Home > News > Exercise for Toxicity Management in Cancer—A Narrative Review
Supportive Cancer Care
Read Time: 17 mins

Exercise for Toxicity Management in Cancer—A Narrative Review

Published Online: February 15th 2018 Oncology & Hematology Review. 2018;14(1):28–37 DOI: https://doi.org/10.17925/OHR.2018.14.1.28
Authors: Ian R Kleckner, Richard F Dunne, Matthew Asare, Calvin Cole, Fergal Fleming, Chunkit Fung, Po-Ju Lin, Karen M Mustian
Quick Links:
Abstract
Article
Article Information
Abstract:
Overview

Although the treatment of cancer is more effective now than ever, patients with cancer still face acute and chronic toxicities such as fatigue, cardiotoxicity, pain, cognitive impairment, and neurotoxicity. In this narrative review, we briefly discuss the use of exercise for toxicity management in patients with cancer, biological mechanisms underlying the toxicities and the effects of exercise, barriers that patients— especially underserved patients—face in adopting and adhering to exercise programs, and new technologies to overcome barriers to exercise. Our conclusions and clinical suggestions are: (1) exercise is safe and effective for treating many toxicities; (2) patients can benefit from a variety of exercise modalities (e.g., walking, cycling, resistance bands, yoga); (3) exercise should be started as soon as possible, even before treatments begin; (4) exercise should be continued as long as possible, as a lifestyle; and (5) barriers to exercise should be identified and addressed, (e.g., continually encouraging patients to exercise, using mobile technology, advocating for safe communities that encourage active lifestyles). Future research should inform definitive clinical guidelines for the use of exercise to ameliorate toxicities from cancer and its treatment.

Keywords

Side effects, toxicities, exercise, yoga, Tai Chi, mechanism, mHealth, disparities

Article:

Forty percent of Americans will be diagnosed with cancer in their lifetimes.1 Due to continued advances in cancer detection and treatment, there are an unprecedented number of cancer survivors. In fact, the 5-year survival rate for all cancers has increased from 50% in the 1970s to 67% during the period of 2006–2012.2 The two most prevalent types of cancer, prostate and breast cancer, have reached a 5-year survival of 99% and 89%, respectively.3 Despite advances in cancer treatments that have improved overall survival, patients still face toxicities from cancer and its treatment that impair quality of life, productivity, and sometimes prohibit the use of maximally effective treatments. The National Cancer Institute (NCI) Community Oncology Research Program (NCORP) Symptom Management Committee has identified high-priority cancer- and treatment-related toxicities as areas for future research. These toxicities are divided into first and second tiers based on their potential to rapidly, significantly, and positively affect cancer care, if they are alleviated.4 The first tier of toxicities includes fatigue, cardiotoxicity, pain, cognitive impairment, and neurotoxicity; the second tier of toxicities includes sleep disturbances, bone damage, metabolic toxicity, and psychological distress. Table 1 describes each toxicity, its prevalence, and how it can be studied using patient report, clinical assessments, and objective biomarkers. We focused our review on the highest-priority toxicities identified by the NCORP Symptom Management Committee;4 and though we acknowledge the importance of other toxicities (nausea, vomiting, sexual dysfunction, hair loss, mucositis, lymphedema, etc.), they are beyond the scope of this review.

A growing body of literature suggests that exercise is safe, feasible, and effective in alleviating or preventing toxicities from cancer and its treatment for patients across the treatment continuum.5–7 As we review herein, dozens of randomized controlled trials (RCTs) have assessed how toxicities from cancer and its treatment are affected by a wide range of exercises, including aerobic exercises such as walking, running, and stationary cycling; resistance exercises such as supervised weight training and the use of therapeutic resistance bands; and other forms of exercise such as yoga and Tai Chi Chuan (herein referred to as Tai Chi). Exercise is effective in treating a wide range of toxicities likely due to its established beneficial effects on multiple biological pathways (e.g. inflammation,8,9 endocrine hormones,9–11 the hypothalamic-pituitary-adrenal [HPA] axis, 9,12 and mitochondria13), psychological pathways (e.g. improved self-worth, improved self-esteem from mastering new skills, greater sense of control, time away from stress),14 and social pathways (e.g. more positive social interactions via improved self-confidence, socializing during/after exercise).15 Section 5 reviews biological mechanisms of the toxicities and effects of exercise in more detail. Indeed, exercise can complement pharmacological therapies, which most often are selected or designed to treat a single toxicity or pathway. Exercise is also feasible because it can be designed to accommodate the unique needs of each patient based on age, health status, and ability.6

Table_1_High_priority_toxicities_from_cancer_and_its_treatment.png

The goal of this paper is to present a broad narrative review of the use of exercise for toxicity management in patients with cancer. First, we review studies of exercise before cancer treatment, during cancer treatment, and after completion of cancer treatment. Next, we review biological mechanisms by which exercise exerts its beneficial effects, to better understand how it can be optimized and individualized. We review disparities in populations who have been understudied with respect to exercise during cancer as well as barriers preventing patients from exercising. Finally, we review technology to track and facilitate exercise adherence. We conclude with suggestions for clinicians to help patients select and adhere to an exercise program. This growing body of literature provides best practice suggestions in most cases, but has not yet reached a level of evidence required to produce definitive guidelines. Our major conclusions and clinical suggestions are summarized in Table 2, with more detailed suggestions for key toxicities listed in Table 3. Our review of studies is not complete, but rather highlights RCTs of exercise, examining one of NCORP’s high-priority toxicities for studies that are particularly definitive (i.e. large sample size, rigorous study design) or particularly informative (i.e. novel measures or interventions).

Table_2_General_principles_and_suggestions_for_clinicians.png

Exercise before cancer treatment

Clinical exercise interventions are often aimed at promoting recovery following surgery (rehabilitation) when patients are typically physically and mentally drained following their procedure. In contrast, “prehabilitation” increases the physiological function of a patient prior to surgery, enhancing tolerance to surgery and subsequent recovery.16 Prehabilitation is important because poor baseline functional reserve increases the risk of postoperative complications following major surgery.17 The feasibility and utility of exercise as a single mode of prehabilitation has been explored in a couple of RCTs and other clinical trials in patients undergoing surgery for cancer resection.18–22 These studies ranged in sample size from 30–112, and showed beneficial effects of 2–6 weeks of aerobic exercise or aerobic plus resistance exercise on quality of life and aerobic capacity measured by an aerobic capacity (VO2max) test or 6-minute walk test. For example, one RCT in 38 patients with liver metastases from colorectal cancer showed that supervised high-intensity interval cycling of 30 minutes/session, three sessions/week for 4 weeks, improved pre-surgical VO2max and quality of life compared to standard care.22 In another RCT of 112 patients scheduled to receive colorectal surgery, simple walking and breathing exercises improved walking capacity (6-minute walk test) both before and after surgery, compared to a cycling and strengthening intervention.20 These results may be due to the fact that the walking and breathing exercises yielded better adherence than cycling and strengthening (90% versus 16%), highlighting the importance of selecting an exercise intervention that a given sample will adhere to. Together, the prior research suggests that exercise prehabilitation is a feasible, safe, and effective way to improve preoperative fitness, provided appropriate exercises are selected (left column of Table 3). However, with only a few prior studies, further research with standardized outcomes is required to determine the optimal duration and mode of delivery before definitive recommendations can be made.

Exercise during cancer treatment

There are several RCTs demonstrating that exercise is safe, feasible, and effective in mitigating most of the NCORP high-priority toxicities (Table 1) when it is prescribed concurrently with chemotherapy, hormonal therapy, or radiation therapy (middle column of Table 3).

