Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: the BEST study

Karin Potthoff, Martina E Schmidt, Joachim Wiskemann, Holger Hof, Oliver Klassen, Nina Habermann, Philipp Beckhove, Juergen Debus, Cornelia M Ulrich, Karen Steindorf, Karin Potthoff, Martina E Schmidt, Joachim Wiskemann, Holger Hof, Oliver Klassen, Nina Habermann, Philipp Beckhove, Juergen Debus, Cornelia M Ulrich, Karen Steindorf

Abstract

Background: Cancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce.Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood.In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy.

Methods/design: The BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed.

Discussion: The BEST study is the first randomized controlled trial comparing progressive resistance training with muscle relaxation training in breast cancer patients during adjuvant radiotherapy. Based on the analysis of physiological, immunological and inflammatory parameters it will contribute to a better understanding of the physiological and psychosocial effects and the biological mechanisms of resistance training. The ultimate goal is the implementation of optimized intervention programs to reduce fatigue, improve quality of life and potentially the prognosis after breast cancer.

Trial registration: ClinicalTrials.gov NCT01468766.

Figures

Figure 1
Figure 1
Study design of the BEST study.
Figure 2
Figure 2
Study flow of the BEST study.

References

    1. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707–16.
    1. Noal S, Levy C, Hardouin A, Rieux C, Heutte N, Segura C, Collet F, Allouache D, Switsers O, Delcambre C, Delozier T, Henry-Amar M, Joly F. One-year longitudinal study of fatigue, cognitive functions, and quality of life after adjuvant radiotherapy for breast cancer. Int J Radiat Oncol Biol Phys. 2011;81:795–803. doi: 10.1016/j.ijrobp.2010.06.037.
    1. Hickok JT, Morrow GR, Roscoe JA, Mustian K, Okunieff P. Occurrence, severity, and longitudinal course of twelve common symptoms in 1129 consecutive patients during radiotherapy for cancer. J Pain Symptom Manage. 2005;30:433–42. doi: 10.1016/j.jpainsymman.2005.04.012.
    1. Jereczek-Fossa BA, Marsiglia HR, Orecchia R. Radiotherapy-related fatigue. Crit Rev Oncol Hematol. 2002;41:317–25. doi: 10.1016/S1040-8428(01)00143-3.
    1. Tavio M, Milan I, Tirelli U. Cancer-related fatigue (review) Int J Oncol. 2002;21:1093–9.
    1. Prue G, Rankin J, Allen J, Gracey J, Cramp F. Cancer-related fatigue: a critical appraisal. Eur J Cancer. 2006;42:846–63. doi: 10.1016/j.ejca.2005.11.026.
    1. Geinitz H, Zimmermann FB, Thamm R, Keller M, Busch R, Molls M. Fatigue in patients with adjuvant radiation therapy for breast cancer: long-term follow-up. J Cancer Res Clin Oncol. 2004;130:327–33. doi: 10.1007/s00432-003-0540-9.
    1. Taunk NK, Haffty BG, Chen S, Khan AJ, Nelson C, Pierce D, Goyal S. Comparison of radiation-induced fatigue across 3 different radiotherapeutic methods for early stage breast cancer. Cancer. 2011;117:4116–24. doi: 10.1002/cncr.26013.
    1. National Comprehensive Cancer Network (NCCN) Oncology: Cancer-Related Fatigue. Fort Washington, PA: NCCN; 2011. NCCN Clinical Practice Guidelines.
    1. Moraska AR, Sood A, Dakhil SR, Sloan JA, Barton D, Atherton PJ, Suh JJ, Griffin PC, Johnson DB, Ali A, Silberstein PT, Duane SF, Loprinzi CL. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Oncol. 2010;28:3673–9. doi: 10.1200/JCO.2010.28.1444.
    1. Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2008;CD006145
    1. Schmitz KH, Courneya KS, Matthews C, Denmark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, Von GV, Schwartz AL. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42:1409–26. doi: 10.1249/MSS.0b013e3181e0c112.
    1. 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;20:123–33. doi: 10.1158/1055-9965.EPI-10-0988.
    1. Cramp F, James A, Lambert J. The effects of resistance training on quality of life in cancer: a systematic literature review and meta-analysis. Support Care Cancer. 2010;18:1367–76. doi: 10.1007/s00520-010-0904-z.
    1. Cheema B, Gaul CA, Lane K, Fiatarone Singh MA. Progressive resistance training in breast cancer: a systematic review of clinical trials. Breast Cancer Res Treat. 2008;109:9–26. doi: 10.1007/s10549-007-9638-0.
