# Exercise as it relates to Disease/Inflammation effects following exercise in chemotherapy patients
## What is the background to this research?

Kleckner et al. 2019 study about exercise and inflammation during chemotherapy identifies possible chemotherapy-related toxicities, such as fatigue, believed to be a result of inflammation. The trial of 293 participants uses a control group and an exercise intervention group. The two groups are assessed before and after the 6-week trial to measure inflammatory cytokines and how they differ between the two groups.
Kleckner et al. as well as other studies are discovering that exercise is improving the quality of life of cancer patients both during and after treatment. Because of studies like these, medical professionals are able to make educated physical activity recommendations for populations receiving chemotherapy, so that existing and future chemotherapy patients can have an improved quality of life.
Improving quality of life is specifically important for those facing a possibly life-threatening disease. The physical and psychological effects of cancer and cancer treatments can lead to an increase in mental health disorders such as anxiety, social function and depression. An improved quality of life plays a big part in the prevention and treatment of these mental disorders.

## Where is the research from?

This study is published in Supportive Care in Cancer, a reputable peer-reviewed journal that is published by Springer Science. The majority of this study's authors hold degrees from the University of Rochester Medical Center. Which is considered the 37th best medical school in medical research.

## What kind of research was this?

This is a randomised clinical trial. Randomised clinical trials are considered to be one of the more reliable types of studies as bias is less likely to occur. Particularly selection bias due to randomisation.

## What did the research involve?

Participants were randomly assorted into two groups at a 1:1 ratio. The two groups were to undertake either standard chemotherapy or standard chemotherapy and an exercise program for 6 weeks. The participants provided written informed consent and underwent the pre-intervention assessments, which included: questionnaires, daily diaries, wearing a pedometer and providing blood samples.
There were multiple requirements to be an eligible participant, which were as follows: 21 or older, primary diagnosis of cancer except for leukaemia, chemotherapy-naive, have a Karnofsky Performance Status of at least 70, radiation therapy-naive, able to perform low-to-moderate intensity exercise, and not been identified as in the active or maintenance stage of exercise behaviour.
Exercise Intervention Group
Participants randomly placed in the exercise intervention group were given a 6-week low-to-moderate intensity, at-home, walking and resistance training based program, that commenced on the first day of chemotherapy treatment. Per week, daily step requirements increased by 5-20%. Resistance-based exercises were performed as follows, 1-4 sets and 8-15 repetitions which increased over time.
Control Group
Participants randomly placed in the control group commenced chemotherapy treatment. They were also offered the exercise program after the study was complete.
The methodology used showed that safety was assured by making sure participants were able to perform everyday tasks as well as low-to-moderate intensity exercise. The exercise program is very realistic in its demands which will allow for fewer dropped-out participants in the exercise intervention group. Validity is also preserved by assuring participants are chemotherapy and radiation therapy-naive allowing for more reliable results. Ethically it is also a good approach. Participants in the control group are offered the exercise program after the study is complete so they are not denied the opportunity to become healthier and improve their quality of life.
Limitations
Although being chemotherapy and radiation therapy-naive is a requirement of this trial, that is not always a population easily acquired, especially in a short period. After cancer is diagnosed it is in the patient's best interest to start treatment early, with treatment starting usually only weeks after a diagnosis and no more than 2 months after. This gives the researchers approximately 60 days to recruit as many chemotherapy-naive cancer patients who are also willing to participate in a clinical trial. Another limitation is dropout rates. Due to the differing demands of the two groups, more participants dropped out of the exercise intervention group than the control group affecting the 1:1 ratio, however, results were not significantly affected.

## What were the basic results?

Three hypotheses were tested.
Hypothesis 1
States, exercise during chemotherapy strengthens correlations between changes in concentrations of IL-6 and IL-10. Participants in the exercise intervention group displayed positive correlations between changes in IL-6 and IL-10, more so than seen in the control group.
Hypothesis 2
States, exercise during chemotherapy strengthens correlations between changes in concentrations of other cytokines. It was found that participants in the exercise intervention group showed stronger correlations in changes in cytokine and receptor concentration than those in the control group. The major correlation values were IL-10:IL-6, IL-10:IL-1β, and IL-10:sTNFR1.
Hypothesis 3
States exercise during chemotherapy produces a more favourable inflammatory state. It was found that for the exercise intervention group, all three of the pro-inflammatory markers decreased significantly, and all three of the anti-inflammatory markers increased significantly. Whereas, for the control group, it was found that only one pro-inflammatory marker decreased significantly and only two anti-inflammatory markers increased significantly.
Due to the results, the researchers are able to confidently say that their findings have shown that a 6-week exercise intervention of low-to-moderate intensity exercise correlates with changes in cytokine concentration during chemotherapy. And through this change in cytokine concentration of specifically IL-6 and IL-10, inflammation is positively regulated.

