For citation purposes: Daroux-Cole L, Pettengell R, Jewell A. Exercise for cancer survivors: A review. OA Cancer 2013 May 20;1(1):5.

Review

 
Novel Therapies

Exercise for cancer survivors: A review

L Daroux-Cole1*, R Pettengell2, A Jewell3*
 

Authors affiliations

(1) PhD Student, Faculty of Sport, Nutrition, and Exercise Science, Kingston University, London, UK

(2) Senior Lecturer/Honorary Consultant, Department of Haematology, St George’s Hospital Medical School, London, UK

(3) Professor of Health Science, Faculty of Health, Social Care and Education, Kingston University and St. George’s, University of London, UK

* Corresponding authors Emails: daroux.cole@gmail.com; a.jewell@sgul.kingston.ac.uk

Abstract

Introduction

As survivorship becomes increasingly common with marked improvements in the detection and treatment of cancer, the deleterious effects of the disease and its treatment need continued attention. Exercise is developing a valuable role in the cancer-rehabilitation process. Over the past two decades, a substantial amount of research has been done on the effects of exercise for cancer survivors. The aim of this review was to provide an overview of some of the psychological and physical benefits of exercise and to explore exercise-induced immune function specific to cancer survivors.

Discussion

It is commonly accepted that physical activity may improve various physical and psychosocial factors in cancer survivors while potentially reducing the rate of recurrence and improving overall survival. Exercise of low-to-moderate intensity is reportedly a feasible and safe option to mediate the effects of medical treatment and may have the ability to attenuate the loss in physical performance typically associated with cancer treatment. Most research in this area is specific to breast and prostate cancer, although recent literature is focusing on other tumour types. Of recent interest is the immunological response of exercise in cancer survivors, both on and off treatment. The cytokine cascade in response to exercise differs from that induced by infection, which leads to the question of how exercise impacts those who are immunocompromised. Although inflammation is linked with the process of tumourigenesis and exercise has been linked with decreased inflammation, surprisingly few studies have examined the immunological impact of exercise within the cancer population.

Conclusion

Physical activity has been found to produce beneficial health-related outcomes for cancer survivors, but exercise dose response is still being explored. Further research is needed to clearly identify the immune response to exercise as experienced by cancer survivors.

Introduction

Treatment outcomes for many cancers continue to improve with an increasing cohort of long-term disease-free survivors. However, late effects of treatment may impact upon patients’ short- and long-term physical and psychosocial health[1,2]. Treatment-related symptoms can last for months or even years post-treatment and may impact upon overall health of the survivor.

Cancer patients are often prescribed drugs to help minimize side effects of chemotherapy and related treatment, but drug therapy is viewed as a short-term solution that only temporarily resolves debilitating side effects[3]. Some of the most debilitating physical symptoms associated with treatment are fatigue, anaemia, muscle wasting, reduced balance and coordination[4]. These physical symptoms can bring about diminished energy and physical performance that may reduce overall mood state and quality of life (QoL)[4,5]. Cognitive functioning may also be impaired after chemotherapy treatment; patients reported having trouble focusing, reading and driving[5]. Increasing levels of physical activity may improve various physical[6,7,8] and psychosocial factors in cancer survivors[6,9], while positively impacting the rate of recurrence and overall survival[8,10,11]. Research suggests that low-to-moderate intensity exercise is a feasible and safe option to mediate the effects of medical treatment[3,4,12]. Endurance exercise training may have the ability to attenuate the loss in physical performance typically associated with cancer treatment[13,14].

Exercise is developing a valuable role in the cancer-rehabilitation process[15]. A review of quantitative data from 82 controlled trials of physical activity interventions for cancer survivors found that exercise was well tolerated both during and after treatment (without adverse events)[16]. This supports the conclusion from a recent American College of Sports Medicine (ACSM) roundtable that exercise training is safe during and after cancer treatment and may result in enhanced physical functioning, QoL and reduced cancer-related fatigue (CRF) in several cancer survivor groups[17,18]. The aim of the current review was to outline some of the psychological and physical benefits and explore the potential impact of exercise on immune function in cancer survivors.

Discussion

Morbidity

A variety of medical complications are often found to be a direct consequence of cancer treatment and negatively affect the QoL in cancer survivors. Cancer-related treatments increase the risk of secondary tumours and affect other systems such as cardiac, pulmonary, endocrine and immunologic functions[8]. Cancer patients may be prone to secondary malignancies, obesity and cardiovascular diseases (CVDs), all of which are known causes of late-term morbidity and mortality[19,20]. Evidence suggests death from CVD and diabetes occurs at a higher rate in cancer survivors than in the general population[20,21].

Exercise has been found to reduce the risk of cancer recurrence and mortality for some cancer survivors[10,22], as well as decrease CVD risk factors by lowering resting blood pressure[23] and resting heart rate[24] markers of systemic inflammation, specifically C-reactive protein (CRP)[25] and tumour necrosis factor-alpha (TNF-α)[26]. Regular exercise offers protection against all-cause mortality[26]. Emerging observational and clinical data signify the importance of physical activity in solid tumour patients and provide increasing evidence that exercise positively impacts major clinical endpoints such as rate of infection, rate of recurrence and overall survival[8,10,11,22].

