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Intervenciones con ejercicios para adultos con cáncer que reciben solo radioterapia

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Antecedentes

A aproximadamente la mitad de las personas con cáncer se les administra radioterapia (RT). La RT sola se utiliza para tratar varios tipos de cáncer en diferentes estadios. Aunque se trata de un tratamiento local, pueden aparecer síntomas sistémicos. Los efectos secundarios relacionados con el cáncer o el tratamiento pueden reducir la actividad física, el rendimiento físico y la calidad de vida (CdV). La bibliografía sugiere que el ejercicio físico puede reducir el riesgo de diversos efectos secundarios del cáncer y de los tratamientos oncológicos, la mortalidad específica por cáncer, la recidiva del cáncer y la mortalidad por cualquier causa.

Objetivos

Evaluar los efectos beneficiosos y perjudiciales del ejercicio más la atención estándar en comparación con la atención estándar sola en adultos con cáncer que reciben RT sola.

Métodos de búsqueda

Se hicieron búsquedas en CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL, resúmenes de congresos y registros de ensayos hasta el 26 de octubre de 2022.

Criterios de selección

Se incluyeron los ensayos controlados aleatorizados (ECA) que reclutaron personas que recibían RT sin tratamiento sistémico adyuvante para cualquier tipo o estadio de cáncer. Se consideró cualquier tipo de intervención con ejercicios, definida como un programa de actividad física planificado, estructurado, repetitivo y orientado a objetivos, además de la atención estándar. Se excluyeron las intervenciones con ejercicios que incluían fisioterapia sola, programas de relajación y enfoques multimodales que combinaban el ejercicio con otras intervenciones no estándar, como la restricción nutricional.

Obtención y análisis de los datos

Se utilizó la metodología Cochrane estándar y el método GRADE para evaluar la certeza de la evidencia. El desenlace principal de la revisión fue la fatiga y los desenlaces secundarios fueron la CdV, el rendimiento físico, los efectos psicosociales, la supervivencia global, la reincorporación al trabajo, las medidas antropométricas y los eventos adversos.

Resultados principales

La búsqueda en la base de datos identificó 5875 registros, de los cuales 430 eran duplicados. Se excluyeron 5324 registros y se evaluó la elegibilidad de las 121 referencias restantes. Se incluyeron tres ECA de dos grupos con 130 participantes. Los tipos de cáncer fueron el de mama y el de próstata. Ambos grupos de tratamiento recibieron la misma atención estándar, pero los grupos de ejercicios también participaron en programas de ejercicios supervisados varias veces por semana mientras se sometían a RT. Las intervenciones con ejercicios incluyeron calentamiento, caminata en cinta rodante (además de ciclismo y ejercicios de estiramiento y fortalecimiento en un estudio) y enfriamiento.

En algunos desenlaces analizados (fatiga, rendimiento físico, CdV), hubo diferencias iniciales entre los grupos de ejercicio y de control.

No fue posible agrupar los resultados de los distintos estudios debido a la considerable heterogeneidad clínica.

Los tres estudios midieron la fatiga. Los análisis, presentados a continuación, mostraron que el ejercicio podría reducir la fatiga (los valores positivos de la DME significan menos fatiga; certeza baja).

• Diferencia de medias estandarizada (DME) 0,96; intervalo de confianza (IC) del 95%: 0,27 a 1,64; 37 participantes (fatiga medida con el Brief Fatigue Inventory [BFI])
• DME 2,42; IC del 95%: 1,71 a 3,13; 54 participantes (fatiga medida con el BFI)
• DME 1,44; IC del 95%: 0,46 a 2,42; 21 participantes (fatiga medida con la Piper Fatigue Scale revisada)

Los tres estudios midieron la CdV, aunque uno no proporcionó datos suficientes para el análisis. Los análisis, presentados a continuación, mostraron que el ejercicio podría tener poco o ningún efecto sobre la CdV (los valores positivos de la DME significan una mejor CdV; certeza baja).

• DME 0,40; IC del 95%: ‐0,26 a 1,05; 37 participantes (calidad de vida medida con la Functional Assessment of Cancer Therapy‐Prostate)
• DME 0,47; IC del 95%: ‐0,40 a 1,34; 21 participantes (calidad de vida medida con el cuestionario de calidad de vida de la Organización Mundial de la Salud [WHOQOL‐BREF])

Los tres estudios midieron el rendimiento físico. Los análisis de dos estudios, presentados a continuación, mostraron que el ejercicio podría mejorar el rendimiento físico, pero no se tiene seguridad acerca de los resultados (los valores positivos de la DME significan un mejor rendimiento físico; certeza muy baja)

• DME 1,25; IC del 95%: 0,54 a 1,97; 37 participantes (movilidad y dolor del hombro medidos en una escala visual analógica)
• DME 3,13 (IC del 95%: 2,32 a 3,95); 54 participantes (rendimiento físico medido con la prueba de caminata de seis minutos)

Los análisis de los datos del tercer estudio mostraron que el ejercicio podría tener poco o ningún efecto sobre el rendimiento físico medido con la prueba de sentarse y levantarse (stand‐and‐sit test), pero no se tiene seguridad acerca de los resultados (DME 0,00; IC del 95%: ‐0,86 a 0,86; los valores de DME positivos significan mejor rendimiento físico; 21 participantes; certeza muy baja).

Dos estudios midieron los efectos psicosociales. Los análisis (presentados a continuación) mostraron que el ejercicio podría tener poco o ningún impacto sobre los efectos psicosociales, pero no se tiene seguridad acerca de los resultados (los valores positivos de la DME significan un mejor bienestar psicosocial; certeza muy baja).

• DME 0,48; IC del 95%: ‐0,18 a 1,13; 37 participantes (efectos psicosociales medidos en la subescala social del WHOQOL‐BREF)
• DME 0,29; IC del 95%: ‐0,57 a 1,15; 21 participantes (efectos psicosociales medidos con el Inventario de Depresión de Beck)

Dos estudios registraron eventos adversos relacionados con los programas de ejercicios y no informaron ningún evento. La certeza de la evidencia se consideró muy baja. Ningún estudio informó eventos adversos no relacionados con el ejercicio.

Ningún estudio informó acerca de los demás desenlaces que se pretendían analizar (supervivencia global, medidas antropométricas, reincorporación al trabajo).

Conclusiones de los autores

Hay poca evidencia sobre los efectos de las intervenciones con ejercicios en las personas con cáncer que reciben RT sola. Aunque todos los estudios incluidos informaron efectos beneficiosos en los grupos de intervención con ejercicios en todos los desenlaces evaluados, los análisis no apoyaron de forma sistemática esta evidencia. Hubo evidencia de certeza baja de que el ejercicio mejoró la fatiga en los tres estudios. En cuanto al rendimiento físico, el análisis mostró evidencia de certeza muy baja de una diferencia a favor del ejercicio en dos estudios, y evidencia de certeza muy baja de ninguna diferencia en un estudio. Se encontró evidencia de certeza muy baja de poca o ninguna diferencia entre los efectos del ejercicio y ningún ejercicio sobre la calidad de vida o los efectos psicosociales. Se redujo la certeza de la evidencia debido al posible sesgo de notificación de los desenlaces, la imprecisión debida a los pequeños tamaños muestrales en un número reducido de estudios y por medidas indirectas de los desenlaces.

En resumen, el ejercicio podría tener algunos desenlaces beneficiosos en las personas con cáncer que reciben RT sola, pero la evidencia que apoya esta afirmación es de certeza baja. Se necesitan estudios de investigación de calidad sobre este tema.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Intervenciones con ejercicios para adultos con cáncer que reciben radioterapia sin tratamiento oncológico adicional

¿Qué es la radioterapia?

El tratamiento con radiación (también llamado radioterapia) administra altas dosis de radiación a una parte específica del cuerpo para destruir las células cancerosas. Una de cada dos personas con cáncer se someterá a radioterapia. Algunas personas reciben solo radioterapia, mientras que otras reciben radioterapia combinada con otros tratamientos contra el cáncer que afectan a todo el organismo (quimioterapia, inmunoterapia o terapia hormonal). Los efectos no deseados de la radioterapia suelen afectar a la parte del cuerpo donde se administra la radiación, pero también puede haber síntomas que afecten a todo el cuerpo. Estos efectos no deseados pueden reducir la actividad física, el rendimiento físico y la calidad de vida. Existe evidencia de que las personas con cáncer que hacen ejercicio podrían tener menos probabilidades de morir de cáncer o por otras causas, menos probabilidades de que el cáncer reaparezca y menos efectos no deseados del tratamiento oncológico.

¿Qué se quería averiguar?

Se quiso averiguar si el ejercicio podría ayudar a mejorar los siguientes desenlaces en personas con cáncer que reciben solo radioterapia.

• Fatiga
• Calidad de vida
• Rendimiento físico
• Efectos psicosociales (como la depresión)
• Supervivencia global
• Reincorporación al trabajo
• Medidas antropométricas (como el peso)
• Efectos no deseados

¿Qué se hizo?

Se realizaron búsquedas en las bases de datos electrónicas de literatura médica para obtener ensayos controlados aleatorizados (ECA) que incluyeran personas con todos los tipos y estadios de cáncer que recibían RT sola. Los ECA elegibles asignaron aleatoriamente a algunos participantes a recibir cualquier tipo de intervención con ejercicios más la atención estándar, y a otros solo a la atención estándar. Se excluyeron las intervenciones con ejercicios que incluían fisioterapia sola, programas de relajación o programas combinados con ejercicio y, por ejemplo, restricciones dietéticas.

Se compararon los resultados de los estudios y se calificó la confianza en la evidencia, en base a factores como los métodos y tamaños de los estudios.

¿Qué se encontró?

Se incluyeron tres estudios que reclutaron a 130 personas con cáncer de mama o de próstata. Los grupos de ejercicios participaron en un programa de ejercicio supervisado de tres a cinco veces por semana durante cinco a ocho semanas. Las intervenciones con ejercicios incluyeron calentamiento, ejercicio aeróbico y enfriamiento.

Se analizaron las diferencias entre los grupos de ejercicios y los grupos de control en los valores de los desenlaces tras la radioterapia. No se pudieron comparar las diferencias entre los grupos en el cambio de los valores de los desenlaces de antes a después de la radioterapia porque los estudios no proporcionaron suficiente información para esta comparación. En algunos desenlaces (fatiga, rendimiento físico, calidad de vida), ya había diferencias entre los grupos de ejercicio y control al principio de los estudios.

El ejercicio podría mejorar la fatiga y tener poco o ningún efecto sobre la calidad de vida. El ejercicio podría mejorar el rendimiento físico, pero los resultados son muy inciertos. El ejercicio podría tener poco o ningún impacto sobre los efectos psicosociales, pero los resultados son muy inciertos. Dos estudios no informaron sobre efectos no deseados del ejercicio. Ningún estudio midió otros desenlaces de interés.