## What conclusions can we take from this research?

Chemotherapy can cause short-term and chronic issues. But with consistent low-to-moderate intensity exercise some of these effects can be reduced due to the effects exercise has on anti- and pro-inflammatory responses.

## Practical advice

This research not only shows that exercise is beneficial towards the inflammatory response of chemotherapy patients, but also what type of exercise is beneficial. This study used home-based, low-to-moderate intensity exercise of walking and resistance training. This is an achievable exercise program for chemotherapy patients as it can be done in the convenience of their own home, reducing costs, and reducing the risk of the patient getting sick, as chemotherapy suppresses the immune system due to a decline in white blood cells.

## Further information/resources

van Vulpen et al. 2017 study is another looking at the effects of exercise on inflammatory responses in chemotherapy patients, specifically breast cancer. The study is similar to Kleckner et al. study, discussing the cytokine IL-6. It provides the audience with further evidence and a better understanding of the implications of exercise on inflammation and chemotherapy, but in a slightly more specific population.
For an audience seeking a simpler explanation, The American Cancer Society has a website clearly explaining how exercise is beneficial for cancer patients by improving quality of life and symptoms such as fatigue.

## References

* ↑ Hamule MM. Vahed AS. Relationship between Mental Health and Quality of Life in Cancer Patients. JSSU. 2010/05/15; 18(2). https://jssu.ssu.ac.ir/article-1-1036-en.html
* 1 2 3 4 5 6 7 8 9 10 11 12 Kleckner IR. Kamen C. Cole C. Fung C. Heckler CE. Guido JJ. Culakova E. Onitilo AA. Conlin A. Kuebler JP. Mohile S. Janelsins M & Mustian KM. Effects of exercise on inflammation in patients receiving chemotherapy: a nationwide NCORP randomized clinical trial. SCC. 2019/04/02.https://link.springer.com/article/10.1007/s00520-019-04772-7#citeas
* ↑ University of Rochester. University of Rochester Medical School Overview. US News. https://www.usnews.com/best-graduate-schools/top-medical-schools/university-of-rochester-04078
* ↑ Akobeng AK. Understanding randomised controlled trials. BMJ journals. 2005/07/22; 90(8). https://adc.bmj.com/content/90/8/840
* ↑ Cancer Research UK. Cancer waiting times. 2022/07/20.https://www.cancerresearchuk.org/about-cancer/cancer-in-general/cancer-waiting-times
* ↑ The American Cancer Society medical and editorial content team. Chemotherapy Side Effects. American Cancer Society. 2020/05/01.https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/chemotherapy-side-effects.html
* ↑ The American Cancer Society medical and editorial content team. Why People with Cancer Are More Likely to Get Infections. American Cancer Society. 2020/03/13.https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/low-blood-counts/infections/why-people-with-cancer-are-at-risk.html#:~:text=Chemotherapy%20(often%20called%20chemo)%20is,cell%2C%20in%20your%20blood).
* ↑ van Vulpen JK. Schmidt ME. Velthuis MJ. Wiskemann J. Schneeweiss A. Vermeulen RC. Habermann N. Ulrich CM. Peeters PH. van der Wall E. May AM & Steindorf K. Effects of physical exercise on markers of inflammation in breast cancer patients during adjuvant chemotherapy. Breast Cancer Research and Treatment volume. 2019/04/02. https://link.springer.com/article/10.1007/s10549-017-4608-7
* ↑ The American Cancer Society medical and editorial content team. Physical Activity and the Person with Cancer. American Cancer Society. 2022/03/16. https://www.cancer.org/treatment/survivorship-during-and-after-treatment/be-healthy-after-treatment/physical-activity-and-the-cancer-patient.html