    1. Bower JE, Ganz PA, Tao ML, Hu W, Belin TR, Sepah S, Cole S, Aziz N. Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res. 2009;15:5534–40. doi: 10.1158/1078-0432.CCR-08-2584.
    1. Stone HB, Coleman CN, Anscher MS, McBride WH. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 2003;4:529–36. doi: 10.1016/S1470-2045(03)01191-4.
    1. Gallet P, Phulpin B, Merlin JL, Leroux A, Bravetti P, Mecellem H, Tran N, Dolivet G. Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring. PLoS One. 2011;6:e29399. doi: 10.1371/journal.pone.0029399.
    1. Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Martin BS, Mackey JR. Effect of exercise training on C-reactive protein in postmenopausal breast cancer survivors: a randomized controlled trial. Brain Behav Immun. 2005;19:381–8. doi: 10.1016/j.bbi.2005.04.001.
    1. Donges CE, Duffield R, Drinkwater EJ. Effects of resistance or aerobic exercise training on interleukin-6, C-reactive protein, and body composition. Med Sci Sports Exerc. 2010;42:304–13.
    1. Campbell PT, Campbell KL, Wener MH, Wood BL, Potter JD, McTiernan A, Ulrich CM. A yearlong exercise intervention decreases CRP among obese postmenopausal women. Med Sci Sports Exerc. 2009;41:1533–9. doi: 10.1249/MSS.0b013e31819c7feb.
    1. Plaisance EP, Grandjean PW. Physical activity and high-sensitivity C-reactive protein. Sports Med. 2006;36:443–58. doi: 10.2165/00007256-200636050-00006.
    1. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol. 2005;98:1154–62. doi: 10.1152/japplphysiol.00164.2004.
    1. Imayama I, Ulrich CM, Alfano CM, Wang C, Xiao L, Wener MH, Campbell KL, Duggan C, Foster-Schubert KE, Kong A, Mason CE, Wang CY, Blackburn GL, Bain CE, Thompson HJ, McTiernan A. Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial. Cancer Res. 2012;72:2314–26. doi: 10.1158/0008-5472.CAN-11-3092.
    1. Lu H. FOXP3 expression and prognosis: role of both the tumor and T cells. J Clin Oncol. 2009;27:1735–6. doi: 10.1200/JCO.2008.20.0675.
    1. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6:295–307. doi: 10.1038/nri1806.
    1. Bonertz A, Weitz J, Pietsch DH, Rahbari NN, Schlude C, Ge Y, Juenger S, Vlodavsky I, Khazaie K, Jaeger D, Reissfelder C, Antolovic D, Aigner M, Koch M, Beckhove P. Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J Clin Invest. 2009;119:3311–21.
    1. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942–9. doi: 10.1038/nm1093.
    1. Leffers N, Gooden MJ, de Jong RA, Hoogeboom BN, ten Hoor KA, Hollema H, Boezen HM, van der Zee AG, Daemen T, Nijman HW. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009;58:449–59. doi: 10.1007/s00262-008-0583-5.
    1. Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24:5373–80. doi: 10.1200/JCO.2006.05.9584.
    1. Aruga T, Suzuki E, Saji S, Horiguchi S, Horiguchi K, Sekine S, Kitagawa D, Funata N, Toi M, Sugihara K, Kuroi K. A low number of tumor-infiltrating FOXP3-positive cells during primary systemic chemotherapy correlates with favorable anti-tumor response in patients with breast cancer. Oncol Rep. 2009;22:273–8.
    1. Rech AJ, Mick R, Kaplan DE, Chang KM, Domchek SM, Vonderheide RH. Homeostasis of peripheral FoxP3(+) CD4 (+) regulatory T cells in patients with early and late stage breast cancer. Cancer Immunol Immunother. 2010;59:599–607. doi: 10.1007/s00262-009-0780-x.
    1. Xu L, Xu W, Qiu S, Xiong S. 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;135:466–75. doi: 10.1016/j.clim.2010.01.014.
    1. Merlo A, Casalini P, Carcangiu ML, Malventano C, Triulzi T, Menard S, Tagliabue E, Balsari A. FOXP3 expression and overall survival in breast cancer. J Clin Oncol. 2009;27:1746–52. doi: 10.1200/JCO.2008.17.9036.
    1. Ibrahim EM, Al-Homaidh A. Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. 2011;28:753–65. doi: 10.1007/s12032-010-9536-x.
    1. Al-Majid S, Gray DP. A Biobehavioral Model for the Study of Exercise Interventions in Cancer-related Fatigue. Biol Res Nurs. 2009;10:381–91. doi: 10.1177/1099800408324431.
    1. Ferguson JM, Marquis JN, Taylor CB. A script for deep muscle relaxation. Dis Nerv Syst. 1977;38:703–8.
