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 McConnachie; Martin 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

doi:10.1249/MSS.0000000000002154

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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Abstract

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 language	English
Pages (from-to)	303-314
Journal	Medicine & Science in Sports & Exercise
Volume	52
Issue number	2
DOIs	https://doi.org/10.1249/MSS.0000000000002154
Publication status	Published - Feb 2020

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van Vulpen, J. K., Sweegers, M. G., Peeters, P. H. M., Courneya, K. S., Newton, R. U., Aaronson, N. K., Jacobsen, P. B., Galvão, D. A., Chinapaw, M. J., Steindorf, K., Irwin, M. L., Stuiver, M. M., Hayes, S., Griffith, K. A., Mesters, I., Knoop, H., Goedendorp, M. M., Mutrie, N., Daley, A. J., ... Buffart, L. M. (2020). Moderators of exercise effects on cancer-related fatigue: a meta-analysis of individual patient data. Medicine & Science in Sports & Exercise, 52(2), 303-314. https://doi.org/10.1249/MSS.0000000000002154

@article{24e60820417a46a0bce63a69286b1b82,

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

abstract = "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.",

keywords = "Exercise, Fatigue, Cancer, Individual Patient Data Meta-Analysis",

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

note = "With supplementary file. ",

year = "2020",

month = feb,

doi = "10.1249/MSS.0000000000002154",

language = "English",

volume = "52",

pages = "303--314",

journal = "Medicine & Science in Sports & Exercise",

issn = "0195-9131",

publisher = "Wolters Kluwer Health ",

number = "2",

}

van Vulpen, JK, Sweegers, MG, Peeters, PHM, Courneya, KS, Newton, RU, Aaronson, NK, Jacobsen, PB, Galvão, DA, Chinapaw, MJ, Steindorf, K, Irwin, ML, Stuiver, MM, Hayes, S, Griffith, KA, Mesters, I, Knoop, H, Goedendorp, MM, Mutrie, N, Daley, AJ, McConnachie, A, Bohus, M, Thorsen, L, Schulz, K-H, Short, CE, James, EL, Plotnikoff, RC, Schmidt, ME, Ulrich, CM, van Beurden, M, Oldenburg, HS, Sonke, GS, van Harten, WH, Schmitz, KH, Winters-Stone, KM, Velthuis, MJ, Taaffe, DR, van Mechelen, W, Kersten, MJ, Nollet, F, Wenzel, J, Wiskemann, J, Verdonck-de Leeuw, IM, Brug, J, May, AM & Buffart, LM 2020, 'Moderators of exercise effects on cancer-related fatigue: a meta-analysis of individual patient data', Medicine & Science in Sports & Exercise, vol. 52, no. 2, pp. 303-314. https://doi.org/10.1249/MSS.0000000000002154

TY - JOUR

T1 - Moderators of exercise effects on cancer-related fatigue

T2 - a meta-analysis of individual patient data

AU - van Vulpen, Jonna K

AU - Sweegers, Maike G

AU - Peeters, Petra H M

AU - Courneya, Kerry S

AU - Newton, Robert U

AU - Aaronson, Neil K

AU - Jacobsen, Paul B

AU - Galvão, Daniel A

AU - Chinapaw, Mai J

AU - Steindorf, Karen

AU - Irwin, Melinda L

AU - Stuiver, Martijn M

AU - Hayes, Sandi

AU - Griffith, Kathleen A

AU - Mesters, Ilse

AU - Knoop, Hans

AU - Goedendorp, Martine M

AU - Mutrie, Nanette

AU - Daley, Amanda J

AU - McConnachie, Alex

AU - Bohus, Martin

AU - Thorsen, Lene

AU - Schulz, Karl-Heinz

AU - Short, Camille E

AU - James, Erica L

AU - Plotnikoff, Ronald C

AU - Schmidt, Martina E

AU - Ulrich, Cornelia M

AU - van Beurden, Marc

AU - Oldenburg, Hester S

AU - Sonke, Gabe S

AU - van Harten, Wim H

AU - Schmitz, Kathryn H

AU - Winters-Stone, Kerri M

AU - Velthuis, Miranda J

AU - Taaffe, Dennis R

AU - van Mechelen, Willem

AU - Kersten, Marie José

AU - Nollet, Frans

AU - Wenzel, Jennifer

AU - Wiskemann, Joachim

AU - Verdonck-de Leeuw, Irma M

AU - Brug, Johannes

AU - May, Anne M

AU - Buffart, Laurien M

N1 - With supplementary file.

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Exercise

KW - Fatigue

KW - Cancer

KW - Individual Patient Data Meta-Analysis

U2 - 10.1249/MSS.0000000000002154

DO - 10.1249/MSS.0000000000002154

M3 - Article

C2 - 31524827

SN - 0195-9131

VL - 52

SP - 303

EP - 314

JO - Medicine & Science in Sports & Exercise

JF - Medicine & Science in Sports & Exercise

IS - 2

ER -

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

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