Los programas de ejercicios en personas con cáncer que reciben RT sola podrían proporcionar algunos beneficios, pero la evidencia que lo respalda es escasa. Debido a la falta de evidencia, no se detectaron ni descartaron diferencias claras en los desenlaces.

¿Cuáles son las limitaciones de la evidencia?

Se tiene poca o muy poca confianza en la evidencia porque los resultados se basan en un pequeño número de estudios que reclutaron a muy pocas personas, las personas de dos estudios sabían en qué grupo estaban y la evidencia se centró en una población específica, mientras que la pregunta que se quería responder era más amplia. Es probable que los estudios de investigación futuros cambien los resultados.

¿Cuál es el grado de actualización de esta evidencia?

La evidencia está actualizada hasta el 26 de octubre de 2022.

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. 

Summary of findings

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Summary of findings 1. Exercise intervention compared to no exercise intervention for people receiving radiation therapy

Population: adults with breast or prostate cancer receiving radiation therapy alone

Settings: medical centre
Intervention: exercise intervention

Comparison: no exercise intervention

Outcome

Narrative synthesis

No of participants (studies)

Certainty of the evidence

Comments

Fatigue

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify less fatigue.

There is evidence of a difference between groups favouring exercise: 

  • SMD 0.96, 95% CI 0.27 to 1.64; 37 participants

  • SMD 2.42, 95% CI 1.71 to 3.13; 54 participants

  • SMD 1.44, 95% CI 0.46 to 2.42; 21 participants

112 (3 studies)

⊕⊕⊝⊝

Lowa,b

 

We did not combine data from different studies owing to clinical heterogeneity.

Quality of life

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify better quality of life.

There is evidence of little or no difference between groups:

  • SMD 0.4, 95% CI −0.26 to 1.05; 37 participants

  • SMD 0.47, 95% CI −0.40 to 1.34; 21 participants

112 (3 studies)

⊕⊕⊝⊝

Lowa,b

We did not combine data from different studies owing to clinical heterogeneity.

In Kulkarni 2013, the difference was not estimable due to lack of data. 

Physical performance

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify better physical performance.

 

Evidence from 2 studies favours exercise; 1 study shows no difference between groups: 

  • SMD 1.25, 95% CI 0.54 to 1.97; 37 participants

  • SMD 3.13, 95% CI 2.32 to 3.95; 54 participants

  • SMD 0.0, 95% CI −0.86 to 0.86; 21 participants

112 (3 studies)

⊕⊝⊝⊝

Very lowa,b,c

We did not combine data from different studies owing to clinical heterogeneity.

Because of the different endpoints in the studies, between‐group comparability is limited.

Psychosocial effects

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify better psychosocial effects.

There is evidence of little or no difference between groups:

  • SMD 0.48, 95% CI −0.18, to 1.13; 37 participants

  • SMD 0.29, 95% CI −0.57 to 1.15; 21 participants

58 (2 studies)

⊕⊝⊝⊝

Very lowa,d

We did not combine data from different studies owing to clinical heterogeneity.

We were unable to analyse data from Kulkarni 2013 owing to poor presentation of results.

Overall survival 

See comment

See comment

See comment

No studies measured overall survival.

Return to work

See comment

See comment

See comment

No studies measured return to work.

Adverse events

 

2 studies reported "no exercise‐related adverse events"

45 (2 studies)

⊕⊝⊝⊝

Very lowa,d

 

The studies only reported exercise‐related adverse events in the intervention groups.

CI: confidence interval; SMD: standardised mean difference.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

a Downgraded one level for risk of bias concerns (participants and personnel administering the exercise intervention were not blinded; possible outcome reporting bias due to missing study protocols).
b Downgraded one level for serious imprecision due to small sample sizes in few studies. 
Downgraded one level for indirectness of outcomes.
Downgraded two levels for very serious imprecision due to very small sample size in few studies. 

Background

Description of the condition

Cancer is a common cause of death worldwide in both high‐ and low‐income countries. The incidence of cancer is increasing as the global population grows and ages. In low‐income countries in particular, the adoption of lifestyle behaviours that are established risk factors for cancer, such as smoking, obesity, lack of exercise, and changing reproductive patterns (lower parity and later maternal age at birth), together with urbanisation and economic development, has further increased the cancer rate (Torre 2015).

Surgery, irradiation, and chemotherapy are considered the three pillars of cancer treatment. Cancer immunotherapy (use of antibodies, small molecules, cells, and viruses that stimulate the host's immune system to attack and destroy tumour cells) is becoming more common and could be considered the fourth pillar of cancer treatment (Smyth 2017).

Half of people with cancer receive radiation therapy (RT) at some point during the course of their disease. In contrast to drug‐based systemic chemotherapy or immunotherapy, which affects the whole body, RT is a localised treatment where the tumour‐destroying effect is focused on a specific area, called the radiation field. Stereotactic RT delivers high doses of radiation to a very precise irradiation field. RT can be delivered alone or in combination with systemic therapies like chemotherapy (chemoradiation or chemoradiotherapy), immuno‐ or hormone therapy. It can also be delivered before surgery (neoadjuvant RT) or after surgery (adjuvant RT). An additional use of RT is to relieve or prevent cancer‐specific symptoms.

Conventional or stereotactic RT alone constitutes a treatment option for various cancers at different stages, including breast cancer, prostate cancer, early stages of lung cancer and Hodgkin's lymphoma, sarcomas, hepatocellular and renal cell carcinomas, endometrial cancer, cancer of salivary glands, non‐melanoma skin cancer, uveal/choroidal melanomas, and meningioma. It is also used to treat local metastases. Furthermore, RT can reduce tumour burden and relieve pain in advanced disease in the palliative setting. People with a contraindication for chemotherapy (e.g. comorbidities) or who refuse systemic treatment methods often receive RT alone.

RT destroys cancer cells through ionising radiation or particle radiation. The radiation damages the DNA of the cells so that they stop dividing or die. Because it is a local treatment, toxic effects predominantly occur in the radiation field; however, systemic symptoms such as fatigue, nausea, loss of appetite, fever, and weakness may also occur, mainly because the body is exposed to large amounts of cell debris and degradation products (Schmoll 2006Stöver 2018). The systemic and local adverse events that arise from RT can lead to exhaustion, weight loss, and physical deconditioning. The term cancer‐related fatigue (CRF) covers the physical, emotional, and cognitive fatigue or exhaustion associated with cancer or cancer treatment (Berger 2015). Between 60% and 90% of people with cancer experience CRF during or after cancer treatment, and more than 30% in their first year after diagnosis (Wagner 2004Weis 2015). Many people with breast cancer receive RT alone, and impairment of lung function due to RT could prevent them from performing physical activity. Up to 30% of all people with breast cancer receiving thoracic RT can develop radiation‐induced pneumonitis as a subacute treatment‐associated toxicity, and they are at high risk of developing radiation‐induced lung fibrosis as late toxicity (Käsmann 2020Keffer 2019). Treatment‐related death is uncommon, and the incidence is strongly related to patient characteristics such as age and BMI, and treatment characteristics such as mean lung dose, irradiated volume, and radiation technique (Chao 2017Kahán 2007Lee 2015).

All these cancer‐ or treatment‐related side effects – including cognitive impairment, sleep disorders, depression, pain, anxiety, and physical disorders – can lead to reduced physical activity, physical performance, and quality of life (QoL) in people with cancer.

Description of the intervention

Exercise is planned, structured, repetitive, and objective‐oriented physical activity in the sense that improving or maintaining one or more components of physical fitness is an intended goal (Caspersen 1985). According to the World Health Organization (WHO), physical activity is one of nine alterable risk factors for cancer. Low physical activity levels, together with obesity, are associated with 20% to 33% of all colorectal, breast, kidney, and gastrointestinal cancers (WHO 2009).

The outdated belief that exercise during cancer therapy could be harmful and that people with cancer should rest until complete remission has no scientific basis (Andrykowski 1989Dimeo 1996). The current literature shows increased survival in people with breast, colon, or colorectal cancer who have higher exercise levels (Barbaric 2010). In one study that enrolled people with colon and colorectal cancer, exercise improved survival rates when combined with standard cancer treatment (Meyerhardt 2006).

One systematic review examined all available evidence on the role of exercise in the management of cancer, without distinguishing between cancer site or stage/grade (Cormie 2017). It demonstrated a sustained trend towards reduced risk of cancer‐specific mortality, recurrence of cancer, and all‐cause mortality in participants with higher levels of exercise after a diagnosis of cancer. The included studies found an association between exercise levels and cancer mortality in participants with several types of cancer, including breast, colorectal, and prostate cancer.

Preliminary evidence suggests that exercise is safe and beneficial and can improve the management of various adverse effects of cancer and cancer treatments (Lipsett 2017). One narrative review evaluated the effects of an exercise programme to alleviate treatment‐related side effects in people with cancer undergoing RT among other cancer treatments, finding benefits in people with breast, prostate, rectal, lung, head, and neck cancer (Piraux 2020).

Research suggests that aerobic exercise, resistance training, and mindful forms of physical activity (e.g. yoga or tai chi) are effective for helping people with cancer manage their disease (Mustian 2012).

How the intervention might work

Physically active people compared with physically inactive people may have a 20% to 40% lower risk of developing several cancer types (Parent 2011). Cancer is a complex disease, and various mechanisms related to the site and stage of cancer, and to the type and quality of the exercise performed, can influence cancer outcomes. Animal models and human epidemiological studies suggest that exercise prior, during, and after cancer treatment provides positive outcomes, and that regular exercise might reduce the risk of developing cancer. The growing use of exercise in people undergoing cancer therapies has shown promising results (improved cardiorespiratory fitness, muscle strength, and physical functioning; Mishra 2014).

Researchers have proposed different biological and immunological mechanisms to explain the protective effect of exercise on cancer outcomes. Alterations in the secretion of sex hormones or insulin and insulin‐like growth factor have a direct effect on the tumour and its biology, and modify the immune system and the whole body composition (Li 2010Westerlind 2003). Exercise is associated with an increased number of anti‐inflammatory, interleukin‐10 (IL‐10)‐producing T‐lymphocytes (Weinhold 2016), and could contribute to a benefit in primary prevention and relapse of cancer. Exercise may normalise the tumour microenvironment, leading to an increase in the transport of systemic therapies to the cancer cells (Pedersen 2015), and a change of the inflammatory status (Zeng 2012).

There are different hypotheses regarding how exercise can influence survival in different cancer types. In breast cancer, exercise may reduce lifetime oestrogen exposure and lower blood oestrogen levels (reducing proliferative activity in breast tissue), improve immune function, decrease insulin resistance, lower fat tissue levels, and reduce bodyweight (Abrahamson 2006Irwin 2005). Exercise may reduce colon and colorectal cancer mortality by shortening gastrointestinal transit time, altering prostaglandin levels and tumour growth‐related hormone pathways (e.g. insulin or insulin‐like growth factors), and increasing adipokines such as adiponectin and leptin (hormones secreted by adipose tissue), all of which can affect a person's inflammatory status (Haydon 2006Meyerhardt 2006Sandhu 2002Schoen 1999Stansfield 2014Westerlind 2003).

