Partial Literature Review

The purpose of this project is to evaluate the effectiveness of a nurse-driven exercise program compared to staying inactive to reduce cancer-related fatigue (CRF) among cancer patients. Cancer-related fatigue remains a significant healthcare problem among cancer patients undergoing treatments such as chemotherapy. The effects of CRF limit cancer patients undergoing treatment to engage in their normal daily activities because they lack energy (Zhang, Li, Zhang, Yu, & Cong, 2018). Specifically, the proposed study endeavors to determine the effectiveness of a nurse-driven exercise program aimed at reducing CRF as compared to when cancer survivors stay inactive. The goal is to assist patients in improving their fatigue levels during their hospital stay and after discharge. Therefore, finding and reviewing the current literature on reducing CRF is important for healthcare providers. This paper will include a search strategy to locate current evidence related to the PICOT question as well as appraise the evidence synthesis the articles reviewed and offer recommendations for practice change. 

Search history

The researcher will perform a comprehensive literature search to locate background evidence and gaps that need to be filled in the literature. The researcher will utilize various databases to search for evidence-based research that addresses the PICOT question. The databases incorporate Google Scholar, Medline through PubMed CINAHL Plus with Full Text, EBSCOhost, and the Cochrane Library. EBSCOhost databases enable users to search several databases simultaneously using keywords (Gusenbauer & Haddaway, 2020). Keywords used for searching the databases include cancer-related fatigue, physical activity, chemotherapy, exercise, cancer survivors, and nurse-driven exercise program. The authors will delimit the search by clicking on "Find all my search terms" and "Also search with a full test of the articles." Full-Text articles will be specified and ensuring that only peer-review articles are included. In the search, the researcher will also specify articles that were published between 2015 and 2020.  All the studies that will be reviewed are those published within the last five years.

Literature Review

Cancer and Cancer-Related Fatigue

From a biological point of view, cancer itself and its related treatments can cause elevated levels of pro-inflammatory cytokines like interleukin 6 and tumor necrosis factors, which have all been linked to CRF. According to Ulrich et al. (2018), cancer is a significant burden on society globally, and the most common cause of death. However, cancer treatment modalities, such as surgery or chemotherapy, are associated with significant adverse events. Lee, Kim, & Jeon, (2018) found that despite enhancement in the prognosis of colorectal cancer, colorectal cancer survivors often suffer from adverse events of cancer treatment, incorporating decreased health-related fitness level. According to Berntsen et al. (2017), cancer-related fatigue (CRF) is a common adverse event experienced by most cancer patients. CRF is a multidimensional term that includes physical, social, emotional, psychological and biological elements that individuals treated for cancer often experience (Berntsen et al., 2017). CRF can be distinguished from other types of fatigue in that it is not alleviated through resting. Matsugaki et al. (2018) argue that the symptoms of cancer patients experience are affected by a range of factors related to the disease itself and the treatments utilized and CRF is one of the symptoms. According to Baguley et al. (2020), cancer-related fatigue is a prevalent, persistent symptom of cancer treatment, thus influencing health-related quality of life, resulting in a significant challenge to the community. 

According to Zhang et al. (2018), increased levels of fatigue are positively associated with a high risk of sleep disturbance and depression. Besides, CRF has been constantly ranked as the most elusive, common, and severe symptoms that patients with cancer undergoing chemotherapy experience. A study conducted by Berntsen et al. (2017) found that physical therapy is beneficial in decreasing CRF. Other studies also show similar results. For instance, Mijwel et al. (2018) found that physical exercise is an effective intervention to improve physical function and decrease fatigue in patients undergoing chemotherapy. Schuler et al. (2017) also conducted a study to examine the effects of a structured, individual sports program on fatigue in patients with advanced cancer. They found that the severe general fatigue experienced by tumour patients can be reduced when patients perform appropriate physical exercise. In their study, Schuler et al. (2017) noted that physical exercise could alleviate CRF. Similarly, Pyszora et al. (2017) noted that a nurse-led exercise program significantly reduced fatigue scores in terms of severity of fatigue and its impact on daily functioning. 