Psychosocial impact of exercise

The psychosocial consequences of a diagnosis and treatment of malignant disease are significant and often protracted. In one study, 22% of malignant patients fulfilled the criteria for psychiatric illness[27]. Many studies have found decreased overall QoL, physical function and increased anxiety and depression amongst cancer survivors when compared with their premorbid measures and with healthy adults[28]. Perceptions of how cancer has affected survivors’ lives may be related to one’s functional abilities and QoL[29]. Exercise can promote adaptation to the many stressors of cancer and related treatment both during and after therapy[30] whilst enhancing one’s capacity to resume normal lifestyle activities including employment and hobbies, resulting in improved QoL, greater independence and sense of control.

Quality of Life (QoL)

Exercise has a positive effect on a broad range of QoL dimensions in cancer patients[31]. Appropriately designed exercise interventions are generally associated with positive QoL outcomes in cancer survivors[30,32]. Exercise is associated with higher QoL and overall life satisfaction scores amongst breast cancer patients on treatment[33]. A meta-analysis reported better QoL in cancer survivors who exercised compared with those who did not: these results were consistent amongst different tumour types (breast, colorectal and gynaecologic cancer and lymphoma)[30]. Another recent meta-analysis showed that the significant positive impact of exercise on QoL (when compared with control groups and with their baseline levels of QoL) was still present at follow-up[32]. Interestingly, exercise dose emerged as an important moderator of QoL; interventions of longer duration and higher aerobic metabolic equivalents (METs) produced greater change in QoL[32].

Health-related quality of life(HRQL), a subcomponent of QoL, has become an integral part of exercise intervention evaluation as patient perception of the benefits of exercise can have a substantial effect on coping and treatment effectiveness[34]. Research has shown that PA is positively associated with HRQL across several cancer groups[35,36].

Overall Mood Disturbance

Mood disturbance is common amongst people with cancer[37]. High mood disturbance is associated with increasing symptoms[38] and negatively impacts upon functional status and QoL[39]. Exercise decreases mood disturbance amongst cancer survivors[40]; even walking has shown an improvement (minimum 90 min, 3 times per week)[41].

Anxiety and Depression

Anxiety and depression afflict 20–50% of cancer patients[42,43]; severity fluctuates depending on the type of cancer, stage of cancer, treatment choice as well as stress and coping strategies of the patient[44]. With regular exercise, cancer survivors experience a reduction in depression and anxiety, thus positively impacting QoL[31,45]. Sessions lasting 30 plus minutes in duration for no more than 12 weeks resulted in the largest anxiety improvements, although even acute exercise has shown a reduction in anxiety levels[41,44,46,47].

Depression is estimated to be four times higher in cancer patients than in general population[48]; 58% of cancer patients experience symptoms of depression[49]. Patients and survivors often experience depressive mood immediately upon diagnosis[50], which may persist long after treatment has finished[51]. The response to exercise has often been positive, thereby resulting in a decrease in depressive symptoms[52], although a number of studies show no change (although no adverse effects have been reported)[53,54].

Fatigue

A common side effect of cancer treatment is fatigue[55], which continues long after the completion of treatment in up to 75% of cancer survivors[56]. Chronic fatigue is often associated with lower levels of physical activity amongst cancer survivors (specifically within the first 5 years after treatment)[57].

CRF is one of the most debilitating and distressing side effects of cancer and treatment[58,59]. Exercise is useful in reducing CRF[18,60], as inactivity contributes to fatigue[61]. Aerobic exercise is effective at reducing fatigue during[41,52,62], and after treatment[15,63,64]. More specifically, aerobic exercise of moderate intensity shows a strong trend towards reducing chronic fatigue in cancer patients[41,65,66]. In a recent systematic review, survivors of several types of cancer who took part in exercise interventions had reduced CRF levels when compared with their usual care (the greatest reduction was seen amongst exercising older patients)[67].

The impact of resistance training on CRF has been recently examined (amongst men with prostate cancer[68]. Although both resistance and aerobic exercise reduced fatigue in the short term, resistance exercise generated longer term fatigue reduction (as well as improved QoL and physical strength)[68]. CRF levels improve in direct proportion to the intensity of resistance exercise performed[67]. Amongst cancer patients with persistent CRF, a combination of endurance (30-min walking) and resistance/coordination exercises performed weekdays for 3 weeks resulted in significant improvements in mental and physical fatigue scores[54].

Transitioning from ‘patient to survivor’

It is commonly accepted that there may be disrupted adjustment at different times during the survivorship experience[69]. The transition period from the completion of treatment to re-entry into one’s ‘normal’ lifestyle is often burdened with disruption, uncertainty and distress[70,71,72]. Once treatment finishes, patients have more time to deal with the psychological struggles of the cancer journey as well as any existing issues from before cancer diagnosis[71,72]. Fifty-three percent of survivors reported that their emotional needs were harder to cope with than physical needs during the transition period[73], suggesting that this time may be particularly important to one’s cancer recovery as it impacts the cancer survivors’ experience of stress, which may exacerbate late effects[73]. Exercise has been shown to reduce stress and provide many psychological benefits to cancer survivors[17,74].