Exercise is associated with reduced incidence of and reduced mortality from several diseases and comorbidities, such as diabetes, hypertension, cardiovascular diseases, obesity, depression, and osteoporosis (Cormie 2017Courneya 2007Pedersen 2006Warburton 2006). Moreover, a higher level of fitness has been associated with better surgical outcomes and fewer complications (Carli 2005Moran 2016).

The positive effects of exercise during cancer treatment are demonstrated improvement in CRF, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction, including muscular function, cardiopulmonary function, and bone density (Mustian 2012Mustian 2017Velthuis 2010). Exercise can improve people's psychological and physical tolerance of treatment regimens, leading to higher rates of treatment completion (van Waart 2015). Exercise can also improve their ability to manage activities of daily life and return to previous routines, such as work (Baumann 2012Colemann 2012Courneya 2009Hwang 2008). It is an effective therapeutic intervention to prepare people for the successful completion of treatments; to reduce acute, chronic, and late side effects; and to improve QoL during and after treatment. In this way, exercise directly and indirectly benefits overall survival.

Why it is important to do this review

There are published systematic reviews about the effects of exercise in people with cancer who have undergone different treatment approaches (Baumann 2018Galvão 2005Lahart 2018Mustian 2017Piraux 2020Thorsen 2008). There are also reviews on exercise in the context of selective treatments, including chemotherapy, surgery, and hormone therapy (Cavalheri 2019Cave 2018Chang 2016Segal 2003). Most available reviews on cancer and exercise focus on one type of cancer or do not distinguish between different cancer treatments. In studies that combine people who receive different treatments (systemic, local, or both), it is difficult to determine which particular therapy benefits most from the addition of exercise. It is also difficult to identify the supportive treatments that most effectively address specific treatment‐related toxicities. Because RT is a local treatment method with its own spectrum of local and systemic side effects, it may not be directly comparable to other cancer therapies. Although most people with cancer receive multimodal treatment, there are indications for RT alone, as described in Description of the condition. To date, there have been no reviews focusing on the effects of exercise on adverse events in people with cancer who undergo RT alone.

The aim of this review was to determine whether exercise in addition to standard care, compared to standard care alone, affects CRF, anthropometric outcomes; systemic or local side effects, or both; overall survival; well‐being; return to work; and psychosocial outcomes in people receiving RT without adjuvant systemic cancer therapy. It should help us determine whether an exercise intervention is beneficial in this population, clarify the most effective type and intensity of exercise intervention, and reach conclusions on feasibility, safety, and efficacy. The results of this Cochrane Review should help to inform future guidelines of cancer and cancer therapies.

Objectives

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

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs), published in any language.

Types of participants

Eligible RCTs enrolled people with cancer receiving RT of any type. Trial participants had to be at least 18 years old at the time of therapy and intervention. We placed no restrictions on sex or ethnicity. We considered all types and stages of cancer. We excluded RCTs that enrolled people who were receiving chemotherapy, hormone therapy, or immunotherapy. Surgical treatment was not an exclusion criterion. We excluded RCTs where participants received any nutrition restriction or diet intervention.

Types of interventions

We defined exercise as a medical intervention involving physical activity that is generated by skeletal muscles and leads to expenditure of energy. 

We considered any type of exercise intervention, but excluded physiotherapy alone and relaxation programmes. We also excluded multimodal approaches that combined exercise with other non‐standard interventions such as nutritional restriction.

After the diagnosis of cancer, the exercise intervention could take place before, during, or after RT. We considered exercise intervention before the start of RT as prehabilitation. Exercise programmes could be supervised or non‐supervised. We only included studies that provided exercise programmes in addition to standard care, where this refers to the accepted and routine care offered to each person for their specific medical condition in the specific study centre

Types of outcome measures

We considered all trials that met our inclusion criteria, irrespective of outcomes reported.

Primary outcomes

Fatigue, measured by a validated questionnaire such as the Multidimensional Fatigue Inventory (MFI 20; Smets 1996), Functional Assessment of Cancer Therapy‐Fatigue (FACT‐F; Cella 2002), Brief Fatigue Inventory (BFI; Mendoza 1999), or Piper Fatigue Scale (PFS; Reeve 2012).

Secondary outcomes

  • QoL (cancer‐specific QoL/cancer site‐specific QoL/health‐related QoL) measured with validated instruments such as the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires (Aaronson 1993)

  • Physical performance (e.g. oxygen system, cardiorespiratory fitness, muscle strength, physical functioning)

  • Psychosocial effects (e.g. depression, anxiety level)

  • Overall survival from randomisation to death or censoring

  • Return to work

  • Anthropometric measurements (e.g. weight, body mass index)

  • Adverse events

Search methods for identification of studies

Electronic searches

To reduce possible language bias, we applied no language restrictions to the searches. For original texts in non‐English languages (Persian and Portuguese in the case of this review), we translated the texts with the help of bilingual native speakers. We did not restrict the searches by publication date or publication status (e.g. abstract, conference proceedings, unpublished data, dissertations, etc).

We searched the following databases:

  • Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 10) in the Cochrane Library (searched 26 October 2022; Appendix 1)

  • MEDLINE Ovid (1946 to 26 October 2022; Appendix 2)

  • Embase Ovid (1980 to 26 October 2022; Appendix 3)

  • CINAHL (1961 to 26 October 2022; Appendix 4)

We designed the initial search strategy for MEDLINE as suggested in the Cochrane Handbook for Systematic Reviews of Interventions, then adapted it to the other databases (Higgins 2022).

Searching other resources

We searched the following trials registries.

We also searched conference proceedings of annual meetings of the following societies for abstracts, if not included in CENTRAL (2010 to October 2022).

  • European Society for Radiotherapy and Oncology (estro.org)

  • American Society for Radiation Oncology (astro.org)

  • American Medical Society for Sports Medicine (amssm.org)

We checked the references of all identified trials and relevant review articles for further literature. In addition, we handsearched trial registries and abstract books of annual conferences of the major societies of radiology, oncology, and sports medicine. 

Data collection and analysis

Selection of studies

We imported all the records from the searches into Covidence 2021. Two review authors (TN, RR) independently screened the titles and abstracts of all records and classified them as "eligible/potentially eligible" or "ineligible". We obtained the full‐text articles of all records that at least one review author had considered eligible or potentially eligible (Higgins 2022). If the full texts were unavailable, we contacted the study authors where possible by telephone or email. Two review authors (TN, RR) independently assessed the full‐text reports against our eligibility criteria, resolving any disagreements by discussion or, if necessary, by involving a third review author (MT). We documented the selection process in sufficient detail to complete a PRISMA flow chart (Page 2021Figure 1).


PRISMA flow diagram summarising the study selection process.

PRISMA flow diagram summarising the study selection process.

Data extraction and management

Two review authors (TN, RR) independently extracted study characteristics and outcome data from the included studies using a piloted data collection form (see Table 1) in Covidence 2021 according to Cochrane guidance (Higgins 2022). We resolved disagreements by discussion or by involving a third review author (MT). One review author (MT) transferred data into the statistical software Review Manager 5 (Review Manager 2020).

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Table 1. Template data extraction form

Study Identification

Sponsorship source

Country

Setting

Comments

Author name

Institution

Email

Address

Methods

Design

Group

Population

Inclusion criteria

Exclusion criteria

Group differences

Interventions

Instruction

Specific intervention

Intervention details

Intensity

Timing

Frequency

Outcomes

Quality of life

Overall health

Fatigue

Physical well‐being

Psychological well‐being

Social well‐being

Environmental well‐being

Emotional well‐being

Functional well‐being

Strength

Flexibility

Depression

Exercise capacity

Maximal oxygen consumption

Metabolic equivalents (METS)

Pain

Forward flexion

Abduction

Internal rotation

External rotation

Relationship with physician

Prostate cancer symptoms

We double‐checked that data had been entered correctly by comparing the data presented in the systematic review with the study reports. A fourth review author (FTB) spot‐checked the accuracy of the study characteristics against the trial reports. We extracted the following items where possible.

  • General information: author, title, source, publication date, country, language, duplicate publications

  • Study characteristics: trial design, aims, setting and dates, source of participants, inclusion and exclusion criteria, comparability of groups, subgroup analysis, statistical methods, power calculations, treatment cross‐overs, compliance with assigned treatment, length of follow‐up, time point of randomisation

  • Participant characteristics: underlying disease; stage of disease; age; sex; ethnicity; number of participants recruited, allocated, evaluated, and lost to follow‐up; type and concept of RT

  • Interventions: type, duration, and intensity of exercise intervention; standard care; duration of follow‐up

  • Outcomes: overall survival, mortality, QoL, fatigue, physical performance (e.g. oxygen system, cardiorespiratory fitness, muscle strength, physical functioning), physical activity level, anthropometric measurements (e.g. weight, body mass index), adverse events, drop‐outs, return to work, psychosocial effects (e.g. depression, anxiety level)

We extracted data from trials reported in more than one publication into a single data extraction form. If these sources did not provide sufficient information, we contacted the study authors for additional details.

Assessment of risk of bias in included studies

Two review authors (TN, RR) independently assessed the risk of bias for each study in Covidence 2021 using the following criteria, as outlined in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2011Higgins 2017).

  • Sequence generation

  • Allocation concealment

  • Blinding (participants, personnel, outcome assessors)

  • Incomplete outcome data

  • Selective outcome reporting

  • Other potential sources of bias

For every criterion, we made one of the following three judgements.

  • Low risk: if the study adequately fulfilled the criterion

  • High risk: if the study did not fulfil the criterion

  • Unclear: if the study report did not provide sufficient information to enable a judgement

We resolved any disagreements by discussion. We summarised the results of this analysis in the risk of bias graph and summary (Figure 2 and Figure 3).


Review authors' judgements about each risk of bias item presented as percentages across all included studies.

Review authors' judgements about each risk of bias item presented as percentages across all included studies.


Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Measures of treatment effect

We uploaded the outcome data for each study to Review Manager 5 to calculate treatment effects. We had planned to calculate continuous outcomes as mean differences (MDs) with 95% confidence intervals (CIs) where studies measured outcomes on the same scale, or standardised mean differences (SMDs) with 95% CIs where studies reporting the same outcome used different scales.

Because no studies reported dichotomous data for any of our outcomes, we did not estimate treatment effect measures as risk ratios (RRs) with 95% CIs. As no studies reported survival data, we could not estimate treatment effects by extracting hazard ratios (HRs) of individual studies and analyse these using the methods described in Parmar 1998 and Tierney 2007.

Unit of analysis issues

As recommended in Chapter 16.5.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), We could not combine arms of studies with multiple treatment groups as subtypes of the same intervention. We could not conduct pairwise meta‐analysis.

