Moderators of exercise effects on cancer-related fatigue: a meta-analysis of individual patient data

Jonna K van Vulpen, Maike G Sweegers, Petra H M Peeters, Kerry S Courneya, Robert U Newton, Neil K Aaronson, Paul B Jacobsen, Daniel A Galvão, Mai J Chinapaw, Karen Steindorf, Melinda L Irwin, Martijn M Stuiver, Sandi Hayes, Kathleen A Griffith, Ilse Mesters, Hans Knoop, Martine M Goedendorp, Nanette Mutrie, Amanda J Daley, Alex McConnachieMartin Bohus, Lene Thorsen, Karl-Heinz Schulz, Camille E Short, Erica L James, Ronald C Plotnikoff, Martina E Schmidt, Cornelia M Ulrich, Marc van Beurden, Hester S Oldenburg, Gabe S Sonke, Wim H van Harten, Kathryn H Schmitz, Kerri M Winters-Stone, Miranda J Velthuis, Dennis R Taaffe, Willem van Mechelen, Marie José Kersten, Frans Nollet, Jennifer Wenzel, Joachim Wiskemann, Irma M Verdonck-de Leeuw, Johannes Brug, Anne M May, Laurien M Buffart

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PURPOSE: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCTs) to investigate moderators of exercise intervention effects on cancer-related fatigue.

METHODS: We used individual patient data from 31 exercise RCTs worldwide, representing 4,366 patients, of whom 3,846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z-score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test.

RESULTS: Exercise interventions had statistically significant beneficial effects on fatigue (β= -0.17 [95% confidence interval (CI) -0.22;-0.12]). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (βdifference= -0.18 [95%CI -0.28;-0.08]). Supervised interventions with a duration ≤12 weeks showed larger effects on fatigue (β= -0.29 [95% CI -0.39;-0.20]) than supervised interventions with a longer duration. 

CONCLUSIONS: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration.

Original languageEnglish
Pages (from-to)303-314
Journal​Medicine & Science in Sports & Exercise
Issue number2
Publication statusPublished - Feb 2020


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