Exercise is Medicine for Cancer Management

Transcription

1 18/8/211 for Cancer Management Presented by: Robert Newton, PhD, Perth, Australia the human genome evolved over at least the last 5, years within an environment of high physical activity the current human genome expects and requires humans to be physically active for normal function and health maintenance Booth et al, JAP 2 Programmed for physical activity Major Chronic Disease and the Role of Exercise 3 Sarcopenia Loss of muscle mass and function 6% of over 8yrs Major cause of loss of independence Anabolic exercise most effective strategy to prevent or reverse sarcopenia Osteoporosis Obesity Evidence is conclusive Lifelong physical activity has strong preventative effect Anabolic exercise - greatest efficacy Example 1 year study of strength and endurance training 1.3% increase BMD in training group 1.2% decrease for control Kemmler et al. Archives of Physical Medicine & Rehabilitation, 23 Exercise and diet modification is the ONLY long term solution Diet modification has most impact BUT Anabolic exercise counteracts muscle and bone loss One kilogram fat approx. 32, Kj Much easier to drop 16, Kj energy intake and increase exercise 16, Kj per week PLUS all the added exercise benefits! Fitness NOT Fatness is the key 1

2 18/8/211 Anxiety and Depression Depression and Resistance Training Appropriate physical activity can result in large improvement in anxiety and depression Recent research has shown resistance training to be more effective than GP care in older people with diagnosed depression Singh NA. et al. A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults. The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences 25 Jun; Vol. 6 (6), pp Singh NA. et al. 25 Depression and Resistance Training Type 2 Diabetes Singh NA. et al. 25 Exercise improves insulin resistance Beneficial for preventing and treating type 2 diabetes 3-5% incidence prevented Aerobic exercise hindered in older, obese, co-morbid patients Resistance exercise safe and effective Willey and Singh. Diabetes Care, 23 1 Alzheimer s Disease Exercise application across spectrum of problem: Reducing risk in general population prophylactic Reversing or slowing progression in early stage Maintaining QOL, structure and function in later stages Exercise and risk of Dementia 12 Population based-study (n=17) 6.2 years follow up Incidence rate of dementia was 13. per 1 person-years (exercise 3 or more times week) 19.7 per 1- person-years (exercise fewer than 3 times week) Exercise is associated with a delay in onset of dementia and Alzheimer's disease Support the effect of exercise beyond musculoskeletal and cardiovascular benefits Larson et al. Ann Intern Med 1:

3 18/8/211 Cancer in Australia 11, new cases of cancer diagnosed in Australia in in 2 Australians will be diagnosed with cancer by the age of 85. Cancer is a leading cause of death in Australia more than 3, people Australian Institute of Health and Welfare Australian Cancer Incidence and Mortality are estimated (ACIM) books 21 to have died from cancer in 21. prevention/detection prescreening screening prediagnosis Physical Activity & Cancer Control Framework DIAGNOSIS treatment preparation CANCER CONTROL CATEGORIES treatment effectiveness recovery postdiagnosis disease palliation prevention pretreatment treatment survivorship end of life Courneya and Friedenreich Sem Onco Nurs 27;23:22-52 Specific phases along the cancer continuum cancer-related time periods survival Physical activity and cancer risk Survival Physically inactive - nearly twice as likely to develop colon cancer 1 Active - 3% reduction in the risk of women of all ages developing breast cancer 2 Reduces prostate cancer incidence of advanced forms and in older men - 7% reduction if >3 hours vigorous per week 3 2 % reduction in risk of Lung cancer Cancer Survival: Time to Get Moving? Data Accumulate Suggesting a Link Between Physical Activity and Cancer Survival Demark-Wahnefried W. Journal of Clinical Oncology. 2(22): Colditz et al. Cancer Causes Control. 8(): Thune & Furberg. Med Sci Sports Exerc. 33(6 Suppl):S Patel et al. Cancer Epidemiol Biomarkers Prev. 1(1): Lee & Oguma. Cancer Epidemiology and Prevention. 3rd ed. University Press, 26 Exercise and Breast Cancer Survival 2987 female nurses who were diagnosed with breast cancer RR of death.5 to.6 < 3 MET-hours per week compared 9 or more. One MET-hour is equivalent to approximately 1 hour of walking at a normal pace. women with breast cancer who follow the US physical activity recommendations may improve their survival. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA. 293(2): Exercise and colorectal cancer survival Colorectal cancer patients <3 MET-hours per week of PA compared to 18+ Adjusted hazard ratio for disease-free survival.51 to.55. Benefit not influenced by sex, BMI, age, or chemotherapy received. physical activity appears to reduce the risk of cancer recurrence and mortality. Meyerhardt JA, et al. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2(22): Meyerhardt JA, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB J Clin Oncol. 2(22):