Dealing with missing data

There are many potential sources of missing data, listed in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), at a study level, outcome level, and summary data level. We contacted the study investigators to request missing numerical outcome data and further information on key study characteristics. Because we received no responses, we made explicit our assumptions for any methods used; for example, that the data were assumed to be missing at random or that missing values were assumed to have a particular value. We addressed the potential impact of missing data on the findings of the review in the Discussion. If numerical outcome data such as standard deviations (SDs) were missing, we calculated them from other available statistics. When specific numbers were missing from the text, we measured them using the scales in the figures in the study report.

Assessment of heterogeneity

Had we conducted meta‐analyses to assess heterogeneity of treatment effects between trials, we could have explored potential causes of heterogeneity through sensitivity and subgroup analyses (Higgins 2022).

Assessment of reporting biases

We assessed any potential reporting bias by investigating unpublished studies (Characteristics of studies awaiting classification). Had we included more than 10 trials in a meta‐analysis, we would have explored potential reporting bias by generating a funnel plot and performing a linear regression test (Higgins 2022).

Data synthesis

Owing to substantial clinical heterogeneity between trials (various types of disease), we did not pool results in a fixed‐effect meta‐analysis or use the random‐effects model for sensitivity analysis of the primary outcome. Instead, we analysed the data from each study without calculating an overall estimate. We performed analyses with the statistical software Review Manager 5 and according to guidance provided in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Review Manager 2020Deeks 2011).

Subgroup analysis and investigation of heterogeneity

Meta‐analysis and subgroup analyses were not possible.

Sensitivity analysis

If the studies had been sufficiently similar, we would have pooled the results and used the random‐effects model as a sensitivity analysis for the primary outcome.

Summary of findings and assessment of the certainty of the evidence

We created a summary of findings table based on the methods described the Cochrane Handbook for Systematic Reviews of Interventions and using GRADEpro software (Higgins 2022GRADEpro). We included the following outcomes.

  • Fatigue

  • QoL

  • Physical performance

  • Psychosocial effects

  • Overall survival

  • Return to work

  • Adverse events

 We chose this order of priority according to the existing data on the topic of 'Physical Activity and Cancer' or 'Exercise and Cancer'. Several studies have investigated fatigue, physical performance, and adverse events in people with cancer after an exercise intervention.

We presented the overall certainty of the evidence for each outcome listed in Types of outcome measures according to the GRADE approach, which takes into account issues related to internal validity (risk of bias, inconsistency, imprecision, publication bias) and external validity (directness of results; Langendam 2013Schünemann 2020). We referred to the GRADE checklist and GRADE Working Group certainty of evidence definitions and the GRADE Working Group grades of evidence (Meader 2014). We downgraded the certainty of the evidence from 'high' by one level for serious (or by two for very serious) concerns for each limitation, and interpreted the resulting grade as follows.

  • High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

  • Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

  • Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Results

Description of studies

Results of the search

The literature search recovered 5875 references, of which 430 were duplicates. In the title and abstract screening, we selected 121 records for the full‐text assessment based on our eligibility criteria. After this process, we included three studies (Hwang 2008Kulkarni 2013Monga 2007). We found one study protocol from the UK in the ISRCTN Registry that would have met our inclusion criteria, but no results have been published to date (ISRCTN26140710). We were unable to obtain a full‐text article even after contacting an investigator. In another study, it was unclear how many people were enrolled and whether they were truly randomised (Milecki 2013). We excluded 118 studies during the full‐text review and recorded the reasons for exclusion in the Characteristics of excluded studies table. Figure 1 summarises the study selection process as recommended in the PRISMA statement (Page 2021).

Included studies

All three included studies were two‐arm RCTs (Hwang 2008Kulkarni 2013Monga 2007). In total, they enrolled 130 individuals with either a breast or prostate cancer diagnosis. The exercise groups participated in an exercise programme several times per week for several weeks. All three studies included treadmill walking in the exercise intervention. Table 2 provides a tabular overview of the inclusion and exclusion criteria of the included studies. Table 3 shows the characteristics of the included studies.

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Table 2. Inclusion and exclusion criteria of included studies

Study

Inclusion criteria

Exclusion criteria

Monga 2007

• Localised prostate cancer

• First time cancer diagnosis

• Ambulatory

• Able to complete self‐report measures

• Concurrent chemotherapy

• Major health problems (uncontrolled hypertension (seated systolic blood pressure < 160 mmHg or seated diastolic blood pressure < 90 mmHg) uncontrolled insulin‐dependent diabetes mellitus, severe arthritis, or obvious cognitive dysfunction)

• Recent history of sudden onset of shortness of breath on exertion or recent history of dizziness, blurred vision, or fainting spells

• Recent history of unstable angina, coronary artery disease, myocardial infarction, or cardiac failure

• Bone, back, or neck pain of recent origin, or inability to exercise

Hwang 2008

• Female sex

• Outpatient waiting list for radiotherapy for breast cancer

• Concurrent major health problems, including:

‐ uncontrolled hypertension;

‐ cardiovascular disease;

‐ acute or chronic respiratory disease; and

‐ cognitive dysfunction.

Kulkarni 2013

• Female sex

• Age 30–60 years

• Clinical diagnosis of stage I or II breast cancer

• Unilateral modified radical mastectomy

• Radiotherapy

• Any cardiovascular abnormality

• Impaired cognitive function

• Musculoskeletal disorders

• Neurological disorders

• Emotional instability

• Very low level of activity

Open in table viewer
Table 3. Characteristics of included studies

ID

Title

Methods

 

 

 

 

 

 

Participants

Recruitment

 

Interventions

Outcomes (assessment tool)

Quality assessment

Study design

Statistical methods

Follow‐up duration

Cancer type and stage

Sex (n)

Mean age (years)

Inclusion criteria 

Exclusion criteria

Type and concept of RT

Intervention group

Control group

Blinding (participants, personnel, outcome assessors)

Other potential sources of bias

Monga 2007

Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy
 

Parallel‐ group, 2‐arm RCT

SASb software: 

• Rank‐sum or 2‐sample t tests

• Univariate or multivariate ANOVA

• Paired‐difference and 2‐sample t tests (equivalent to univariate ANOVA)

• Nonparametric Wilcoxon rank‐sum and signed‐rank tests

P ≤ 0.05 considered significant for all comparisons.

8 weeks

Localized prostate cancer

 

Only male (30)

Intervention group: 68 (SD 4.2); control group: 70.6 (SD 5.3); overall: 69.24 (SD 4.82)

 

• Localized prostate cancer

• Only first‐time cancer diagnosis

• Ambulatory

• Able to complete self‐report measures

• Concurrent chemotherapy 

• Major health problems (uncontrolled hypertension, uncontrolled insulin‐dependent diabetes mellitus, severe arthritis, and obvious cognitive dysfunction) 

• Recent history of sudden onset of shortness of breath on exertion or recent history of dizziness, blurred vision, or fainting spells

• Recent history of unstable angina, coronary artery disease, myocardial infarction, or cardiac failure •Bone, back, or neck pain of recent origin, or inability to exercise

Over a 2‐year period, participants referred to the radiotherapy service at the Houston Veterans Affairs Medical Center for radiation treatment of localised prostate cancer were approached for participation
 

External beam radiotherapy:

all participants received radiotherapy for 7–8 weeks from a Varian 2100 linear accelerator with 18‐MV photon beams. Each participant received 68 to 70Gy in 34 to 38 fractions at 1.80 to 2.0Gy per fraction.

3 times/week for 8 weeks: aerobic (cardiovascular conditioning) exercise program with 10‐minute warm‐up, 30‐minute aerobic segment (treadmill walking), and 5–10‐minute cool‐down period

Standard care that included patient education and radiotherapy without exercise prescription

 

• Cardiovascular fitness (Bruce treadmill test + METS + target HR)

• Flexibility (modified sit‐and‐reach test)

• Strength (stand‐and‐sit test)

• Fatigue (PFS)

• QoL (FACT‐P)

• Prostate cancer symptoms

• Depression (BDI)

Control group was aware of the exercise arm of the study.
 

Transcription error between tables (3 and 4/5) for "FACT‐P" and "Prostate cancer symptoms".

Hwang 2008

Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer
 

Parallel‐ group, 2‐arm RCT

SPSS version 10.0 software (SPSS Inc., Chicago, IL, USA):

• Independent‐samples t tests

• ANCOVA in which groups were compared according to follow‐up data with baseline data as the covariate

P value < 0.05 taken as significant.
 

5 weeks

Breast cancer

 Only female (40)

46.3 (SD 8.52)

• Women on outpatient waiting list for radiotherapy for breast cancer

• Concurrent major health problems

• Uncontrolled hypertension

• Cardiovascular disease

• Acute or chronic respiratory disease

• Cognitive dysfunction.
 

Consecutive unselected women on the outpatient waiting list for radiotherapy for breast cancer were approached at their first planned visit.
 

Participants were irradiated with a dose of 50 Gy during 5 weeks with a dose per fraction of 2 Gy.
 

3 times/week for 5 weeks: supervised exercise program with 10‐minute warm‐up, 30 minutes of exercise (shoulder stretching exercises, aerobic exercise, and strengthening exercise), and a 10‐minute cool‐down (relaxation period)

Standard care that included showing participants how to perform shoulder ROM exercises and encouraging them to continue with normal activities.

• QoL (overall, psychological, environmental, social, physical; WHOQOL‐BREF)

• Fatigue (BFI)

• ROM of shoulder (forward flexion, abduction, and internal rotation and external rotation)

• Pain (VAS)

• Adverse events

 —

 —

Kulkarni 2013

A randomized controlled trial of the effectiveness of aerobic training for patients with breast cancer undergoing radiotherapy
 

Parallel‐ group, 2‐arm RCT

Not reported.
 

0–6 weeks

Breast cancer, stage I or II

Only female (60)
 

45.59 (SD 7.33)

• Age 30–60 years

• Clinical diagnosis of stage I or II breast cancer

• Unilateral modified radical mastectomy

•Radiotherapy

•Any cardiovascular abnormality

•Impaired cognitive function

• Musculoskeletal disorders

•Neurological disorders

•Emotional instability

•Very low level of activity

Not reported

 Not reported

5 times/week for 6 weeks: aerobic training combined with conventional physiotherapy. Aerobic training consisted of a 10‐minute warm‐up (mild stretching of large muscle groups), 10–30 minutes treadmill walking at self‐adjusted speeds, and 10‐minute cool‐down

Standard care plus conventional physiotherapy 

• Fatigue (BFI)

• Exercise capacity (6‐minute walk test)

• VO2max

• QoL (WHOQOL‐BREF)

• Adverse events

Participants were blinded to the intervention that they were allocated to. Physiotherapists were not blinded because they had to schedule the intervention sessions. 

Calculation error of the SD of the average age in the results section.
Bar chart for fatigue does not match the numbers given in the text.

