POSITIVE study: physical exercise program in non-operable lung cancer patients undergoing palliative treatment

Joachim Wiskemann, Simone Hummler, Christina Diepold, Melanie Keil, Ulrich Abel, Karen Steindorf, Philipp Beckhove, Cornelia M Ulrich, Martin Steins, Michael Thomas, Joachim Wiskemann, Simone Hummler, Christina Diepold, Melanie Keil, Ulrich Abel, Karen Steindorf, Philipp Beckhove, Cornelia M Ulrich, Martin Steins, Michael Thomas

Abstract

Background: Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting.

Methods/design: The POSITIVE study is a randomized, controlled trial investigating the effects of a 24-week exercise intervention during palliative treatment on quality of life, physical performance and immune function in advanced, non-operable lung cancer patients. 250 patients will be recruited in the Clinic for Thoracic Diseases in Heidelberg, enrolment begun in November 2013. Main inclusion criterion is histologically confirmed NSCLC (stage IIIa, IIIb, IV) or SCLC (Limited Disease-SCLC, Extensive Disease-SCLC) not amenable to surgery. Patients are randomized into two groups. Both groups receive weekly care management phone calls (CMPCs) with the goal to assess symptoms and side effects. Additionally, one group receives a combined resistance and endurance training (3x/week). Primary endpoints are quality of life assessed by the Functional Assessment of Cancer Therapy for patients with lung cancer (FACT-L, subcategory Physical Well-Being) and General Fatigue measured by the Multidimensional Fatigue Inventory (MFI-20). Secondary endpoints are physical performance (maximal voluntary isometric contraction, 6-min walk distance), psychosocial (depression and anxiety) and immunological parameters and overall survival.

Discussion: The aim of the POSITIVE trial is the evaluation of effects of a 24-week structured and guided exercise intervention during palliative treatment stages. Analysis of various outcomes (such as quality of life, physical performance, self-efficacy, psychosocial and immunological parameters) will contribute to a better understanding of the potential of exercise in advanced lung cancer patients. In contrast to other studies with advanced oncological patients the POSITIVE trial provides weekly phone calls to support patients both in the intervention and control group and to segregate the impact of physical activity on quality of life.

Trial registration: ClinicalTrials.gov NCT02055508 (Date: December 12, 2013).

Keywords: Care management phone calls; Fatigue; Lung cancer; Palliative treatment; Physical exercise; Quality of life.

Figures

Fig. 1
Fig. 1
Study design. Study design of the POSITIVE study (Part III)

