Oncology Exercise: The Prescription and why STAR Programs need PMR MDs on the TeamNancy Hutchison, MD
Medical Director Cancer Rehabilitation and SurvivorshipVirginia Piper Cancer InstituteCourage Kenny Rehabilitation InstituteAllinaHealthMinneapolis, MN
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• Prehab– Physically frail individuals have higher morbidity and
mortality from cancer treatment– Exercise and nutritional interventions designed to build
muscle improve outcomes• During treatment– Physical activity during chemotherapy has positive effects
on physical outcomes• Post treatment– Physically active cancer survivors have a lower risk of
cancer recurrences and improved survival compared with those who are inactive
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Strong evidence for positive effect of physical activity at all phases of cancer treatment
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• 2.5 hours/week moderate-intensity (50-70%APHRmax) or
• 1.25 hours/week vigorous-intensity (70-85%APHRmax)
• Adapted to impairment
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ACSM Recommendations for Exercise with Cancer Survivors
Schmitz KH. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42(7):1409–26.
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• To stay alive, the body has to be able to deliver enough oxygen to enough metabolically active skeletal muscle for ATP synthesis by muscular contraction driving energy production
• VO2 peak/max is an objective measure of cardiopulmonary fitness– Stands for maximal oxygen consumption, maximal oxygen
uptake, peak oxygen uptake or maximal aerobic capacity
– Varies between individuals
– Inversely associated with death in cancer patients and healthy individuals
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Any impairment of the O2 transport chain makes the body less able to use O2
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• Anticancer therapies (various types of chemo, hormonal therapies, biologic therapies and radiation) cause reduced function at multiple parts of the O2 transport system
– Pulmonary
– Cardiac muscle
– Skeletal muscle (reduced oxidative phosphorylation)
– Vascular (arterial stiffness)
– Hematologic (blood-anemia)
– These injuries, in conjunction with indirect lifestyle effects (inactivity) “synergistically cause marked impairments.”
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Inactivity and subclinical organ system damage: the “multiple hit”
Jones, L. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol . 2007. 50: 1435-1441
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• Physical activity has positive effects on physiology, body composition, physical functions, psychological outcomes, BMI, peak oxygen consumption, peak power output, and quality of life• “Exercise therapy is a well-tolerated and safe
adjunct to [cancer]therapy that can mitigate several common treatment-related side effects among cancer patients “
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Physical activity is necessary for the energy system of the body to function
Fong, D. Physical activity for cancer survivors: meta-analysis of randomisedcontrolled trials. BMJ 2012;344:e70Jones, L. Exercise-oncology research: Past, present, and future. Acta Oncologica, 2013; 52: 195–215
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• Latent and anticipated treatment morbidity, causing reduced functional organ reserve, can lead to late organ failure that would be reduced or eliminated by early intervention
• Think prehab
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Latent disease is the new paradigm in physical survivorship care
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• Cardiovascular reserve capacity assessment by resting ECHO is not prognostic • Ejection fraction does not correlate with VO2
max• Despite normal LVEF, cardiorespiratory fitness
was shown to be significantly impaired in patients with early breast cancer a mean of 3 years after completion of treatment compared to same age women with no history of breast cancer
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Static assessment does not reflect functional capacity
Koelwyn, G. Running on empty: cardiovascular reserve capacity and late effects of therapy in cancer survivorship. (2012) December. JCO 30(36):4458-4461
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• MET= estimate of the metabolic cost of an activity
• One MET = 3.5 ml/kg/min is resting energy consumption
• VO2/3.5 = MET
• VO2 of 1 l/min expends about 5 kcal of energy (depends on what is used for ATP production: glucose, fatty acids)
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Metabolic Equivalent (MET)
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• Light: 1-3 METs – light meal prep, sponge bathe, walk 2 mph
• Light-Moderate: 3-4 METs – shower, drive, walk 3 mph
• Moderate: 4-5 METs – raking leaves, walk 3.5 mph, bicycle 8 mph, sexual
intercourse, occasional lifting under 50#• Heavy: 5-7 METs – shoveling snow, walk 4-5 mph, tennis, frequent
lifting/carrying over 50#• Very Heavy: >7 METs – moving heavy furniture, running 5 mph, swimming laps,
frequent lifting/carrying >50#
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Energy Cost of Various Activities
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Activity METs/hour
Walking slowly < 2 mph 2
Light gardening 2
House cleaning 2
Walking briskly 3 mph 3.3
Heavy yard work or gardening 4
Stair climbing 4
Bicycling <10 mph 4
Shoveling snow 6
Rowing or kayaking 6-8
Aerobic calisthenics 6-10
Swimming crawl, slow 8
Bicycling 10-16 mph 6-10
Running 8 mph 13.511
METs/hour: Physical Activity
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• 71 prospective studies analyzing the effect of physical activity on cancer mortality
• Confirmed benefit 3-6 MET-h/week of physical activity after cancer diagnosis provides significant protective effect
• Cancer survivors who completed 15 MET hours/week of physical activity had 27% lower risk of cancer mortality
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Physical Activity: amount matters
Li, T. DoseResponseEffectPhysActivCaMortality.2016 BrJSportsMed. 50(6):339-45
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• Physical Activity: Good– Non-specific, uses skeletal muscles, expends energy
• Exercise: Better– Specific, planned, repetitive
The goal of exercise is to improve physical fitness of a specific system
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Exercise and Cancer: Beyond Activity
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• Improved survival?