ANCOVA: analysis of covariance; ANOVA: analysis of variance; BDI: Beck Depression Inventory; BFI: Brief Fatigue Inventory; FACT‐P: Functional Assessment of Cancer Therapy‐Prostate; HR: heart rate; METS: metabolic equivalent of task; n = number of participants; PFS: Piper Fatigue Scale; QoL: quality of life; RCT: randomised controlled trial; ROM: range of motion; SD: standard deviation; VAS: visual analogue scale; VO2 max: maximal oxygen consumption; WHOQOL‐BREF: World Health Organization Quality of Life Questionnaire.

Study Characteristics

Hwang 2008 was conducted in South Korea and enrolled 40 women who had undergone breast cancer surgery (modified radical mastectomy (MRM), breast‐conserving surgery (BCS) with axillary lymph node dissection (ALND), or BCS with sentinel lymph node biopsy (SLNB)) and were on the outpatient waiting list for RT. They received a total dose of 50 Gy at 2 Gy per fraction over five weeks. Three participants randomised to the control group did not wish to have their follow‐up measurements taken; after these dropouts, the control group comprised 20 participants with a mean age of 46.3 (SD 9.5) years. The exercise group comprised 17 participants with a mean age of 46.3 (SD 7.5) years. The control group had slightly better baseline scores for fatigue, physical performance and QoL.

Kulkarni 2013 was conducted in India and enrolled 60 women aged 30 to 60 years who had stage I or stage II breast cancer, had undergone unilateral MRM, and were receiving RT. Four women in the control group and two in the exercise group dropped out of the study before completion. The control group comprised 26 participants with a mean age of 46.42 (SD 8.3) years, and the exercise group comprised 28 participants with a mean age of 44.82 (SD 3.4) years. Both groups had comparable baseline characteristics. The control group had slightly better baseline scores for fatigue and physical performance.

Monga 2007 was conducted in the USA and enrolled 30 individuals with localised prostate cancer who had been referred for primary RT. All participants received doses of 68 Gy to 70 Gy in 34 to 38 fractions at 1.80 Gy to 2.0 Gy per fraction over seven to eight weeks. The control group comprised 10 participants with a mean age of 70.6 (SD 5.3) years and the exercise group comprised 11 participants with a mean age of 68 (SD 4.2) years. Nine participants dropped out before the intervention started. All baseline characteristics, such as ethnicity or medical conditions (hypertension, diabetes, coronary artery disease, chronic obstructive pulmonary disease), were evenly distributed between the groups. The control group had slightly better baseline scores for fatigue, physical performance, and QoL.

Interventions

In Hwang 2008, participants in the exercise group took part in a supervised exercise programme three times per week for five weeks. Each session consisted of a 10‐minute warm‐up, 30 minutes of various exercises (shoulder stretching, walking on a treadmill, cycling, and strengthening exercises), and a 10‐minutes relaxation period. The investigators monitored heart rate (HR) to ensure participant were training at 50% to 70% of their age‐adjusted maximum HR. The participants in the control group received standard care, which included patient education, instruction on shoulder range of motion exercises, and encouragement to continue with normal activities.

Kulkarni 2013 combined conventional physiotherapy with aerobic exercise. The participants in the control group received standard care and conventional physiotherapy. Aerobic training took place under the supervision of a physiotherapist five times per week for six weeks, and each session lasted 30 to 50 minutes. Each training session began with 10 minutes of warm‐up exercises, including light stretching. Participants then walked on a treadmill without incline at a self‐regulated speed. Walking time was 10 minutes at the beginning of the programme, and was increased to 30 minutes over the six weeks of training. Lastly, during a 10‐minute cool‐down period, participants slowed their walking pace on the treadmill then performed some stretching exercises. Investigators calculated the target HR in beats per minute (bpm) for these sessions as follows.

  •  Target HR = 0.4 to 0.6 x (maximum HR − resting HR) + resting HR

The maximum HR (bpm) used in this formula was 220 − age of participant in years.

In Monga 2007, the exercise programme was led by a kinesiotherapist under medical supervision. The control group received standard care, which included patient education. Exercise interventions took place in the morning before daily RT three times per week for eight weeks. A session consisted of a 10‐minute warm‐up, a 30‐minute aerobic section (walking on a treadmill), and a 5‐ to 10‐minute cool‐down. Throughout the aerobic section, participants were instructed to maintain their target HR, calculated using the following formula.

  • Target HR = 0.65 × (maximum HR − resting HR) + resting HR

The investigators determined the maximum HR before the start of the exercise during a measurement of maximum oxygen consumption. Resting HR was measured weekly and target HR recalculated accordingly. 

Outcomes

All three studies assessed baseline characteristics before the start of RT and the endpoints after completion of RT. 

All three studies examined fatigue, QoL, and physical performance. Hwang 2008 and Monga 2007 reported psychosocial effects; the results for this outcome were unclear in Kulkarni 2013.

Hwang 2008 and Kulkarni 2013 assessed fatigue using the BFI (Mendoza 1999). This is a one‐page questionnaire with nine items and scores from 0 (no fatigue) to 10 (most fatigue imaginable). The simplicity of this instrument makes it very informative. It has a reported reliability of up to 0.97 (Mendoza 1999). Monga 2007 examined fatigue using the revised PFS (PFS‐Revised; Annunziata 2010), which was developed specifically for people with cancer and contains questions related to behaviour/severity, affective meaning, sensory meaning, and cognitive meaning/mood. Participants rate each sub‐aspect on a scale from 0 to 10, with higher scores representing greater fatigue (Reeve 2012).

To assess QoL, Hwang 2008 and Kulkarni 2013 used the WHO QoL questionnaire WHOQOL‐BREF (Whoqol Group 1998). This is the short form of the WHOQOL‐100, which WHO originally designed as a disease‐independent health questionnaire. It includes the four major domains of physiological health, mental health, social relationships, and environment, in addition to general health and general QoL. The domains are divided into a total of 24 sub‐aspects, which are rated from 1 to 5, with higher scores indicating better QoL. Monga 2007 examined QoL using the Functional Assessment of Cancer Therapy‐Prostate (FACT‐P; Esper 1997). This is an extension of the general version (FACT‐G), which examines physical well‐being; relationship with friends, acquaintances, and family; relationship with physicians; psychological well‐being; and functioning. FACT‐P contains a further 12 items specifically related to prostate cancer, including sexuality and bowel or bladder weaknesses (Esper 1997).

To assess physical performance, Hwang 2008 evaluated shoulder mobility and pain on a VAS, and Kulkarni 2013 calculated maximum oxygen consumption (VO2 max) using the HR and exercise capacity measured during a six‐minute walk test (ATS Committee 2002). Monga 2007 evaluated lower extremity strength (stand‐and‐sit test), flexibility (sit‐and‐reach test), and cardiac performance (Bruce Treadmill Test). 

Monga 2007 examined psychosocial effects using the Beck Depression Inventory (BDI; Beck 1961), while Hwang 2008 examined social well‐being on the WHOQOL‐BREF social subscale.

Studies awaiting classification

We found one study protocol from the UK in the ISRCTN Registry (isrctn.com) that would have met our inclusion criteria, but no results have been published to date (ISRCTN26140710). The study protocol was submitted in September 2004 and the last revision was noted in October 2014. The overall trial start date was 1 November 2003 and the overall trial end date is noted as 1 November 2008. The investigators aimed to randomise 10 women with breast cancer to an exercise intervention or control, and analyse their results to answer the following questions.

  • Do fitness levels and perceptions of QoL change during and following RT treatment for breast cancer?

  • Does an individualised exercise programme during RT treatment for cancer affect fitness levels?

  • Does perception of QoL change during and following RT as a result of exercise intervention?

Owing to the very small number of participants, we did not expect this study to have an important impact on our overall results.

We found one study conducted in Poland and published in 2013 (Milecki 2013). According to the abstract, it enrolled 46 people, of whom 25 participated in aerobic training. According to the baseline characteristics table, the study enrolled 66 people, of whom 35 participated in aerobic training. The report provided an adequate description of participants and the exercise intervention. All participants in this study underwent breast surgery then, four to five weeks later, received external beam radiation treatments seven days per week for five weeks. The affected breast and regional lymph nodes received a total dose of 50 Gy in a daily fraction of 2 Gy. Aerobic training consisted of a supervised exercise session five times per week for six weeks. Each session consisted of a two‐minute warm‐up, 40 minutes of cycling, and a 3‐minute relaxation period.

We did not include this study because of the discrepancy in participant numbers and because it is unclear if participants were truly randomised.

Ongoing studies

We found two study protocols in ClinicalTrials.gov (clinicaltrials.gov) that appear to meet our inclusion criteria.

NCT04507789 is a Turkish study investigating the effects of exercise interventions on upper extremity function in 40 women receiving RT to the axillary region after breast cancer surgery. The start date was October 10, 2020, and the anticipated study end date was April 10, 2021. The study authors will compare outcomes related to upper limb function between two groups and also within the groups after completion of RT.

NCT04506476 is a single‐centre, three‐arm RCT being conducted at the University Hospital of Tuebingen, Germany. The study start date was 1 August 2020 and the expected study duration is five years. The study authors aim to enrol 201 participants and investigate the benefit of activity tracker‐based exercise training in relation to CRF during adjuvant RT in women with breast cancer. They will measure QoL and intensity of fatigue using the fatigue subscale of the Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire three months after completion of RT.

Excluded studies

We provided a justification for exclusion of 118 studies excluded during full‐text assessment in the Characteristics of excluded studies table. Forty‐eight studies did not have RT as an inclusion criterion, 43 did not exclude people receiving chemotherapy, 12 did not exclude people receiving hormone therapy, 12 were not RCTs, and three were expert opinions (Figure 1).

Risk of bias in included studies

Due to the insufficient reporting all three studies we judged the overall risk of bias of the included trials as unclear.

For detailed information see the Characteristics of included studies table.

Allocation

We judged the risk of bias in random sequence generation to be low in Monga 2007 and unclear in Hwang 2008 and Kulkarni 2013. All three studies described randomisation and achieved a balanced distribution of baseline participant characteristics, but only Monga 2007 described a stratified randomisation with approximately equal numbers of prior exercisers in both groups. No studies described the exact allocation process and whether there was any concealment of the allocation sequence (unclear bias).

Blinding

We judged Monga 2007 to be at high risk of performance bias as it blinded neither participants nor staff. As the investigators used many subjective questionnaires to measure outcomes, knowledge about participation and group assignment alone could have influenced the response pattern. In contrast, Hwang 2008 did not report whether participants gave their informed consent to participate in an exercise study, and did not indicate who carried out the analyses, so we cannot judge risk of performance and detection bias at this time. Only Kulkarni 2013 reported blinding of the participants: the study included two active groups, but only one with additional aerobic training. The physiotherapists in Kulkarni 2013 were not blinded because they had to schedule the intervention sessions. However, as lack of blinding did not affect the endpoints (the blinded participants completed the questionnaires), we judged the risk of performance and detection bias to be low for this study.