Exercise during chemotherapy

A recent meta-analysis,23 systematic review,24 and Cochrane review25 found that exercise significantly reduced fatigue both during or after completion of adjuvant chemotherapy. This exercise-induced improvement in fatigue was largest in studies using only aerobic exercise, although combined aerobic plus resistance training was effective too.23 For example, a recent three-arm RCT of 230 patients with breast cancer receiving adjuvant chemotherapy (the (the Physical Exercise During Adjuvant Chemotherapy Effectiveness Study [PACES])) compared (1) usual care, (2) an unsupervised low-intensity walking program of at least 30 minutes/day, 5 days/week, and (3) conditioned plus supervised moderate- to high-intensity aerobic plus resistance exercise program of 50 minutes/session, two sessions/week.26 The high-intensity exercise program reduced general fatigue more than usual care, and it reduced physical fatigue more than the low-intensity walking program. Several smaller RCTs suggest that fatigue during chemotherapy can be treated using yoga, with 60 patients with breast cancer receiving either standard care or yoga performed for 60 minutes/session, two sessions/week for 8 weeks,27 and Tai Chi, with 96 patients with lung cancer receiving either low-impact exercise (control) or Tai Chi performed for 60 minutes/session, every other day for 12 weeks.28

For cardiotoxicity, the higher-intensity aerobic and resistance exercise routine in the PACES trial significantly improved endurance and maximal short exercise capacity, assessed using a graded bicycle test, compared to usual care.26 In a separate study of 269 patients with mixed tumor types in both adjuvant and palliative chemotherapy settings, high-intensity resistance, aerobic, and relaxation exercise improved VO2max by 10.7% compared to usual care, which showed no change.29 Another study in 301 patients with breast cancer (the Combined Aerobic and Resistance Exercise [CARE] trial) showed that high-dose aerobic exercise (50–60 minutes/session, three sessions/week) increased VO2max more than low-dose aerobic exercise (25–30 minutes/session, 3 sessions/week).30

Both low- and high-intensity exercise interventions are effective in reducing pain in patients receiving chemotherapy, according to results from the PACES trial.26 Aerobic exercises may be particularly effective for pain control in patients receiving chemotherapy, as suggested by the 301 patients with breast cancer in the CARE trial, showing that high-dose aerobic exercise reduced pain more than combined aerobic plus resistance exercise.30 Cognitive impairment was improved by exercise in at least two studies. One was an RCT of 479 patients receiving chemotherapy comparing unsupervised low–moderate intensity walking and resistance exercise, when compared to usual care for 6 weeks.31 Another was an RCT of 48 patients receiving myeloablative chemotherapy followed by autologous stem cell transplant, wherein subjects were randomized to 40 minutes/day of ergometric and resistance exercises, had lower rates of cognitive impairment and exhibited better psychosocial function compared to patients in the physiotherapy control condition.32

For chemotherapy-induced peripheral neuropathy (CIPN), exercise significantly improved patient-reported numbness and tingling in an RCT comparing a 6-week unsupervised low–moderate intensity walking and resistance exercise routine to usual care in 355 patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy.33,34 In a separate trial of 60 patients with lymphoma receiving chemotherapy, a supervised moderate-intensity aerobic, resistance, and sensorimotor exercise intervention of 60 minutes/session, 2 sessions/week, significantly improved balance and reduced neuropathy symptoms compared to standard care.35

In regards to second-tier toxicities patients may experience while receiving chemotherapy (Table 1), aerobic and/or resistance exercise has been shown to improve sleep36 and self-esteem;37,38 however, several studies have demonstrated no improvement in depression and anxiety.27,38

Table_3_Example_studies_showing_beneficial.png

Table_3_Cont.png

Exercise during radiation therapy

Several RCTs have shown that many forms of exercise reduce fatigue during radiation treatment in patients with breast cancer39–41 and patients with prostate cancer.39,42–44 One study tested supervised moderate-intensity aerobic exercise for three sessions/week, at 50–60% VO2max using a cycle ergometer, treadmill, or elliptical; or supervised moderate-intensity resistance exercise for three sessions/week, with 10 exercises, at 60–70%, of their one-repetition maximum (independently tested) versus usual care, for 24 weeks, in 121 patients with prostate cancer.42 Another study tested yoga versus brief supportive therapy for 60 minutes/session, 3–7 sessions/week, for 6 weeks in 80 patients with breast cancer.45 Exercise RCTs have also shown improvements in cardiovascular fitness during radiation treatment in patients with breast cancer (e.g. 46 patients randomized to supervised moderate-intensity cycling or usual care control; 20 patients randomized to unsupervised moderate-intensity walking or placebo stretching control),46,47 whereas some studies have shown no effects (e.g. 126 patients randomized to unsupervised home-based walking or usual care).48 The null findings from Griffith et al.48 might have been because the exercise dose was insufficient (e.g., intensity was too low), as the other studies tracked exercise intensity objectively, using heart rate monitors. In one study examining cardiovascular fitness in patients with breast cancer receiving radiation therapy, 7 weeks of aerobic exercise increased VO2max, red blood cell count, and hemoglobin count, whereas patients randomized to the placebo stretching group became worse on all three measures.47 These results show that not only can exercise protect against treatment-induced toxicities, but exercise can actually improve cardiovascular fitness during cancer treatments.

The treatment of radiation-induced pain with exercise is also well-studied, with several RCTs showing benefits.40,48–50 One study in 60 patients showed that 2 weeks of resistance training, performed during radiation therapy, reduced patient-reported pain and opiate medication use both 3 months and 6 months after completion of radiation treatment, compared to passive physical therapy control.50 The use of exercise to treat cognitive impairment and neurotoxicity from radiation has not been well studied in humans, but several RCTs in animal models have shown that exercise protected against radiation-induced cognitive impairment when radiation was delivered to the brain.51 RCTs in humans have shown that exercise is effective for many second tier radiation-induced toxicities as well, including sleep problems (e.g. insomnia),41 bone damage (e.g. sparing radiation-induced bone loss in patients with bone metastases),52 metabolic toxicity (e.g. reducing appetite loss),41 and psychological distress (e.g. reducing negative effects and anxiety).45,53

Exercise during hormonal therapy

During treatment with aromatase inhibitors, exercise has proven helpful in reducing joint pain,54,55 bone pain,54,55 and bone damage,56,57 and exercise has been suggested to treat cognitive impairment based on successful treatments in animal models.58 In men receiving androgen deprivation therapy for prostate cancer, an RCT of 155 patients demonstrated that a 12-week resistance exercise routine improved fatigue, quality of life, and upper and lower body muscular fitness, when compared to usual care, although no improvement was seen in weight, body mass index, or waist circumference.59

Exercise after completion of cancer treatment (survivorship)

A growing body of evidence suggests that exercise is safe and effective in reducing toxicities experienced after completion of cancer treatments (right column of Table 3). As reviewed below, studies have tested aerobic exercise, combined aerobic and resistance exercise, and mindfulness-based exercise.

