Exercise interventions for people undergoing multimodal cancer treatment that includes surgery New

Abstract

Abstract Background

People undergoing multimodal cancer treatment are at an increased risk of adverse events. Physical fitness significantly reduces following cancer treatment, which is related to poor postoperative outcome. Exercise training can stimulate skeletal muscle adaptations, such as increased mitochondrial content and improved oxygen uptake capacity may contribute to improved physical fitness.

Objectives

To determine the effects of exercise interventions for people undergoing multimodal treatment for cancer, including surgery, on physical fitness, safety, health‐related quality of life (HRQoL), fatigue, and postoperative outcomes.

Search methods

We searched electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, SPORTDiscus, and trial registries up to October 2018.

Selection criteria

We included randomised controlled trials (RCTs) that compared the effects of exercise training with usual care, on physical fitness, safety, HRQoL, fatigue, and postoperative outcomes in people undergoing multimodal cancer treatment, including surgery.

Data collection and analysis

Two review authors independently selected studies, performed the data extraction, assessed the risk of bias, and rated the quality of the studies using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We pooled data for meta‐analyses, where possible, and reported these as mean differences using the random‐effects model.

Main results

Eleven RCTs were identified involving 1067 participants; 568 were randomly allocated to an exercise intervention and 499 to a usual care control group. The majority of participants received treatment for breast cancer (73%). Due to the nature of the intervention, it was not possible to blind the participants or personnel delivering the intervention. The risk of detection bias was either high or unclear in some cases, whilst most other domains were rated as low risk. The included studies were of moderate to very low‐certainty evidence. Pooled data demonstrated that exercise training may have little or no difference on physical fitness (VO2 max) compared to usual care (mean difference (MD) 0.05 L/min‐1, 95% confidence interval (CI) ‐0.03 to 0.13; I2 = 0%; 2 studies, 381 participants; low‐certainty evidence). Included studies also showed in terms of adverse effects (safety), that it may be of benefit to exercise (8 studies, 507 participants; low‐certainty evidence). Furthermore, exercise training probably made little or no difference on HRQoL (EORTC global health status subscale) compared to usual care (MD 2.29, 95% CI ‐1.06 to 5.65; I2 = 0%; 3 studies, 472 participants; moderate‐certainty evidence). However, exercise training probably reduces fatigue (multidimensional fatigue inventory) compared to usual care (MD ‐1.05, 95% CI ‐1.83 to ‐0.28; I2 = 0%; 3 studies, 449 participants moderate‐certainty evidence). No studies reported postoperative outcomes.

Authors' conclusions

The findings should be interpreted with caution in view of the low number of studies, the overall low‐certainty of the combined evidence, and the variation in included cancer types (mainly people with breast cancer), treatments, exercise interventions, and outcomes. Exercise training may, or may not, confer modest benefit on physical fitness and HRQoL. Limited evidence suggests that exercise training is probably not harmful and probably reduces fatigue. These findings highlight the need for more RCTs, particularly in the neoadjuvant setting.

Author(s)

Lisa A Loughney, Malcolm A West, Graham J Kemp, Michael PW Grocott, Sandy Jack

Abstract

Plain language summary

Exercise training interventions for people with cancer during cancer treatment before or after surgery

Background 
 People who are diagnosed with cancer will often undergo intensive treatment in the hope of achieving a cure. Such treatments may include surgery, chemotherapy, and chemoradiotherapy, frequently given in combination. These treatments can cause side effects (adverse effects), for example, making people feel less fit and more tired, and decreasing their quality of life. These adverse effects may be prevented, or at least reduced, if people with cancer undertake an exercise training programme during cancer treatment. In the past, people with cancer were told to rest, but current recommendations are to stay as active as possible.

Review question
 In adult patients undergoing cancer surgery, what is the impact of exercise training versus usual care on fitness, safety, quality of life, fatigue (tiredness), and clinical outcomes?