Incomplete outcome data

Monga 2007 reported all measured endpoints. There was no evidence of incompleteness and no report of study dropouts. Therefore, we considered the study at low risk of attrition bias. In contrast, Hwang 2008 and Kulkarni 2013 reported study dropouts without explaining how incomplete outcome data were handled. Furthermore, it was unclear whether all questionnaires were completely filled out. We judged both studies at unclear risk of attrition bias.

Selective reporting

As no study protocol is available for any of the included studies, and we received no response to our requests for additional information, we considered the risk for reporting bias to be unclear for all three trials.

Other potential sources of bias

Monga 2007 administered a general activity level questionnaire before the allocation process so that the groups were balanced in terms of exercise behaviour at baseline, but neither Hwang 2008 nor Kulkarni 2013 evaluated previous exercise habits. We identified no other potential sources of bias. Therefore, we judged risk of other bias to be low in Monga 2007 and unclear in Hwang 2008 and Kulkarni 2013

Effects of interventions

See: Summary of findings 1 Exercise intervention compared to no exercise intervention for people receiving radiation therapy

Three two‐arm RCTs with 130 participants were included in this review (Hwang 2008Kulkarni 2013Monga 2007). Participants had either a breast or prostate cancer diagnosis. As we did not consider the data sufficiently homogeneous to be pooled, owing to the different cancer diagnoses and assessment tools, we displayed the analyses for each study separately in a collective forest plot. Our analyses and forest plots are based on post‐RT assessments. We were unable to analyse the changes scores between pre‐ and post‐RT assessments because Hwang 2008 and Kulkarni 2013 provided insufficient data, and some data in Monga 2007 appeared to be inaccurate. For some endpoints (fatigue, physical performance, QoL), the control groups showed slightly better scores before RT. However, the exercise group scores had improved after RT, and the control group scores had not. We were unable to account for this difference in our analysis, but it is a factor to consider when interpreting the results. 

Fatigue 

All three studies reported fatigue. Monga 2007 measured this outcome with the PFS‐Revised, while Hwang 2008 and Kulkarni 2013 used the BFI. All three studies provided low‐certainty evidence that exercise improves fatigue (summary of findings Table 1Analysis 1.1). The results of the individual analyses are presented below (positive SMD values signify less fatigue).

  • SMD 0.96, 95% CI 0.27 to 1.64; 37 participant (Hwang 2008)

  • SMD 2.42, 95% CI 1.71 to 3.13; 54 participants (Kulkarni 2013)

  • SMD 1.44, 95% CI 0.46 to 2.42; 21 participants (Monga 2007)

All studies reported reduced fatigue scores in the exercise group at the post‐RT assessment compared to the pre‐RT assessment (P value not reported in Hwang 2008; P < 0.001 in Kulkarni 2013; P = 0.02 in Monga 2007), or a significant difference between the groups in change scores from pre‐ to post‐RT assessment, favouring the exercise group (P < 0.05 in Hwang 2008; P value not reported in Kulkarni 2013; P < 0.001 in Monga 2007). Fatigue increased in the control groups in Hwang 2008 and Monga 2007 and remained unchanged in Kulkarni 2013, where the control group received physiotherapy (without aerobic exercise) plus standard care. Unfortunately, no studies provided accurate exact numbers for further analysis.

Further research might affect the estimate and our confidence in the estimate.

Quality of life

All three studies reported QoL. Hwang 2008 and Kulkarni 2013 used the WHOQOL‐BREF, while Monga 2007 used the FACT‐P. Kulkarni 2013 did not provide sufficient data for analysis. The other two studies provided low‐certainty evidence that exercise may have little or no effect on QoL (summary of findings Table 1Analysis 1.2). The results of the individual analyses are presented below (positive SMD values signify better QoL).

  • SMD 0.40, 95% CI −0.26 to 1.05; 37 participants (Hwang 2008)

  • SMD 0.47, 95% CI −0.40 to 1.34; 21 participants (Monga 2007)

All three studies reported differences between the two groups in change scores from the pre‐RT assessment to the post‐RT assessment, favouring the exercise group (P < 0.05 in Hwang 2008; P < 0.001 in Kulkarni 2013; P = 0.006 in Monga 2007). Monga 2007 also reported an improvement in QoL in the exercise group at the post‐RT assessment compared to the pre‐RT assessment (P = 0.04). Hwang 2008 and Monga 2007 reported that QoL decreased in the control groups after RT. In Kulkarni 2013, physiotherapy alone was inferior to the exercise group, which received additional aerobic training. Unfortunately, no studies provided accurate exact numbers for further analysis.

Further research might affect the estimate and our confidence in the estimate.

Physical performance

All three studies reported physical performance. Hwang 2008 measured pain on a VAS, Kulkarni 2013 used the six‐minute walk test, and Monga 2007 used the stand‐and‐sit test. Hwang 2008 and Kulkarni 2013 provided very low‐certainty evidence that exercise may improve physical performance, while Monga 2007 provided very‐low certainty evidence of no difference between the groups (summary of findings Table 1Analysis 1.3). The analyses of the individual studies are presented below (positive SMD values signify better physical performance).

  • SMD 1.25, 95% CI 0.54 to 1.97; 37 participants (Hwang 2008)

  • SMD⁠⁠⁠⁠⁠⁠ 3.13 (95% CI 2.32 to 3.95; 54 participants (Kulkarni 2013)

  • SMD 0.00, 95% CI −0.86 to 0.86; 21 participants (Monga 2007)

All three studies reported a difference between the groups in change scores from pre‐RT assessment to post‐RT assessment, favouring the exercise group (P < 0.05 in Hwang 2008; P < 0.001 in Kulkarni 2013; P < 0.001 in Monga 2007). Monga 2007 also reported an improvement in physical performance in the exercise group from pre‐RT assessment to post‐RT assessment (P < 0.001). Unfortunately, no studies provided accurate exact numbers for further analysis.

We are very uncertain about the estimate.

Psychosocial effects

Two studies reported psychosocial effects. Hwang 2008 measured this outcome using the WHOQOL‐BREF social subscale, and Monga 2007 used the BDI. There was very‐low certainty evidence that exercise may have little or no effect on psychosocial effects (summary of findings Table 1Analysis 1.4) The analyses of the individual studies are presented below (positive SMD values signify better psychosocial well‐being).

  • SMD 0.48, 95% CI −0.18 to 1.13; 37 participants (Hwang 2008)

  • SMD 0.29, 95% CI −0.57 to 1.15; 21 participants (Monga 2007)

Both studies reported differences between groups in change scores from pre‐RT assessment to post‐RT assessment, favouring the exercise group (P < 0.001 in Hwang 2008; P = 0.002 in Monga 2007). Monga 2007 also reported an improvement in social well‐being in the exercise group from pre‐RT assessment to post‐RT assessment (P = 0.02). Both studies reported a decrease in the corresponding scores in the control groups after RT.

We are very uncertain about the estimate.

Overall survival

No studies reported overall survival.

Return to work

Non studies reported return to work.

Adverse events

Hwang 2008 and Kulkarni 2013 recorded exercise‐related adverse events and reported no events. They did not record adverse events that were not related to exercise.

We estimated the certainty of the evidence as very low (summary of findings Table 1). The evidence is very uncertain about the effect of exercise on adverse events in this group.

Discussion

Summary of main results

In this review, we identified three RCTs evaluating exercise interventions for adults with cancer receiving RT alone (Hwang 2008Kulkarni 2013Monga 2007). Two studies are awaiting classification (ISRCTN26140710Milecki 2013). 

All three included studies had two study arms. They enrolled a total of 130 people who had either a breast cancer or prostate cancer diagnosis. The exercise groups attended an exercise programme several times per week for several weeks. All three studies assessed fatigue, QoL, and physical performance as outcomes. Two studies also reported psychosocial effects (Hwang 2008Monga 2007), and two recorded exercise‐related adverse events (Hwang 2008Kulkarni 2013). The investigators of all three studies measured baseline characteristics and scores before the start of RT and measured the outcomes after completion of RT. Our analyses are based on the end scores. In some outcomes (fatigue, physical performance, QoL), the control groups had slightly better baseline scores before RT. However, in most cases, the control groups had worsened or not improved after RT, while the exercise group scores had improved. Kulkarni 2013 reported a smaller improvement in QoL in the control group (physiotherapy) versus the exercise group (physiotherapy plus aerobic exercise). We were unable to analyse differences in change scores between the pre‐ and post‐RT assessments because of limited data. This could explain the differences between our results and those reported by the study authors.

The following list summarises the most relevant findings of this review.

  • Exercise interventions are possible in people with breast and prostate cancer undergoing RT without additional systemic cancer treatment.

  • Our analyses of follow‐up data from each study showed low‐certainty evidence of reduced fatigue in the exercise group versus the control group. All three studies reported significant decreases in fatigue from baseline in the group that received the exercise intervention in addition to standard care, versus no change or increased fatigue in the control groups. Exercise may reduce fatigue. 

  • Our analyses of the follow‐up QoL data from two studies showed low‐certainty evidence of little or no difference between the groups (Hwang 2008Monga 2007). Kulkarni 2013 provided insufficient data for analysis. However, all three studies reported better change scores in the exercise group compared to the control group. Exercise may improve QoL. 

  • Our analyses of the follow‐up data for physical performance from two studies showed very low‐certainty evidence of a difference between the groups in favour of exercise (Hwang 2008Kulkarni 2013); while our analysis of the data from the third study showed very‐low certainty evidence of little or no difference (Monga 2007). All three studies reported better physical performance change scores in the exercise group compared to the control group. The evidence is very uncertain about the effect of exercise on physical performance.

  • Our analyses of the follow‐up data for psychosocial effects from two studies showed very low‐certainty evidence of little or no difference between the groups (Hwang 2008Monga 2007). However, both studies reported better change scores in the exercise groups compared to the control groups. The evidence is very uncertain about the effect of exercise on psychosocial effects in this cohort.

  • Two studies reported that there were no exercise‐related adverse events; they did not identify and record treatment‐related adverse events (Hwang 2008Kulkarni 2013). Monga 2007 did not report adverse events of any type. The evidence is very uncertain about the effect of exercise on adverse events.

  • No studies reported outcome assessments for overall survival, anthropometric measurements, or return to work in any of the studies.

  • Whenever there was evidence of a difference between the groups, the results of our analyses generally favoured exercise. However, our analyses showed less evidence of a difference between the groups than reported by the study authors. No study reported accurate exact numbers for every assessed outcome.

  • The authors of all studies concluded that a supervised exercise training programme during RT alone for breast or prostate cancer leads to positive physical and psychological benefits and reduces fatigue. The exercise groups had better results than the control groups in all participant‐rated endpoints.

  • Kulkarni 2013 reported that conventional physiotherapy alone was not helpful for improving participants' overall physical condition, and Hwang 2008 found no evidence of negative effects associated with exercise in cancer survivors.