Aerobic exercise

One RCT in 86 breast cancer survivors showed that a 12-week unsupervised low–moderate intensity, home-based walking program, significantly reduced fatigue and exhibited a trend toward improving overall mood and body esteem.60 Another RCT in 116 lung cancer survivors who walked 3 days/week for 40 minutes/day with weekly counseling, improved their anxiety and depression levels.61

Combined walking and strength training

An RCT in 66 patients with stage IV lung or colorectal cancer post-treatment showed that an 8-week home-based resistance band exercise program, combined with incremental walking, improved the mobility, fatigue, and sleep quality compared to usual care.62 In another study, a 12-month exercise program (6 months of supervised aerobic and resistance exercise, followed by 6 months of home-based exercise maintenance) improved the physical function and health-related quality of life in 100 older long-term prostate cancer survivors compared to the physical activity education control condition.63

Mindfulness-based exercise

Several studies have investigated the effects of yoga on cancer-related toxicities such as sleep disturbances,64,65 fatigue,54,64,66–68 psychological distress,68 cognitive impairment,69,70 musculoskeletal symptoms,54 and menopausal symptoms.64 An RCT of yoga in 410 cancer survivors, compared standard care to standard care plus a 4-week program called Yoga for Cancer Survivors (YOCAS©®), which includes breathing exercises, postures, and meditation for 75 minutes/session, two sessions/week for 4 weeks.65 YOCAS significantly improved sleep quality,65 fatigue,54 global side-effect burden,54 memory difficulties,70 and musculoskeletal pain and discomfort,54 compared to standard care. A separate RCT comparing 12 weeks of Iyengar yoga for 90 minutes/session, two sessions/week, to health education among 31 breast cancer survivors showed that yoga reduced fatigue and depression.67 Another study in 37 breast cancer survivors, showed that an 8-week yoga program consisting of postures, breathing exercises, meditation, study of pertinent topics, and group discussion for 120 minutes/session, one session/week, significantly improved sleep disturbance, fatigue, and menopausal symptoms (e.g. hot flash, joint pain, menopause-related distress), compared to wait-list control.64 Several studies of one RCT in 21 breast cancer survivors demonstrated that a 12-week Tai Chi intervention performed for 60 minutes/session, three sessions/week, improved aerobic capacity, muscular strength, flexibility, body composition, self-esteem, quality of life,71–73 and bone health (increases in bone formation, decreases in bone resorption), compared to psychosocial support control.74

Biological mechanisms of toxicities and the effects of exercise

Although a complete review of mechanisms of exercise is out of the scope of this review, we highlight several biological mechanisms involved in toxicities from cancer and its treatment as well as the effects of exercise. These pathways include inflammation,8,9 endocrine hormones,9–11 the HPA axis,9,12 and mitochondria.13 Exercise can exert beneficial effects on all of these pathways simultaneously, partially explaining how exercise can have widespread beneficial effects on several cancer- and treatment-related toxicities.

It is well known that the immune system, including multiple inflammatory signaling pathways, is adversely affected by cancer,75 chemotherapy,76,77 radiation,78 and surgery.79 Although inflammation can be part of the healthy healing process, excessive chronic inflammation might lead to fatigue,80,81 pain,82 cognitive impairment,83 neuropathy,84,85 sleep disturbances,86 bone damage,87 metabolic toxicities (muscle wasting, cachexia),88,89 and psychological distress (anxiety, depression).88,90 Inflammation is mediated by an array of small proteins called cytokines, which act as inter-cellular signals that are secreted by various tissues in response to foreign invaders, ingested foods/drugs, stress, exercise, etc. Cytokines circulate in the blood and then bind to cell-surface receptors, whose activation triggers cascades of genetic and biochemical events related to the cell cycle, immune function, and inflammation.91 Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor agonist (IL-1RA), and interleukin (IL)-6 have been implicated in the development of cancer-related fatigue,80 cancer-related depression and anxiety (along with IL-8),90 and cancer cachexia.89,92–95 Chronic immune activation leads to dysfunction of the endocrine system, HPA axis, mitochondria,80 and dysregulation in the secretion of pro-inflammatory cytokines.80,88 The systemic effect of chronic immune activation adversely alters hormone release, cell respiration, and ultimately skeletal muscle synthesis and function, which may alter production of ghrelin and reactive oxygen species.

Ghrelin is a peptide hormone that is an endogenous ligand to the hypothalamic growth hormone (GH) secretagogue receptor (i.e. binding of ghrelin to this receptor induces the release of GH).96 GH release increases the amount of circulating insulin-like growth factor 1 (IGF-1)97 which, when bound to its receptor IGF-1R, signals the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Mammalian target of rapamycin (mTOR), the downstream target of the PI3K/protein kinase B (Akt) pathway, is phosphorylated and thus increases protein synthesis and inhibits protein degradation.97 Dysfunction of the endocrine system and HPA axis might interfere with this pathway, thus contributing to major cancer- and treatment-related metabolic toxicities.

Mitochondrial abnormalities that lead to oxidative stress, caused by increases in reactive oxygen species, have been linked to distress (e.g. depression) and muscle wasting.98–101 Depression involves dysregulation of monoamine neurotransmitters such as serotonin and norepinephrine, and hypersensitivity of the HPA axis.88 Specifically, research suggests that alterations in these pathways are related to an enhanced inflammatory response.88,92,102

Exercise is a promising treatment for many cancer-related toxicities because exercise affects multiple biological pathways. In particular, exercise has potent and well-studied anti-inflammatory effects.8 During exercise, IL-6 is released by contracting muscles in healthy individuals as well as cancer patients.103 This pro-inflammatory cytokine exerts anti-inflammatory effects by inhibiting the production of TNF-α and IL-1,104,105 and increasing production of anti-inflammatory IL-10. Progressive resistance training has also been shown to upregulate transcription factors that increase muscle protein synthesis through the phosphorylation of mTOR.106 Indeed, both resistance and endurance training are capable of reducing disease-induced muscle proteolysis through enhanced phosphorylation of Akt and the Forkhead transcription factor (FoxO1). Phosphorylation of FoxO1 prevents its relocation into the nucleus where it upregulates the transcription of atrophy genes.107 Thus, the beneficial effects of exercise on fatigue, cardiotoxicity, pain, cognitive impairment, neurotoxicity, etc., as discussed previously, might occur partly through exercise-induced changes in inflammation.

Health disparities in cancer and exercise research

Underserved cancer patients and survivors are less likely to be physically active at every stage of the cancer continuum.108,109 Underserved individuals in this context include racial and ethnic minorities (African Americans, Hispanics, and Asian Americans) and vulnerable populations (low socioeconomic status, low educational attainment, those residing in rural communities, sexual and gender minorities, geriatrics). Racial minority patients with breast cancer are less likely to participate in physical activity after a diagnosis109 and their participation in exercise declines during treatment.110 Cancer survivors are more like to be physically active if they are white (52% were active) or Asian-American (48%) versus Hispanic (39%) or African-American (32%).111 Studies have also found that physical activity participation rates are very low for cancer patients who live in rural communities.112,113

Both structural and personal barriers limit physical activity in underserved populations.114 Structural barriers include neighborhood or community safety concerns,115117 lack of sidewalks and physical activity facilities,115,118,119 and lack of physically active role models.116,120 Socioeconomic stratifications affect health outcomes and quality of life of underserved cancer patients and they perpetuate disparities in who decides to exercise. Personal barriers to exercise include lack of time,115,121 lack of motivation,115,118,122 tiredness/fatigue,115,123 lack of knowledge,123,124 health conditions,115,118 physical appearance concerns,116,120,123 cost of facilities,115,118,123,125,126 and lack of social support.115,120,124 Additionally, most cancer patients report that they do not discuss exercise with their oncologist or primary care physician as part of their cancer treatments,127,128 despite the patient’s interest in learning more about exercise,129 and despite the fact that exercise adherence is increased if clinicians are involved in making recommendations for exercise.130 This leaves significant room for improvement to help patients initiate and adhere to an exercise program. Notwithstanding those barriers, underserved individuals can benefit from exercise to manage toxicities from cancer and its treatment.131

Clinicians can have a significant impact on initiating and adhering to an exercise program, especially for underserved patients. Physicians should recognize that underserved cancer patients are less likely to exercise, so they can be proactive in their discussions with patients. To reach underserved populations, physicians can network and partner with their communities and stakeholders (e.g. churches, gyms). Partnering with their communities will not only build a mutual respect and trust especially among the underserved communities but will also provide physicians opportunities to educate other members of the community about exercise and cancer care. Of course, education alone will likely not change a patient’s exercise behavior; support and resources from the community and clinical team are crucial to improvement. For example, patient navigators can provide assistance to patients who may need transportation or child care. In addition, the combined efforts from local government, federal government, community health centers, community members, and law enforcement should ensure safe neighborhoods, install sidewalks, and improve access to exercise facilities with reduced or free cost for individuals in need.

