Review
Exercise intervention in people with cancer undergoing neoadjuvant cancer treatment and surgery: A systematic review

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Abstract

Background

Neoadjuvant cancer treatment decreases physical fitness. Low levels of physical fitness are associated with poor surgical outcome. Exercise training can stimulate skeletal muscle adaptations, such as increased mitochondrial content and improved oxygen uptake capacity that may contribute to improving physical fitness. This systematic review evaluates the evidence in support of exercise training in people with cancer undergoing the “dual hit” of neoadjuvant cancer treatment and surgery.

Methods

We conducted a systematic database search of Embase Ovid, Ovid Medline without Revisions, SPORTDiscus, Web of Science, Cochrane Central Register of Controlled Trials Library and ClinicalTrials.gov to identify trials addressing the effect of exercise training in people scheduled for neoadjuvant cancer treatment and surgery. Data extraction and analysis were based on a pre-defined plan.

Results

The database search yielded 6489 candidate abstracts. Ninety-four references included the required terms. Four studies were eligible for inclusion (breast cancer, locally advanced rectal cancer). All studies reported that exercise training was safe and feasible and that adherence rates were acceptable (66–96%). In-hospital exercise training improves physical fitness however the impact on HRQoL and other clinical important outcomes was uncertain.

Conclusion

This is the first systematic review of the effects of exercise training in people scheduled for “dual-hit” treatment. This evidence synthesis indicates that this approach is safe and feasible but that there are insufficient controlled trials in this area to draw reliable conclusions about the efficacy of such an intervention, the optimal characteristics of the intervention, or the impact on clinical or patient reported outcomes.

Section snippets

Background

Cancer is associated with cachexia which, in the pre-operative period, has been shown to influence perioperative outcome, increasing the risk of complications, mortality and length of stay in major gastrointestinal surgery.1 Chemotherapy has been related to skeletal muscle wasting, oxidative stress, mitochondrial death2 and reduced in vivo mitochondrial function.3 Furthermore, cancer treatment has been linked to decreased physical fitness levels, which appears to be related to the type of

Objectives

The objective of this systematic review is to evaluate methods, safety and feasibility, outcome (in terms both of physical fitness and post-operative outcome) and health-related quality of life (HRQoL), in studies of exercise interventions in people with cancer undergoing both neoadjuvant cancer treatment and surgery.

Research questions

i) Is exercise training in people with cancer during neoadjuvant cancer treatment safe and feasible? ii) Does it improve physical fitness (including physical capacity and physical activity)? iii) Does it improve HRQoL? iv) Does it improve surgical outcome?

Overview of methods and hypotheses

All clinical trials that involved an exercise training programme in people with cancer undergoing both neoadjuvant cancer treatment and surgery were included in the systematic search. Abstracts were screened and reviewed against pre-defined inclusion and exclusion criteria by two independent assessors (LL and MW), and assessed using the Downs and Black quality assessment tool.17 Data was extracted by one investigator in accordance with pre-defined criteria.

The primary hypothesis was: exercise

Meta-analysis

A decision to conduct a meta-analysis was based on the following pre-defined criteria;

  • To increase power; detecting a real effect as statistically significant if it exists. However, many individual studies are too small to detect small effects, but when several are combined there is a higher chance of detecting an effect.

  • To improve precision; the estimation of an intervention effect can be improved when it is based on more information.

  • To answer questions not posed by the individual studies.

  • To

Database search

The database search yielded 6489 candidate abstracts (Appendix 2 illustrates a flow chart of the comprehensive systematic search conducted for this review). After review of the candidate abstracts by two independent reviewers (LL and MW), 94 references included the required terms, of which 92 references were excluded as they did not meet all inclusion criteria. Two references were extracted for full text review. A manual search through all the references cited in the two full text papers

Summary of findings

This is the first systematic review of reports of exercise training interventions in people with cancer undergoing neoadjuvant cancer treatment and surgery. All studies reported that exercise training was safe and feasible in the neoadjuvant setting in both breast and rectal cancer, although sample sizes were small. Overall adherence was reasonable, 66–96%. Supervised, moderate-severe intensity exercise training, tailored to individual CPET's, significantly improved important physical fitness

Implications for research

To our knowledge, this is the first systematic review including all reported studies of people with cancer undergoing neoadjuvant cancer treatment and surgery. Because of the lack of adequately powered RCTs in this area, it remains unclear what is the optimal time to initiate an exercise programme and what kind of programme is most effective in improving clinically important outcome measures. Future studies will need to examine the mechanisms of cancer treatment and different exercise

Conflict of interest

M.P.W.G. received honoraria for speaking, for travel expenses, or both from Edwards Life science, Fresenius-Kabi, BOC Medical (Linde Group), Ely-Lilly Critical Care, and Cortex GmBH. He has also received research grants from National Institute of Health Research, Association of Anaesthetists of Great Britain and Ireland, Sir Halley Stuart Trust, and Francis and Augustus Newman Foundation. He leads the Xtreme-Everest hypoxia research consortium, who have received unrestricted research grant

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