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Effects of Exercise on Persons with Metastatic Cancer Beaton, Rebekah; Pagdin-Friesen, Wendy; Robertson, Christa; Vigar, Cathy; Watson, Heather 2008-08-21

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Effects of Exercise on Persons with Metastatic Cancer Rebekah Beaton BSc, MPT candidate Wendy Pagdin-Friesen BA, BEd, MPT candidate Christa Robertson BSc, MPT candidate Cathy Vigar BSc, MPT candidate Heather Watson BSc, BEd, MPT candidate Supervisor- Dr. Susan Harris Outline y Background yMethods yResults yDiscussion y Conclusion y Acknowledgements Background y The Canadian Cancer Institute estimates that in 2008, in Canada there will be: y 166,400 new cases of cancer y 73,800 cancer-related deaths1 yOf persons with a new cancer diagnosis 30% will already have metastatic disease2 yOnce metastasis has occurred, prognosis is generally poor3 Cancer Statistics Metastatic Cancer y Creates different challenges than that of non- metastatic cancer as it is a palliative disease4-8 y It causes declines in quality of life (QOL), psychological barriers and fatigue4-8 y Persons with metastatic cancer are now living longer9 y Suggest the need for research on interventions aimed at improving QOL Previous Research y Focused on exercise interventions for persons with local or regional cancer10-14 y Many reviews investigated the impacts of exercise on fatigue7,10-15 y Fatigue is a prevalent symptom y 90% of persons with cancer experience cancer-related fatigue6 y Cancer-related fatigue has also been linked with symptoms of anxiety and depression6 Previous Research y Demonstrated physical exercise is an effective intervention to improve QOL & fatigue in persons with non-metastatic cancer7,10-15 y Traditionally, persons with metastatic cancer were encouraged to rest7 y Rest is no longer considered an appropriate intervention y New literature is emerging regarding the potential benefits of exercise for persons with metastatic cancer5,7,16,17 Purpose To synthesize the available literature on the effects of exercise on QOL and physical measures in persons with metastatic cancer Review Questions 1. What exercise interventions are being used for persons with metastatic cancer? 2. What is the effect of these interventions in respect to QOL and physical measures? 3. What research needs to be completed in the future? 4. Investigate the adverse effects and attrition rates documented in the studies. Definition of Metastatic Cancer y The spread of cancer from one part of the body to another3 • For the purpose of this review it includes: • advanced cancer • palliative cancer • stage IV cancer • Frequent sites of metastases include: • lung, liver, breast & bone9 Quality of Life (QOL) Environment Social relations Level of independence Physical health Spirituality QOL18 Exercise • “Any planned, structured, and repetitive bodily movement done to improve or maintain one or more components of physical fitness”19  Search Strategy Up to and including May 8, 2008 Databases: y Medline, Embase, CINAHL, PsychInfo, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Databases of Systematic Reviews (EBM Reviews-Ovid) and PEDro Keywords: y metastatic OR palliative OR advanced AND y cancer OR neoplasm AND y exercise OR physical activity OR exercise therapy OR physical fitness Inclusion Criteria y Population: persons with metastatic or advanced or palliative cancer y Intervention: exercise as the intervention or a component of the intervention y Publication: in a peer-reviewed journal y Comparisons and outcome measures: not screened at the initial stages to include all relevant studies Exclusion Criteria Population: y Persons with lymphoma, melanoma or myeloma y Less than 50% of the sample had metastatic or advanced cancer y When results of those with metastatic cancer could not be separated from those with non-metastatic cancer Type: y Studies in a language other than English or French y Newspaper editorials, single article reviews and qualitative research studies Data Extraction y Tool developed by reviewers y Pilot tested by two reviewers y Extraction was performed on each study by one reviewer and then checked by a second reviewer y Data extracted from 12 studies: methods, participants, inclusion/exclusion