Immobility and Effects on CRF  

Immobility is related to a wide range of adverse outcomes that negatively affect individuals with cancer. Immobility among cancer patients is a deconditioning associated with prolonged bed rest (Matsugaki et al., 2018). Studies show that persistent bed rest leads to muscle strength decline of about 10 percent every week. Therefore, continued mobility for an extended period of five weeks may further cause the proximal lower extremity muscles to lose as much as 24 percent of their force and muscle shortening as well as leading to joint contractures. In the past years, physicians often advised cancer patients to rest and refrain from any physical activity for comfort reasons. However, studies indicated that while these patients avoid strenuous activity resulted in less discomfort, the recommended inactivity induced muscle wasting, leading to weakness, tachycardia, as well as fatigue. Research also indicates that muscle wasting among cancer patients is associated with a potential decrease in the responsiveness to cancer treatments and may further lead to a rise in morbidity and mortality. According to Minnella et al. (018), preserving muscle tone and minimizing muscle wasting via regular exercise can significantly lead to positive outcomes in persons experiencing CRF. 

Effects of Exercise on CRF

Lack of physical exercise among cancer patients undergoing treatment has been cited as one of the most consistently identified risk factor for all cancer mortalities. Studies indicate that routine physical activity can positively affect an individual’s psychological well-being through decreasing stress, anxiety, and depression. There is a significant pool of evidence that exercise is beneficial in reducing CRF. However, recommendations for an individualized exercise program in cancer patients undergoing treatment need to take account of the stage of cancer, the patient’s stage, the pain condition, and psychosocial status of the patient. Therefore, treatment should be started at a lower intensity and gradually increased as the person’s aerobic capacity enhances. 

Studies also indicate that rare adverse events from exercise occur, incorporating back, wrist, lower leg, and rotator cuff injury. A study by Zhang et al. (2018), which investigated the feasibility of a nurse-led home-based exercise and cognitive behavioral therapy for ovarian cancer adults with cancer-related fatigue on outcomes of fatigue, found that Nurse-delivered home-based E & CBT have measurable benefits in assisting women with ovarian cancer to reduce cancer-related fatigue, depressive symptoms, and enhancing their quality of sleep. The study by Matsugaki et al. (2018) to verify the immediate effect of exercise therapy on CRF in cancer patients suggested that exercise therapy targeting a rating of 4 on the CR-10 can immediately decrease CRF in cancer patients. Similarly, Mijwel et al. (2017) also conducted a study to examine the effects of concurrent resistance and high-intensity training or concurrent moderate-intensity aerobic and high-intensity interval training to normal care on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy. The authors concluded that Sixteen weeks of RT-HIIT significantly enhanced muscle strength and decreased pain sensitivity. This study proved that physical exercise is an effective intervention to improve physical functioning and reducing fatigue in cancer patients undergoing chemotherapy. 

Further, Lee et al. (2019) also conducted a study to assess the feasibility and efficacy of a 6-week home-based exercise program on the level of physical activity and physical fitness in stage II to III colorectal cancer survivors. They concluded that the 6-week home-based mixed aerobic and resistance exercise program was feasible and effective in enhancing physical activity level and physical fitness in stage II to III colorectal cancer survivors. However, this study did not indicate the feasibility of the exercise program to reduce CRF. Moreover, Pyszora et al. (2017) conducted a study to assess the effect of a physiotherapy program on CRF and other symptoms in individuals diagnosed with advanced cancer and concluded that physiotherapy program had positive effects on CRF and other symptoms in patients with advanced cancer who received palliative care. The results of this study suggested that physiotherapy is a safe and effective technique for managing CRF. 

Berntsen et al. (2017) also conducted a study to examine whether exercise intensity affects fatigue and health-related quality of life in individuals undergoing adjuvant cancer treatment. Though this is an ongoing study, the authors believe that it will contribute to the comprehension of the value of exercise and exercise intensity in decreasing fatigue and enhancing health-related quality of life and, potentially, clinical outcomes. Another ongoing study by Ulrich et al. (2018) that that used a Precision-Exercise-Prescription (PEP) intervention to examine the effect of a personalized exercise program on physical function, as measured by the 6 min walk test in patients with NSCLC and patients with secondary lung cancer who are undergoing surgical treatment. This study will also provide insight on how cancer patients undergoing surgery can use PEP to maintain, regain, and enhance their physical function during the continuum from surgery to cancer survivorship. Compared to other studies reviewed, this study does not show how exercise and CRF are correlated. 

