Systematic or Meta-analysis StudiesExercise training in childhood cancer: A systematic review and meta-analysis of randomized controlled trials
Introduction
Children and adolescents with cancer frequently experience treatment-related side effects, many of which can persist after treatment has ended [1]. In addition, patients’ physical capacity is typically impaired during [2], [3] and after [3], [4] treatment, as reflected by low values of cardiorespiratory fitness (CRF) and muscle strength, or by a decreased ability to perform activities of daily living (ADLs) [5], which in turn negatively affects their wellbeing and quality of life (QoL) [6]. Although the impairment in the physical capacity of pediatric cancer patients is likely multifactorial, physical inactivity is an important contributor [2]. Indeed, when compared with pre-diagnosis levels, children and adolescents with cancer experience a 74% and 91% reduction in their habitual physical activity levels during home and in-patient stays, respectively [7]. Some authors have raised attention to the low mobilization patterns of children hospitalized for the treatment of oncologic or hematologic conditions [8]. In children receiving hematopoietic stem cell transplantation (HSCT), physical inactivity and especially bedrest can further decrease their poor CRF and aggravate the muscle atrophy that they frequently suffer as a side effect of immunosuppressive therapy [9].
There is a strong rationale to postulate that including physical exercise as part of standard care for patients with childhood cancer could help to reduce the side effects of cancer treatment as well as physical decline. In this regard, a 2016 Cochrane meta-analysis found that the effects of exercise interventions performed by children with acute lymphoblastic leukemia (ALL) within the first 5 years from diagnosis (either during or after cancer treatment) were not yet convincing, although some benefits were shown for physical capacity indicators (CRF, muscle strength), and health-related QoL [10]. A number of studies analyzing the effects of exercise on ALL or other pediatric cancers have been published during the last year [11], [12], [13], [14]. The primary objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to compare the effects of exercise training intervention (duration ≥ 3 weeks, vs. a control group not performing exercise) for children with any type of cancer during treatment or within the first year after its end, on physical capacity and safety (i.e., risk of mortality or disease relapse, adverse events). The secondary objective was to analyze exercise training effects on body composition, physical activity levels, QoL, immune function, and adherence to the exercise program.
Section snippets
Patients and methods
This conduct and reporting of the current systematic review and meta-analysis conform to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (see the checklist in Supplementary File 1) [15].
Quality assessment and publication bias
The risk of bias in the included studies was overall low (Fig. 2). Most studies failed to perform/report an appropriate random sequence generation and allocation concealment. Due to the nature of the interventions, blinding of patients was not feasible. However, this could be a potential confounding factor and we therefore considered all the included studies to have a high risk of performance bias. In addition, the sample size of the included studies was overall low, with the largest study
Discussion
The main finding of this systematic review is that the inclusion of an exercise training intervention during cancer treatment significantly improves the functional mobility of pediatric cancer patients (i.e., their ability to cope with ADLs as reflected by a valid test, the TUDS test) without increasing their risk of mortality or recurrence. Moreover, no major adverse events or health-related issues attributable to the testing or exercise training sessions were noted. Therefore, exercise
Conclusions
The inclusion of exercise training interventions in children with any type of cancer during treatment and/or shortly after it improves functional mobility during ADLs without increasing the risk of mortality, recurrence, or associated adverse effects. More RCTs analyzing the effects of fully supervised exercise training interventions are needed, as well as the development of a core-set of outcomes in pediatric oncology exercise research. Conducting multi-centric trials could help to avoid one
Contributors
AL and CFL designed the study. ASL, JSM and PLV collected the data and did the analysis. CRC, JSM, PLV wrote the first draft. AL, CFL and TT edited the final manuscript. All authors reviewed, wrote and approved the final version. The corresponding author had final responsibility for the decision to submit for publication.
Conflicts of interest disclosure
The authors declare that they have no conflict of interest.
Funding/support
Research by the authors is supported by the Spanish Ministry of Education, Culture and Sport [JSM, contract #FPU14/03435; CRC, contract #FPU16/03956]; Universidad de Alcalá [PLV, contract #FPI2016]; the Spanish Ministry of Economy and Competitiveness and Fondos Feder [AL, grant #PI15/00558]; Universidad Europea de Madrid [grant number R-0007/17]; and Fundación Uno entre Cien Mil. The authors thank Dr. Kenneth McCreath for his editorial work.
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