4 18/8/211 Exercise and Prostate Cancer Survival Compared to Chemotherapy Men with 3 hours per week of vigorous activity had a 9% lower risk of all-cause mortality. 61% lower risk of PCa death Kenfield et al. Physical Activity and Survival After Prostate Cancer Diagnosis in the Health Professionals Follow-Up Study. Journal of Clinical Oncology, 211. Data from these studies suggest a reduced risk of recurrence of 5% to 6%. Such an effect parallels that of trastuzumab for HER-2 positive breast cancer patients, an agent heralded by the oncologic care community and by the Director of the National Cancer Institute, Andrew C. von Eschenbach, MD, as a major advance and turning point in eliminating suffering and death from cancer. Demark-Wahnefried W. Journal of Clinical Oncology. 2(22): Fitness NOT Fatness Relative Risk of Death BMI vs Fitness

5 18/8/211 Don t die of something else! 28 Cancer, heart attack, stroke, back pain, bad knees, crook hips, diabetes... Your physiology does not care! Other chronic disease processes march on. Injury and disability will only exacerbate with rest strategy Stay active regardless the alternative is worse! There is no pharmacological intervention that holds a greater promise of improving health and promoting independence in the elderly than does exercise Evans & Campbell, Journal of Nutrition, 1993 Thank You r.newton@ecu.edu.au 5

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9 8/28/ ; /. ( / Level of Evidence, ; Percent (%) Overwhelming (A) Safety Overwhelming (A) Aerobic Fitness Overwhelming (A) Aerobic Fitness Overwhelming (A) Muscle Strength Overwhelming (A) Muscle Strength Overwhelming (A) Physical Function Emerging (B) Physical Function Overwhelming (A) Fatigue Emerging (B) Fatigue Emerging (B) Body Comp Emerging (B) Body Comp Emerging (B) Quality of Life Emerging (B) Quality of Life Emerging (B) Anxiety Emerging (B) Anxiety Emerging (B) Body Image Emerging (B) +, A 6 -- (! Chemotherapy + Radiation Safety - 7 &) &'" A Level of Evidence 7 7 3, Surgery Only 9 Radiation Only 9 Obese Patients Normal Weight Patients -1 /& -2 /:& /& -3 - ;& $%& -5-6 G 'P5, %P5, ) 6 -- E ;,!< 3 J J L 3

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11 8/28/211 Relative Risk 1% 9% 8% 7% 6% 5% % 3% 2% 1% % -21% -2% < >17.3 Cardiorespiratory fitness Category Jones et al, Cancer 21 QOL 2 """ Sedentary Low Activity Meeting Guidelines 5& 56& Coups et al, 29. " )"" + ", ) 7) 18 " ", " + " + " / ) 9, '$%5) 1 : ") 1," "" ;""< Jones et al, Cancer, Quality of Life Fatigue Baseline Follow-Up Fat %6 $ %=$) 1 Weight (kg) Chest Press Leg Press Baseline 1-Weeks m Six-Minute Walk Distance Baseline 1-Weeks No. Chair No. Chair Stands No. Arm Curls Stands Up and Go Time (s) Baseline 1-Weeks Peddle-McIntyre et al, Lung Cancer, in Press 2

12 8/28/211 I knew I was in desperate need of physical activity, however did not know where or how to safely start. I was tired, and becoming more tired. Every day activities were getting increasingly difficult. I feel well and emotionally I am happier, although I still have to keep working on becoming stronger and more active. Female lung cancer survivor,"" 3," - +. : +, +, 3 +, + $ > 39!!"$%&'!(%)!(+!)%!($,-%.%!.$&)!+/ "!+!&-!?32 -?3@. :2 3

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16 Established Risk Factor Prostate cancer is largely associate with aging Physical Exercise and Prostate Cancer Survivorship 85% 65 years Daniel Galvão, Director ECU Stage Distribution Five-year Survival Rates Common Treatments Stage Distribution (%) 5-year Survival (%) Localised Distant Localised Distant All stages Active surveillance Prostatectomy Radiation therapy Androgen deprivation Chemotherapy non treatment surgical removal external/brachytherapy LHRHa, orchiectomy antiandrogen metastatic castration-resistant! " Common Adverse Effects Radiation Prostatectomy sexual dysfunction (impotence) urinary dysfunction (incontinence) bowel dysfunction fatigue urinary dysfunction (incontinence) sexual dysfunction (impotence) Hormone Treatment Androgen deprivation (ADT) Eliminates testosterone production (LHRHa) Improve survival in locally advanced disease and palliate metastases Increasingly used in the management of PCa ADT Reduces Testosterone PCa Control Chemotherapy cardiovascular, infection, nausea, diarrhea, fatigue Treatment Side Effects Catalona et al. CA Cancer J Clin 1999; Michaelson et al. CA Cancer J Clin 28; Petrylak et al. N Engl J Med 2 Sharifi et al. JAMA 25;29:238-1