criteria, intervention, attrition, adherence, and outcomes. Quality Assessment Randomized Controlled Trials (RCT’s) y Modified van Tulder Criteria20 y One criterion added: “Was the study’s purpose clearly stated?” y Low = 0-4, Medium = 5-8, High = 9-12 Case Series y Modified Case Series Criteria21 y Removal of criterion 6: comparison of sub-series y Low = 1-2, Medium = 2.5-3.5, High = 4-5 Case Reports y Case Study Methodological Quality Assessment Tool22 y Low = 1-3, Medium = 4-5, High = 6-7 Data Synthesis y Study characteristics were compiled in a table y Meta-analysis was not possible due to study heterogeneity in: • Study populations • Exercise interventions • Outcome measures • Study designs  Articles found through hand searching N = 1 Studies included after evaluation of full text N = 12 (96% Agreement) Full text reviewed N = 27 (84.7% Agreement) Abstracts reviewed N = 225 Studies included after title screening N = 224 (100% Agreement) Titles reviewed after inital search of databases Total = 674 12 Included Studies: 5 RCT’s y Rummans24: 103 persons with advanced cancer of various primary sites participated in a multi-dimensional exercise program for 3 weeks y Brown4: 115 persons from the Rummans et al.24 study, followed for 4 weeks to investigate if improvements in quality of life (QOL) impact fatigue in patients y Lapid23: Geriatric subgroup of 33 persons from the Rummans et al24 study followed for 4 weeks y Headley16: 38 women with advanced breast cancer completed seated exercises for 12 weeks y Segal25: 60 men with palliative prostate cancer completed resistance exercises for 12 weeks 12 Included Studies: 5 Case Series y Oldervoll26: 52 persons w/ metastatic cancer of various 1° sites completed circuit training, standing balance & aerobic endurance ex’s for 6 wks y Adamsen, 200327: 27 persons w/ advanced cancer of various 1° sites participated in a multi-dimensional intervention: resistance ex & stationary cycling for 6 wks y Adamsen, 200628: As per Adamsen 200327 w/ 115 participants y Carson29: 21 women with metastatic breast cancer performed yoga exercises for 8 wks y Porock7: 9 persons w/ metastatic cancer of various 1° sites performed individual home exercises for 2-4 wks 12 Included Studies: 2 Case Reports y Crevenna30: 1 female with metastatic breast cancer performed ergometric cycling for 1 year y Kelm31: 1 male with metastatic adenocarcinoma of the rectum completed endurance training and strength exercises for 13 weeks And then there were TEN y Rummans et al.24, Brown et al.4 & Lapid et al.23 were based on the same study sample y To demonstrate the breadth of literature all 3 studies were included in the characteristics table y To prevent skewing of the results, only Rummans et al.24 was included in the text of the results & discussion sections, resulting a total of 10 studies Study Characteristics Population y Cancer status: five studies25,26,29-31 metastatic, four studies16,24,27,28 advanced and one study25 palliative y Primary cancer sites: varied y Concurrent treatment: eight studies included persons undergoing concurrent chemotherapy & four studies included persons undergoing radiation therapy Characteristics of the Studies Intervention y Type: included yoga, balance, coordination, aerobic & strength training y Frequency: generally 2-3 x/wk for 3-13 wk y Intensity: strength @ 40-95% of 1RM 25,27,28,31 & aerobic @ low-moderate intensity7,30,31 Most Frequent Outcome Tools y Physical measures: 1RM27,28,31 & VO2 max27,28,30 y QOL measures: EORTC QLQ-3026-28 & the SF 36 27,28,30 Inclusion & Exclusion Criteria Differed across studies in regards to: y Life expectancy e.g. Porock8 versus Oldervoll26 y Co-morbidities e.g. bone metastases/lesions y Mental health status e.g. Adamsen28 Attrition, Adherence & Adverse Effects Attrition: y RCT’s –ranged from 7-16% y Case Series –ranged from 14-35% y Case Reports –0% Adherence: ranged from 75-100% Adverse Effects: no adverse effects were noted Quality Assessment - RCT’s y Three RCT’s assessed with the modified van Tulder Criteria20 y All were rated as high quality (9/12) y All failed to conceal the treatment allocation and blind the patient to the intervention (criterion C & D) y Two studies24,25 did not blind the therapist to the intervention (criterion F ) y Headley et al.16 was