Abstract

Background

Radiation therapy (RT) is given to about half of all people with cancer. RT alone is used to treat various cancers at different stages. Although it is a local treatment, systemic symptoms may occur. Cancer‐ or treatment‐related side effects can lead to a reduction in physical activity, physical performance, and quality of life (QoL). The literature suggests that physical exercise can reduce the risk of various side effects of cancer and cancer treatments, cancer‐specific mortality, recurrence of cancer, and all‐cause mortality.

Objectives

To evaluate the benefits and harms of exercise plus standard care compared with standard care alone in adults with cancer receiving RT alone.

Search methods

We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL, conference proceedings and trial registries up to 26 October 2022.

Selection criteria

We included randomised controlled trials (RCTs) that enrolled people who were receiving RT without adjuvant systemic treatment for any type or stage of cancer. We considered any type of exercise intervention, defined as a planned, structured, repetitive, objective‐oriented physical activity programme in addition to standard care. We excluded exercise interventions that involved physiotherapy alone, relaxation programmes, and multimodal approaches that combined exercise with other non‐standard interventions such as nutritional restriction.

Data collection and analysis

We used standard Cochrane methodology and the GRADE approach for assessing the certainty of the evidence. Our primary outcome was fatigue and the secondary outcomes were QoL, physical performance, psychosocial effects, overall survival, return to work, anthropometric measurements, and adverse events.

Main results

Database searching identified 5875 records, of which 430 were duplicates. We excluded 5324 records and the remaining 121 references were assessed for eligibility. We included three two‐arm RCTs with 130 participants. Cancer types were breast and prostate cancer. Both treatment groups received the same standard care, but the exercise groups also participated in supervised exercise programmes several times per week while undergoing RT. Exercise interventions included warm‐up, treadmill walking (in addition to cycling and stretching and strengthening exercises in one study), and cool‐down.

In some analysed endpoints (fatigue, physical performance, QoL), there were baseline differences between exercise and control groups.

We were unable to pool the results of the different studies owing to substantial clinical heterogeneity.

All three studies measured fatigue. Our analyses, presented below, showed that exercise may reduce fatigue (positive SMD values signify less fatigue; low certainty).

• Standardised mean difference (SMD) 0.96, 95% confidence interval (CI) 0.27 to 1.64; 37 participants (fatigue measured with Brief Fatigue Inventory (BFI))-• SMD 2.42, 95% CI 1.71 to 3.13; 54 participants (fatigue measured with BFI)-• SMD 1.44, 95% CI 0.46 to 2.42; 21 participants (fatigue measured with revised Piper Fatigue Scale)

All three studies measured QoL, although one provided insufficient data for analysis. Our analyses, presented below, showed that exercise may have little or no effect on QoL (positive SMD values signify better QoL; low certainty).

• SMD 0.40, 95% CI −0.26 to 1.05; 37 participants (QoL measured with Functional Assessment of Cancer Therapy‐Prostate)-• SMD 0.47, 95% CI −0.40 to 1.34; 21 participants (QoL measured with World Health Organization QoL questionnaire (WHOQOL‐BREF))

All three studies measured physical performance. Our analyses of two studies, presented below, showed that exercise may improve physical performance, but we are very unsure about the results (positive SMD values signify better physical performance; very low certainty)

• SMD 1.25, 95% CI 0.54 to 1.97; 37 participants (shoulder mobility and pain measured on a visual analogue scale)-• SMD⁠⁠⁠⁠⁠⁠ 3.13 (95% CI 2.32 to 3.95; 54 participants (physical performance measured with the six‐minute walk test)

Our analyses of data from the third study showed that exercise may have little or no effect on physical performance measured with the stand‐and‐sit test, but we are very unsure about the results (SMD 0.00, 95% CI −0.86 to 0.86, positive SMD values signify better physical performance; 21 participants; very low certainty).

Two studies measured psychosocial effects. Our analyses (presented below) showed that exercise may have little or no effect on psychosocial effects, but we are very unsure about the results (positive SMD values signify better psychosocial well‐being; very low certainty).

• SMD 0.48, 95% CI −0.18 to 1.13; 37 participants (psychosocial effects measured on the WHOQOL‐BREF social subscale)-• SMD 0.29, 95% CI −0.57 to 1.15; 21 participants (psychosocial effects measured with the Beck Depression Inventory)

Two studies recorded adverse events related to the exercise programmes and reported no events. We estimated the certainty of the evidence as very low. No studies reported adverse events unrelated to exercise.

No studies reported the other outcomes we intended to analyse (overall survival, anthropometric measurements, return to work).

Authors' conclusions

There is little evidence on the effects of exercise interventions in people with cancer who are receiving RT alone. While all included studies reported benefits for the exercise intervention groups in all assessed outcomes, our analyses did not consistently support this evidence. There was low‐certainty evidence that exercise improved fatigue in all three studies. Regarding physical performance, our analysis showed very low‐certainty evidence of a difference favouring exercise in two studies, and very low‐certainty evidence of no difference in one study. We found very low‐certainty evidence of little or no difference between the effects of exercise and no exercise on quality of life or psychosocial effects. We downgraded the certainty of the evidence for possible outcome reporting bias, imprecision due to small sample sizes in a small number of studies, and indirectness of outcomes.

In summary, exercise may have some beneficial outcomes in people with cancer who are receiving RT alone, but the evidence supporting this statement is of low certainty. There is a need for high‐quality research on this topic.