    1. Schmidt ME, Wiskemann J, Krakowski-Roosen H, Knicker AJ, Habermann N, Schneeweiss A, Ulrich CM, Steindorf K. Progressive resistance versus relaxation training for breast cancer patients during adjuvant chemotherapy: Design and rationale of a randomized controlled trial (BEATE study) Contemp Clin Trials. 2013;34:117–25. doi: 10.1016/j.cct.2012.10.006.
    1. Brzycki M. Strength testing: predicting a one-rep max from reps to fatigue. Hlth Phys Educ Rec Dance. 1993;64:88–90.
    1. American College of Sports Medicine. American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009;41:687–708. 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;41:1510–30. doi: 10.1249/MSS.0b013e3181a0c95c.
    1. Glaus A, Muller S. [Measuring fatigue of cancer patients in the German-speaking region: development of the Fatigue Assessment Questionnaire] Pflege. 2001;14:161–70. doi: 10.1024/1012-5302.14.3.161.
    1. Beutel ME, Hinz A, Albani C, Brahler E. Fatigue assessment questionnaire: standardization of a cancer-specific instrument based on the general population. Oncology. 2006;70:351–7. doi: 10.1159/000098108.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76. doi: 10.1093/jnci/85.5.365.
    1. Fayers PM, Aaronson NK, Bjordal K, Curran D, Groenvold M, Curran D, Bottomley A. EORTC Scoring Manual. 3. Brussels: European Organisation for Research and Treatment of Cancer; 2001.
    1. European Organisation for Research and Treatment of Cancer. EORTC Reference Values. [ ]
    1. Schwarz R, Hinz A. Reference data for the quality of life questionnaire EORTC QLQ-C30 in the general German population. Eur J Cancer. 2001;37:1345–51. doi: 10.1016/S0959-8049(00)00447-0.
    1. Cocks K, King MT, Velikova G, Martyn St-James M, Fayers PM, Brown JM. Evidence-based guidelines for determination of sample size and interpretation of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30. J Clin Oncol. 2011;29:89–96. doi: 10.1200/JCO.2010.28.0107.
    1. Schroevers MJ, Sanderman R, Van SE, Ranchor AV. The evaluation of the Center for Epidemiologic Studies Depression (CES-D) scale: Depressed and Positive Affect in cancer patients and healthy reference subjects. Qual Life Res. 2000;9:1015–29. doi: 10.1023/A:1016673003237.
    1. Reitan RM. The relation of the trail making test to organic brain damage. J Consult Psychol. 1955;19:393–4.
    1. Sanchez-Cubillo I, Perianez JA, Adrover-Roig D, Rodriguez-Sanchez JM, Rios-Lago M, Tirapu J, Barcelo F. Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities. J Int Neuropsychol Soc. 2009;15:438–50. doi: 10.1017/S1355617709090626.
    1. Pavy JJ, Denekamp J, Letschert J, Littbrand B, Mornex F, Bernier J, Gonzales-Gonzales D, Horiot JC, Bolla M, Bartelink H. EORTC Late Effects Working Group. Late effects toxicity scoring: the SOMA scale. Radiother Oncol. 1995;35:11–5. doi: 10.1016/0167-8140(95)97448-M.
    1. Drouin JM, Valovich-mcLeod TC, Shultz SJ, Gansneder BM, Perrin DH. Reliability and validity of the Biodex system 3 pro isokinetic dynamometer velocity, torque and position measurements. Eur J Appl Physiol. 2004;91:22–9. doi: 10.1007/s00421-003-0933-0.
    1. Eitzen I, Hakestad KA, Risberg MA. Inter- and intrarater reliability of isokinetic thigh muscle strength tests in postmenopausal women with osteopenia. Arch Phys Med Rehabil. 2012;93:420–7. doi: 10.1016/j.apmr.2011.10.001.
    1. Webber SC, Porter MM. Reliability of ankle isometric, isotonic, and isokinetic strength and power testing in older women. Phys Ther. 2010;90:1165–75. doi: 10.2522/ptj.20090394.
    1. Jones LW, Eves ND, Haykowsky M, Joy AA, Douglas PS. Cardiorespiratory exercise testing in clinical oncology research: systematic review and practice recommendations. Lancet Oncol. 2008;9:757–65. doi: 10.1016/S1470-2045(08)70195-5.
    1. Valentinuzzi ME. Bioelectrical impedance techniques in medicine. Part I: Bioimpedance measurement. First section: general concepts. Crit Rev Biomed Eng. 1996;24:223–55.
    1. Segal KR, Burastero S, Chun A, Coronel P, Pierson RN Jr, Wang J. Estimation of extracellular and total body water by multiple-frequency bioelectrical-impedance measurement. Am J Clin Nutr. 1991;54:26–9.
    1. Volgyi E, Tylavsky FA, Lyytikainen A, Suominen H, Alen M, Cheng S. Assessing body composition with DXA and bioimpedance: effects of obesity, physical activity, and age. Obesity (Silver Spring) 2008;16:700–5. doi: 10.1038/oby.2007.94.