Another study by Minnella et al. (2018) also investigated whether pre-habilitation exercise was effective in improving functional status in patients undergoing esophagogastric cancer resection. In this study, the primary outcome was also measured by a change in functional capacity, measured with an absolute change in 6-minute walk distance. The authors concluded that prehabilitation enhances perioperative functional capacity in esophagogastric surgery. Besides, the authors also found that keeping patients from physical and nutritional status decline could have a considerable effect on the cancer care continuum.

Critique of Evidence

All the studies reviewed to address the issue of CRF, which is particularly prevalent among patients undergoing cancer treatment. For instance, Matsugaki et al. (2018) noted that the symptoms experienced by cancer patients are affected by several factors, and CRF is the most common symptom. The strength of this study is that the authors were able to find that exercise therapy targeting a rating of 4 on the CR-10 can be performed without aggravating CRF. However, this study lacked a control group, which made it impossible to demonstrate the exact effects of exercise therapy. Besides, the study did not clarify how exercise therapy caused an immediate decrease in CRF. 

On the other hand, the study by Zhang et al. (2018) also addressed the issue of CRF and noted that high levels of fatigue had been observed in ovarian cancer patients. The strength of this study was the well-balanced socio-demographic and medical variables at baseline in both control and experimental groups. This study also had limited availability of research time since only outcome changes in two-time points during the intervention period were examined. Even though the study by Ulrich is still an ongoing one, it is the first randomized controlled trial to investigate a personalized exercise program for both patients with primary and secondary lung cancer. The strength of this study is that the exercise intervention was designed to be aligned with and easily translatable into clinical workflow and spanned the whole continuum of care from the pre-surgery to post-surgery duration incorporating lung cancer survivorship. However, one limitation of this study is that the cost of the intervention delivered for weekly phone calls may be too high, thus may hinder the implementation of the intervention. 

Further, the study by Minnella et al. (2018) also noted preserving functional capacity through pre-habilitation exercise is an essential element in the care of cancer patients. The strength of this study lies on the fact that it showed that by attenuating functional impairment, pre-habilitation in cancer treatment pathways is of significant value. However, this study had several limitations. For instance, the study used a small sample size of 68 from 222 patients which preclude secondary outcomes. Besides, the variability of neoadjuvant treatment in terms of duration and regimen could limit the consistency, generalizability, and applicability of the study findings. 

Additionally, the study by Mijwel et al. (22018) showed that physical exercise is an effective intervention to reduce CRF. The strength of this study is that OptiTrain intervention used is a sufficiently powered, supervised, in-clinic, randomized intervention trialling two types of progressive exercise regimens with validated measures. Again, the attendance rates were within the range commonly reported in exercise trials. The limitation of this study was that the first assessment was performed after one cycle of chemotherapy that could affect the applicability of the study. Moreover, a selection bias may have been introduced by the relatively large number of UC-patients, thus reducing participation directly after randomization. Again, the study by Schuler et al. (2017) had some strengths and limitations. The strength of this study was that it added evidence for the advantages physical exercise can offer in improving fatigue as well as a source for the careful reconsideration of daily clinical routine and possible prescription of physical therapy. However, the limitation of the study was that since blinding in this type of trial is not possible, several possible confounders occur

Gaps in Evidence

There are gaps in the reviewed studies. Out of the ten reviewed studies, no single study demonstrated how the exercise program reduced CRF. For instance, while Matsugaki et al. (2018) verified the immediate effect of exercise therapy on CRF, but did not describe how CRF changes immediately after an exercise intervention. Therefore, there is a need for the current study to investigate how exercise leads to changes in CRF during the intervention period. Besides, from the reviewed literature, it is clear that further investigation is required to determine the optimal modality of the exercise intervention in reducing CRF and its effect on overall oncologic patient outcomes. Moreover, the reviewed studies have not investigated and identified the factors involved in immediate decreases in CRF.

Implication for Practice 

As an oncology nurse who works in the surgical unit, I am intimately concerned with the havoc that CRF can inflict on the lives of cancer patients undergoing treatment. While virtually all cancer patients are encouraged to exercise after undergoing chemotherapy, some individuals are highly resistant to this type of plan of care. Therefore, the reviewed research will provide recommendations that are made clear by the research evidence. The evidence reviewed also offer alternatives methods of managing CRF that might be helpful in my clinical practice. For instance, the study by Zhang et al. (2019) used both cognitive behavioral therapies in conjunction with a nurse-led home-based exercise program to reduce CRF. This study shows that when exercise is augmented with other techniques, the outcomes are greater improvement in the management of CRF. Besides, the ongoing studies by Ulrich et al. (2018) and Berntsen et al. (2017) hold great potential for aiding practitioners in their efforts to improve the care for cancer patients and reduce CRF. Therefore, as an oncology nurse, nurse, one should stay abreast of these studies to promote a nurse-led exercise program to reduce CRF. The intervention will promote quality of life while ensuring that the CRF is significantly reduced.