Physiological effects of exercise training

It is widely accepted that regular physical activity protects against a number of physiological disorders including numerous cancers and has been found to enhance health, longevity and well-being beyond the effectiveness of medical treatment[75]. Improved heart and lung function, skeletal muscle function, improved body composition, increased life expectancy, increased bone mass density and whole-body metabolism are seen with regular exercise; the protective effect of exercise occurs through improved glucose uptake and insulin sensitivity[76], lowered blood pressure[77], decreased resting heart rate[24] and improved blood lipid profile[75]. Adaptation to exercise starts immediately (even with acute exercise), progresses with continued exposure and is specific to both training stimuli and genetic make-up[78].

Physical Efficiency

Due to the deleterious effects of cancer and its treatment, patients often experience a loss of physical capacity. Both chemotherapy and radiotherapy appear to have a negative impact on the cardiorespiratory system[79] and muscular function[80]. Patients are often unable to maintain their pre-disease level of physical activity and functioning and report reduced physical and role functioning due to physical conditions[81]. Resulting muscle atrophy and cardiopulmonary toxicities make physical exercise taxing; decreased oxygen uptake can make regular daily activities feel very challenging[82].

Improvements in aerobic capacity have been observed with exercise, amongst both patients undergoing treatment and those who have completed treatment[16,83,84]. Functional ability, the measure of an individual’s capability to perform everyday activities, is rated as the most important, yet least possessed dimension of QoL amongst cancer survivors[85]. By making daily tasks easier to perform, aerobic capacity positively impacts functional ability. Various types of exercise interventions, including walking, running, home-based activity, strength, stretching and aerobic programmes, have resulted in improved functional ability, aerobic capacity or physical functioning amongst cancer patients and survivors[41,52,86,87]. Research findings indicate that both aerobic capacity and ensuing functional ability improve with regular participation in physical activity.

Muscle Wasting

Skeletal muscle is important for physical function, immune function and metabolic regulation and is responsible for a large portion of glucose metabolism. Skeletal muscle wasting, a common side effect of cancer treatment[88] is often present (to some degree) at the time of diagnosis, but is more prevalent with advanced malignancies[89]. Unfortunately, muscle wasting brings reduced functional ability and weakness[90,91] and negatively affects responsiveness to treatment (increasing morbidity and mortality)[92]. It is also suggested that muscle atrophy during cancer may play a significant role in the development of metabolic syndrome[93].

Resistance training may reduce skeletal muscle wasting (specific to cancer) and stimulate growth in muscle strength and mass[88]; muscular strength gains are common amongst exercising cancer patients and survivors[16]. In prostate cancer patients for example, resistance training alone has resulted in increased muscle mass, reduced treatment-related side effects[94] and increased muscle strength[68,94]. Improved QoL[9] and physical performance scores also resulted from resistance training amongst this group[94].

Weight Maintenance

A number of studies have focused on adiposity in cancer and survivorship[95,96,97,98], as body composition changes are common amongst cancer patients[97,99,100]. Weight gain is an adverse effect of treatment for many cancer types[97] and has been associated with an increased risk for recurrence and death[101,102,103] (approximately 30–50% of breast cancer deaths among post-menopausal women can be attributed to being overweight)[104]. Despite strong evidence of the statistically and clinically significant associations between low levels of activity and obesity, and cancer recurrence and death, sedentary lifestyle and obesity remain prevalent amongst cancer survivors[103,104,105,106]. Obesity is associated with insulin resistance in breast[107] and prostate cancer patients[95,96].

Immune Function and Exercise Training

As stated in the ‘2011 Position Statement, Immune Function and Exercise (part one)’, acute and chronic exercise affect immune production and function[108]. It is suggested that the protective effect of exercise may be due, in part, to the anti-inflammatory effect of regular exercise mediated by cytokine production and release (creating an anti-inflammatory environment) and/or decreased adiposity. Research shows that participants who are sedentary are more susceptible to infection and disease than are their healthy counterparts, suggesting physical activity enhances immune function[109,110,111].

Cancer is associated with chronic low-grade systemic inflammation[26]; regular exercise produces a long-term anti-inflammatory effect. Regular physical activity is inversely related to serum concentration of inflammatory markers[112], has been found to reduce CRP[25] and suppress TNF-α production, thereby defending against TNF- α-induced insulin resistance (low-grade systemic inflammation is linked with insulin resistance)[26,113].

The mechanism behind the anti-inflammatory effect of exercise is not fully understood, but it is generally accepted that it results from both acute and chronic exercise[110]. It is hypothesised that physical activity causes an increase in the systemic levels of some cytokines with anti-inflammatory properties[110,114]. Skeletal muscle, recently been identified as an endocrine organ, produces and releases cytokines (myokines) upon contraction[115]. During exercise, the level of circulating IL-6 largely increases (up to 100-fold), IL-10 increases, and levels of circulating cytokine inhibitors (such as IL-1ra and sTNF-R) marginally increase. The release of TNF-α and CRP is also impacted by exercise.