• Reduced morbidity?
• Improved aerobic capacity?
• Increase in lean muscle?
• Decrease in fat?
• Weight loss?
• Well being?
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If exercise improves physical fitness, what is the goal of physical fitness?
Depends on the type and amount of exercise
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• Exercise prescription specificity allows goal setting• If the goal is – to reduce long term mortality by 30%, prescribe 15
MET hours/week activity– weight loss, prescribe a regimen that has been
shown to induce weight loss and change body composition
– reduced morbidity/mortality from upcoming surgery, prescribe a regimen that builds the metabolic engine, the muscles
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Goal mismatch = unmet goals
Hirschey, R. Exploration of Exercise Outcomes among Breast Cancer Survivors. 2016. Cancer Nursing. DOI: 10.1097/NCC.0000000000000362
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“It is clear that, when correctly prescribed, exercise possesses potent pleiotropic drug-like effects that can dramatically alter host and tumor phenotypes”
Jones L and Dewhirst M. Therapeutic Properties of Aerobic Training After a Cancer Diagnosis: More Than a One Trick Pony? Journal National Cancer Institute. 2014;106(4)
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Exercise oncology: exercise modulation of tumor microenvironment
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• Increase aerobic fitness• Increase muscle strength• Reduce body weight• Improve body composition• Stimulate lymph flow• Improve flexibility• Decrease fatigue• Improve well-being
The intervention and dose have to be individualized and specific for the desired effect, like a medication
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Effects of Exercise: determined by exercise type
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Principles of Exercise Training to Increase Fitness
Exercise Training Principle Definition
Individualization specific % of peak workload specified for that individual
Specificity training specific to the system you want to change
Progression increase in intensity to avoid adaptation
Overload workload must be greater that what already doing
Reversibility when intervention removed, return to baseline
Diminishing returns degree of improvement decreases with fitness, requiring increased effort for further improvement
Initial Values improvement greatest with lower initial
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Component of exercise prescription (FITT) Definition
Frequency number of times per week
Intensity prescribed intensity (ex: #RM, VO2, Borg, HR, ROM limits)
Time duration
Type Aerobic, Resistance, Stretching
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Components of an Exercise Prescription: FITT
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Training Principle %Aerobic Studies %Resistance Studies %Mixed Studies
Specificity 64 100 75
Progression 50 67 25
Overload 28 33 25
Initial Values 50 100 67
Diminishing Returns 21* 21* 21*
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Cancer Exercise Research: adherence to training principles
*only 21% of all studies reported results from follow up after interventionMajority of studies did not repeat all outcome measures at completion
Campbell, K. Review of exercise studies in breast cancer survivors: attention to principlesof exercise training. Br J Sports Med 2012;46:909–916.
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FITT Exercise Prescription Component % of studies reporting
Frequency 97
Intensity 79
Time 79*
Type 79**
Adherence 0
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Cancer Exercise Research: adherence to FITT prescription
1/3 of studies failed to report a minimum of one component of the FITT prescription making the intervention impossible to replicate
*100% of resistance studies, but not of aerobic/mixed reported Time
** some studies did not state the type of aerobic intervention
Campbell, K. Review of exercise studies in breast cancer survivors: attention to principlesof exercise training. Br J Sports Med 2012;46:909–916.
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• Non-linear training has been shown superior in sports medicine and needs to be researched in oncology to find the optimal regimen for desired effects.