Technology to enhance exercise tracking and adherence

Mobile technology is a rapidly developing and promising way to help patients exercise more by tracking their exercise and providing feedback to enhance motivation and adherence. Nearly two-thirds of adults in the United States own a smartphone132 and technological advancements have enabled these devices to monitor health behaviors and provide convenient feedback.133 Wearable digital activity trackers have similar capabilities but may have more consumer appeal than a smartphone. Some of these devices are fairly accurate for measuring steps walked, with one study showing wrist-worn activity trackers underestimating steps by 1–23%, smartphone applications underestimating steps by 6–7%, and pedometers overestimating steps by up to a mere 1%.134 However, for obtaining heart rate data, the current generation of wrist-worn devices do not perform well, with one study showing 95% of estimated heart rate values varying by 30 beats per minute under or over the gold-standard electrocardiogram.135

Mobile devices are also being incorporated into behavioral interventions in an approach called mobile health, or mHealth. This new breed of interventions utilize mobile computing and communication technologies for a range of functions, such as clinical decision support systems, data collection tools for healthcare professionals, and supporting health behavior change for management of chronic diseases such as obesity and diabetes.136 The use of mobile health interventions is a rapidly expanding area of research and practice,133,137,138 and has only recently been applied to cancer patients and survivors.139,140 Next, we review the use of mobile behavioral interventions in the general population and in cancer patients specifically.

Mobile health behavioral interventions in the general population

In healthy adults, dozens of studies have suggested that the use of a pedometer, a relatively minimalist mobile health intervention, significantly increases physical activity, decreases body mass index, and decreases blood pressure.141 Short-term studies have shown that more rigorous mobile health behavioral intervention results in modest improvements in weight loss in the general population.142,143 Recently, an RCT entitled Innovative Approaches to Diet, Exercise, and Activity (IDEA) examined the effectiveness of pedometers for long-term health behavior modifications.144 At the beginning of the study, all participants were prescribed a low-calorie diet and physical activity program, with group counseling sessions. At 6 months, they were randomized to either the standard intervention group, which utilized self-monitoring of diet and physical activity using a website, or the enhanced intervention group, which utilized digital activity trackers and accompanying web interface to monitor diet and physical activity. While both groups had significant improvements in body composition, fitness, physical activity, and diet, these improvements were not statistically significantly different between the two groups. Furthermore, among adults with a relatively high body mass index of 25–40 kg/m2, integration of digital activity trackers to a standard behavioral intervention resulted in less weight loss over 24 months. However, the use of digital activity trackers was not initiated until 6 months after the onset of intervention, which may have hindered how the technology was used.

Mobile health behavioral interventions among cancer patients and survivors

A recent systematic review examined interactive web-based interventions that aimed to increase patient empowerment and physical activity for various chronic conditions in the general population.145 This review identified seven elements that can be translated into mobile health recommendations for cancer survivors: education, self-monitoring, feedback/tailored information, self-management training, personal exercise program, and communication with either healthcare providers or patients (e.g. chat, email). These essential components may serve as the foundation for designing future interactive mobile health interventions for cancer survivors, with the ultimate goal to improve their health status and quality of life. Importantly, two recent studies demonstrated feasibility and improved physical activity levels from two mobile health interventions: a 6-week, web-based, behavioral modification program for adult cancer survivors,139 and a technology-based, 6-month lifestyle intervention via either telemedicine or text messaging, for patients with endometrial cancer.140

Suggestions for clinicians

A growing body of evidence shows that exercise is safe, feasible, and effective to ameliorate several side effects of cancer and its treatments along the cancer treatment continuum. Our six principles and clinical suggestions are summarized in Table 2. The literature provides best practice suggestions for clinicians to prescribe exercise for treating or preventing certain toxicities, but does not yet provide definitive guidelines in terms of exercise type, frequency, intensity, and duration for all toxicities.

Prior research has provided an excellent starting point for the dose of exercise recommended for cancer patients, including special considerations and suggested modifications.6,7 The American College of Sports Medicine indicates cancer patients and survivors should slowly progress to 150 minutes/week of moderate-intensity aerobic exercise, or 75 minutes/week of vigorous intensity exercise, combined with 2–3 days of strength training across all major muscle groups, plus regular stretching.6 Higher-intensity exercise has been shown to be more effective for certain toxicities (e.g. cardiotoxicity,29 fatigue26) but only if that exercise is feasible.20 These results are consistent with the idea of an inverted-U association between exercise response and exercise dose (training intensity, session duration), suggested in reviews of exercise in relation to cancer toxicities,146 cancer mortality,147 heart disease,148 and healthy aging149 (i.e. a moderate dose exercise is best). Thus, exercise recommendations should be started slowly and, optimally, individualized with the help of an exercise professional who is familiar with the needs of cancer patients. Table 3 lists specific exercise regimens shown to be beneficial in an RCT.

Conclusions

The advent of improved cancer screening techniques and new anti-neoplastic therapies have led to improved overall survival for patients with cancer over the past 20 years. Additionally, patients living with cancer can be more active due, in part, to improvements in supportive care and clinical trials that have challenged the concept of over-treatment. These phenomena have opened the door to studying the utility of exercise in patients with cancer on treatment and cancer survivorship. Biological mechanisms of both cancer and its treatments, specifically chemotherapy, radiation, and hormonal therapy, that lead to inflammation, muscle breakdown, and functional limitations can be targeted using exercise. Furthermore, clinical trials suggest that exercise can treat many high-priority toxicities (Table 1)—namely fatigue, cardiotoxicity, pain, cognitive impairment, neurotoxicity, sleep disturbances, bone damage, metabolic toxicity, and psychological distress—sometimes before, during, and after cancer treatment (example exercise regimens in Table 3). The development of wearable activity trackers and mHealth interventions has enhanced our ability to measure patient activity, and how it may affect cancer and treatment-related toxicities. Many of these studies include low-cost, home-based interventions that are convenient and achievable in these populations. Despite the seemingly accessible nature of exercise, disparities still exist in employing the use of exercise in underserved communities. As the multitude of benefits of exercise in patients with cancer continue to come forth, it is important for healthcare providers and community leaders to address and remove barriers that patients may face so interventions like exercise can reach and help more and more patients each day.

Article Information:
Disclosure

Ian R Kleckner, Richard F Dunne, Matthew Asare, Calvin Cole, Fergal Fleming, Chunkit Fung, Po-Ju Lin and Karen M Mustian have nothing to disclose in relation to this article.

Correspondence

Ian Kleckner, Cancer Control Center, Department of Surgery, University of Rochester Medical Center, 265 Crittenden Blvd., Box CU 420658, Rochester, NY 14642. E: Ian_Kleckner@URMC.Rochester.edu

Support

Funding was provided by the National Cancer Institute, including funds from NCORP parent grant U10 CA037420, NCORP supplement U10 CA037420, and R25 CA102618.

