Exercise as it relates to Disease, Aerobic Exercise for Treatment Related Fatigue in Men Receiving Radiotherapy for Loca

This is an analysis of the original article “A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma,” by Windsor et al (2004)[1] .

What is the background to this research?

Location of Prostate Gland ( https://upload.wikimedia.org/wikipedia/commons/a/a6/Prostate_Cancer.png ) (Image: BruceBlaus, CC BY-SA 4.0)

Prostate cancer, caused by abnormal cells growing more quickly than a normal prostate, is an age dependent disease that affects the male population across the world. Localized prostate carcinoma refers to the stage in which the cancer has not spread beyond the prostate [2].

Facts about prostate cancer:

• Is third most common cancer diagnosed in Australia [3]
• Is the third most common cause of cancer death. [3]
• In 2013, 19233 new cases were diagnosed in Australia. [3]
• Rates are projected to rise by 12% in the UK between 2014 and 2035 (6)

External beam radical therapy (EBRT) is a non-surgical treatment for prostate cancer, using high-energy x-rays. It remains one of the primary treatment methods for patients with localized prostate cancer, and aim to kill all cancer cells [4]. EBRT treatment is painless [5], but can cause side effects, commonly fatigue, up to months following treatment [6].

Radiotherapy induced fatigue is a common early and chronic side effect in up to 80% of patients [7], and is associated with psychological and physiological complications. Inactivity is known to increase fatigue; where as physical activity may be beneficial [5]. Windsor et al have conducted a study to examine potential benefits of regular walking for patients receiving radiotherapy.

Where is this research from?

This study was performed in the UK by three health professionals based in Dundee, Scotland, from different departments, including:

• Phyllis Windsor- Department of Radiotherapy and Oncology, Ninewells Hospital and Medical School.
• Kathleen Nicol- Physiotherapy Department, Ninewells Hospital and Medical School
• Joan Potter- Community Perth and Kinross Tayside Primary Care Trust

Windsor is a cancer specialist, and has previously been involved in 7 research items.
The completed study was published in the American Cancer Society, 2004.

What kind of research was this?

This study was an un-blinded, randomised controlled trial that investigated the effects of aerobic exercise on fatigue related to radiotherapy. It was conducted over a 4-week period, in which patients underwent 20 fractions of radiotherapy, with a follow up 4 weeks post completion of treatment. Ethical approval was granted by the Tayside Local Research Ethics Committee, and patients were randomised to the trial by telephone calling the Scottish Cancer Therapy Network randomisation line [1], avoiding selection bias.
A randomised controlled trial is considered the most appropriate design for clinical trails [8], and was chosen for increased comparability of the control and exercise intervention groups to facilitate statistical analysis.

What did the research involve?

The trial involved 66 male subjects aged 52-82 years (M=68.8yrs), recruited from December 2001-2002, via an outpatient waiting list for radiotherapy [1].

Exclusion Criteria included:

• Physical frailty due to age and comorbidity, such as unstable or severe angina
• Recent myocardial infraction
• Dementia.

Each participant was treated prone, using a three field, beam-directed radiotherapy technique with 6 megavolt photons to maintain consistency. A control and an exercise intervention group were utilized to obtain results. The exercise group participants were required to complete continuous walking for 30 minutes, on at least 3 days of each week of radiotherapy with a target heart rate (HR) 60-70% of maximum. Duration of activity and HR were recorded with wristband HR monitor.

Components of the research included:

Scottish Physical Activity Questionnaire (SPAQ) was administered at baseline to assess participants attitude towards activity and usual activity levels |
| Exercise Adherence | * All participants kept a patient-activity diary over the duration of receiving radiotherapy. Exercise group recorded frequency, duration of walking and HR achieved. Control group recorded frequency and duration of everyday aerobic activity
Patients were contacted weekly. Control group by a nurse about general health, and exercise group by a physiotherapist who encouraged adherence to exercise. |
| Statistical Analyses | Various tests were used to assess the significance of group differences and variables |

Despite a randomised controlled trial being the most appropriate method to conduct this study, Limitations surrounding the specific methodology include:

• There is no “gold-standard” instrument for the measurement of fatigue and it should be noted the BFI doesn’t capture cognitive, affective and somatic components of fatigue
• Small sample size
• Self reporting questionnaires can be bias, over or under exaggerated affecting reliability

What were the basic results?