able to blind the therapist to the intervention (criterion F) Quality Assessment - Case Series y Five case series were assessed with the modified Case Series Criteria21 y All five studies were rated as medium quality y None of the case series were able to fulfill blinding (criterion 5.2) or representative sampling (criterion 1) y Carson et al.29 did not have explicit inclusion criteria (criterion 2) Quality Assessment - Case Reports y Two case reports were assessed using the Case Study Methodological Quality Assessment Tool22 y Crevenna et al.30 was rated high quality (6/7) y Kelm et al.31 was rated medium quality (4/7) y Both failed to clearly state their hypothesis (criterion B) y The effect size in the Kelm et al.31 study was not clinically important (criterion F) and limitations were not identified (criterion G) Levels of Evidence Three RCT’s = 2B Five case series = 4 Two case reports = 5 Assigned using the Oxford Centre for Evidence-Based Medicine (CEBM) Levels of Evidence32 Oxford CEBM Level 2B Improvements in physical measures including: • Increased upper and lower extremity muscle endurance25 Improvements in QOL measures including: • Improved quality of life16,24,25 • Increased overall spiritual well being in the intervention group, and increased emotional distress in the control group24 • The intervention group experienced a slower decline in total QOL16 Oxford CEBM Level 4 Improvements in physical measures including: • Increased strength and aerobic fitness27,28 • Increased physical activity28 • Increased walking distance and faster sit-to-stand26 Oxford CEBM Level 4 Improvements in QOL measures including: • Increased levels of invigoration and acceptance30 • Decreased physical fatigue26 • Increased role emotional, social and dyspnea subscales26 • Improved role-physical score28 • General increase in QOL29 • Decreased anxiety8 Oxford CEBM Level 5 Improvements in physical measures including: • Increased aerobic fitness30,31 • Improved respiratory function31 • Increased or maintained 1 RM31  Limitations Heterogeneity of: y study samples y decreased external validity y exercise interventions y unable to determine optimal frequency, intensity, exercise type and session duration y outcome measures y No single measure for QOL33 Limitations Outcome Measures y Reliable and valid outcome measures found to be most widely used25,34-37: y European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC-QLQ-C30) y Functional Assessment of Chronic Illness Therapy (FACIT) y Symptom Distress Scale (SDS) y 36-Item Short Form (SF-36) y Multidimensional Fatigue Inventory (MFI) y Hospital Anxiety and Depression Scales (HADS) Attrition y Short life expectancy and debilitating symptoms make retention of participants challenging y It could be expected that attrition rates would be higher than normal for this population33 y However, all 10 studies have attrition rates well below normal range Adherence & Adverse Effects y Documented adherence rates ranged from 75% to 100% y No comment on potential reasons y Speculation: individualized programming, group participation or even noticeable improvements as motivators? y No adverse effects documented Implications for Future Practice y Provides evidence to support exercise as a safe and effective intervention for persons with metastatic cancer y Unable to direct a specific exercise prescription y Exercise has a positive effect on QOL and physical status y Important to communicate benefits and goals of exercise to patients and their families Recommendations for Future Research y Conduct larger and more rigorous RCT’s y Investigate metastatic cancer sub-groups y Use consistent terminology to define cancer status y Determine acceptable attrition rates y Clarify optimal (or minimal) exercise prescription y Use consistent outcome measures  1. There is a positive association between exercise and changes in both QOL and physical status. 2. Clinicians working with persons with metastatic cancer should use caution with exercise prescription, as there is currently no agreement upon optimal exercise parameters. 