Open Access

This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

Received

2017-09-29T00:00:00

References

  1. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62:220–41.
  2. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2013. Bethesda, MD, US: National Cancer Institute, 2016. Available at: https://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016 (accessed November 23, 2017).
  3. American Cancer Society. Cancer Treatment & Survivorship Facts & Figures 2016-2017. Atlanta, GA, US: American Cancer Society, 2016.
  4. NCI NCORP Symptom Management Quality of Life Steering Committee. 2015 Strategic Priorities, 2015. Available at: www.cancer.gov/about-nci/organization/ccct/steering-committees/2015-SxQoLSC-StrategicPriorities (accessed January 9, 2018).
  5. Kilari D, Soto-Perez-de-Celis E, Mohile SG, et al. Designing exercise clinical trials for older adults with cancer: Recommendations from 2015 Cancer and Aging Research Group NCI U13 Meeting. J Geriatr Oncol, 2016;7:293–304.
  6. Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42:1409–26.
  7. Mustian KM, Sprod LK, Janelsins M, et al. Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: a review. Oncol Hematol Rev. 2012;8:81–8.
  8. Gleeson M, Bishop NC, Stensel DJ, et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011;11:607–15.
  9. Pascoe MC, Bauer IE. A systematic review of randomised control trials on the effects of yoga on stress measures and mood. J Psychiatr Res. 2015;68:270–82.
  10. Hackney AC, Lane AR. Exercise and the regulation of endocrine hormones. Prog Mol Biol Transl Sci. 2015;135:293–311.
  11. Ball D. Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle. J Endocrinol. 2015;224:R79–95.
  12. Heijnen S, Hommel B, Kibele A, Colzato LS. Neuromodulation of aerobic exercise-a review. Front Psychol. 2015;6:1890.
  13. Bishop DJ, Granata C, Eynon N. Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content? Biochim Biophys Acta. 2014;1840:1266–75.
  14. Psychological well-being: does physical activity make us feel good? In: Biddle Stuart JH, Mutrie N, Psychology of Physical Activity: Determinants, Well-Being and Interventions, 2nd ed. New York, NY, US: Routledge, 2008;163–198.
  15. Davis A, Taylor J, Cohen E. Social bonds and exercise: evidence for a reciprocal relationship. PLoS One. 2015;10:e0136705.
  16. Topp R, Ditmyer M, King K, et al. The effect of bed rest and potential of prehabilitation on patients in the intensive care unit. AACN Clin Issues. 2002;13:263–76.
  17. Reilly DF, McNeely MJ, Doerner D, et al. Self-reported exercise tolerance and the risk of serious perioperative complications. Arch Intern Med. 1999;159:2185–92.
  18. Banerjee S, Manley K, Thomas L, et al. Preoperative exercise protocol to aid recovery of radical cystectomy: Results of a feasibility study. European Urology Supplements. 2013;12:125.
  19. Jensen BT, Petersen AK, Jensen JB, et al. Efficacy of a multiprofessional rehabilitation programme in radical cystectomy pathways: a prospective randomized controlled trial. Scand J Urol. 2015;49:133–41.
  20. Carli F, Charlebois P, Stein B, et al. Randomized clinical trial of prehabilitation in colorectal surgery. Br J Surg. 2010;97:1187–97.
  21. Dronkers JJ, Lamberts H, Reutelingsperger IM, et al. Preoperative therapeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study. Clin Rehabil. 2010;24:614–22.
  22. Dunne DF, Jack S, Jones RP, et al. Randomized clinical trial of prehabilitation before planned liver resection. Br J Surg. 2016;103:504–12.
  23. Mustian KM, Alfano CM, Heckler C, et al. Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncol. 2017;3:961–8.
  24. Meneses-Echavez JF, Gonzalez-Jimenez E, Ramirez-Velez R. Effects of supervised multimodal exercise interventions on cancer-related fatigue: systematic review and meta-analysis of randomized controlled trials. Biomed Res Int. 2015;2015:328636.
  25. Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2012;11:CD006145.
  26. van Waart H, Stuiver MM, van Harten WH, et al. Effect of low-intensity physical activity and moderate- to high-intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: results of the PACES Randomized Clinical Trial. J Clin Oncol. 2015;33:1918–27.
  27. Taso CJ, Lin HS, Lin WL, et al. The effect of yoga exercise on improving depression, anxiety, and fatigue in women with breast cancer: a randomized controlled trial. J Nurs Res. 2014;22:155–64.
  28. Zhang LL, Wang SZ, Chen HL, Yuan AZ. Tai Chi exercise for cancer-related fatigue in patients with lung cancer undergoing chemotherapy: a randomized controlled trial. J Pain Symptom Manage. 2016;51:504–11.
  29. Adamsen L, Quist M, Andersen C, et al. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ. 2009;339:b3410.
  30. Courneya KS, McKenzie DC, Mackey JR, et al. Effects of exercise dose and type during breast cancer chemotherapy: multicenter randomized trial. J Natl Cancer Inst.2013;105:1821–32.
  31. Mustian KM, Janelsins MC, Peppone L, et al. EXCAP exercise effects on cognitive impairment and inflammation: A URCC NCORP RCT in 479 cancer patients. J Clin Oncol. 2015;33(suppl):abstr 9504.
  32. Oechsle K, Aslan Z, Suesse Y, et al. Multimodal exercise training during myeloablative chemotherapy: a prospective randomized pilot trial. Support Care Cancer. 2014;22:63–9.
  33. Kleckner I, Kamen C, Peppone L, et al. A URCC NCORP nationwide randomized controlled trial investigating the effect of exercise on chemotherapy-induced peripheral neuropathy in 314 cancer patients. J Clin Oncol. 2016;34(suppl):abstr 10000.
  34. Kleckner IR, Kamen C, Gewandter JS, et al. Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial. Support Care Cancer. 2017; doi: 10.1007/s00520-017-4013-0. [Epub ahead of print].
  35. Streckmann F, Kneis S, Leifert JA, et al. Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Ann Oncol. 2014;25:493–9.
  36. Courneya KS, Segal RJ, Mackey JR, et al. Effects of exercise dose and type on sleep quality in breast cancer patients receiving chemotherapy: a multicenter randomized trial. Breast Cancer Res Treat. 2014;144:361–9.
  37. Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007;25:4396–404.
  38. Gokal K, Wallis D, Ahmed S, et al. Effects of a self-managed home-based walking intervention on psychosocial health outcomes for breast cancer patients receiving chemotherapy: a randomised controlled trial. Support Care Cancer. 2016;24:1139–66.
  39. Mustian KM, Peppone L, Darling TV, et al. A 4-week home-based aerobic and resistance exercise program during radiation therapy: a pilot randomized clinical trial. J Support Oncol. 2009;7:158–67.
  40. Steindorf K, Schmidt ME, Klassen O, et al. Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life. Ann Oncol. 2014;25:2237–43.
  41. Vadiraja SH, Rao MR, Nagendra RH, et al. Effects of yoga on symptom management in breast cancer patients: A randomized controlled trial. Int J Yoga. 2009;2:73–9.
  42. Segal RJ, Reid RD, Courneya KS, et al. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J Clin Oncol. 2009;27:344–51.
  43. Monga U, Garber SL, Thornby J, et al. Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy. Arch Phys Med Rehabil. 2007;88:1416–22.
  44. Tseng YD, Martin NE. How can I help myself? A critical review of modifiable behaviors, medications, and complementary alternative medicine for men receiving radiotherapy for prostate cancer. Semin Radiat Oncol. 2013;23:173–81.
  45. Vadiraja HS, Rao MR, Nagarathna R, et al. Effects of yoga program on quality of life and affect in early breast cancer patients undergoing adjuvant radiotherapy: a randomized controlled trial. Complement Ther Med. 2009;17:274–80.