• A study of colorectal cancer survivors with HIE (with intervals 85-95% Max HR) was found to elicit increases in lean mass as well as decreased body mass and fat, but no changes were associated with MIE– HIE had significantly greater increase in aerobic capacity than MIE
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Interval training as new exercise principle
Sasso, A framework for prescription in exercise-oncology research. Journal of Cachexia, Sarcopenia and Muscle 2015; 6: 115–124
Devin, J. The influence of high-intensity compared with moderate-intensity exercise training on cardiorespiratory fitness and body composition in colorectal cancer survivors: a randomized controlled trial.J Cancer Surviv (2016) 10:467–479.
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• In spite of strong evidence translated into NCCN, ACS, ASCO guidelines, most cancer survivors do not meet recommended exercise guidelines
• Most cancer survivors reduce activity after cancer treatment• Many cancer survivors have risk factors that are barriers for
recommended exercise guidelines• Oncologists and primary care providers are uncomfortable
prescribing exercise interventions in proscribed guidelines
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Considerations for exercise as intervention in cancer care
Sabatino, SA.Provider counseling about health behaviors among cancer survivors in the US.JCO 2007;25(15):2100-2106
Mizrahi, D. Quantifying physical activity and the associated barriers for women with ovarian cáncer. Int J Gynecol Cancer 2015;25: 577-583
Mols, F. Chemotherapy-induced peripheral neuropathy, physical activity and health-related quality of life among colorectal cancer survivors from the PROFILES registry. 2015. JCaSurviv. 9(3):512-22
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• In a study on pre-exercise risk assessment for cancer survivors the authors summarized the concern:
• 90% of cancer survivors have at least one comorbid condition
• 39% have cardiac-specific comorbid conditions
• 53% of cancer survivors have functional limitations as a result of comorbid conditions
• 63% of cancer survivors report a need for rehabilitation
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Exercise is relatively safe but does have risk of adverse events
Brown, J. Development of a Risk-Screening Tool for Cancer Survivors to Participate in Unsupervised Moderate- to Vigorous-Intensity Exercise: Results From a Survey Study. PM R 7 (2015) 113-122
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• Brown et al synthesized the peer-reviewed guidelines for exercise and cancer survivorship
• Looked at 82 health factors that may warrant a pre-exercise evaluation before the survivor starts unsupervised moderate- to vigorous-intensity exercise– clinical health factors– comorbidity and device health factors– Medications
• Surveyed experts (oncologists, physiatrists, PT, OT, exercise physiologists, researchers, epidemiologists)
• Of the 50 health factors in the 3 domains, 41 (82%) were identified as needing a pre-exercise medical evaluation before the survivor engaged in unsupervised moderate- to vigorous-intensity exercise
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Cancer Exercise Risk Assessment: Beyond Cardiopulmonary
Brown, J. Development of a Risk-Screening Tool for Cancer Survivors to Participate in Unsupervised Moderate- to Vigorous-Intensity Exercise: Results From a Survey Study. PM R 7 (2015) 113-122
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• NCCN algorithm: – includes evaluation of health status, comorbidities and
environmental barriers • Categories of Risk:– Low: high baseline physical activity and no
comorbidities– Moderate: peripheral neuropathy, arthritis and msk
“issues”, poor bone health, lymphedema– High: history of abdominal surgery or lung surgery,
ostomy, cardiopulmonary comorbidities (CAD, COPD, etc), extreme fatigue, ataxia, severe nutritional deficiencies, worsening or changing physical condition
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NCCN Physical Activity Guidelines: algorithm for evaluation and prescription
NCCN Survivorship Guidelines v1.2016 Physical Activity
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NCCN Physical Activity Recommendations by Risk Category
Risk Category NCCN Specific Recs Follow up
Low Gen PA* Periodic re-eval by recommending provider
Medium Gen PA* + Consider Med Eval & Consider Trained Personnel
Specificguidelines for lymphedema, neuropathy, fatigue, poor bone health
Recommending provider sets and follows ex prescription goals, increases and re-evals
High MedicalClearance Required& Trained Personnel Required
Specific guidelines for above + ostomy, stem cell transplant
Recommending provider sets and follows ex prescription goals, increases and re-evals
*General physical activity guidelines for cancer survivors
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• Wolin (2012) identified that exercise as a standard of care in oncology requires development of an infrastructure where patients can be referred to qualified professionals to prescribe
• Brown et al (2014) showed that only 21% of CRC survivors were able to be prescribed unsupervised exercise at the dose recommended by ACS/ACSM/NCCN at 6 months post treatment
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Current guidelines for cancer exercise require qualified rehab professionals for most survivors
Wolin, KY Implementing the exercise guidelines for cancer survivors. J Support Oncol. 2012;10(5):171-177
Brown, J Prescription or Proscription of Exercise in Colorectal Cancer Care. Med Sci Sports Exerc.2014;46(12): 2202–2209.