17 PSA, Testosterone, Muscle/Fat Changes at 36 weeks n = 25 n = 72 Baseline Multi-site National Study Intermittent Androgen Suppression Western Australia Sir Charles Gairdner Hospital Maximal Androgen Blockage 36 weeks Variables Baseline 36 weeks % change PSA 22.6 (3.1).23 (.5) (.5) Testosterone 15.1 (.6).8 (.3) (.3) Whole body LM (kg) 55.8 (.8) 5. (.8) -2. (.) ASM (kg) 23. (.3) 22. (.3) -.2 (.5) Whole body FM (kg) 2.8 (.7) 23.1 (.7) (2.3) Trunk FM (kg) 12.1 (.) 13.1 (.) +12. (2.5) (Eulexin 25mg TDS, Lucrin 22.5mg depot) Galvão et al. British Journal of Urology International 28;12:-7 Galvão et al. British Journal of Urology International 28;12:-7 p<.1 Long-term DXA Changes Absolute Change (Kg) itreat phase kg FAT POST phase baseline level -1.5 kg Muscle itreat POST 26% failed to recover at 2 months Odds of regaining eugonadal levels of testosterone reduced by 5% if 7yr Months from BL Whole Body Fat Whole Body Lean Spry et al. British Journal of Urology International 29;1(6):86-12 DXA BMD Regional Changes Cancer Treatment-Induced Bone Loss BMD 9 months change Lumbar spine -3.9% Total Hip -1.5% Upper limb -1.3% Lower Limb -.6% p<.1 Galvão et al. British Journal of Urology International 28;12:-7 Higano C. Nature Clinical Practice Urology 28;5:2-3 2

18 Prevalence of Osteoporosis Baseline & Yrs On ADT Percentage of patients Androgen deprivation therapy duration (years) Overall prevalence of osteoporosis, osteopenia, and normal BMD according to ADT duration. Patients had not received ADT at time of BMD measurement. Morote et al. Urology 27;69: 5 5 Relationship Between BMD & Fracture Risk Fracture risk Osteoporosis Osteopenia BMD T-score, SD units Impaired physical function and balance Reduced upper and lower body muscle strength Shahinian et al. New England Journal of Medicine 25;352:15-6 Galvão et al. Prostate Cancer Prostatic Dis. 29;12(2): Surveillance, Epidemiology and End Results (SEER) and Medicare database; records from local and local regional Increased risk associated with Androgen Suppression Diabetes % Coronary heart disease 16% Myocardial infarction 11% Sudden death 16% Alibhai et Journal of Clinical Oncology 21;28(3):538-5 Keating et al. Journal of Clinical Oncology 26;2:

19 Decline in Physical Reserve Capacity recognizes the metabolic and cardiovascular risks associated with androgen suppression as significant adverse effects Musculoskeletal Fitness Physical Reserve Capacity Disability Condition Age, years Normal Aging ADT Treated Men ADT Sarcopenia-Related Disorders Circulation 21 Feb;121(6):833-) & CA Cancer J Clin 21 May;6(3):19-21 Galvão et al. Prostate Cancer & Prostatic Diseases 27;1():3-6 Current Available Treatments Bisphosphonates are the only established treatment to reverse low BMD (additional toxicities) NO established treatment to reverse body composition alterations, physical function decline, risk factors for metabolic, cardiovascular complications and frailty during ADT What Can Exercise Offer? Symptoms toxicities PSA fatigue quality of life muscle function physical performance (balance) aerobic capacity body composition no adverse effects Galvão & Newton. J Clinical Oncology 25;23: Segal et al. JCO 23 Resistance Exercise in Hypogonadal Men (ADT) baseline week 1 week 2 prostate cancer patients on ADT - resistance training exercise group improved symptoms of fatigue and health-related quality of life compared to the non-exercise group moderate intensity short time period can confer substantial benefits Strength Change (kg) % 2% Chest press Seated row p<.1 Segal et al. J Clinical Oncology 23: $%&''()+