  46. Milecki P, Hojan K, Ozga-Majchrzak O, Molinska-Glura M. Exercise tolerance in breast cancer patients during radiotherapy after aerobic training. Contemp Oncol (Pozn). 2013;17:205–9.
  47. Drouin JS, Young TJ, Beeler J, et al. Random control clinical trial on the effects of aerobic exercise training on erythrocyte levels during radiation treatment for breast cancer. Cancer. 2006;107:2490–5.
  48. Griffith K, Wenzel J, Shang J, et al. Impact of a walking intervention on cardiorespiratory fitness, self-reported physical function, and pain in patients undergoing treatment for solid tumors. Cancer. 2009;115:4874–84.
  49. Hwang JH, Chang HJ, Shim YH, et al. Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer. Yonsei Med J. 2008;49:443–50.
  50. Rief H, Welzel T, Omlor G, et al. Pain response of resistance training of the paravertebral musculature under radiotherapy in patients with spinal bone metastases–a randomized trial. BMC Cancer. 2014;14:485.
  51. Zimmer P, Baumann FT, Oberste M, et al. Effects of exercise interventions and physical activity behavior on cancer related cognitive impairments: a systematic review. Biomed Res Int. 2016;2016:1820954.
  52. Rief H, Bruckner T, Schlampp I, et al. Resistance training concomitant to radiotherapy of spinal bone metastases - survival and prognostic factors of a randomized trial. Radiat Oncol. 2016;11:97.
  53. Rao MR, Raghuram N, Nagendra HR, et al. Anxiolytic effects of a yoga program in early breast cancer patients undergoing conventional treatment: a randomized controlled trial. Complement Ther Med. 2009;17:1–8.
  54. Peppone LJ, Janelsins MC, Kamen C, et al. The effect of YOCAS©® yoga for musculoskeletal symptoms among breast cancer survivors on hormonal therapy. Breast Cancer Res Treat. 2015;150:597–604.
  55. Irwin ML, Cartmel B, Gross CP, et al. Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol. 2015;33:1104–11.
  56. Knobf MT, Jeon S, Smith B, et al. Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy. Breast Cancer Res Treat. 2016;155:491–500.
  57. Winters-Stone KM, Dobek J, Nail L, et al. Strength training stops bone loss and builds muscle in postmenopausal breast cancer survivors: a randomized, controlled trial. Breast Cancer Res Treat. 2011;127:447–56.
  58. Li C, Zhou C, Li R. Can exercise ameliorate aromatase inhibitor-induced cognitive decline in breast cancer patients? Mol Neurobiol. 2016;53:4238–46.
  59. Segal RJ, Reid RD, Courneya KS, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer J Clin Oncol. 2003;21:1653–9.
  60. Pinto BM, Rabin C, Dunsiger S. Home-based exercise among cancer survivors: adherence and its predictors. Psychooncology. 2009;18:369–76.
  61. Chen HM, Tsai CM, Wu YC, et al. Randomised controlled trial on the effectiveness of home-based walking exercise on anxiety, depression and cancer-related symptoms in patients with lung cancer. Br J Cancer. 2015;112:438–45.
  62. Cheville AL, Kollasch J, Vandenberg J, et al. A home-based exercise program to improve function, fatigue, and sleep quality in patients with Stage IV lung and colorectal cancer: a randomized controlled trial. J Pain Symptom Manage. 2013;45:811–21.
  63. Buffart LM, Newton RU, Chinapaw MJ, et al. The effect, moderators, and mediators of resistance and aerobic exercise on health-related quality of life in older long-term survivors of prostate cancer. Cancer. 2015;121:2821–30.
  64. Carson JW, Carson KM, Porter LS, et al. Yoga of Awareness program for menopausal symptoms in breast cancer survivors: results from a randomized trial. Support Care Cancer. 2009;17:1301–9.
  65. Mustian KM, Sprod LK, Janelsins M, et al. Multicenter, randomized controlled trial of yoga for sleep quality among cancer survivors. J Clin Oncol. 2013;31:3233–41.
  66. Kiecolt-Glaser JK, Bennett JM, Andridge R, et al. Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2014;32:1040–9.
  67. Bower JE, Garet D, Sternlieb B, et al. Yoga for persistent fatigue in breast cancer survivors: a randomized controlled trial. Cancer. 2012;118:3766–75.
  68. Banasik J, Williams H, Haberman M, et al. Effect of Iyengar yoga practice on fatigue and diurnal salivary cortisol concentration in breast cancer survivors. J Am Acad Nurse Pract. 2011;23:135–42.
  69. Derry HM, Jaremka LM, Bennett JM, et al. Yoga and self-reported cognitive problems in breast cancer survivors: a randomized controlled trial. Psychooncology. 2015;24:958–66.
  70. Janelsins MC, Peppone LJ, Heckler CE, et al. YOCAS©® yoga reduces self-reported memory difficulty in cancer survivors in a nationwide randomized clinical trial: investigating relationships between memory and sleep. Integr Cancer Ther. 2016;15:263–71.
  71. Mustian KM, Katula JA, Gill DL, et al. Tai Chi Chuan, health-related quality of life and self-esteem: a randomized trial with breast cancer survivors. Support Care Cancer. 2004;12:871–6.
  72. Mustian KM, Katula JA, Zhao H. A pilot study to assess the influence of Tai Chi Chuan on functional capacity among breast cancer survivors. J Support Oncol. 2006;4:139–45.
  73. Mustian KM, Palesh OG, Flecksteiner SA. Tai Chi Chuan for breast cancer survivors. Med Sport Sci. 2008;52:209–17.
  74. Peppone LJ, Mustian KM, Janelsins MC, et al. Effects of a structured weight-bearing exercise program on bone metabolism among breast cancer survivors: a feasibility trial. Clin Breast Cancer. 2010;10:224–9.
  75. Wang K, Karin M. Tumor-elicited inflammation and colorectal cancer. Adv Cancer Res. 2015;128:173–96.
  76. Collado-Hidalgo A, Bower JE, Ganz PA, et al. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res. 2006;12:2759–66.
  77. Pusztai L, Mendoza TR, Reuben JM, et al. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine. 2004;25:94–102.
  78. Schaue D, Micewicz ED, Ratikan JA, Xie MW, Cheng G, McBride WH. Radiation and inflammation. Semin Radiat Oncol. 2015;25:4–10.
  79. Paddison JS, Booth RJ, Fuchs D, Hill AG. Peritoneal inflammation and fatigue experiences following colorectal surgery: a pilot study. Psychoneuroendocrinology. 2008;33:446–54.
  80. Saligan LN, Olson K, Filler K, et al. The biology of cancer-related fatigue: a review of the literature. Support Care Cancer. 2015;23:2461–78.
  81. Zargar-Shoshtari K, Hill AG. Postoperative fatigue: a review. World J Surg. 2009;33:738–45.
  82. Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184–7.
  83. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102–13.
  84. Lees JG, Makker PG, Tonkin RS, et al. Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy. Eur J Cancer. 2017;73:22–9.
  85. Wang XM, Lehky TJ, Brell JM, Dorsey SG. Discovering cytokines as targets for chemotherapy-induced painful peripheral neuropathy. Cytokine. 2012;59:3–9.
  86. Kamath J. Cancer-related fatigue, inflammation and thyrotropin-releasing hormone. Curr Aging Sci. 2012;5:195–202.
  87. Abu-Amer Y. Inflammation, cancer, and bone loss. Curr Opin Pharmacol. 2009;9:427–33.
  88. Illman J, Corringham R, Robinson D, Jr., et al. Are inflammatory cytokines the common link between cancer-associated cachexia and depression? J Support Oncol. 2005;3:37–50.
  89. Mueller TC, Bachmann J, Prokopchuk O, et al. Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia–can findings from animal models be translated to humans? BMC Cancer. 2015;16:75.
  90. Oliveira Miranda D, Soares de Lima TA, Ribeiro Azevedo L, et al. Proinflammatory cytokines correlate with depression and anxiety in colorectal cancer patients. Biomed Res Int. 2014;2014:739650.