    1. Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007;60:1234–8. doi: 10.1016/j.jclinepi.2007.02.006.
    1. Yang L, Tsiatis A. Efficiency Study of Estimators for a Treatment Effect in a Pretest-Posttest Trial. Am Stat. 2001;55:314–21. doi: 10.1198/000313001753272466.
    1. Robert Koch Institut. Health Reporting. [ ]
    1. Mock V, Dow KH, Meares CJ, Grimm PM, Dienemann JA, Haisfield-Wolfe ME, Quitasol W, Mitchell S, Chakravarthy A, Gage I. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncol Nurs Forum. 1997;24:991–1000.
    1. Mock V, Frangakis C, Davidson NE, Ropka ME, Pickett M, Poniatowski B, Stewart KJ, Cameron L, Zawacki K, Podewils LJ, Cohen G, McCorkle R. Exercise manages fatigue during breast cancer treatment: a randomized controlled trial. Psychooncology. 2005;14:464–77. doi: 10.1002/pon.863.
    1. Mustian KM, Peppone L, Darling TV, Palesh O, Heckler CE, Morrow GR. 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.
    1. Mutrie N, Campbell AM, Whyte F, McConnachie A, Emslie C, Lee L, Kearney N, Walker A, Ritchie D. Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial. BMJ. 2007;334:517. doi: 10.1136/.
    1. Segal R, Evans W, Johnson D, Smith J, Colletta S, Gayton J, Woodard S, Wells G, Reid R. Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial. J Clin Oncol. 2001;19:657–65.
    1. Caiozzo VJ, Giedzinski E, Baker M, Suarez T, Izadi A, Lan M, Cho-Lim J, Tseng BP, Limoli CL. The radiosensitivity of satellite cells: cell cycle regulation, apoptosis and oxidative stress. Radiat Res. 2010;174:582–9. doi: 10.1667/RR2190.1.
    1. 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;106:2076–83. doi: 10.1002/cncr.21829.
    1. De Backer IC, Vreugdenhil G, Nijziel MR, Kester AD, Van BE, Schep G. Long-term follow-up after cancer rehabilitation using high-intensity resistance training: persistent improvement of physical performance and quality of life. Br J Cancer. 2008;99:30–6. doi: 10.1038/sj.bjc.6604433.
    1. De Backer IC, Schep G, Backx FJ, Vreugdenhil G, Kuipers H. Resistance training in cancer survivors: a systematic review. Int J Sports Med. 2009;30:703–12. doi: 10.1055/s-0029-1225330.
    1. Courneya KS, Segal RJ, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, Ladha AB, Proulx C, Vallance JK, Lane K, Yasui Y, McKenzie DC. 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. doi: 10.1200/JCO.2006.08.2024.
    1. Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, Venner PM, Quinney HA, Jones LW, D’Angelo ME, Wells GA. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2003;21:1653–9. doi: 10.1200/JCO.2003.09.534.
    1. Segal RJ, Reid RD, Courneya KS, Sigal RJ, Kenny GP, Prud’Homme DG, Malone SC, Wells GA, Scott CG, Slovinec D’Angelo ME. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J Clin Oncol. 2009;27:344–51.
    1. Winters-Stone KM, Dobek J, Bennett JA, Nail LM, Leo MC, Schwartz A. The effect of resistance training on muscle strength and physical function in older, postmenopausal breast cancer survivors: a randomized controlled trial. J Cancer Surviv. 2012;6:189–99. doi: 10.1007/s11764-011-0210-x.
    1. Headley JA, Ownby KK, John LD. The effect of seated exercise on fatigue and quality of life in women with advanced breast cancer. Oncol Nurs Forum. 2004;31:977–83. doi: 10.1188/04.ONF.977-983.
    1. Yuen HK, Sword D. Home-based exercise to alleviate fatigue and improve functional capacity among breast cancer survivors. J Allied Health. 2007;36:e257–e275.
    1. Emslie C, Whyte F, Campbell A, Mutrie N, Lee L, Ritchie D, Kearney N. ‘I wouldn’t have been interested in just sitting round a table talking about cancer’; exploring the experiences of women with breast cancer in a group exercise trial. Health Educ Res. 2007;22:827–38.
    1. Fors EA, Bertheussen GF, Thune I, Juvet LK, Elvsaas IK, Oldervoll L, Anker G, Falkmer U, Lundgren S, Leivseth G. Psychosocial interventions as part of breast cancer rehabilitation programs? Results from a systematic review. Psychooncology. 2011;20:909–18.
    1. Goedendorp MM, Gielissen MF, Verhagen CA, Bleijenberg G. Psychosocial interventions for reducing fatigue during cancer treatment in adults. Cochrane Database Syst Rev. 2009;CD006953

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner