Exercise as Medicine for Cancer Management Robert U. Newton, PhD
What is Anabolic Exercise? Repetitive movements performed against resistance Resistance limits number completed e.g. 10 reps per set (10RM) Heavier loads result in less repetitions to failure Different RM ranges result in vastly different structural and functional adaptations
What is Aerobic Exercise? Emphasizes cardiorespiratory system Longer duration exercise involving large muscle groups in repetitive actions Continuous or intermittent 20 minutes or longer at 60% HRmax or higher Jogging, rowing, cycling, swimming, walking
Survival! Cancer Survival: Time to Get Moving? Data Accumulate Suggesting a Link Between Physical Activity and Cancer Survival Demark-Wahnefried W. Journal of Clinical Oncology. 24(22):3517-8. 2006.
Exercise and Breast Cancer Survival 2987 female nurses who were diagnosed with breast cancer RR of death 0.5 to 0.6 < 3 MET-hours per week compared 9 or more. One MET-hour is equivalent to approximately 1 hour of walking at a normal pace. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA. 293(20):2479-86. 2005
Relative risk of death from breast cancer Exercise for breast cancer survival 1 0.8 20% 50% 46% 40% 0.6 0.4 0.2 0 <3 MET hrs/wk 3-8.9 MET hrs/wk 9-14.9 MET hrs/wk 15-23.9 MET hrs/wk 24 MET hrs/wk < 1 hr activity 1-3 hrs activity 3-5 hrs activity 3-5 hrs mod.- vig. activity >5 hrs mod.- vig. activity Holmes et al. Journal of the American Medical Association, 2005
Exercise for colorectal cancer survival Colorectal cancer patients <3 MET-hours per week of PA compared to 18+ Adjusted hazard ratio for disease-free survival 0.51 to 0.55. 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. 24(22):3527-34. 2006. Meyerhardt JA, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol. 24(22):3535-41. 2006.
Exercise and Prostate Cancer Survival Men with 3 hours per week of vigorous activity had a 49% 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, 2011.
Compared to Chemotherapy Data from these studies suggest a reduced risk of recurrence of 50% to 60%. 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. 24(22):3517-8. 2006.
Side Effects from Hormone Treatment (ADT) for Prostate Cancer Poor balance Decline in Physical Capacity Strength decline Fatigue ADT Hormone Muscle loss Metabolic Syndrome Osteoporosis Skeletal Fractures Cardiovascular morbidity
Variables Baseline 36 weeks % change PSA 22.6 (3.1) 0.23 (0.05) -98.2 (0.5)* Testosterone 15.1 (0.6) 0.80 (0.03) -93.3 (0.3)* Whole body LM (kg) 55.8 (0.8) 54.4 (0.8) -2.4 (0.4)* ASM (kg) 23.4 (0.3) 22.4 (0.3) -4.2 (0.5)* Whole body FM (kg) 20.8 (0.7) 23.1 (0.7) +13.8 (2.3)* Trunk FM (kg) 12.1 (0.4) 13.1 (0.4) +12.0 (2.5)* Galvão, Newton et al. British Journal of Urology International 2008;102:44-47
Clinical Exercise Trials - Prostate Cancer
Galvão, Newton et al. 2006 Treatment Design ADT UCT Sample 11 Intervention Protocol 20-week (2x) resistance 2-4 sets 6-12RM Primary endpoint muscle function Main results muscle fun. physical perf. balance muscle thickness body composition Galvão, Newton et al Med Sci Sports Exerc 2006;23:899-909
Strength Change (kg) Galvão, Newton et al. 2006 baseline week 10 week 20 60 50 40 30 20 10 40% 42% * 0 Chest press Seated row * p<0.001 Galvão, Newton et al Med Sci Sports Exerc 2006;23:899-909
Treatment Design ADT (24% Radiation) RCT Sample 57 Intervention Protocol Primary endpoint 12-week (2x) resistance & aerobic 2-4 sets 6-12RM 15-20 min 60-85%MHR 10-13RPE lean mass Galvão et al. J Clinical Oncology 2010;10;28(2):340-7