  91. Holdsworth SR, Gan PY. Cytokines: names and numbers you should care about. Clin J Am Soc Nephrol. 2015;10:2243–54.
  92. Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metabolism. 2012;16:153–66.
  93. Tisdale MJ. Molecular pathways leading to cancer cachexia. Physiology (Bethesda). 2005;20:340–8.
  94. Vaughan VC, Martin P, Lewandowski PA. Cancer cachexia: impact, mechanisms and emerging treatments. J Cachexia Sarcopenia Muscle. 2013;4:95–109.
  95. Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14:754–62.
  96. Eisenstein J, Greenberg A. Ghrelin: update 2003, Nutr Rev. 2003;61:101.
  97. Velloso CP. Regulation of muscle mass by growth hormone and IGF-I. Br J Pharmacol. 2008;154:557–68.
  98. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J., 1996;313:17–29.
  99. Ansari MA, Scheff SW. Oxidative stress in the progression of Alzheimer disease in the frontal cortex. J Neuropathol Exp Neurol. 2010;69:155–167.
  100. Bandyopadhyay U, Das D, Banerjee RK. Reactive oxygen species: oxidative damage and pathogenesis. Current Science. 1999;77:658–66.
  101. Arthur PG, Grounds MD, Shavlakadze T. Oxidative stress as a therapeutic target during muscle wasting: considering the complex interactions. Curr Opin Clin Nutr Metab Care. 2008;11:408–16.
  102. López-Armada MJ, Riveiro-Naveira RR, Vaamonde-García C, Valcárcel-Ares MN. Mitochondrial dysfunction and the inflammatory response. Mitochondrion. 2013;13:106–18.
  103. Galvao DA, Nosaka K, Taaffe DR, et al. Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer Prostatic Dis. 2008;11:160–5.
  104. Starkie R, Ostrowski SR, Jauffred S, et al. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J. 2003;17:884–6.
  105. Schindler R, Mancilla J, Endres S, et al. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990;75:40–7.
  106. Bowen TS, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle. 2015;6:197–207.
  107. Wang XH, Du J, Klein JD, et al. Exercise ameliorates chronic kidney disease-induced defects in muscle protein metabolism and progenitor cell function. Kidney Int. 2009;76:751–9.
  108. Hair BY, Hayes S, Tse CK, et al. Racial differences in physical activity among breast cancer survivors: implications for breast cancer care. Cancer. 2014;120:2174–82.
  109. Carlson SA, Fulton JE, Schoenborn CA, Loustalot F. Trend and prevalence estimates based on the 2008 Physical Activity Guidelines for Americans. Am J Prev Med. 2010;39:305–13.
  110. Kwan ML, Sternfeld B, Ergas IJ, et al. Change in physical activity during active treatment in a prospective study of breast cancer survivors. Breast Cancer Res Treat. 2012;131:679–90.
  111. Paxton RJ, Phillips KL, Jones LA, et al. Associations among physical activity, body mass index, and health-related quality of life by race/ethnicity in a diverse sample of breast cancer survivors. Cancer. 2012;118:4024–31.
  112. Reis JP, Bowles HR, Ainsworth BE, et al. Nonoccupational physical activity by degree of urbanization and U.S. geographic region. Med Sci Sports Exerc. 2004;36:2093–8.
  113. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007;116:1081–93.
  114. Joseph RP, Ainsworth BE, Keller C, Dodgson JE. Barriers to physical activity among African American women: an integrative review of the literature. Women Health. 2015;55:679–99.
  115. Bopp M, Lattimore D, Wilcox S, et al. Understanding physical activity participation in members of an African American church: a qualitative study. Health Educ Res., 2007;22:815–26.
  116. Henderson KA, Ainsworth BE. Enablers and constraints to walking for older African American and American Indian women: the Cultural Activity Participation Study. Res Q Exerc Sport. 2000;71:313–21.
  117. Ingram D, Wilbur J, McDevitt J, Buchholz S. Women’s walking program for African American women: expectations and recommendations from participants as experts. Women Health. 2011;51:566–82.
  118. Hoebeke R. Low-income women’s perceived barriers to physical activity: focus group results. Appl Nurs Res. 2008;21:60–5.
  119. Strong LL, Reitzel LR, Wetter DW, McNeill LH. Associations of perceived neighborhood physical and social environments with physical activity and television viewing in African-American men and women. Am J Health Promot. 2013;27:401–9.
  120. Harley AE, Odoms-Young A, Beard B, et al. African American social and cultural contexts and physical activity: strategies for navigating challenges to participation. Women Health. 2009;49:84–100.
  121. Dunn MZ. Psychosocial mediators of a walking intervention among African American women. J Transcult Nurs. 2008;19:40–6.
  122. Genkinger JM, Jehn ML, Sapun M, et al. Does weight status influence perceptions of physical activity barriers among African-American women? Ethn Dis. 2006;16:78–84.
  123. Pekmezi D, Marcus B, Meneses K, et al. Developing an intervention to address physical activity barriers for African-American women in the deep south (USA). Womens Health (Lond). 2013;9:301–12.
  124. Wilcox S, Oberrecht L, Bopp M, et al. A qualitative study of exercise in older African American and white women in rural South Carolina: perceptions, barriers, and motivations. J Women Aging. 2005;17:37–53.
  125. Im EO, Ko Y, Hwang H, et al. Racial/ethnic differences in midlife women’s attitudes toward physical activity. J Midwifery Womens Health. 2013;58:440–50.
  126. Kirchhoff AC, Elliott L, Schlichting JA, Chin MH. Strategies for physical activity maintenance in African American women. Am J Health Behav. 2008;32:517–24.
  127. Mustian KM, Griggs JJ, Morrow GR, et al. Exercise and side effects among 749 patients during and after treatment for cancer: a University of Rochester Cancer Center Community Clinical Oncology Program Study. Support Care Cancer. 2006;14:732–41.
  128. Jones LW, Courneya KS. Exercise discussions during cancer treatment consultations. Cancer Pract. 2002;10:66–74.
  129. Yates JS, Mustian KM, Morrow GR, et al. Prevalence of complementary and alternative medicine use in cancer patients during treatment. Support Care Cancer. 2005;13:806–11.
  130. Jones LW, Courneya KS, Fairey AS, Mackey JR. Effects of an oncologist’s recommendation to exercise on self-reported exercise behavior in newly diagnosed breast cancer survivors: a single-blind, randomized controlled trial. Ann Behav Med. 2004;28:105–13.
  131. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report, 2008. Washington, DC, US: U.S. Department of Health and Human Services, 2008. Available at: https://health.gov/paguidelines/report/ (accessed November 22, 2017).
  132. Smith A. US Smartphone Use in 2015, 2015. Available at: www.pewinternet.org/2015/04/01/us-smartphone-use-in-2015/ (accessed February 24, 2016).
  133. Patel MS, Asch DA, Volpp KG. Wearable devices as facilitators, not drivers, of health behavior change. JAMA. 2015;313:459–60.
  134. Case MA, Burwick HA, Volpp KG, Patel MS. Accuracy of smartphone applications and wearable devices for tracking physical activity data. JAMA. 2015;313:625–6.
  135. Wang R, Blackburn G, Desai M, et al. Accuracy of wrist-worn heart rate monitors. JAMA Cardiol. 2017;2:104–6.
  136. Free C, Phillips G, Felix L, et al. The effectiveness of M-health technologies for improving health and health services: a systematic review protocol. BMC Res Notes. 2010;3:250.
  137. Bort-Roig J, Gilson ND, Puig-Ribera A, et al. Measuring and influencing physical activity with smartphone technology: a systematic review. Sports Med. 2014;44:671–86.
  138. Powell AC, Landman AB, Bates DW. In search of a few good apps. JAMA. 2014;311:1851–2.