Conclusion

Based on the literature, physical exercise intervention is effective in reducing CRF. These studies can be used by oncology nurses as a reference for evidence-based clinical nursing practices and home-based interventions to reduce CRF. Besides, the literature indicates that treatment of fatigue in advanced cancer patients should incorporate an appropriate selection of physiotherapy techniques suited for the patient depending on the health status and cancer stage. The literature thus provides a pool of evidence-based intervention that oncology nurse could use to reduce CRF while improving the quality of life of their patients.

References

Baguley, B. J., Skinner, T. L., Jenkins, D. G., & Wright, O. R. (2020). Mediterranean-style dietary pattern improves cancer-related fatigue and quality of life in men with prostate cancer treated with androgen deprivation therapy: A pilot randomized control trial. Clinical Nutrition.

Berntsen, S., Aaronson, N. K., Buffart, L., Börjeson, S., Demmelmaier, I., Hellbom, M., ... & Raastad, T. (2017). Design of a randomized controlled trial of physical training and cancer (Phys-Can)–the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome. BMC cancer17(1), 218.

Gusenbauer, M., & Haddaway, N. R. (2020). Which academic search systems are suitable for systematic reviews or metaanalyses? Evaluating retrieval qualities of Google Scholar, PubMed, and 26 other resources. Research synthesis methods11(2), 181-217.

Ingham-Broomfield, J. R. (2016). A nurses' guide to the hierarchy of research designs and evidence. Australian Journal of Advanced Nursing (Online)33(3), 38.

Lee, M. K., Kim, N. K., & Jeon, J. Y. (2018). Effect of the 6-week home-based exercise program on physical activity level and physical fitness in colorectal cancer survivors: A randomized controlled pilot study. PloS one13(4), e0196220.

Matsugaki, R., Akebi, T., Shitama, H., Wada, F., & Saeki, S. (2018). Immediate effects of exercise intervention on cancer-related fatigue. Journal of physical therapy science30(2), 262-265.

Mijwel, S., Backman, M., Bolam, K. A., Olofsson, E., Norrbom, J., Bergh, J., ... & Rundqvist, H. (2018). Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial. Breast cancer research and treatment169(1), 93-103.

Minnella, E. M., Awasthi, R., Loiselle, S. E., Agnihotram, R. V., Ferri, L. E., & Carli, F. (2018). Effect of exercise and nutrition prehabilitation on functional capacity in esophagogastric cancer surgery: a randomized clinical trial. JAMA surgery153(12), 1081-1089.

Minnella, E. M., Awasthi, R., Loiselle, S. E., Agnihotram, R. V., Ferri, L. E., & Carli, F. (2018). Effect of exercise and nutrition prehabilitation on functional capacity in esophagogastric cancer surgery: a randomized clinical trial. JAMA surgery153(12), 1081-1089.

Pyszora, A., Budzyński, J., Wójcik, A., Prokop, A., & Krajnik, M. (2017). Physiotherapy programme reduces fatigue in patients with advanced cancer receiving palliative care: randomized controlled trial. Supportive Care in Cancer25(9), 2899-2908.

Schuler, M. K., Hentschel, L., Kisel, W., Kramer, M., Lenz, F., Hornemann, B., ... & Kroschinsky, F. (2017). Impact of different exercise programs on severe fatigue in patients undergoing anticancer treatment—a randomized controlled trial. Journal of pain and symptom management53(1), 57-66.

Ulrich, C. M., Himbert, C., Boucher, K., Wetter, D. W., Hess, R., Kim, J., & Marcus, R. (2018). Precision-Exercise-Prescription in patients with lung cancer undergoing surgery: rationale and design of the PEP study trial. BMJ open8(12).

Zhang, Q., Li, F., Zhang, H., Yu, X., & Cong, Y. (2018). Effects of nurse-led home-based exercise & cognitive behavioral therapy on reducing cancer-related fatigue in patients with ovarian cancer during and after chemotherapy: A randomized controlled trial. International journal of nursing studies78, 52.

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