Moderators of Exercise Effects on Cancer-related Fatigue: A Meta-analysis of Individual Patient Data

J.K. Van Vulpen; M.G. Sweegers; P.H.M. Peeters; K.S. Courneya; R.U. Newton; N.K. Aaronson; P.B. Jacobsen; D.A. Galvao; M.J. Chinapaw; K. Steindorf; M.L. Irwin; M.M. Stuiver; S. Hayes; K.A. Griffith; I. Mesters; H. Knoop; M.M. Goedendorp; N. Mutrie; A.J. Daley; A. McConnachie; M. Bohus; L. Thorsen; K.H. Schulz; C.E. Short; E.L. James; R.C. Plotnikoff; M.E. Schmidt; C.M. Ulrich; M. Van Beurden; H.S. Oldenburg; G.S. Sonke; W.H. Van Harten; K.H. Schmitz; K.M. Winters-Stone; M.J. Velthuis; D.R. Taaffe; W. Van Mechelen; M.J. Kersten; F. Nollet; J. Wenzel; J. Wiskemann; I.M. Verdonck-de Leeuw; J. Brug; A.M. May; L.M. Buffart

doi:10.1249/MSS.0000000000002154

Moderators of Exercise Effects on Cancer-related Fatigue: A Meta-analysis of Individual Patient Data

J.K. Van Vulpen, M.G. Sweegers, P.H.M. Peeters, K.S. Courneya, R.U. Newton, N.K. Aaronson, P.B. Jacobsen, D.A. Galvao, M.J. Chinapaw, K. Steindorf, M.L. Irwin, M.M. Stuiver, S. Hayes, K.A. Griffith, I. Mesters, H. Knoop, M.M. Goedendorp, N. Mutrie, A.J. Daley, A. McConnachieM. Bohus, L. Thorsen, K.H. Schulz, C.E. Short, E.L. James, R.C. Plotnikoff, M.E. Schmidt, C.M. Ulrich, M. Van Beurden, H.S. Oldenburg, G.S. Sonke, W.H. Van Harten, K.H. Schmitz, K.M. Winters-Stone, M.J. Velthuis, D.R. Taaffe, W. Van Mechelen, M.J. Kersten, F. Nollet, J. Wenzel, J. Wiskemann, I.M. Verdonck-de Leeuw, J. Brug, A.M. May, L.M. Buffart^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue.Methods We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 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 (beta = -0.17; 95% confidence interval [CI], -0.22 to -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 (beta (difference) = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration <= 12 wk showed larger effects on fatigue (beta = -0.29; 95% CI, -0.39 to -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
Number of pages	12
Journal	Medicine and Science in Sports and Exercise
Volume	52
Issue number	2
DOIs	https://doi.org/10.1249/MSS.0000000000002154
Publication status	Published - 1 Feb 2020

Keywords

adjuvant chemotherapy
aerobic exercise
androgen deprivation therapy
breast-cancer
cancer
cardiorespiratory fitness
cognitive-behavioral therapy
exercise
fatigue
individual patient data meta-analysis
physical-exercise
prostate-cancer
quality-of-life
randomized controlled-trial
FATIGUE
PHYSICAL-EXERCISE
RANDOMIZED CONTROLLED-TRIAL
CANCER
BREAST-CANCER
CARDIORESPIRATORY FITNESS
COGNITIVE-BEHAVIORAL THERAPY
PROSTATE-CANCER
AEROBIC EXERCISE
QUALITY-OF-LIFE
ADJUVANT CHEMOTHERAPY
EXERCISE
INDIVIDUAL PATIENT DATA META-ANALYSIS
ANDROGEN DEPRIVATION THERAPY

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10.1249/MSS.0000000000002154

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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., Galvao, 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 and Science in Sports and Exercise, 52(2), 303-314. https://doi.org/10.1249/MSS.0000000000002154

