Harms of exercise training in patients with cancer undergoing systemic treatment: a systematic review and meta-analysis of published and unpublished controlled trials

Simon N Thomsen; Ian M Lahart; Laura M Thomsen; Martin K Fridh; Anders Larsen; Morten Mau-Sørensen; Kate A Bolam; Ciaran M Fairman; Jesper F Christensen; Casper Simonsen

doi:10.1016/j.eclinm.2023.101937

Harms of exercise training in patients with cancer undergoing systemic treatment: a systematic review and meta-analysis of published and unpublished controlled trials

EClinicalMedicine. 2023 Apr 6:59:101937. doi: 10.1016/j.eclinm.2023.101937. eCollection 2023 May.

Authors

Affiliations

¹ Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen OE, Denmark.
² Faculty of Health, Education, and Wellbeing, School of Sport, University of Wolverhampton, Walsall Campus, Walsall, WS1 3BD, UK.
³ Department of Pediatrics and Adolescent Medicine, The Juliane Marie Center, University Hospital of Copenhagen - Rigshospitalet, Juliane Maries Vej 9, 2100, Copenhagen OE, Denmark.
⁴ University Hospitals Centre for Health Research, Copenhagen University Hospital - Rigshospitalet, Ryesgade 27, 2200, Copenhagen N, Denmark.
⁵ Department of Oncology, Centre for Cancer and Organ Diseases, University Hospital of Copenhagen - Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen OE, Denmark.
⁶ Department of Physical Activity and Health, The Swedish School of Sport and Health Sciences, Lidingovagen, 5626, Stockholm, Sweden.
⁷ Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Alfred Nobels Alle 23, 141 35, Stockholm, Sweden.
⁸ Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
⁹ Department of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
¹⁰ Digestive Disease Center, Bispebjerg Hospital, Nielsine Nielsens Vej 11, 2400, Copenhagen, Denmark.

Abstract

Background: Exercise is recommended for people with cancer. The aim of this study was to evaluate the harms of exercise in patients with cancer undergoing systemic treatment.

Methods: This systematic review and meta-analysis included published and unpublished controlled trials comparing exercise interventions versus controls in adults with cancer scheduled to undergo systemic treatment. The primary outcomes were adverse events, health-care utilization, and treatment tolerability and response. Eleven electronic databases and trial registries were systematically searched with no date or language restrictions. The latest searches were performed on April 26, 2022. The risk of bias was judged using RoB2 and ROBINS-I, and the certainty of evidence for primary outcomes was assessed using GRADE. Data were statistically synthesised using pre-specified random-effect meta-analyses. The protocol for this study was registered in the PROESPERO database (ID: CRD42021266882).

Findings: 129 controlled trials including 12,044 participants were eligible. Primary meta-analyses revealed evidence of a higher risk of some harms, including serious adverse events (risk ratio [95% CI]: 1.87 [1.47-2.39], I² = 0%, n = 1722, k = 10), thromboses (risk ratio [95% CI]: 1.67 [1.11-2.51], I² = 0%, n = 934, k = 6), and fractures (risk ratio [95% CI]: 3.07 [3.03-3.11], I² = 0%, n = 203, k = 2) in intervention versus control. In contrast, we found evidence of a lower risk of fever (risk ratio [95% CI]: 0.69 [0.55-0.87], I² = 0% n = 1109, k = 7) and a higher relative dose intensity of systemic treatment (difference in means [95% CI]: 1.50% [0.14-2.85], I² = 0% n = 1110, k = 13) in intervention versus control. For all outcomes, we downgraded the certainty of evidence due to imprecision, risk of bias, and indirectness, resulting in very low certainty of evidence.

Interpretation: The harms of exercise in patients with cancer undergoing systemic treatment are uncertain, and there is currently insufficient data on harms to make evidence-based risk-benefits assessments of the application of structured exercise in this population.

Funding: There was no funding for this study.

Keywords: Adverse events; Cancer; Chemotherapy; Exercise; Harms; Oncology.