Jones LW. Evidence-based risk assessment and recommendations for physical activity clearance: Cancer. Appl Physiol
Nutr Metab. 2011;36: S101-S112.Jones LW. Pre-exercise screening and prescription guidelines for cancer patients. Lancet Oncol. 2010;11: 914-916
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• In order to prescribe exercise and assess risk vs benefit– Know correct evaluation test
• Most important is measure of cardiopulmonary fitness/oxygen transport system
– Know parameters of normal
– Know how to utilize results to recommend intervention
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Using Principles of Overload and Initial Values
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• Measures oxygen uptake (VO2) by peripheral tissues (reported as ml/kg/min)
• Differs from cardiac stress test in use of spirometer and gas analyzers of expired air
• During exercise VO2 increases with work load
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CPET: Cardiopulmonary Exercise Test measures all components of O2 transport
Balady, G. Clinician’s Guide to Cardiopulmonary Exercise Testing in Adults. Circulation. 2010;122:191-225
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– VO2 max: increase in workload no longer increases VO2 (plateau) • Depends on age/sex • Good: 30-50, Very poor: 20-30
– VO2 peak: highest VO2 measured in the test if clear plateau is not seen
– Anaerobic threshold (AT), ventilatory threshold (VT) or Lactate threshold (reported as ml/kg/min)• Workload at which expired CO2 begins to increase exponentially
relative to the increase in VO2• Oxygen supply to the muscle is not meeting the oxygen need• Key parameter to assess adequacy of the muscle “engine”• AT active adult is 25(65-74yo) to 30(15 to 24yo), sedentary
15(65-74yo) to 30(15-24yo)
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Key CPET Concepts for Cancer Patients
Herdy, A. Reference Values for Cardiopulmonary Exercise Testing for Sedentary and Active Men and Women. ArqBrasCardiol (2011) 96(1): 54-9
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• Playing a more frequent role in the cancer setting for evaluation of cardiopulmonary fitness
• Evaluates risk of oncologic intervention• Pre and Post treatment evaluation to guide exercise
prescription• Provides risk assessment of hospital mortality/morbidity
for major abdominal surgeries (using AT)• AT is more accurate predictor of cancer treatment
mortality/morbidity than VO2 max on CPET
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It’s all about oxygen and muscle: standardize evaluation of high risk patient
Jones, L Cardiorespiratory exercise testing. 2008 Lancet
ATS/ACCP guidelines. Statement on Cardiopulmonary exercise testing. Am J Resp Crit Care Med 2003;167:211-77
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• Neoadjuvant chemotherapy reduces AT
• For some patients (particularly older, sedentary adults) chemotherapy renders them unsuitable surgical candidates with high risk of mortality
• CPET after neoadjuvant chemotherapy and prior to major abdominal or chest surgery is recommended
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The evaluation of physical fitness in cancer can mean life or death
West MA, Loughney L, Lythgoe D, et al. Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study. Br J Anaesth 2014; 114: 244–51
Jack S, West MA, Rawa D, et al. The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery. Eur J Surg Oncol 2014; 40: 1313–20
Sinclair, R. Fitness after chemotherapy. BrJAnes (2016)116(1):140
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Anaerobic Threshold (AT) by CPET Mortality
>11 ml/kg/min <1%
<11 ml/kg/min 18%
<8 ml/kg/min 50%
10-20 ml/kg/min Post op morbidity expected, may need inpatient rehab
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Correlation AT and Morbidity/Mortality Major Abdominal Surgery
Levett, D. Cardiopulmonary Exercise Testing for Risk Prediction in Major Abdominal Surgery. Anesthesiology Clin 33 (2015) 1–16Junejo, M. Cardiopulmonary Exercise Testing for Preoperative Risk Assessment before Pancreaticoduodenectomy for Cancer. Ann Surg Oncol (2014) 21:1929–1936Chandrabalan, V. Pre-operative cardiopulmonary exercise testing predicts adverse post-operative events and non-progression to adjuvant therapy after major pancreatic surgery. HPB (2013) 15, 899–907West, M. Cardiopulmonary exercise variables are associated with postoperative morbidity after major colonic surgery:a prospective blinded observational study.BrJAnes (2014) 112 (4): 665–71
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– Extrapolate from a submaximal work rate– Potential error exists because of
• 10-12 SD in beats/min for max heart rate in healthy individuals• Medications • Other variables in calculation of APMHR• Variation more prominent in cancer patients due to extended period of
autonomic dysfunction (HR response) from cancer treatment
