions (SMD = ‒0.05, 95%CI-0.64-0.55, P = 0.87). Exercise duration prior to tumor inoculation was a statistical moderator for changes in body mass under tumor presence (P = 0.04).

Limitations: No human trials were identified. A large study heterogeneity was present, probably due to different exercise modalities and outcome reporting.

Conclusion: Exercise does not seem to affect cancer-cachexia in rodents. However, the linear regression revealed that exercise duration prior to tumor inoculation led to reduced cachexia-severity, possibly strengthening the rationale for the use of exercise in cancer patients at cachexia risk.

Keywords: cancer cachexia; clinical exercise science; exercise oncology; exercise training; muscle wasting; supportive cancer therapy; tissue wasting syndrome.

Figure 1.

Flowchart of the search process.

Figure 2.

Body mass and mass of gastrocnemius, soleus, and tibialis muscles comparing tumor-bearing exercise training interventions (EX) and tumor-bearing control (CON), using absolute values of endpoint comparisons. Abbreviations: CI, confidence intervals; ES, effects size Cohen’s d (corrected for small samples); df, degrees of freedom; I² and Q (Cochran’s Q) describe heterogeneity; RE, random effects model. Pin [a] = C26 2 weeks, Pin [b] = C26 8 weeks, Pin [c] = LLC 4 weeks, Khamoui [a] = aerobic exercise, Khamoui [b] = strength exercise, Jee [a] = moderate aerobic exercise, Jee [b] = intense aerobic exercise.

Figure 3.

Changes in body mass comparing tumor-bearing exercise training interventions and tumor-bearing control. Abbreviations: CI, confidence interval; ES, effects size Cohen’s d (corrected for small samples); df, degrees of freedom; I² and Q (Cochran’s Q) describe heterogeneity; RE, random effects model. Pin [a] = C26 2 weeks, Pin [b] = C26 8 weeks, Pin [c] = LLC 4 weeks.

Figure 4.

Funnel plot for publication bias assessment including the trim-and-fill function to plot potentially missing publications as well as the contour function to visualize a significance threshold.