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90. doi: 10.3322/caac.20107.
    1. UK CS: CancerStats Incidence 2008 - UK. 2011.
    1. Howlader N, Noone A, Krapcho M. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations) Bethesda, MD: National Cancer Institute; 2012. Lung cancer.
    1. Goldstraw P, Corwley J, Chansky K, International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of Malignant Tumours. J Thorac Oncol. 2007;2:706–714. doi: 10.1097/JTO.0b013e31812f3c1a.
    1. Johnsen AT, Petersen MA, Pedersen L, Groenvold M. Symptoms and problems in a nationally representative sample of advanced cancer patients. Palliat Med. 2009;23(6):491–501. doi: 10.1177/0269216309105400.
    1. Thompson E, Sola I, Subirana M. Non-invasive interventions for improving well-being and quality of life in patients with lung cancer--a systematic review of the evidence. Lung Cancer. 2005;50(2):163–176. doi: 10.1016/j.lungcan.2005.06.004.
    1. Cooley ME. Symptoms in adults with lung cancer. A systematic research review. J Pain Symptom Manage. 2000;19:137–153. doi: 10.1016/S0885-3924(99)00150-5.
    1. Held-Warmkessel J, Schiech L. NSCLC-recent advances. Nursing. 2014;44(2):32–42. doi: 10.1097/01.NURSE.0000441877.57254.95.
    1. Iyer S, Taylor-Stokes G, Roughley A. Symptom burden and quality of life in advanced non-small cell lung cancer patients in France and Germany. Lung Cancer. 2013;81(2):288–293.
    1. Larsson M, Ljung L, Johansson BB. Health-related quality of life in advanced non-small cell lung cancer: correlates and comparisons to normative data. Eur J Cancer Care (Engl) 2012;21(5):642–649. doi: 10.1111/j.1365-2354.2012.01346.x.
    1. Kuehr L, Wiskemann J, Abel U, Ulrich CM, Hummler S, Thomas M. Exercise in patients with Non-Small-Cell Lung Cancer (NSCLC) Med Sci Sports Exerc. 2014;46(4):656–663. doi: 10.1249/MSS.0000000000000158.
    1. Lakoski SG, Eves ND, Douglas PS, Jones LW. Exercise rehabilitation in patients with cancer. Nat Rev Clin Oncol. 2012;9(5):288–296. doi: 10.1038/nrclinonc.2012.27.
    1. Mock V, Pickett M, Ropka ME, Muscari Lin E, Stewart KJ, Rhodes VA, McDaniel R, Grimm PM, Krumm S, McCorkle R. Fatigue and quality of life outcomes of exercise during cancer treatment. Cancer Pract. 2001;9(3):119–127. doi: 10.1046/j.1523-5394.2001.009003119.x.
    1. Arbane G, Tropman D, Jackson D, Garrod R. Evaluation of an early exercise intervention after thoracotomy for non-small cell lung cancer (NSCLC), effects on quality of life, muscle strength and exercise tolerance: randomised controlled trial. Lung Cancer. 2011;71(2):229–234. doi: 10.1016/j.lungcan.2010.04.025.
    1. Hoffman A, Brintnall R, Brown J, von Eye A, Jones L, Alderink G, Ritz-Holland D, Enter M, Patzelt L, Vanotteren G. Too sick not to exercise: using a 6-week, home-based exercise intervention for cancer-related fatigue self-management for postsurgical non-small cell lung cancer patients. Cancer Nurs. 2013;36(3):175–188. doi: 10.1097/NCC.0b013e31826c7763.
    1. Jones LW, Eves ND, Peterson BL, Garst J, Crawford J, West MJ, Mabe S, Harpole D, Kraus WE, Douglas PS. Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study. Cancer. 2008;113(12):3430–3439. doi: 10.1002/cncr.23967.
    1. Jones LW, Peddle CJ, Eves ND, Haykowsky MJ, Courneya KS, Mackey JR, Joy AA, Kumar V, Winton TW, Reiman T. Effects of presurgical exercise training on cardiorespiratory fitness among patients undergoing thoracic surgery for malignant lung lesions. Cancer. 2007;110(3):590–598. doi: 10.1002/cncr.22830.
    1. Peddle C, Jones L, Eves ND, Reiman T, Sellar CM, Winton T, Courneya K. Effects of presurgical exercise training on quality of life in patients undergoing lung resection for suspected malignancy: a pilot study. Cancer Nurs. 2009;32(2):158–165. doi: 10.1097/NCC.0b013e3181982ca1.
    1. Adamsen L, Stage M, Laursen J, Rorth M, Quist M. Exercise and relaxation intervention for patients with advanced lung cancer: a qualitative feasibility study. Scand J Med Sci Sports. 2012;22(6):804–815. doi: 10.1111/j.1600-0838.2011.01323.x.
    1. Cheville AL, Kollasch J, Vandenberg J, Shen T, Grithey A, Gamble G, Basford JR. 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(5):811–821. doi: 10.1016/j.jpainsymman.2012.05.006.