Author(s)

Maike Trommer, Simone Marnitz, Nicole Skoetz, Ronja Rupp, Timo Niels, Janis Morgenthaler, Sebastian Theurich, Michael vonBergwelt-Baildon, Christian Baues, Freerk T Baumann

Abstract

Plain language summary

Exercise interventions for adults with cancer who are receiving radiation therapy without additional cancer therapy

What is radiation therapy?

Radiation therapy (also called radiotherapy) is a treatment that delivers high doses of radiation to a specific part of the body to kill cancer cells. One in two people with cancer will undergo radiation therapy. Some people receive radiation therapy alone, while others receive radiation therapy combined with other cancer treatments that affect the whole body (chemotherapy, immunotherapy, or hormone therapy). The unwanted effects of radiation therapy usually affect the part of the body where the radiation is delivered, but there may also be symptoms that affect the whole body. These unwanted effects can lead to reduced physical activity, physical performance, and quality of life. There is evidence that people with cancer who perform exercise may be less likely to die from cancer or from other causes, may be less likely to have their cancer return, and may have fewer unwanted effects of cancer treatment. 

What did we want to find out?

We wanted to find out if exercise could help to improve the following outcomes in people with cancer receiving radiation therapy alone.

• Fatigue-• Quality of life-• Physical performance-• Psychosocial effects (such as depression)-• Overall survival-• Return to work-• Anthropometric measurements (such as weight)-• Unwanted effects

What did we do?

We searched electronic medical literature databases for randomised controlled trials (RCTs) that enrolled people with all types and stages of cancer who were receiving RT alone. Eligible RCTs randomly assigned some participants to receive any type of exercise intervention plus standard care and others to standard care alone. We excluded exercise interventions that involved physiotherapy alone, relaxation programmes, or combination programmes with exercise and, for example, dietary restrictions.

We compared the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We included three studies that enrolled 130 people with breast or prostate cancer. The exercise groups participated in a supervised exercise programme three to five times per week for five to eight weeks. The exercise interventions included warm‐up, aerobic exercise, and cool‐down.

We analysed the differences between the exercise groups and control groups in the outcome values after radiation therapy. We could not compare the differences between the groups in the change in outcome values from before to after radiotherapy because the studies did not provide enough information for this comparison. In some outcomes (fatigue, physical performance, quality of life), there were already differences between the exercise and control groups at the beginning of the studies.

Exercise may improve fatigue and may have little or no effect on quality of life. Exercise may improve physical performance, but we are very uncertain about the results. Exercise may have little or no effect on psychosocial effects, but we are very uncertain about the results. Two studies reported no unwanted effects of exercise. No studies measured our other outcomes of interest. 

Exercise programmes in people with cancer receiving RT alone may provide some benefits, but the evidence to support this is poor. Due to the lack of evidence, we could not detect and also not rule out clear differences in outcomes.

What are the limitations of the evidence?

We have little or very little confidence in the evidence because the results are based on a small number of studies that enrolled very few people, because the people in two studies knew which group they were in, and because the evidence focused on a specific population whereas the question we wanted to answer was broader. Further research is likely to change our results.

How up to date is the evidence?

The evidence is up to date to 26 October 2022. 

Author(s)

Maike Trommer, Simone Marnitz, Nicole Skoetz, Ronja Rupp, Timo Niels, Janis Morgenthaler, Sebastian Theurich, Michael vonBergwelt-Baildon, Christian Baues, Freerk T Baumann

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

For fatigue, which was the primary outcome of our review, there was low‐certainty evidence of a difference between the exercise and control groups favouring exercise in all three included studies. For physical performance, two studies provided very low‐certainty evidence of a difference between the groups favouring exercise, while one study provided very‐low certainty evidence of little or no difference. For the other assessed outcomes, our analyses showed low or very‐low certainty evidence of little or no difference between the groups in post‐RT scores. Two studies reported that no exercise‐related adverse events occurred during the exercise intervention period. There were no further reports about adverse events.

All three studies reported improvements in all assessed outcomes in the exercise groups. Due to insufficient available data and the lack of accurate exact numbers, we were unable to consistently support these results in our analyses. 

In summary, exercise interventions may be beneficial for people with cancer undergoing RT alone, but we only have low‐ to very low‐certainty evidence to support this statement. Although there are indications that exercise may have physical and psychological benefits for people with breast or prostate cancer receiving radiation therapy (RT) alone, we cannot reach solid conclusions or provide recommendations for clinical practice based on the scientific data currently available. 

Implications for research 

Exercise has become a very important topic in the area of additional supportive care. To date, there are no data on survival rates or short‐ and long‐term adverse events. Overall, the evidence is limited and there is a need for large, well‐conducted randomised controlled trials and high‐quality reviews on this topic. Future studies should clearly and fully report the most important outcomes, including overall survival, quality of life, physical and social well‐being, improvements in symptoms, and return to work. They should also record all adverse events, examining whether they occur as a result of particular exercise programme, in which types of cancer they occur, whether exercise could exacerbate radiation‐induced adverse events, and, conversely, whether exercise could prevent or mitigate adverse events. Since many people with breast cancer receive RT alone, studies should report RT‐induced adverse events affecting lung function, as these could impede patients' ability to exercise. It is also crucial to investigate the effects of exercise interventions in more types of cancer requiring RT alone. To date, it is difficult to assess when and how exercise interventions are appropriate and beneficial for people with cancer undergoing RT alone. We need additional high‐quality studies on this topic to guide healthcare professionals when making decisions about optimal supportive therapy. 

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