3. Further research in the area should focus on large-scale RCT’s to identify optimal and safe exercise parameters for this population. Concluding Statements Acknowledgments y Susan Harris - Clinical Faculty, Department of Physical Therapy, UBC y Charlotte Beck - Health Sciences Reference Librarian, UBC y Angela Busch - Associate Professor, School of Physical Therapy, University of Saskatchewan y Elizabeth Dean -Professor, Department of Physical Therapy, UBC y Physiotherapy Canada for considering our review for publication (submitted July 1, 2008) References 1. Canadian Cancer Society. General cancer stats for 2008 [cited 2008 April 1]. Available at:,2283,3172_14423__langId- en,00.html. 2. Goodman CC, Boissonnault WG, Fuller KS. Pathology: implications for the physical therapist. 2nd ed. Missoula: Saunders; 2002. 3. National Cancer Institute. Metastatic cancer: questions and answers [cited 2007 Aug 1]. Available at: Types/metastatic. 4. Brown P, Clark MM, Atherton P, Huschka M, Sloan JA, Gamble G, et al. Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer? American Journal of Clinical Oncology. 2006 Feb;29(1):52-8. 5. Oldervoll LM, Loge JH, Paltiel H, Asp MB, Vidvei U, Hjermstad MJ, et al. Are palliative cancer patients willing and able to participate in a physical exercise program? Palliat Support Care. 2005 Dec;3(4):281-7. 6. Prue G, Rankin J, Allen J, Gracey J, Cramp F. Cancer-related fatigue: a critical appraisal. Eur.J.Cancer 2006 May;42(7):846-863. 7. Porock D, Kristjanson LJ, Tinnelly K, Duke T, Blight J. An exercise intervention for advanced cancer patients experiencing fatigue: a pilot study. J.Palliat.Care 2000;16(3):30-36. 8. Edwards AGK, Hailey S, Maxwell M. The Cochrane Collaboration. Psychological interventions for women with metastatic breast cancer. Cochrane Database of Systematic Reviews 2006;4. 9. Leonard R, Rodger A, Dixon J. Metastatic breast cancer. Dixon M, editor. ABC of breast diseases. London: BMJ Books, 2000: 65-71. 10. Monninkhof EM, Elias SG, Vlems FA, van der Tweel I, Schuit AJ, Voskuil DW, et al. Physical activity and breast cancer: a systematic review. Epidemiology 2007 Jan;18(1):137-157. 11. Schmitz KH, Holtzman J, Courneya KS, Masse LC, Duval S, Kane R. Controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiology, Biomarkers & Prevention 2005 Jul;14(7):1588-1595. 12. Stevinson C, Lawlor DA, Fox KR. Exercise interventions for cancer patients: systematic review of controlled trials. Cancer Causes & Control 2004 Dec;15(10):1035-1056. 13. Knols R, Aaronson NK, Uebelhart D, Fransen J, Aufdemkampe G. 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J Sport Exercise Psychol. 2007 Feb;29(1):118-27. 18. Lox C, Ginis K, Petruzello S. The psychology of exercise: integrating theory and practice. Scottsdale: Holcomb Hathawawy Publishers; 2003. 19. Armstrong L, Balady GJ, Berry MJ, Davis SE, Davy BM, Davy KP, et al. American College of Sports Medicine’s guidelines for exercise testing and prescription. 7th ed. Whaley MH, Brubaker PH, Otto RM, editors. Baltimore (MD): Lippincott, Williams and Wilkins; 2006. p.66. 20. van Tulder M, Furlan A, Bombardier C, Bouter L. The editorial board of the Cochrane Collaboration Back Review Group. Spine. 28(12):1290-1299, June 15, 2003. 21. Kahn KS, TerRiet G, Popay J, Nixon J, Kleijnen J. Centre for Reviews and Dissemination. Conducting the review. 2007. Stage II PHASE 5: Study quality assessment. p.5-20 22. Arscott S, Desaulles P, Hughes K, Kotzo S, Preto R. (unpublished). Case study methodological quality assessment tool. 2006. 23. Lapid MI, Rummans TA, Brown PD, Frost MH, Johnson ME, Huschka MM, et al. Improving the QOL of geriatric cancer patients with a structured multidisciplinary intervention: a randomized controlled trial. Palliative supportive care. 2007;5(2):107-14. 24. Rummans TA, Clark MM, Sloan JA, Frost MH, Bostwick JM, Atherton PJ, et al. Impacting QOL for patients with advanced cancer with a structured multidisciplinary intervention: a randomized controlled trial. Journal of clinical oncology. 2006;24(4):635-41. 25. Segal RJ, Reid DR, Courneya KS, Malone SC, Parliament MB, Scott CG, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. Journal of clinical oncology. 2003;21(9):1653- 59. 26. Oldervoll LM, Loge JH, Paltiel H, Asp MB, Vidvei U, Wiken AN, et al. The effect of a physical exercise program in palliative care: A phase II study. Journal of Pain & Symptom Management. 2006 May;31(5):421-30. 27. 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