– Can be used to assess functional capacity (walk tests)• Distance covered is a strong independent predictor of morbidity and
mortality for various disorders• Provide prognostic indicators beyond subjective performance scales
– Not sensitive enough to assess treatment effects in patients with early stage disease who do not have substantial underlying deficits
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Submaximal Tests Without Gas Exchange Measurement
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• 6MWD has best evidence for use in PT as submaximal measure of cardiopulmonary fitness
• Measure 6MWD pre and post exercise intervention• Discuss pre-post 6MWD results with the patient and
explain meaning for cancer treatment and survivorship
• Document pre-post 6MWD results with norms and significance for the patient
• The 6MWD in healthy adults is from 400 meters (438 yards) to 700 meters (765 yards)
• Improvement in 6MWD of 50 meters(55 yards) or 14% increase is meaningful clinical change
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6 Minute Walk Distance for Cancer Exercise Treatment in PT
Holland A Updating the Minimal Important Difference for Six-Minute Walk Distance in Patients With Chronic Obstructive Pulmonary Disease. Arch Phys Med Rehabil 2010; 91:221-5
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• Study looked at upper and lower cut-off of 6MWD to predict AT between 21 ml/kg/min - 11 ml/kg/min – Above 563 m (616 yd)
– Below 427 m (467 yd)
• For 8 ml/kg/min threshold AT– Above 405 m (423 yd)
– Below 269 m (294 yd)
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6 MWD and AT
Sinclair, Validity of the 6 min walk test in prediction of the anaerobicthreshold before major non-cardiac surgery. Br J Anes. 2012. 108 (1): 30–5 (2012)
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• Specific to the oncology population (breast, colon, etc) the prescribing provider must be qualified to– Assess impairments– Order and analyze laboratory, imaging and functional tests (including CPET)– Evaluate the risks/benefits of the recommended exercise– Assess cancer morbidity effects on exercise
• neuropathy, hematologic abnormalities, cardiopulmonary status, sarcopenia, malnourishment, nausea, fatigue, lymphedema, dehydration
– Implement safe modifications that will still achieve the desired effect• Prescribing provider must
– Know and adhere to exercise training principles– Prescribe according to FITT– Incorporate exercise physiology and sports medicine advances into cancer
rehabilitation– Follow patients over time to re-evaluate for status changes and updating exercise
prescription (Principle #5 Reversibility)– Understand the neuro-musculo-skeletal system as well as heart/lung
• Necessitate physician (or extender) as qualified prescriber– PMR specialty has training in all of these areas– Other medical specialties must develop proficiency to be qualified to prescribe
cancer exercise
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Qualifications for providers evaluating fitness and prescribing exercise in cancer
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– Understand how to utilize information from cardiopulmonary fitness tests
– Understand how to utilize dietary principles for reversing protein-calorie malnourishment
– Know and adhere to exercise training principles– Prescribe according to FITT– Incorporate exercise physiology and sports medicine
advances into cancer rehabilitation– Follow patients over time to re-evaluate for status
changes and updating exercise prescription (Principle #5 Reversibility)
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Cancer Exercise Prescribing Provider Must
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• Requires physician (or extender) as qualified prescriber– PMR specialty has training in all areas of physical performance and
physical function– Other medical specialties must develop proficiency to be qualified
to prescribe cancer exercise• Optimal clinic has PMR MD, PT/OT
– Collaborating with exercise physiologists, performance dieticians, psychologists, weight management specialists
– Working closely with medical and surgical oncologists for risk stratification and interventions to improve safety and outcomes from oncology treatment
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The Future Cancer Rehab Clinic
Wijeysundera, D. Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery. BMJ Open 2016;6:e010359. doi:10.1136/bmjopen-2015-010359
McMahon, A. Building bridges in dietary counselling: an exploratory study examining the usefulness of wellness andWell-being concepts (2014) JHumNutrDiet 29:75–85
Polak,R. Time for Food-Including Nutrition On Physiatrists Tables. PM R 8 (2016) 388-390
Thank you!
Nancy A Hutchison, MD
Physical Medicine and Rehabilitation
Courage Kenny Rehabilitation Institute/Virginia Piper Cancer Institute, divisions of AllinaHealth
800 East 28th Street
MR12109
Minneapolis, MN 55407
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