@article{053e6a2b943c4f61ab867cfa91725ca9,

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 (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue.Methods We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 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 (beta = -0.17; 95% confidence interval [CI], -0.22 to -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 (beta (difference) = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration <= 12 wk showed larger effects on fatigue (beta = -0.29; 95% CI, -0.39 to -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 = "adjuvant chemotherapy, aerobic exercise, androgen deprivation therapy, breast-cancer, cancer, cardiorespiratory fitness, cognitive-behavioral therapy, exercise, fatigue, individual patient data meta-analysis, physical-exercise, prostate-cancer, quality-of-life, randomized controlled-trial, FATIGUE, PHYSICAL-EXERCISE, RANDOMIZED CONTROLLED-TRIAL, CANCER, BREAST-CANCER, CARDIORESPIRATORY FITNESS, COGNITIVE-BEHAVIORAL THERAPY, PROSTATE-CANCER, AEROBIC EXERCISE, QUALITY-OF-LIFE, ADJUVANT CHEMOTHERAPY, EXERCISE, INDIVIDUAL PATIENT DATA META-ANALYSIS, ANDROGEN DEPRIVATION THERAPY",

author = "{Van Vulpen}, J.K. and M.G. Sweegers and P.H.M. Peeters and K.S. Courneya and R.U. Newton and N.K. Aaronson and P.B. Jacobsen and D.A. Galvao and M.J. Chinapaw and K. Steindorf and M.L. Irwin and M.M. Stuiver and S. Hayes and K.A. Griffith and I. Mesters and H. Knoop and M.M. Goedendorp and N. Mutrie and A.J. Daley and A. McConnachie and M. Bohus and L. Thorsen and K.H. Schulz and C.E. Short and E.L. James and R.C. Plotnikoff and M.E. Schmidt and C.M. Ulrich and {Van Beurden}, M. and H.S. Oldenburg and G.S. Sonke and {Van Harten}, W.H. and K.H. Schmitz and K.M. Winters-Stone and M.J. Velthuis and D.R. Taaffe and {Van Mechelen}, W. and M.J. Kersten and F. Nollet and J. Wenzel and J. Wiskemann and {Verdonck-de Leeuw}, I.M. and J. Brug and A.M. May and L.M. Buffart",

note = "Funding Information: The content is solely the responsibility of the authors and does not necessarily represent the official views of the (U.S.) National Institutes of Health. Funding Information: In conclusion, we found that exercise has statistically significant beneficial effects on fatigue in patients with cancer. These benefits are consistent across subgroups formed on the basis of demographic and clinical characteristics. The effect of exercise interventions on fatigue is significantly larger when performed under supervision. Differential effects of duration and potential roles of adherence and contamination in these findings need further exploration. Our results support implementation of exercise, preferably supervised exercise interventions, in clinical practice. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and results of the present study do not constitute endorsement by ACSM. Conflicts of interest: None declared. Source of funding: The POLARIS study is supported by the Bas Mulder Award, granted to L. M. Buffart by the Alpe d{\textquoteright}HuZes foundation/Dutch Cancer Society (VU2011–5045). The contribution of J. K. van Vulpen is financially supported by the World Cancer Research Fund The Netherlands (WCRF NL, project number 2013/997). Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the (U.S.) National Institutes of Health. Publisher Copyright: {\textcopyright} Lippincott Williams & Wilkins.",

year = "2020",

month = feb,

day = "1",

doi = "10.1249/MSS.0000000000002154",

language = "English",

volume = "52",

pages = "303--314",

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

issn = "0195-9131",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "2",

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Van Vulpen, JK, Sweegers, MG, Peeters, PHM, Courneya, KS, Newton, RU, Aaronson, NK, Jacobsen, PB, Galvao, 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, KH, 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 and Science in Sports and 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: A Meta-analysis of Individual Patient Data

AU - Van Vulpen, J.K.

AU - Sweegers, M.G.

AU - Peeters, P.H.M.

AU - Courneya, K.S.

AU - Newton, R.U.

AU - Aaronson, N.K.

AU - Jacobsen, P.B.

AU - Galvao, D.A.