IL-6 has been referred to as an ‘inflammatory-responsive’ cytokine because it does not directly induce inflammation with exercise[116]. Exercise-induced increases in IL-6 have been found to decrease plasma TNF-α, thus decreasing inflammation by blocking the production of TNF-α[26,117]. Muscle-derived IL-6 can decrease the production of TNF-α and IL-1 β and therefore may be responsible for the beneficial effects of exercise on CRF[110]. The normal response to infection is an increase in proinflammatory cytokines, TNF-α and IL-1β, but these seem not to increase with exercise, indicating that the cytokine cascade caused by exercise differs from that induced by infection (refer to Figure 1)[26,118].

Comparison of sepsis-induced verses exercise-induced increases in circulating cytokines. During sepsis, there is a steep increase in circulating TNF-α, which is followed by an increase in interleukin (IL)-6. In contrast, during exercise, the marked increase in IL-6 is not preceded by elevated TNF-α. From Pedersen & Febbraio (2008) with permission from the American Physiological Society (licence 3116880987934).

Both cancer and its treatment (chemotherapy, surgery and radiotherapy) elevate the level of proinflammatory cytokines (TNF-α, IL-1 and IL-6)[119]. Although inflammation is linked with the process of tumourigenesis[120] and exercise has been linked with decreased inflammation, surprisingly few studies have examined the immunological impact of exercise within the cancer population, specifically in terms of inflammation reduction and anti-tumour immunity[108]. The effect of exercise on tumour progression was examined in a mouse model of breast cancer; the reduction in tumour progression was associated with IL-6, monocyte chemoattractant protein (MCP-1) and spleen weight[121]. Further research is needed to suggest a relationship between exercise and tumour progression in humans.

The ‘2011 Position Statement, Immune Function and Exercise (part one)’ reports that the biological mechanisms relating exercise and cancer are not clearly understood and suggest that the impact specific to tumour type is even less clear[108]. To date, ‘no studies have examined the role of exercise in minimizing the immunosuppressive environment that is created by the presence of the tumour’ (2011 Position Statement, Immune Function and Exercise: part one[108]). It is suggested that if the anti-tumour protection offered by exercise occurs, the results should be evident in immune-mediated diseases such as lymphomas[108]. The appropriate exercise dose needed to bring about enhanced immunity is still unknown. It has been proposed that immunity responds in an ‘inverted J’ format: As exercise intensity increases, immunity improves but only to a point; immunity begins to decline if exercise is too intense, suggesting that exhaustive exercise may suppress immune function and increase susceptibility to disease[122]. Further research is needed to substantiate these findings.

Conclusion

As survivorship becomes increasingly common with marked improvements in the detection and treatment of cancer, the deleterious effects of the disease and its treatment need continued attention. Treatment-induced psychological and physical impairment along with the increased risk of secondary malignancies and CVDs substantiate the need for holistic health interventions specific to this population. Physical activity has been found to produce beneficial health-related outcomes for cancer survivors, but the exact dose response is still being explored.

Abbreviations list

ACSM, American College of Sports Medicine; CRF, cancer-related fatigue; CRP, C-reactive protein; CVD, cardiovascular disease; HRQL, Health-related quality of life; MCP, monocyte chemoattractant protein; MET, metabolic equivalent; QoL, quality of life; TNF-α, tumour necrosis factor-alpha

Authors contribution

All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.

Competing interests

None declared.

Conflict of interests

None declared.

A.M.E

All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.