    1. Quist M, Adamsen L, Rorth K, Laursen JH, Christensen KB, Langer SW. The impact of multidimensional exercise intervention on physical and functional capacity, anxiety, and depression in patients with advanced-stage lung cancer undergoing chemotherapy. Integr Cancer Ther. 2015;14(4):341–349. doi: 10.1177/1534735415572887.
    1. Quist M, Rorth M, Langer S, Jones LW, Laursen JH, Pappot H, Christensen KB, Adamsen L. Safety and feasibility of a combined exercise intervention for inoperable lung cancer patients undergoing chemotherapy: a pilot study. Lung Cancer. 2011;75(2):203–208. doi: 10.1016/j.lungcan.2011.07.006.
    1. Temel JS, Greer JA, Goldberg S, Vogel PD, Sullivan M, Pirl WF, Lynch TJ, Christiani DC, Smith MR. A structured exercise program for patients with advanced non-small cell lung cancer. J Thorac Oncol. 2009;4(5):595–601. doi: 10.1097/JTO.0b013e31819d18e5.
    1. Hummler S, Zoz M, Thomas M, Ulrich CM, Huber G, Wiskemann J. Pilot study on fatigue levels in patients with lung cancer: correlations with muscle strength and 6-minute walk tests. Oncol Res Treat. 2014;37:36–41. doi: 10.1159/000358157.
    1. McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008;8(3):205–211. doi: 10.1038/nrc2325.
    1. Fairey A, Courneya K, Field C, Bell G, Jones L, Mackey J. Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors. J Appl Physiol. 1985;98(4):1534–1540. doi: 10.1152/japplphysiol.00566.2004.
    1. Timmons B, Cieslak T. Human natural killer cell subsets and acute exercise: a brief review. Exerc Immunol Rev. 2008;14:8–23.
    1. Peters C, Lötzerich H, Niemeier B, Schüle K, Uhlenbruck G. Influence of a moderate exercise training on natural killer cytotoxicity and personality traits in cancer patients. Anticancer Res. 1994;14(3A):1033–1036.
    1. Peters C, Lötzerich H, Niemeier B, Schüle K, Uhlenbruck G. Exercise, cancer and the immune rsponse of monocytes. Anticancer Res. 1995;15(1):175–179.
    1. Galvao D, Nosaka K, Taaffe D, Peake J, Spry N, Suzuki K, Yamaya K, McGuigan M, Kristjanson L, Newtin R. Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer Prostatic Dis. 2008;11(2):160–165. doi: 10.1038/sj.pcan.4500991.
    1. Goh J, Kirk E, Lee S, Ladiges W. Exercise, physical activity and breast cancer: the role of tumor-associated macropages. Exerc Immunol Rev. 2012;18:158–176.
    1. Chen M, Chen H, Jen C. Exercise training upregulates macrophages MKP-1 and affects immune responses in mice. Med Sci Sports Exerc. 2010;42(12):2173–2179. doi: 10.1249/MSS.0b013e3181e2158d.
    1. Kawada S, Kobayashi K, Ohtani M, Fukusaki C. Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res. 2010;24(3):846–851. doi: 10.1519/JSC.0b013e3181c7c299.
    1. Shore S, Shepard R. Immune responses to exercise in children treated for cancer. J Sports Med Phys Fitness. 1999;39(3):240–243.
    1. Boas S, Joswiak M, Nixon P, Kurland G, O’Connor M, Bufalino K, Orenstein D, Whiteside T. Effects of anaerobic exercise in the immune system in eight- to seventeen-year-old trained and untrained boys. J Pediatr. 1996;129(6):846–855. doi: 10.1016/S0022-3476(96)70028-8.
    1. Na Y, Kim M, Kim Y, Ha Y, Yoon D. Exercise therapy effect on natural killer cell cytotoxic activity in stomach cancer patients after curative surgery. Arch Phys Med Rehabil. 2000;81(6):777–779. doi: 10.1016/S0003-9993(00)90110-2.
    1. Eisenstein E, Williams CB. The T(reg)/Th17 cell balance: a new paradigm for autoimmunity. Pediatr Res. 2009;65:26R–31R. doi: 10.1203/PDR.0b013e31819e76c7.
    1. Tan W. Tumour-infiltrating regulatory T cells stimulates maamary cancer metastasis through RANKL-RANK signalling. Nature. 2011;470(7335):548–553. doi: 10.1038/nature09707.
    1. Xu L. Enrichment of CCR6 + Foxp3+ regulatory T cells in the tumor mass correlates with impaired CD8+ T cell function and poor prognosis of breast cancer. Clin Immunol. 2010;135(3):466–475. doi: 10.1016/j.clim.2010.01.014.
    1. Yan M. Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res. 2011;13(2):R47. doi: 10.1186/bcr2869.
    1. Christensen JF, Jones LW, Andersen JL, Daugaad G, Rorth M, Hojman P. Muscle dysfunction in cancer patients. Ann Oncol. 2014;25(5):947–958. doi: 10.1093/annonc/mdt551.
    1. Kruijsen-Jaarsma M, Revesz D, Bierings MB, Buffart LM, Takken T. Effects of exercise on immune function in patients with cancer: a systematic review. Exerc Immunol Rev. 2013;19:120–143.
    1. Paramanandam V, Dunn V. Exercise for the management of cancer-related fatigue in lung cancer: a systematic review. Eur J Cancer Care (Engl) 2014;24(1):4–14. doi: 10.1111/ecc.12198.