  139. Bantum EO, Albright CL, White KK, et al. Surviving and thriving with cancer using a Web-based health behavior change intervention: randomized controlled trial. J Med Internet Res. 2014;16:e54.
  140. Haggerty AF, Huepenbecker S, Sarwer DB, et al. The use of novel technology-based weight loss interventions for obese women with endometrial hyperplasia and cancer. Gynecol Oncol. 2016;140:239–44.
  141. Bravata DM, Smith-Spangler C, Sundaram V, et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA. 2007;298:2296–304.
  142. Pellegrini CA, Verba SD, Otto AD, et al. The comparison of a technology-based system and an in-person behavioral weight loss intervention. Obesity (Silver Spring). 2012;20:356–63.
  143. Polzien KM, Jakicic JM, Tate DF, Otto AD. The efficacy of a technology-based system in a short-term behavioral weight loss intervention. Obesity (Silver Spring). 2007;15:825–30.
  144. Jakicic JM, Davis KK, Rogers RJ, et al. Effect of wearable technology combined with a lifestyle intervention on long-term weight loss: the IDEA randomized clinical trial. JAMA. 2016;316:1161–71.
  145. Kuijpers W, Groen WG, Aaronson NK, van Harten WH. A systematic review of web-based interventions for patient empowerment and physical activity in chronic diseases: relevance for cancer survivors. J Med Internet Res. 2013;15:e37.
  146. Carayol M, Bernard P, Boiche J, et al. Psychological effect of exercise in women with breast cancer receiving adjuvant therapy: what is the optimal dose needed? Ann Oncol. 2013;24:291–300.
  147. Li T, Wei S, Shi Y, et al. The dose-response effect of physical activity on cancer mortality: findings from 71 prospective cohort studies. Br J Sports Med. 2016;50:339–45.
  148. Simon HB. Exercise and health: dose and response, considering both ends of the curve. Am J Med. 2015;128:1171–77.
  149. Borde R, Hortobagyi T, Granacher U. Dose-response relationships of resistance training in healthy old adults: a systematic review and meta-analysis. Sports Med. 2015;45:1693–720.
  150. Berger AM, Abernethy AP, Atkinson A, et al. NCCN clinical practice guidelines cancer-related fatigue. J Natl Compr Canc Netw. 2010;8:904–31.
  151. Stone P, Richardson A, Ream E, et al. Cancer-related fatigue: inevitable, unimportant and untreatable? Results of a multi-centre patient survey. Cancer Fatigue Forum. Ann Oncol. 2000;11:971–5.
  152. Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer. 1999;85:1186–96.
  153. Stein KD, Martin SC, Hann DM, Jacobsen PB. A multidimensional measure of fatigue for use with cancer patients. Cancer Pract. 1998;6:143–52.
  154. National Comprehensive Cancer Network. Cardiac Toxicity, 2017. Available at: www.nccn.org/patients/resources/life_with_cancer/managing_symptoms/cardiac_toxicity.aspx (accessed July 28, 2017).
  155. Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375:1457–67.
  156. IASP Task Force on Taxonomy. Part III: Pain Terms, A Current List with Definitions and Notes on Usage. In: Merskey H, Bogduk N, eds., Classification of Chronic Pain, 2nd ed. Seattle, WA, US: IASP Press, 1994;209–14.
  157. Chang VT, Hwang SS, Feuerman M, Kasimis BS. Symptom and quality of life survey of medical oncology patients at a veterans affairs medical center: a role for symptom assessment. Cancer. 2000;88:1175–83.
  158. Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975;1:277–99.
  159. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23:129–38.
  160. Dietrich J, Monje M, Wefel J, Meyers C. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist. 2008;13:1285–95.
  161. Janelsins MC, Kohli S, Mohile SG, et al. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011;38:431–8.
  162. Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993;11:570–9.
  163. Barnett JH, Blackwell AD, Sahakian BJ, Robbins TW. The Paired Associates Learning (PAL) test: 30 years of CANTAB translational neuroscience from laboratory to bedside in dementia research. Curr Top Behav Neurosci. 2016;28:449–74.
  164. Postma TJ, Aaronson NK, Heimans JJ, et al. The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer. 2005;41:1135–9.
  165. Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain. 2014;155:2461–70.
  166. Vasquez S, Guidon M, McHugh E, et al. Chemotherapy induced peripheral neuropathy: the modified total neuropathy score in clinical practice. Ir J Med Sci. 2014;183:53–8.
  167. Wang F, Zhang J, Yu J, et al. Diagnostic accuracy of monofilament tests for detecting diabetic peripheral neuropathy: a systematic review and meta-analysis. J Diabetes Res. 2017;2017:8787261.
  168. Botelho MC, Conde MG, Rebelo Braz NM. Functional aspects in ageing adults with diabetic neuropathy. A review. Curr Diabetes Rev. 2015;12:114–9.
  169. Costa AR, Fontes F, Pereira S, et al. Impact of breast cancer treatments on sleep disturbances - A systematic review. Breast. 2014;23:697–709.
  170. Fiorentino L, Rissling M, Liu L, Ancoli-Israel S. The symptom cluster of sleep, fatigue and depressive symptoms in breast cancer patients: severity of the problem and treatment options. Drug Discov Today Dis Models. 2011;8:167–73.
  171. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality Index (PSQI): A new instrument for psychiatric research and practice. Psychiatry Research. 1989;28:193–213.
  172. Madsen MT, Huang C, Gogenur I. Actigraphy for measurements of sleep in relation to oncological treatment of patients with cancer: a systematic review. Sleep Med Rev. 2015;20:73–83.
  173. Van Poznak CH. Bone health in adults treated with endocrine therapy for early breast or prostate cancer. Am Soc Clin Oncol Educ Book. 2015:e567–74.
  174. Hirbe A, Morgan EA, Uluckan O, Weilbaecher K. Skeletal complications of breast cancer therapies. Clin Cancer Res. 2006;12(20 Pt 2):6309s–14s.
  175. Leonard MB. Assessment of bone health in children and adolescents with cancer: promises and pitfalls of current techniques. Med Pediatr Oncol. 2003;41:198–207.
  176. Burch J, Rice S, Yang H, et al. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups. Health Technol Assess. 2014;18:1–180.
  177. Dodson S, Baracos VE, Jatoi A, et al. Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies. Annu Rev Med. 2011;62:265–79.
  178. Nguyen PL, Alibhai SM, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67:825–36.
  179. Mondello P, Lacquaniti A, Mondello S, et al. Emerging markers of cachexia predict survival in cancer patients. BMC Cancer. 2014;14:828.
  180. Holland JC, Andersen B, Breitbart WS, et al. Distress management: clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2010;8:448–85.
  181. Watts S, Leydon G, Birch B, et al. Depression and anxiety in prostate cancer: a systematic review and meta-analysis of prevalence rates. BMJ Open. 2014;4:e003901.
  182. Mitchell AJ, Ferguson DW, Gill J, et al. Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis. Lancet Oncol. 2013;14:721–32.
  183. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–70.
  184. Radloff L. A self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–01.
  185. Carson JW, Carson KM, Olsen MK, et al. Mindful Yoga for women with metastatic breast cancer: design of a randomized controlled trial. BMC Complement Altern Med. 2017;17:153.
  186. Rief H, Jensen AD, Bruckner T, et al. Isometric muscle training of the spine musculature in patients with spinal bony metastases under radiation therapy. BMC Cancer. 2011;11:482.

Further Resources

Share this Article
Related Content In Supportive Cancer Care
  • Copied to clipboard!
    accredited arrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-whiteticktimetranscriptup-arrowwebinar Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72