  • To date, there are no data on overall survival or short‐ and long‐term adverse events in this cohort.

  • All three studies were very small and had limitations due to risk of bias and poor documentation.

  • The certainty of the evidence for all outcomes was either low or very low.

  • Studies investigating the effects of exercise interventions for people with cancer receiving RT alone are still scarce and of limited quality, although exercise has become a very important topic in the area of supportive care.

Overall completeness and applicability of evidence

We conducted a broad‐term literature search, which resulted in a very large number of initial hits.

From this search, we identified three studies that focused on RT in addition to an exercise intervention. We also identified one study from the UK with no published results (ISRCTN26140710). However, the study protocol describes a cohort of only 10 women, so we did not expect this study to have an impact on our overall results. We identified another study with unclear participant numbers and randomisation process (Milecki 2013).

We defined 'RT alone' as RT without adjuvant systemic therapy (chemotherapy, immunotherapy, or hormone therapy; surgery was not an exclusion criterion). This likely explains why only three studies met our eligibility criteria. Most cancer types are treated with a multimodal treatment approach. There are still indications for RT alone for which exercise might be beneficial, some of which are reflected in our review. In two studies where the participants had surgery and adjuvant RT, the surgical procedure may have influenced study outcomes (Hwang 2008Kulkarni 2013). 

The studies enrolled 130 participants, of whom 112 completed follow‐up. One notable reason for dropouts was participants randomised to the control group deciding they would rather participate in the exercise group.

Hwang 2008 and Kulkarni 2013 included pre‐surgical women with breast cancer with adjuvant RT, while Monga 2007 included men with prostate cancer and primary RT. Thus, the participants have different baselines, which weakens the comparability of the results.

Duration of follow‐up was very limited in all three studies, so we are unable to draw any long‐term conclusions from the results.

Only Hwang 2008 and Kulkarni 2013 recorded adverse events (specifically, those related to exercise during the intervention period) and reported that none occurred. There were no reports on short‐ or long‐term adverse events, RT‐related adverse events, or any comparisons between the control and exercise groups.

All three studies excluded severe pre‐existing medical conditions. The results are therefore not directly applicable to participants with severe pre‐existing medical conditions. Most studies on exercise enrol people who are capable of completing the exercise sessions.

Nether Hwang 2008 nor Kulkarni 2013 collected baseline activity level.

In all three studies, the randomisation process was unclear and the information on the study design was superficial. The mere knowledge of being allocated to the exercise group could increase the participant's motivation and thus falsely improve their results. Only Kulkarni 2013 blinded participants by treating both the control and the exercise group with conventional physiotherapy. The addition of aerobic training was not recognisable as an intervention for the exercise group participants.

The studies collected data at only two time points, once before and once after the RT. An interim assessment or longer‐term follow‐up would have made the results more reliable. It remains unclear at what point in time the benefits of exercise interventions are detectable.

Both Hwang 2008 and Kulkarni 2013 presented some results in graphs without absolute numbers, which made the reading and the analyses imprecise. We did not analyse the endpoints for which we were unable to obtain scores including SD. The tables in Monga 2007 initially appeared very detailed and explicit, but we found several inconsistencies between the different tables (prostate cancer symptoms, FACT‐P values, varying SDs) and the reported average weight of the control group was clearly erroneous (80.1 lb (36.3 kg)). Consequently, we were unable to analyse change scores, and our analyses only reflect the follow‐up scores without taking into account the baseline differences between the groups. This may partly explain why the results of our analyses differ from the results reported in the individual studies. Because they only provided P values (and inaccurate numbers in the case of Monga 2007), further analyses were not possible.

There is scarce evidence on the effects of exercise in people with cancer undergoing RT alone. Furthermore, no studies reported data on adverse events not related to exercise or on survival rates, which were among our secondary outcomes.

Quality of the evidence

RCTs provide high certainty in effect estimates. Serious limitations such as risk of bias, imprecision, inconsistency between studies, indirectness, or publication bias lower our certainty that the effect estimates reflect the true effects in our target population. There were no study protocols available for any of the included studies, so we were unable to assess risk of bias in some categories. Overall, we found poor documentation and resulting uncertainties in the assessment of the systematic error, and we graded the certainty of the evidence as low or very low.

For fatigue and QoL, we downgraded for lack of blinding of study participants and personnel, possible outcome reporting bias due to missing study protocols, and serious imprecision due to small sample sizes in a small number of studies. The certainty of the evidence is low.

For physical performance the studies reported different endpoints, which limited between group comparability. We downgraded for lack of blinding of study participants and personnel, possible outcome reporting bias due to missing study protocols, and very serious imprecision due to very small sample size in a small number of studies. The certainty of the evidence is very low. 

For psychosocial effects, we were unable to analyse the data from Kulkarni 2013 due to poor presentation of results. We downgraded for lack of blinding of study participants and personnel, possible outcome reporting bias due to missing study protocols, serious imprecision due to small sample sizes in a small number of studies, and indirectness of outcomes. The certainty of the evidence is very low.

No studies reported overall survival, anthropometric measurements, or return to work.

Reported adverse events only affected the exercise groups because studies only reported exercise‐related adverse events. Monga 2007 did not record adverse events of any type. We downgraded for lack of blinding of study participants and personnel, possible outcome reporting bias due to missing study protocols, serious imprecision due to small sample sizes in a small number of studies, and indirectness of outcomes. The certainty of the evidence is very low.

For further details please see the summary of findings Table 1Figure 2, and Figure 3.

Potential biases in the review process

Two or three review authors double‐checked all processes in this review to detect any possible errors at an early stage.

The main limitation of this systematic review is the very small number of appropriate RCTs that met our inclusion criteria. We conducted an extensive literature search with no language restriction, but it is still possible that we overlooked RCTs (e.g. in foreign languages, unpublished, in progress, or published only as dissertations). Therefore, we cannot rule out publication bias or language bias.

Agreements and disagreements with other studies or reviews

Strong evidence exists on the benefits of exercise for people with cancer. One 2017 systematic review of exercise studies in the cancer literature noted that exercise is beneficial before, during, and after cancer treatment, for all cancer types and for a variety of cancer‐related adverse events (Stout 2017). The authors concluded that exercise interventions are generally feasible and safe, but that people with cancer should be screened and that clinical practice guidelines need further development. 

Consistent with our review, the most commonly studied cancer types in the literature on exercise interventions are breast, prostate, and colorectal cancer (Stout 2017). Our three included studies addressed prostate cancer (N = 1) and breast cancer (N = 2). Many systematic reviews have focused on a single cancer type (Baumann 2012Capozzi 2016Cheema 2008Cramer 2014Cramer 2017Granger 2011Keogh 2011McNeely 2006Van Dijck 2016van Vulpen 2016). We decided to include all cancer types, as most reviews have shown positive results from exercise regardless of the primary cancer diagnosis.

To our knowledge, this is the first systematic review to focus on exercise interventions for people with cancer undergoing RT alone. Several systematic reviews have evaluated the effectiveness of exercise for people with cancer undergoing systemic and multimodal treatment approaches (Zeng 2019Cave 2018Loughney 2018). We considered that adjuvant systemic treatment would have a major impact on the measured outcomes.

Cancer treatment modalities and combinations are usually based on the type of cancer and the severity of the disease, and are associated with specific adverse events. Some reviews focus on the effect of exercise on a single physical impairment (Meneses‐Echavez 2015Kwan 2011Mustian 2017), while most provide sub‐analyses for specific adverse events. We included all types of physical impairments.

Cancer‐related fatigue (CRF) is the most commonly studied physical impairment in systematic reviews investigating the role of exercise in people with cancer. Emerging evidence indicates a significant benefit of exercise for reducing CRF (Capozzi 2016Cramp 2012Keogh 2011Larkin 2014Loughney 2018Meneses‐Echavez 2015Mustian 2017van Vulpen 2016). In line with these conclusions, our results also suggest that exercise interventions during RT alone can improve fatigue.

The literature provides evidence that exercise usually has a positive effect on QoL in people with cancer (Capozzi 2016Keogh 2011Knips 2019McNeely 2006Smits 2015Van Dijck 2016). We also identified studies that found no evidence of a significant impact on QoL (Cramer 2014Granger 2011). In one of our included studies, the authors considered that because the exercise intervention improved physical performance, the improvement in QoL could be due to an improved physical and psychological state during RT (Kulkarni 2013).

Exercise interventions have shown a strong positive impact on several physical fitness measures, particularly VO2 max (McNeely 2006Van Dijck 2016), strength (Capozzi 2016Cheema 2008Keogh 2011), flexibility (Cheema 2008), and several measures of cardiorespiratory fitness (Cheema 2008Cramer 2014). The studies included in this review also reported positive effects on physical performance.

Data on the effects of exercise interventions on psychological functioning are diverse. There are reviews demonstrating positive effects (Cheema 2008Cramer 2017), but there are also inconclusive reports on this topic (Knips 2019). Some studies also report only moderate to nonexistent improvements of cognitive functions with exercise interventions (van Vulpen 2016Zimmer 2016). A wide range of instruments are available for measuring psychosocial effects, and the concept of psychosocial effects covers a range of cognitive impairments. The results of this review suggest that exercise interventions in people with cancer receiving RT alone may have a positive effect on specific impairments as measured by the corresponding tools, but the evidence is very uncertain.

PRISMA flow diagram summarising the study selection process.

Figuras y tablas -
Figure 1

PRISMA flow diagram summarising the study selection process.

Review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figuras y tablas -
Figure 2

Review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 1: Fatigue

Figuras y tablas -
Analysis 1.1

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 1: Fatigue

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 2: Overall Quality of Life (QoL)

Figuras y tablas -
Analysis 1.2

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 2: Overall Quality of Life (QoL)

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 3: Physical performance

Figuras y tablas -
Analysis 1.3

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 3: Physical performance

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 4: Psychosocial effects

Figuras y tablas -
Analysis 1.4

Comparison 1: Exercise intervention plus standard of care versus standard of care alone, Outcome 4: Psychosocial effects

Summary of findings 1. Exercise intervention compared to no exercise intervention for people receiving radiation therapy

Population: adults with breast or prostate cancer receiving radiation therapy alone

Settings: medical centre
Intervention: exercise intervention

Comparison: no exercise intervention

Outcome

Narrative synthesis

No of participants (studies)

Certainty of the evidence

Comments

Fatigue

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify less fatigue.

There is evidence of a difference between groups favouring exercise: 

  • SMD 0.96, 95% CI 0.27 to 1.64; 37 participants

  • SMD 2.42, 95% CI 1.71 to 3.13; 54 participants

  • SMD 1.44, 95% CI 0.46 to 2.42; 21 participants

112 (3 studies)

⊕⊕⊝⊝

Lowa,b

 

We did not combine data from different studies owing to clinical heterogeneity.

Quality of life

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify better quality of life.