20 Resistance Exercise in Hypogonadal Men (ADT) Percent Change (%) % 1% 7% 22% 1% 5% Chair rise Stair Climb -m w alk $%&''()+ 6 m backw ard w alk 6 m usual w alk 6 m fast w alk p<.5 Treatment Design ADT (2% Radiation) RCT Sample 57 Intervention Protocol Primary endpoint 12-week (2x) resistance & aerobic 2- sets 6-12RM 15-2 min 6-85%MHR 1-13RPE lean mass Galvão et al. J Clinical Oncology 21;1;28(2):3-7 DXA Regional and Whole Body Composition Kilograms Adjusted group difference in mean change (95%CI) over 12 weeks ANCOVA (baseline, ADT time, antiandrogen, medications, education) p=.7 (.1-1.5) p=.3 ( ) p< ) p=.19 (.9-1.) Quality of Life: SF-36 Profile Units Adjusted group difference in mean change (95%CI) over 12 weeks 17 ANCOVA (baseline, ADT time, antiandrogen, medications, education) p=.22 p=.19 ( ) ( ) p=.96 ( ) Whole Lean ASM Upper Lean Lower Lean Whole Fat -3-8 Physical Role-P Pain G Health Vitality Social Role-E M Health PHC MHC Galvão et al. J Clinical Oncology 21;1;28(2):3-7 Galvão et al. J Clinical Oncology 21;1;28(2):3-7 Summary of key Results Acute Versus Chronic Exposure to Androgen Suppression Lean Mass +1kg EX>CO Muscle Strength +5-31kg EX>CO Aerobic Capacity -7sec EX>CO Dynamic Balance -sec EX>CO General Health +12 EX>CO Vitality +12 EX>CO Fatigue -11 EX>CO CRP -3.5 mg/l EX>CO Galvão et al. J Clinical Oncology 21;1;28(2):3-7 Galvão et al. Journal of Urology 211 5

21 Increases Physical Reserve Capacity Musculoskeletal Fitness Physical Reserve Capacity Disability Condition Normal Aging ADT Treated Resistance Trained ADT treated Age, years ADT Sarcopenia-Related Disorders Perth, Joondalup, Nedlands, Fremantle, Mandurah, Bunbury, Brisbane (QLD) Perth, Fremantle, Joondalup, Mandurah, Bunbury, Newcastle, Nelson Bay, Maitland, Wellington (NZ) Galvão et al. Prostate Cancer & Prostatic Diseases 27;1():3-6 Newton et al. BMC Cancer 29 Jun 29;9:21; Galvão et al BMC Cancer 29 Dec 2;9:19 Position Stand First position statement on exercise for cancer survivors Comprehensive review over 7 studies Broad prescription incorporating low to moderate intensity, regular frequency (3-5 times/week) for at least 2 minutes per session involving aerobic, resistance or mixed exercise modes Some is better than none more is better than less Hayes et al. J Science Medicine Sport 29;12: Guiding Accredited Exercise Physiologists (AEPs), who are -year university trained allied health professionals (registered with Medicare Australia) specializing in the delivery of exercise programs for the prevention management of chronic diseases, to work with cancer patients More EPs are trained in this clinical exercise area and cancer survivors nationally are benefiting from this highly translational research Hayes et al. J Science Medicine Sport 29;12: Prostate Cancer During and after treatment Effects of exercise on key endpoints Results from 12 RCTs Focus on adult cancers and sites with the most evidence Evaluation of Evidence A-D Breast, Prostate, Colon, Hematological, Gynecological A - overwhelming data from RCTs B - few RCTs exist C - uncontrolled, nonrandomized and/or observational studies D - insufficient for categories A-C Evidence category A Safety Evidence category A Aerobic Fitness Evidence category A Muscle Strength Evidence category A Fatigue Evidence category B Body Size/Composition Evidence category B Quality of Life Evidence category B Physical Function Schmitz et al. American College of Sports Medicine Med Sci Sports Exerc. 21;2(7): Schmitz et al. American College of Sports Medicine Med Sci Sports Exerc. 21;2(7):

22 Guidelines to Implement Exercise Programs Exercise is safe during and after cancer treatments Results in improvements in physical functioning, QoL and cancerrelated fatigue in several cancer survivor groups Implications for disease outcomes and survival are still unknown Cancer survivors follow PA Guidelines, with specific exercise programming adaptations based on disease and treatment-related adverse effects Advice to avoid inactivity, even in cancer patients with existing disease or undergoing difficult treatments, is likely helpful Schmitz et al. American College of Sports Medicine Med Sci Sports Exerc. 21;2(7): Translation of Research: Vario Wellness Clinic Cancer Survivors Program Life Now Cancer Council WA Diabetes Program Weight loss for Wellness Living Longer Living Stronger Fighting Fit Veterans Osteoporosis Program Weight to Go Kids Research Support: Thank You! Health and Wellness Institute Edith Cowan University Building Telephone: Internet: 7