References

  • 1. . Canadian Cancer Society. About Cancer [Internet]. Canada: Canadian Cancer Society; 2011 [cited 2011, March 25]. Available from:. .
  • 2. Yung L, Linch D. Hodgkin’s lymphoma. Lancet 2003 Mar;361(9361):943-51.
  • 3. Battaglini CL, Hackney AC, Garcia R, Groff D, Evans E, Shea T. The effects of an exercise program in leukemia patients. Integr Cancer Ther 2009 Jun;8(2):130-9.
  • 4. Chang PH, Lai YH, Shun SC, Lin LY, Chen ML, Yang Y. Effects of a walking intervention on fatigue-related experiences of hospitalized acute myelogenous leukemia patients undergoing chemotherapy: a randomized controlled trial. J Pain Symptom Manage 2008 May;35(5):524-34.
  • 5. Myers J, Prakash M, Froelicher V, Do D, Partington , S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002 Mar;346(11):793-801.
  • 6. Courneya KS . Exercise in cancer survivors: An overview of research. Med Sci Sports Exerc 2003 Nov;351846-52.
  • 7. Segal R, Evans W, Johnson D, Smith J, Colletta S, Gayton J. Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial. J Clin Oncol 2001 Feb;19657-65.
  • 8. Bellizzi KM, Rowland JH, Arora NK, Hamilton AS, Miller MF, Aziz NM. Physical activity and quality of life in adult survivors of non-Hodgkin's lymphoma. J Clin Oncol 2009 Feb;27(6):960-6.
  • 9. Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 2003 May;21(9):1653-9.
  • 10. Meyerhardt JA, Heseltine D, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer. J Clin Oncol 2006 Aug;24(22):3535-41.
  • 11. Elter T, Stipanov M, Heuser E, von Bergwelt-Baildon M, Bloch W, Hallek M. Is physical exercise possible in patients with critical cytopenia undergoing intensive chemotherapy for acute leukemia or aggressive lymphoma?. Int J Hematol 2009 Sep;90(2):199-204.
  • 12. Doyle C, Kushi LH, Byers T, Courneya KS, Demark-Wahnefried W, Grant B. Nutrition, Physical Activity and Cancer Survivorship Advisory Committee; American Cancer Society. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin 2006 Nov–Dec;56(6):323-53.
  • 13. Dimeo F, Schwartz S, Fietz T, Wanjura T, Bö ning D, Thiel E. Effects of endurance training on the physical performance of patients with hematological malignancies during chemotherapy. Support Care Cancer 2003 Oct;11(10):623-8.
  • 14. Liu RDKS, Chinapaw MJM, Huijgens PC, van Mechelen W. Physical exercise interventions in haematological cancer patients, feasible to conduct but effectiveness to be established: A systematic literature review. Cancer Treat Rev 2009 Apr;35(2):185-92.
  • 15. Burnham TR, Wilcox A. Effects of exercise on physiological and psychological variables in cancer survivors. Med Sci Sports Exerc 2002 Dec;34(12):1863-7.
  • 16. Speck RM, Courneya KS, Masse LC, Duval S, Schmitz KH. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv 2010 Jun;487-100.
  • 17. Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefriend W, Galvao DA, Pinto BM. American college of sports medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 2010 Jul;42(7):1409-26.
  • 18. McMillan EM, Newhouse IJ. Exercise is an effective treatment modality to reduce cancer related fatigue and improve physical capacity in patients and survivors with CRF. Appl Physiol Nutr Metab 2011 Dec;36(6):892-903.
  • 19. Straus DJ . Long-term survivorship at a price: late-term, therapy-associated toxicities in the adult Hodgkin lymphoma patient. Ther Adv Hematol 2011 Apr;2(2):111-9.
  • 20. Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol 2007 Sep;25(25):3991-4008.
  • 21. Roper K, McDermott K, Cooley ME, Daley K, Fawcett J. Health-related quality of life in adults with Hodgkin disease: The state of the science. Cancer Nurs 2009 Nov–Dec;32(6):E1-17.
  • 22. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA 2005 May;293(20):2479-86.
  • 23. Wiley RL, Dunn CL, Cox RH, Hueppchen NA, Scott MS. Isometric exercise training lowers resting blood pressure. Med Sci Sports Exerc 1992 Jul;24(7):749.
  • 24. Melo RC, Santos MDB, Silva E, Quiterio RJ, Moreno MA, Reis MS. Effects of age and physical activity on the autonomic control of heart rate in healthy men. Braz J Med Biol Res 2005 Sep;38(9):1331-8.
  • 25. Borodulin K, Laatikainen T, Salomaa V, Jousilahti P. Associations of leisure time physical activity self-rated physical fitness, and estimated aerobic fitness with serum C-reactive protein among 3,803 adults. Atherosclerosis 2006 Apr;185(2):381-7.
  • 26. Petersen AM, Pedersen BK. The role of IL-6 in mediating the anti-inflammatory effects of exercise. J Physiol Pharmacol 2006 Nov;57(Suppl 10):43-51.
  • 27. Kornblith AB, Anderson J, Cella DF, Tross S, Zuckerman E, Cherin E. Hodgkin disease survivors at increased risk for problems in psychosocial adaptation. The Cancer and Leukemia Group B. Cancer 1992 Oct;70(8):2214-24.
  • 28. Mols F, Aaronson NK, Vingerhoets A, Coebergh JW, Vreugdenhil G, Lybeert MLM. Quality of life among long-term non-Hodgkin lymphoma survivors: a population-based study. Cancer 2007 Apr;109(8):1659-67.