    1. Borg G. Perceived exertion and pain scales. Champaign: Human Kinetics; 1998, 1 sr edn.
    1. Wiskemann J, Dreger P, Schwerdtfeger R, Bondong A, Huber G, Kleindienst N, Ulrich CM, Bohus M. Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood. 2011;117(9):2604–2613. doi: 10.1182/blood-2010-09-306308.
    1. Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42(7):1409–1426. doi: 10.1249/MSS.0b013e3181e0c112.
    1. American College of Sports Medicine position stand Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009;41(3):687–708. doi: 10.1249/MSS.0b013e3181915670.
    1. Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg CR, Salem GJ, Skinner JS. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc. 2009;41(7):1510–1530. doi: 10.1249/MSS.0b013e3181a0c95c.
    1. Cella DF, Bonomi AE, Lloyd SR, Tulsky DS, Kaplan E, Bonomi P. Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer. 1995;12(3):199–220. doi: 10.1016/0169-5002(95)00450-F.
    1. Peddle-McIntyre CJ, Bell G, Fenton D, McCargar L, Courneya KS. Feasibility and preliminary efficacy of progressive resistance exercise training in lung cancer survivors. Lung Cancer. 2012;75(1):126–132. doi: 10.1016/j.lungcan.2011.05.026.
    1. Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733–742. doi: 10.1056/NEJMoa1000678.
    1. Thongprasert S, Duffield E, Saijo N, Wu YL, Yang JC, Chu DT, Liao M, Chen YM, Kuo HP, Negoro S, et al. Health-related quality of life in a randomized phase III first-line study of gefinitib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS) J Thorac Oncol. 2011;6(11):1872–1880. doi: 10.1097/JTO.0b013e31822adaf7.
    1. Löwe B, Wahl I, Rose M, Spitzer C, Glaesmer H, Wingenfeld K, Schneider A, Brähler E. A 4-item measure of depression and aniety: validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J Affect Disord. 2010;122(1-2):86–95. doi: 10.1016/j.jad.2009.06.019.
    1. Smets EM, Garssen B, Cull A, de Haes JC. Application of the multidimensional fatigue inventory (MFI-20) in cancer patients receiving chemotherapy. Br J Cancer. 1996;73(2):241–245. doi: 10.1038/bjc.1996.42.
    1. Bartsch HH, Weis J, Moser MT. Cancer-related fatigue in patients attending oncological rehabilitation programs: prevalence, patterns and predictors. Onkologie. 2003;26(1):51–57.
    1. Mehnert A, Scherwath A, Schirmer L, Schleimer B, Petersen C, Schulz-Kindmann F, Zander AR, Koch U. The association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life in breast cancer survivors following standard adjuvant versus high-dose chemotherapy. Patient Educ Couns. 2007;66(1):108–118. doi: 10.1016/j.pec.2006.11.005.
    1. Munch TN, Strömgren AS, Pedersen L, Petersen MA, Hoermann L, Gorenvold M. Multidimensioonal measurement of fatigue in advanced cancer patients in palliative care: an application of the multidimensional fatigue inventory. J Pain Symptom Manage. 2006;31(6):533–541. doi: 10.1016/j.jpainsymman.2005.11.012.
    1. Mehnert A, Vehling S, Höcker A, Lehmann C, Koch U: Demoralization and Depression in Patients with Advanced Cancer: Validation of the German Version of the Demoralization Scale. J Pain Symptom Manage. 2011;42(5):768–776.
    1. Wein S, Sulke A, Stemmer S. The oncologist’s role in managing depression, anxiety, and demoralization with advanced cancer. Cancer J. 2010;16(5):493–499. doi: 10.1097/PPO.0b013e3181f28b64.
    1. Schmitt GM, Lohaus A, Salewski C. Control beliefs and patient compliance: an empirical study exemplified by adolescents with diabetes mellitus, bronchial asthma and alopecia areata. Psychother Psychosom Med Psychol. 1989;39(1):33–40.
    1. Watson M, Pruyn J, Greer S, van den Borne B. Locus of control and adjustment to cancer. Psychol Rep. 1990;66(1):39–48. doi: 10.2466/pr0.1990.66.1.39.
    1. Gioulbasanis I, Baracos VE, Giannousi Z, Xyrafas A, Martin L, Georgoulias V, Mavroudis D. Baseline nutritional evaluation in metastatic lung cancer patients: Mini Nutrional Assessment versus weight loss history. Ann Oncol. 2011;22(4):835–841. doi: 10.1093/annonc/mdq440.
    1. Enright PL. The six-minute walk test. RespirCare. 2003;48(8):783–785.
    1. Yuen HK, Sword D. Home-based exercise to alleviate fatigue and improve functional capacity among breast cancer survivors. J Allied Health. 2007;36(4):e257–275.