Key results
 We included 11 studies involving 1067 participants, published up until October 2018. The majority of people (73%) received treatment for breast cancer. Participants were randomly assigned to receive an exercise programme or usual care (no exercise training). The included studies suggested that exercise training may make little or no difference to physical fitness levels. The included studies also highlighted that it is probably safe to exercise, as the number of adverse events were low. The findings also showed that exercise training may make little or no difference to quality of life, but that it probably reduces fatigue (tiredness). We do not know whether it improves postoperative recovery, as no study reported this.

Quality of the evidence
 The overall quality (certainty) of the evidence was moderate to very low for all of the outcomes, mainly because of the small number of studies and low number of participants, as well as study limitations.

Conclusion
 The findings of this review should be interpreted with caution due to the overall low‐certainty of the evidence, variation in cancer types and treatments, exercise interventions, and outcomes measured. We are moderately certain that exercise training during adjuvant treatment (chemotherapy or radiotherapy treatment after surgery) reduces fatigue.

This is a new area of research, and more information is needed to help us understand whether exercise benefits people undergoing cancer treatment. Future studies should also concentrate on people with a new diagnosis of cancer who have chemotherapy or radiotherapy prior to surgery (known as neoadjuvant treatment), to tell us whether exercise training prior to surgery is important.

Author(s)

Lisa A Loughney, Malcolm A West, Graham J Kemp, Michael PW Grocott, Sandy Jack

Reviewer's Conclusions

Authors' conclusions

Implications for practice

The included studies demonstrated low‐certainty evidence that exercise training may make little or no difference to physical fitness. The included studies also showed that it is probably safe to exercise. Moderate‐certainty evidence suggests that exercise training probably makes little or no difference to HRQoL, but that exercise probably reduces fatigue. The current evidence is based on a small number of studies which greatly varied by cancer treatment, exercise intervention, and outcomes. The characteristics and setting (supervised or home) of an exercise programme are not known, therefore, more research is required to inform implications for practice.

Implications for research

This review makes it clear that a more focused approach is required in future studies to include similar outcome measures and similar duration of exercise interventions for better inter‐study comparisons. Furthermore, blinding of outcome assessors is required. Additionally, most of this work included people with breast cancer (73%), therefore, more research is required with other cancer patient groups. Future work should include those undergoing more major surgery, such as bowel surgery. For example, it has been shown that, in people with colorectal and oesophageal cancer, neoadjuvant cancer treatments significantly reduce physical fitness before surgery and this reduction is linked to poor postoperative outcomes (Jack 2014; West 2014). Although it is encouraging that five of the ongoing studies identified are investigating exercise interventions in the neoadjuvant setting, there is an urgent requirement for adequately powered RCTs and to investigate effects on postoperative outcomes. A cancer diagnosis may lead individuals to make positive changes to their health behaviours, a concept sometimes called the 'teachable moment'. Future work should investigate the effectiveness of exercise training, initiated at cancer diagnosis, throughout the entire cancer care journey. Better understanding of the optimal training duration, pattern, intensity, and composition of such interventions will be needed to maximise efficacy. The included studies in this review demonstrated that the countries currently leading this area of research are the USA with four studies, Korea and the Netherlands with two studies each, and Norway, Australia, and Denmark with one study each. Perhaps international collaboration to advance generalisable research in this area is required to answer these important research questions. Furthermore, addressing the substantial heterogeneity in both interventions and outcome measurements should also be a priority for researchers. Efforts to harmonise or standardise reporting of characteristics of exercise interventions and outcome measures to quantify physical exercise outcomes within such studies would be of value in improving opportunities to compare, contrast, and combine such data in order to better understand the impact of interventions for people with cancer (Myles 2016). We suggest answering the following specified research questions in future studies:

  • What is the optimal time to initiate an exercise programme and what kind of programme is the most effective in improving clinically important outcome measures?
  • What is the optimal prescribable dose of exercise and in what format will this most benefit cancer patients?
  • Does combining aerobic and resistance exercise programmes improve the response and provide greater outcome benefits?
  • Is a home‐based exercise training intervention as effective as supervised training in‐hospital intervention? Although home programmes may be cheaper and more convenient for the patient, to date, the evidence suggests that they may not be as effective with low adherence rates. Also, what are the social benefits of exercising in groups compared to home programmes?

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