There is evidence of little or no difference between groups:

  • SMD 0.4, 95% CI −0.26 to 1.05; 37 participants

  • SMD 0.47, 95% CI −0.40 to 1.34; 21 participants

112 (3 studies)

⊕⊕⊝⊝

Lowa,b

We did not combine data from different studies owing to clinical heterogeneity.

In Kulkarni 2013, the difference was not estimable due to lack of data. 

Physical performance

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify better physical performance.

 

Evidence from 2 studies favours exercise; 1 study shows no difference between groups: 

  • SMD 1.25, 95% CI 0.54 to 1.97; 37 participants

  • SMD 3.13, 95% CI 2.32 to 3.95; 54 participants

  • SMD 0.0, 95% CI −0.86 to 0.86; 21 participants

112 (3 studies)

⊕⊝⊝⊝

Very lowa,b,c

We did not combine data from different studies owing to clinical heterogeneity.

Because of the different endpoints in the studies, between‐group comparability is limited.

Psychosocial effects

Measured at 5‐8 weeks (short term); end scores. Positive SMD values signify better psychosocial effects.

There is evidence of little or no difference between groups:

  • SMD 0.48, 95% CI −0.18, to 1.13; 37 participants

  • SMD 0.29, 95% CI −0.57 to 1.15; 21 participants

58 (2 studies)

⊕⊝⊝⊝

Very lowa,d

We did not combine data from different studies owing to clinical heterogeneity.

We were unable to analyse data from Kulkarni 2013 owing to poor presentation of results.

Overall survival 

See comment

See comment

See comment

No studies measured overall survival.

Return to work

See comment

See comment

See comment

No studies measured return to work.

Adverse events

 

2 studies reported "no exercise‐related adverse events"

45 (2 studies)

⊕⊝⊝⊝

Very lowa,d

 

The studies only reported exercise‐related adverse events in the intervention groups.

CI: confidence interval; SMD: standardised mean difference.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

a Downgraded one level for risk of bias concerns (participants and personnel administering the exercise intervention were not blinded; possible outcome reporting bias due to missing study protocols).
b Downgraded one level for serious imprecision due to small sample sizes in few studies. 
Downgraded one level for indirectness of outcomes.
Downgraded two levels for very serious imprecision due to very small sample size in few studies. 

Figuras y tablas -
Summary of findings 1. Exercise intervention compared to no exercise intervention for people receiving radiation therapy
Table 1. Template data extraction form

Study Identification

Sponsorship source

Country

Setting

Comments

Author name

Institution

Email

Address

Methods

Design

Group

Population

Inclusion criteria

Exclusion criteria

Group differences

Interventions

Instruction

Specific intervention

Intervention details

Intensity

Timing

Frequency

Outcomes

Quality of life

Overall health

Fatigue

Physical well‐being

Psychological well‐being

Social well‐being

Environmental well‐being

Emotional well‐being

Functional well‐being

Strength

Flexibility

Depression

Exercise capacity

Maximal oxygen consumption

Metabolic equivalents (METS)

Pain

Forward flexion

Abduction

Internal rotation

External rotation

Relationship with physician

Prostate cancer symptoms

Figuras y tablas -
Table 1. Template data extraction form
Table 2. Inclusion and exclusion criteria of included studies

Study

Inclusion criteria

Exclusion criteria

Monga 2007

• Localised prostate cancer

• First time cancer diagnosis

• Ambulatory

• Able to complete self‐report measures

• Concurrent chemotherapy

• Major health problems (uncontrolled hypertension (seated systolic blood pressure < 160 mmHg or seated diastolic blood pressure < 90 mmHg) uncontrolled insulin‐dependent diabetes mellitus, severe arthritis, or obvious cognitive dysfunction)

• Recent history of sudden onset of shortness of breath on exertion or recent history of dizziness, blurred vision, or fainting spells

• Recent history of unstable angina, coronary artery disease, myocardial infarction, or cardiac failure

• Bone, back, or neck pain of recent origin, or inability to exercise

Hwang 2008

• Female sex

• Outpatient waiting list for radiotherapy for breast cancer

• Concurrent major health problems, including:

‐ uncontrolled hypertension;

‐ cardiovascular disease;

‐ acute or chronic respiratory disease; and

‐ cognitive dysfunction.

Kulkarni 2013

• Female sex

• Age 30–60 years

• Clinical diagnosis of stage I or II breast cancer

• Unilateral modified radical mastectomy

• Radiotherapy

• Any cardiovascular abnormality

• Impaired cognitive function

• Musculoskeletal disorders

• Neurological disorders

• Emotional instability

• Very low level of activity

Figuras y tablas -
Table 2. Inclusion and exclusion criteria of included studies
Table 3. Characteristics of included studies

ID

Title

Methods

 

 

 

 

 

 

Participants

Recruitment

 

Interventions

Outcomes (assessment tool)

Quality assessment

Study design

Statistical methods

Follow‐up duration

Cancer type and stage

Sex (n)

Mean age (years)

Inclusion criteria 

Exclusion criteria

Type and concept of RT

Intervention group

Control group

Blinding (participants, personnel, outcome assessors)

Other potential sources of bias

Monga 2007

Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy
 

Parallel‐ group, 2‐arm RCT

SASb software: 

• Rank‐sum or 2‐sample t tests

• Univariate or multivariate ANOVA

• Paired‐difference and 2‐sample t tests (equivalent to univariate ANOVA)

• Nonparametric Wilcoxon rank‐sum and signed‐rank tests

P ≤ 0.05 considered significant for all comparisons.

8 weeks

Localized prostate cancer

 

Only male (30)

Intervention group: 68 (SD 4.2); control group: 70.6 (SD 5.3); overall: 69.24 (SD 4.82)

 

• Localized prostate cancer

• Only first‐time cancer diagnosis

• Ambulatory

• Able to complete self‐report measures

• Concurrent chemotherapy 

• Major health problems (uncontrolled hypertension, uncontrolled insulin‐dependent diabetes mellitus, severe arthritis, and obvious cognitive dysfunction) 

• Recent history of sudden onset of shortness of breath on exertion or recent history of dizziness, blurred vision, or fainting spells

• Recent history of unstable angina, coronary artery disease, myocardial infarction, or cardiac failure •Bone, back, or neck pain of recent origin, or inability to exercise

Over a 2‐year period, participants referred to the radiotherapy service at the Houston Veterans Affairs Medical Center for radiation treatment of localised prostate cancer were approached for participation
 

External beam radiotherapy:

all participants received radiotherapy for 7–8 weeks from a Varian 2100 linear accelerator with 18‐MV photon beams. Each participant received 68 to 70Gy in 34 to 38 fractions at 1.80 to 2.0Gy per fraction.

3 times/week for 8 weeks: aerobic (cardiovascular conditioning) exercise program with 10‐minute warm‐up, 30‐minute aerobic segment (treadmill walking), and 5–10‐minute cool‐down period

Standard care that included patient education and radiotherapy without exercise prescription

 

• Cardiovascular fitness (Bruce treadmill test + METS + target HR)

• Flexibility (modified sit‐and‐reach test)

• Strength (stand‐and‐sit test)

• Fatigue (PFS)

• QoL (FACT‐P)

• Prostate cancer symptoms

• Depression (BDI)

Control group was aware of the exercise arm of the study.
 

Transcription error between tables (3 and 4/5) for "FACT‐P" and "Prostate cancer symptoms".

Hwang 2008

Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer
 

Parallel‐ group, 2‐arm RCT

SPSS version 10.0 software (SPSS Inc., Chicago, IL, USA):

• Independent‐samples t tests

• ANCOVA in which groups were compared according to follow‐up data with baseline data as the covariate

P value < 0.05 taken as significant.
 

5 weeks

Breast cancer

 Only female (40)

46.3 (SD 8.52)

• Women on outpatient waiting list for radiotherapy for breast cancer

• Concurrent major health problems

• Uncontrolled hypertension

• Cardiovascular disease

• Acute or chronic respiratory disease

• Cognitive dysfunction.
 

Consecutive unselected women on the outpatient waiting list for radiotherapy for breast cancer were approached at their first planned visit.
 

Participants were irradiated with a dose of 50 Gy during 5 weeks with a dose per fraction of 2 Gy.
 

3 times/week for 5 weeks: supervised exercise program with 10‐minute warm‐up, 30 minutes of exercise (shoulder stretching exercises, aerobic exercise, and strengthening exercise), and a 10‐minute cool‐down (relaxation period)

Standard care that included showing participants how to perform shoulder ROM exercises and encouraging them to continue with normal activities.

• QoL (overall, psychological, environmental, social, physical; WHOQOL‐BREF)

• Fatigue (BFI)

• ROM of shoulder (forward flexion, abduction, and internal rotation and external rotation)

• Pain (VAS)

• Adverse events

 —

 —

Kulkarni 2013

A randomized controlled trial of the effectiveness of aerobic training for patients with breast cancer undergoing radiotherapy
 

Parallel‐ group, 2‐arm RCT

Not reported.
 

0–6 weeks

Breast cancer, stage I or II

Only female (60)
 

45.59 (SD 7.33)

• Age 30–60 years

• Clinical diagnosis of stage I or II breast cancer

• Unilateral modified radical mastectomy

•Radiotherapy

•Any cardiovascular abnormality

•Impaired cognitive function

• Musculoskeletal disorders

•Neurological disorders

•Emotional instability

•Very low level of activity

Not reported

 Not reported

5 times/week for 6 weeks: aerobic training combined with conventional physiotherapy. Aerobic training consisted of a 10‐minute warm‐up (mild stretching of large muscle groups), 10–30 minutes treadmill walking at self‐adjusted speeds, and 10‐minute cool‐down

Standard care plus conventional physiotherapy 

• Fatigue (BFI)

• Exercise capacity (6‐minute walk test)

• VO2max

• QoL (WHOQOL‐BREF)

• Adverse events

Participants were blinded to the intervention that they were allocated to. Physiotherapists were not blinded because they had to schedule the intervention sessions. 

Calculation error of the SD of the average age in the results section.
Bar chart for fatigue does not match the numbers given in the text.

ANCOVA: analysis of covariance; ANOVA: analysis of variance; BDI: Beck Depression Inventory; BFI: Brief Fatigue Inventory; FACT‐P: Functional Assessment of Cancer Therapy‐Prostate; HR: heart rate; METS: metabolic equivalent of task; n = number of participants; PFS: Piper Fatigue Scale; QoL: quality of life; RCT: randomised controlled trial; ROM: range of motion; SD: standard deviation; VAS: visual analogue scale; VO2 max: maximal oxygen consumption; WHOQOL‐BREF: World Health Organization Quality of Life Questionnaire.

Figuras y tablas -
Table 3. Characteristics of included studies
Comparison 1. Exercise intervention plus standard of care versus standard of care alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Fatigue Show forest plot

3

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.2 Overall Quality of Life (QoL) Show forest plot

3

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.3 Physical performance Show forest plot

3

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

1.4 Psychosocial effects Show forest plot

3

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 1. Exercise intervention plus standard of care versus standard of care alone