Main findings included:

Fatigue

• Significant increase in fatigue scores at the end of radiotherapy compared with the baseline for the control group, and no significant difference in fatigue scores for the exercise group
• Mean BFI scores for the control group and exercise group did not differ significantly at baseline, after 4 weeks of radiotherapy or 4 week follow up

Physical Functioning

• No differences were observed with regard to resting or exercise heart-rate values over the course of the trial.
• The mean shuttle-test distance for the control group at baseline was 479.1 (± 19.8 meters) compared with 467.6 (± 23.2) meters at the end of radiotherapy; for the exercise group it was 511.6 (± 31.2 metres), compared with 579.1 (± 27) meters respectively.
• Therefore the shuttle test distance did not differ significantly between groups at baseline, but did differ a the end of radiotherapy

Adherence

• Control group showed a small, non significant decline in hours of reported aerobic activity per week
• All patients in the exercise group recorded at least 1.5 hours of aerobic exercise at the recommended percentage maximum heart rate per week throughout radiotherapy

How did the researchers interpret the results?

The researchers determined that adhering to regular walking or aerobic exercise whilst receiving radiotherapy showed no significant change in fatigue over time, where as little involvement in aerobic activity lead to a significant increase in fatigue from baseline to end of radiotherapy.

Due to the small sample size used in this trial, it could be considered that jumping to such final conclusions is an over-emphasis of the researchers findings. It should also be noted, that some findings in the paper added no statistical evidence, suggesting that further research and trials are required to increase accuracy and reliability in the future.

What conclusions can we take from this research?

It can be concluded that:

• There is an overall strong association between aerobic exercise and fatigue [1]
• Participants who don’t participate in aerobic exercise during treatment can expect a decline in physical function
• Effectiveness of the intervention is dependent on the compliancy rate of the participants
• Area is promising, but needs further research

In a similar study, walking exercise intervention for radiation fatigue was also trialed in women who received 6 weeks of radiotherapy for early stage breast carcinoma. It was demonstrated that women who exercise show a trend toward improved physical and psychosocial function, where as those who don’t showed a decline in physical function over time [9].

This study, and various others conducted after 2004, including a trial undertaken by Mustian et al that incorporates resistance as well as aerobic exercise [10] have been supportive of Windor et al findings.

Practical Advice

• The protocols employed by author should be replicated, with much larger sample size to ensure results are valid and reliable.
• If successful, the intervention should significantly improve fatigue in patients receiving radiotherapy
• This study may stimulate further research because author identified there is currently lack of knowledge, yet potential to make a difference.
• Is radiotherapy likely to remain the most common type of treatment for this type of cancer?

Further Reading

Referencing

• ↑ a b c d Windsor, P. M., Nicol, K. F. and Potter, J., 2004, A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma. Cancer, 101: 550–557.
• ↑ Prostate.org.au, 2017, Localised Prostate Cancer | PCFA. Online] Available from: [http://www.prostate.org.au/awareness/for-recently-diagnosed-men-and-their-families/localised-prostate-cancer/diagnosis/ [Accessed 30 Aug. 2017].
• ↑ a b c 2. Cancer Council Australia, 2016, Understanding Porstate Cancer: A guide for people with cancer, their families and friends. Online] Available from [http://www.cancer.org.au/content/about_cancer/ebooks/cancertypes/Understanding_Prostate_cancer_booklet_April_2016.pdf#_ga=2.3361264.1383609269.1504076130-758357156.1503982627 [Accessed 30 Aug. 2017]
• ↑ 3. Aral, I., 2016, External beam Radiotherapy in Prostate Cancer. Online] Available from: [http://emedicine.medscape.com/article/454283-overview#showall [Accessed 30 Aug. 2017].
• ↑ a b Prostate Cancer UK, 2016, External beam radiotherapy. Online] Available from: [https://prostatecanceruk.org/prostate-information/treatments/external-beam-radiotherapy [Accessed 30 Aug, 2017]
• ↑ http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/radiotherapy/side-effects/general-radiotherapy/tiredness
• ↑ Jereczek-Fossa, B., Marsiglia, H & Orecchia, R., 2002. Radiotherapy-related fatigue. Critical reviews in oncology/hematology. 41. 317-25.
• ↑ National health and Medical Research Council. (2009). NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. NHMRC. Available from: https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf
• ↑ Mock V, Dow KH, Meares CJ, et al. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncol Nurs Forum. 1997; 24: 991–1000.
• ↑ Mustian, Karen M. et al. “A 4-Week Home-Based Aerobic and Resistance Exercise Program During Radiation Therapy: A Pilot Randomized Clinical Trial.” The Journal of Supportive Oncology 7.5 (2009): 158–167. Print.

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