AU - Chinapaw, M.J.

AU - Steindorf, K.

AU - Irwin, M.L.

AU - Stuiver, M.M.

AU - Hayes, S.

AU - Griffith, K.A.

AU - Mesters, I.

AU - Knoop, H.

AU - Goedendorp, M.M.

AU - Mutrie, N.

AU - Daley, A.J.

AU - McConnachie, A.

AU - Bohus, M.

AU - Thorsen, L.

AU - Schulz, K.H.

AU - Short, C.E.

AU - James, E.L.

AU - Plotnikoff, R.C.

AU - Schmidt, M.E.

AU - Ulrich, C.M.

AU - Van Beurden, M.

AU - Oldenburg, H.S.

AU - Sonke, G.S.

AU - Van Harten, W.H.

AU - Schmitz, K.H.

AU - Winters-Stone, K.M.

AU - Velthuis, M.J.

AU - Taaffe, D.R.

AU - Van Mechelen, W.

AU - Kersten, M.J.

AU - Nollet, F.

AU - Wenzel, J.

AU - Wiskemann, J.

AU - Verdonck-de Leeuw, I.M.

AU - Brug, J.

AU - May, A.M.

AU - Buffart, L.M.

N1 - Funding Information: The content is solely the responsibility of the authors and does not necessarily represent the official views of the (U.S.) National Institutes of Health. Funding Information: In conclusion, we found that exercise has statistically significant beneficial effects on fatigue in patients with cancer. These benefits are consistent across subgroups formed on the basis of demographic and clinical characteristics. The effect of exercise interventions on fatigue is significantly larger when performed under supervision. Differential effects of duration and potential roles of adherence and contamination in these findings need further exploration. Our results support implementation of exercise, preferably supervised exercise interventions, in clinical practice. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and results of the present study do not constitute endorsement by ACSM. Conflicts of interest: None declared. Source of funding: The POLARIS study is supported by the Bas Mulder Award, granted to L. M. Buffart by the Alpe d’HuZes foundation/Dutch Cancer Society (VU2011–5045). The contribution of J. K. van Vulpen is financially supported by the World Cancer Research Fund The Netherlands (WCRF NL, project number 2013/997). Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the (U.S.) National Institutes of Health. Publisher Copyright: © Lippincott Williams & Wilkins.

PY - 2020/2/1

Y1 - 2020/2/1

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 (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue.Methods We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 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 (beta = -0.17; 95% confidence interval [CI], -0.22 to -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 (beta (difference) = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration <= 12 wk showed larger effects on fatigue (beta = -0.29; 95% CI, -0.39 to -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 (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue.Methods We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 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 (beta = -0.17; 95% confidence interval [CI], -0.22 to -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 (beta (difference) = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration <= 12 wk showed larger effects on fatigue (beta = -0.29; 95% CI, -0.39 to -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 - adjuvant chemotherapy

KW - aerobic exercise

KW - androgen deprivation therapy

KW - breast-cancer

KW - cancer

KW - cardiorespiratory fitness

KW - cognitive-behavioral therapy

KW - exercise

KW - fatigue

KW - individual patient data meta-analysis

KW - physical-exercise

KW - prostate-cancer

KW - quality-of-life

KW - randomized controlled-trial

KW - FATIGUE

KW - PHYSICAL-EXERCISE

KW - RANDOMIZED CONTROLLED-TRIAL

KW - CANCER

KW - BREAST-CANCER

KW - CARDIORESPIRATORY FITNESS

KW - COGNITIVE-BEHAVIORAL THERAPY

KW - PROSTATE-CANCER

KW - AEROBIC EXERCISE

KW - QUALITY-OF-LIFE

KW - ADJUVANT CHEMOTHERAPY

KW - EXERCISE

KW - INDIVIDUAL PATIENT DATA META-ANALYSIS

KW - ANDROGEN DEPRIVATION THERAPY

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 and Science in Sports and Exercise

JF - Medicine and Science in Sports and Exercise

IS - 2

ER -