Summary of key Results Lean Mass ~1kg EX>CO Muscle Strength 5-31kg EX>CO Aerobic Capacity -7 sec EX>CO Dynamic Balance -4 sec EX>CO General Health +12 EX>CO Vitality +12 EX>CO Fatigue -11 EX>CO CRP -3.5 mg/l EX>CO NO change in PSA or testosterone in either group Galvão, Newton et al. J Clinical Oncology 2010;10;28(2):340-7
Percent Change (%) Resistance Exercise and ADT 35 30 27% 10% 7% 22% 14% 5% * 25 20 15 10 5 0 Chair rise Stair Climb 400 -m w alk Galvão, et Newton al Med et Sci al. Sports J Clinical Exerc Oncology 2006;23:899-909 2010;10;28(2):340-7 6 m backw ard w alk 6 m usual w alk 6 m fast w alk * p<0.05
Regional and Whole Body Composition Kilograms Adjusted group difference in mean change (95%CI) over 12 weeks ANCOVA (baseline, ADT time, antiandrogen, # medications, education) 0.9 0.8 p=.047 (0.01-1.5) p=.003 (0.29-1.3) 0.7 0.6 0.5 p=.019 (0.09-1.0) 0.4 0.3 p<.001 (0.11-0.42) 0.2 0.1 0-0.1 p=.964 (-0.82-0.79) Whole Lean ASM Upper Lean Lower Lean Whole Fat Galvão, Newton et al. J Clinical Oncology 2010;10;28(2):340-7
Further Side Effects from Hormone Treatment (ADT) for Prostate Cancer Poor balance Decline in Physical Capacity Strength decline Fatigue ADT Hormone Muscle loss Metabolic Syndrome Osteoporosis Skeletal Fractures Cardiovascular morbidity
Cancer Treatment-Induced Bone Loss Higano C. Nature Clinical Practice Urology 2008;5:24-34
Percentage of patients Prevalence of Osteoporosis Baseline & Yrs On ADT 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. 2007;69: 500 504.
Newton, Galvão et al. BMC Cancer 2009;9:210
Impact Exercise for Bone Health
Lumbar spine BMD (% change over 6 months) Newton et al 2013 In Review
Bone Metastases Funded PCFA 2012-2013
Exercise for lymphoedema Lymphoedema affects ~20-30% of breast cancer survivors Historically upper body exercise has been discouraged for women who have or are at risk of lymphoedema for fear of exacerbating the condition L-Dex Score 50 40 30 20 10 Acute Impact of Exercise on Lymphoedema Bioimpedence Spectroscopy Heavier Weights Lighter Weights Change in L-Dex Score 6 4 2 0-2 -4 Impact of Regular Exercise on Lymphoedema Bioimpedence Spectroscopy 0 Pre Immediately Post 24 hours Post 72 hours Post -6 Cormie et al. 2013 Heavier Weights Lighter Weights No Exercise
Exercise for lymphoedema A bout of resistance exercise does NOT cause an increase in swelling or worsening of symptom severity This is the case for both heavier & lighter weights Regular resistance exercise over 3 months results in: swelling (i.e. does NOT increase swelling) strength physical function Similar effects observed for both heavier & lighter weights Cormie et al. 2013 Percent Change (%) Percent Change (%) 80 60 40 20 0 50 40 30 20 10 0 Chest Press 1RM * * Heavier Weights Lighter Weights No Exercise Seated Row 1RM * * Heavier Weights Lighter Weights No Exercise
Exercise for Sexual Health
Exercise for Sexual Health
First guidelines of exercise prescription for cancer survivors Comprehensive review of over 70 studies (large majority of trials in Breast Cancer) Attempt some exercise - minimum every second day preferably most days of the week regardless of disease stage or current treatment
Generic Exercise Prescription Mode Aerobic Dosage 150min per week moderate intensity (RPE 5-6 out of 10) or 120min per week vigorous intensity (RPE 7-8 out of 10) Resistance 6-10 exercises 6-12RM 2-3x per week 3-4 sets per exercise Nelson et al. Med Sci Sports Exerc 39:1435-45, 2007
Thank You r.newton@ecu.edu.au