  • 29. Zebrack BJ, Yi J, Petersen L, Ganz PA. The impact of cancer and quality of life for long-term survivors. Psychooncology 2008 Sep;17(9):891-900.
  • 30. Knobf MT, Musanti R, Dorward J. Exercise and quality of life outcomes in patients with cancer. Semin Oncol Nurs 2007 Nov;23(4):285-96.
  • 31. Courneya KS, Mackey JR, Jones LW. Coping with cancer: Can exercise help?. 2000 May;2849-73.
  • 32. Ferrer RA, Huedo-Medina TB, Johnson BT, Ryan S, Pescatello LS. Exercise interventions for cancer survivors: a meta-analysis of quality of life outcomes. Ann Behav Med 2011 Feb;41(1):32-47.
  • 33. Courneya KS, Friedenreich CM. Relationship between exercise during treatment and current QOL among survivors of breast cancer. 1997;1535-57.
  • 34. Goodwin PJ, Black JT, Bordeleau LJ, Ganz PA. Health related quality-of-life measurement in randomized clinical trials in breast cancer—Taking stock. J Natl Cancer Inst 2003 Feb;95(4):263-81.
  • 35. Courneya KS . Exercise in cancer survivors: an overview of research. Med Sci Sports Exerc 2003 Nov;35(11):1846-52.
  • 36. Knols R, Aaronson NK, Uebelhart D, Fransen J, Aufdemkampe G. Physical exercise in cancer patients during and after medical treatment: A systematic review of randomized and controlled clinical trials. J Clin Oncol 2005 Jun;23(16):3830-42.
  • 37. Deng G, Cassileth BR. Integrative oncology: complementary therapies for pain, anxiety, and mood disturbance. CA Cancer J Clin 2005 Mar–Apr;55(2):109-16.
  • 38. Lee E-H, Yae Chung B, Boog Park H, Hong Chun K. Relationships of mood disturbance and social support to symptom experience in Korean women with breast cancer. J Pain Symptom Manage 2004 May;27(5):425-33.
  • 39. Cheng KK, Lee DT. Effects of pain, fatigue, insomnia, and mood disturbance on functional status and quality of life of elderly patients with cancer. Crit Rev Oncol Hematol 2011 May;78(2):127-37.
  • 40. Segar ML, Katch VL, Roth RS, Garcia AW, Portner TI, Glickman SG. The effect of aerobic exercise on self-esteem and depressive and anxiety symptoms among breast cancer survivors. Oncol Nurs Forum 1998 Jan–Feb;25(1):107-13.
  • 41. Mock V, Pickett M, Ropka ME, Muscari Lin E, Stewart KJ. Fatigue and quality of life outcomes of exercise during cancer treatment. Cancer Pract 2001 May–Jun;9(3):119-27.
  • 42. Pirl WF, Roth AJ. Diagnosis and treatment of depression in cancer patients. Oncology (Huntington) 1999 Sep;13(9):1293-301.
  • 43. Schwenk W, Bohm B, Muller JM. Influence of laparoscopic or conventional colorectal resection on postoperative quality of life. Surg Endosc 1998;123(5):483-90.
  • 44. Schneider CM, Dennehy CA, Carter SD. Exercise and cancer recovery. IL: Human Kinetics Champaign 2003.
  • 45. MacVicar MG, Winningham ML, Nickel JL. Effects of aerobic interval training on cancer patients' functional capacity. Nurs Res 1989 Nov–Dec;38(6):348-51.
  • 46. Blanchard CM, Courneya KS, Laing D. Effects of acute exercise on state anxiety in breast cancer survivors. Oncol Nurs Forum 2001 Nov–Dec;28(10):1617-21.
  • 47. Mock V, Dow KH, Meares CJ, Grimm PM, Dienemann JA, Haisfield-Wolfe ME. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncol Nurs Forum 1997 Jul;24(6):991-1000.
  • 48. Pirl WF . Evidence report on the occurrence, assessment, and treatment of depression in cancer patients. JNCI Monographs 2004(32):32-9.
  • 49. Massie MJ . Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr 2004;3257-71.
  • 50. Snyderman D, Wynn D. Depression in cancer patients. Prim Care 2009 Dec;36(4):703-19.
  • 51. Jacobsen PB, Jim HS. Psychosocial interventions for anxiety and depression in adult cancer patients: Achievements and challenges. CA Cancer J Clin 2008 Jul–Aug;58(4):214-30.
  • 52. Mutrie N, Campbell AM, Whyte F, McConnacchie A, Emslie C, Lee L. Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial. BMJ 2007 March;334(7592):517.
  • 53. Ohira T, Schmitz KH, Ahmed RL, Yee D. Effects of weight training on quality of life in recent breast cancer survivors: The weight training for breast cancer survivors (WTBS) study. Cancer 2006;106(9):2076-83.
  • 54. Dimeo F, Schwartz N, Wesel N, Voight A, Thiel E. Effects of an endurance and resistance exercise program on persistent cancer-related fatigue after treatment. Ann Oncol 2008 Aug;19(8):1495-9.
  • 55. Blaney J, Lowe-Strong A, Rankin J, Campbell A, Allen J, Gracey J. The Cancer Rehabilitation Journey: Barriers to and facilitators of exercise among patients with cancer-related fatigue. Phys Ther 2010 Aug;90(8):1135-47.
  • 56. . National Comprehensive Cancer Network CRF Panel [internet]. Practice Guidelines in Oncology – v.2.2005. Cancer-Related Fatigue [cited nov 2011] 2005.
  • 57. Thorsen L, Gjerset GM, Fossa SD, Loge JH. 3019 POSTER reduction of physical exercise is associated with chronic fatigue and poor physical health within 5 years after cancer treatment. Eur J Cancer 2011;47S228-S228.