    1. Knols RH, Stappaerts KH, Fransen J, Uebelhart D, Aufdemkampe G. Isometric strength measurement for muscle weakness in cancer patients: reproducibility of isometric muscle strength measurements with a hand-held pull-gauge dynamometer in cancer patients. SupportCare Cancer. 2002;10(5):430–438. doi: 10.1007/s00520-002-0343-6.
    1. Bonertz A, Weitz J, Pietsch DH, Rahbari NN, Schlude C, Ge Y, Juenger S, Vlodavsky I, Khazaie K, Jager D, et al. Antigen-specific Tregs control T cell responses against a limited repertoire of tumor in patients with colorectal carcinoma. J Clin Invest. 2009;119(11):3311–3321.
    1. Dhillon HM, van der Ploeg HP, Bell ML, Boyer M, Clarke S, Vardy J. The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol. BMC Cancer. 2012;12:572. doi: 10.1186/1471-2407-12-572.
    1. Henke C, Cabri J, Fricke L, Pankow W, Kandilakis G, Feyer P, de Wit M. Strength and endurance training in the treatment of lung cancer patients in stages IIIA/IIIB/IV. Support Care Cancer. 2014;22(1):95–101. doi: 10.1007/s00520-013-1925-1.
    1. Hwang CL, Yu C, Shih J, Yang P, Wu Y. Effects of exercise training on exercise capacity in patients with non-small cell lung cancer receiving targeted therapy. Support Care Cancer. 2012;20(12):169–177. doi: 10.1007/s00520-012-1452-5.
    1. Jensen W, Oechsle K, Baumann H, Mehnert A, Klose H, Bloch W, Bokemeyer C, Baumann F. Effects of exercise training programs on physical performance and quality of life in patients with metastatic lung cancer undergoing palliative chemotherapy - A study protocol. Contemp Clin Trials. 2014;37(1):120–128. doi: 10.1016/j.cct.2013.11.013.
    1. Spruit MA, Janssen PA, Willemsen S, Hochstenbag M, Wouters EF. Exercise capacity before and after 8-week multidisciplinary inpatient rehabilitation program in lung cancer patients: a pilot study. Lung Cancer. 2006;52:257–260. doi: 10.1016/j.lungcan.2006.01.003.
    1. Granger CL, McDonald CF, Berney S, Chao C, Denehy L. Exercise intervention to improve exercise capacity and health related quality of life for patients with Non-small cell lung cancer: a systematic review. Lung Cancer. 2011;72(2):139–153. doi: 10.1016/j.lungcan.2011.01.006.
    1. Peppercorn J, Smith TJ, Helft PR, Debono DJ, Berry SR, Wollins DS, Hayes DM, Von Roenn JH, Schnipper LE, American Society of Clinical Oncology American society of clinical oncology statement: toward individualized care for patients with advanced cancer. J Clin Oncol. 2011;29(6):755–760. doi: 10.1200/JCO.2010.33.1744.
    1. Antoni MH. Psychosocial intervention effects on adaption, disease course and behavioral processes in cancer. Brain Behav Immun. 2012;30:88–98. doi: 10.1016/j.bbi.2012.05.009.
    1. Jones LW, Hornsby WE, Goetzinger A, Forbes LM, Sherrard EL, Quist M, Lane AT, West M, Eves ND, Gradison M, et al. Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer. Lung Cancer. 2012;76(2):248–252. doi: 10.1016/j.lungcan.2011.10.009.
    1. Kasymjanova G, Correa JA, Kreisman H, Dajczman E, Pepe C, Dobson S, Lajeunesse L, Sharma R, Small D. Prognostic value of the six-minute walk in advanced non-small cell lung cancer. J Thorac Oncol. 2009;4(5):602–607. doi: 10.1097/JTO.0b013e31819e77e8.
    1. Jones L, Eves ND, Kraus WE, Potti A, Crawford J, Blumenthal JA, Peterson BL, Douglas PS. The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design. BMC Cancer. 2010;10:155. doi: 10.1186/1471-2407-10-155.
    1. Hepple R, Mackinnon SLM, Goodman JM, Thomas SG, Plyley MJ. Resistance and aerobic training in older men: effects on VO2 peak and the capillary supply to skeletal muscle. J Appl Physiol. 1997;82(4):1305–1310.
    1. Hepple R, Mackinnon SLM, Goodman JM, Thomas SG, Plyley MJ. Quantitating the capillary supply and the response to resistance training in older men. Eur J Physiol. 1997;433:238–244. doi: 10.1007/s004240050273.
    1. Karvinen KH, Esposito D, Raedeke TD, Vick J, Walker PR: Effect of an exercise training intervention with resistance bands on blood cell counts during chemotherapy for lung cancer: a pilot randomized controlled trial. Springer Plus. 2014;3:15.
    1. Crisafulli A, Tocco F, Melis F, Milia R, Concu A. Natural Killer cells responsiveness to physical exercise: a brief review. Open J Immunol. 2013;3(4):190–200. doi: 10.4236/oji.2013.34024.
    1. Kangas M, Bovbjerg DH, Montgomery GH. Cancer-related fatigue: a systematic and meta-analytic review of non-pharmacological therapies for cancer patients. PsycholBull. 2008;134(5):700–741.

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