  • 58. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of cancer-related fatigue. Oncologist 2007;12(Suppl 1):22-34.
  • 59. Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR. Cancer-related fatigue: the scale of the problem. Oncologist 2007;12(Suppl 1):4-10.
  • 60. Escalante CP . Treatment of cancer-related fatigue: an update. Support Care Cancer 2003 Feb;1179-83.
  • 61. Dohnalek LJ . Patients undergoing bone marrow transplant benefit from exercise class. Oncol Nurs Forum 1997 Jul;24(6):966.
  • 62. Mock V, Frangakis C, Davidson NE, Ropka ME, Pickett M, Poniatowski B. Exercise manages fatigue during breast cancer treatment: a randomized controlled trial. Psychooncology 2005 Jun;14(6):464-77.
  • 63. Daley AJ . Effects of supervised exercise training on cardiopulmonary function and fatigue in breast cancer survivors during and after treatment. Breast Diseases: A Year Book Quarterly 2008;19(1):83-4.
  • 64. Pinto BM, Frierson GM, Rabin C, Trunzo JJ, Marcus BH. Home-based physical activity intervention for breast cancer patients. J Clin Oncol 2005 May;23(15):3577-87.
  • 65. Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW. Effect of exercise training on C-reactive protein in postmenopausal breast cancer survivors: A randomized controlled trial. Brain Behav Immun 2005 Sep;19(5):381-8.
  • 66. Courneya KS, Segal RJ, Mackey JR, Gelmon K, Reid RD, Friedenreich CM. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol 2007 Oct;25(28):4396-404.
  • 67. Brown JC, Huedo-Medina TB, Pescatello LS, Pescatello SM, Ferrer RA, Johnson BT. Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2011 Jan;20(1):123-33.
  • 68. Segal RJ, Reid RD, Courneya KS, Sigal RJ, Kenny GP, Prud' Homme DG. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J Clin Oncol 2009 Jan;27(3):344-51.
  • 69. Costanzo ES, Lutgendorf SK, Mattes ML, Trehan S, Robinson CB, Tewfik F. Adjusting to life after treatment: distress and quality of life following treatment for breast cancer. Br J Cancer 2007 Dec;97(12):1625-31.
  • 70. Ward SE, Viergutz G, Tormey D, deMuth J, Paulen A. Patients' reactions to completion of adjuvant breast cancer therapy. Nurs Res 1992 Nov–Dec;41(6):362-6.
  • 71. Lethborg CE, Kissane D, Ivon Burns W, Snyder R. “Cast Adrift”: the experience of completing treatment among women with early stage breast cancer. J Psychosoc Oncol 2000;18(4):73-90.
  • 72. Schnipper HH . Life after breast cancer. J Clin Oncol 2001 Aug;19(15):3581-4.
  • 73. Wolff SN . The burden of cancer survivorship; a pandemic of treatment success. In: Feuersteim, M. editor. Handbook of Cancer Survivorship. New York: Springer 2006p247.
  • 74. Spence RR, Heesch KC, Brown WJ. Exercise and cancer rehabilitation: a systematic review. Cancer Treat Rev 2010 Apr;36(2):185-94.
  • 75. Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports 2006 Feb;16(Suppl 1):3-63.
  • 76. Holloszy JO . Exercise-induced increase in muscle insulin sensitivity. J Appl Physiol 2005 Jul;99(1):338-43.
  • 77. Blair SN, Goodyear NN, Gibbons LW, Cooper KH. Physical fitness and incidence of hypertension in healthy normotensive men and women. JAMA 1984 Jul;252(4):487-90.
  • 78. Baechle TR . editor Essentials of strength training and conditioning. National Strength and Conditioning Association. IL: Human Kinetics Champaign; 1994p259.
  • 79. Dimeo F . Radiotherapy-related fatigue and exercise for cancer patients: a review of the literature and suggestions for future research. Front Radiat Ther Oncol 2002;3749-56.
  • 80. Al-Majid S, McCarthy DO. Cancer-induced fatigue and skeletal muscle wasting: the role of exercise. Biol Res Nurs 2001 Jan;1(2):186-97.
  • 81. Kurtz ME, Kurtz JC, Stommel M, Given CW, Given B. Loss of physical functioning among geriatric cancer patients: relationships to cancer site, treatment, comorbidity and age. Eur J Cancer 1997 Dec;33(14):2352-8.
  • 82. Davis MO, Walsh D. Mechanisms of fatigue. J Support Oncol 2010;8164-74.
  • 83. Dimeo F, Rumberger BG, Keul J. Aerobic exercise as therapy for cancer fatigue. Med Sci Sports Exerc 1998 Apr;30(4):475-8.
  • 84. Dimeo FC, Stieglitz RD, Novelli-Fischer U, Fetscher S, Keul J. Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer 1999 May;85(10):2273-7.
  • 85. Courneya KS, Friedenreich CM. Determinants of exercise during colorectal cancer treatment: an application of the theory of planned behavior. Oncol Nurs Forum 1997 Nov–Dec;24(10):1715-23.
  • 86. Schwartz AL . Patterns of exercise and fatigue in physically active cancer survivors. Oncol Nurs Forum 1998 Apr;25(3):485-96.
  • 87. Kolden G, Strauman T, Ward A, Kuta J, Woods T, Schneider K. A pilot study of Group Exercise Training (GET) for women with breast cancer: Feasibility and health benefits. Psychooncology 2002 Sep–Oct;11(5):447-56.
  • 88. Al-Majid S, Waters H. The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise. Biol Res Nurs 2008 Jul;10(1):7-20.
  • 89. Wigmore SJ, Plester CE, Richardson RA, Fearon KC. Changes in nutritional status associated with unresectable pancreatic cancer. Br J Cancer 1997;75(1):106-9.
  • 90. Argilés JM, Busquets S, Felipe A, López-Soriano FJ. Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia. Int J Biochem Cell Biol Array;37(5):.
  • 91. Muscaritoli M, Bossola M, Aversa Z, Bellantone R, Rossi Fanelli F. Prevention and treatment of cancer cachexia: new insights into and old problem. Eur J Cancer 2006 Jan;42(1):31-41.
  • 92. Andreyev HJN, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?. Eur J Cancer 1998 Mar;34(4):503-9.
  • 93. Bedbrook M, Mourtzakis M. Muscle atrophy in cancer: a role for nutrition and exercise. Appl Physiol Nutr Metab 2009 Oct;34(5):950-6.
  • 94. Galvao DA, Nosaka K, Taaffe DR, Spry NA, Kristjanson L, McGuigan MR. Benefits of resistance training in men undertaking androgen deprivation therapy for prostate cancer. Innovations for an Ageing Society 2006 Jul184-96.
  • 95. Basaria S, Dobs AS. Controversies regarding transdermal androgen therapy in postmenopausal women. J Clin Endocrinol Metab 2006 Dec;91(12):4743-52.
  • 96. Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol 2006 Aug;24(24):3979-83.
  • 97. Demark-Wahnefried W, Peterson BL, Winer EP, Marks L, Aziz N, Marcom PK. Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 2001 May;19(9):2381-9.
  • 98. Ligibel JA, Campbell N, Partridge A, Chen WY, Salinardi T, Chen H. Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol 2008;26(6):907-12.
  • 99. Galvao DA, Taaffe DR, Spry N, Joseph D, Turner D, Newton RU. Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer Prostatic Dis 2009;12(2):198-203.
  • 100. Demark-Wahnefried W, Case LD, Blackwell K, Marcom PK, Kraus W, Aziz N. Results of a diet/exercise feasibility trial to prevent adverse body composition change in breast cancer patients on adjuvant chemotherapy. Clin Breast Cancer 2008 Feb;8(1):70-9.
  • 101. Kroenke CH, Chen WY, Rosner B, Holmes MD. Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 2005 Mar;231370-8.
  • 102. Borugian MJ, Sheps SB, Kim-Sing C, Van Patten C, Potter JD, Dunn B. Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?. Cancer Epidemiol Biomarkers Prev 2004 Jul;13(7):1163-72.
  • 103. Goodwin PJ, Ennis M, Pritchard KI. Fasting insulin and outcome in early-stage breast cancer: Results of a prospective cohort study. J Clin Oncol 2002 Jan;20(1):42-51.
  • 104. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003 Apr;348(17):1625-38.
  • 105. Holick CN, Newcomb PA, Trentham-Dietz A, Titus-Ernstoff L, Bersch AJ, Stampfer MJ. Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 2008 Feb;17(2):379-86.
  • 106. Irwin ML . Influence of pre- and post-diagnosis physical activity on survival in breast cancer survivors: the Health, Eating, Activity, and Lifestyle (HEAL) study. J Clin Oncol 2008;261-7.
  • 107. Goodwin PJ, Sridhar SS. Health-related quality of life in cancer patients – more answers but many questions remain. J Natl Cancer Inst 2009 Jun;101(12):838-9.
  • 108. Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC. Position Statement. Part One: Immune Function And Exercise. Exerc Immunol Rev 2011;76-63.
  • 109. Nieman DC . Current perspective on exercise immunology. Curr Sports Med Rep 2003 Oct;2(5):239-42.
  • 110. Woods JA, Vieira VJ, Keylock KT. Exercise, inflammation, and innate immunity. Immunol Allergy Clin North Am 2009 May;29(2):381-93.
  • 111. Kohut ML, Senchina DS. Reversing age-associated immunosenescence via exercise. Exerc Immunol Rev 2004;106-41.
  • 112. Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol 2005 May;45(10):1563-9.
  • 113. Plomgaard P, Penkowa M, Pedersen BK. Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles. Exerc Immunol Rev 2005;11(4):53-63.
  • 114. Mathur N, Pedersen BK. Exercise as a mean to control low grade systemic inflammation. Mediators Inflamm [internet] 2008 Nov 11 [cited 2012 Nov 12]; 2008.
  • 115. Febbraio MA, Pedersen BK. Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exerc Sport Sci Rev. 2005 Jul;33(3):114-9.
  • 116. Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev 2000 Jul;80(3):1055-81.
  • 117. Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 2003;17884-6.
  • 118. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on musclederived interleukin-6. Physiol Rev 2008 Oct;88(4):1379-406.
  • 119. Morrow GR, Andrews PL, Hickok JT, Roscoe JA, Matteson S. Fatigue associated with cancer and its treatment. Support Care Cancer 2002 Jul;10(5):389-98.
  • 120. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002860-7.
  • 121. Murphy EA, Davis JM, Barrilleaux TL, McClellan JL, Steiner JL, Carmichael MD. Benefits of exercise training on breast cancer progression and inflammation in C3 (1) SV40Tag mice. Cytokine 2011 Aug;55(2):274-9.
  • 122. Woods JA, Davis JM, Smith JA, Nieman DC. Exercise and cellular innate immune function. Med Sci Sports Exerc 1999 Jan;31(1):57.
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