Exercise is a
Cancer "Drug":
WHY and HOW
do I use this in
my practice?
Gail Gamble, MD
Moderator
November 14, 2014
AAPMR Annual Assembly
Faculty Introductions
Gail Gamble, MD
Rehabilitation Institute of Chicago
Lynn Gerber, MD
George Mason University
Sam Shahpar, MD
Rehabilitation Institute of Chicago
Kim Barker, MD
University of Texas Southwestern
Andrea Cheville, MD
Mayo Clinic
Don McKenzie, MD PhD University of British Columbia
Sarah Eickmeyer, MD
University of Kansas Medical Center
Session 1: Exercise treats cancer comorbidity across the spectrum of disease:
An evidence-based discussion






Introduction – Gail Gamble, MD
Exercise and cancer-related fatigue: Evidence
base and future research directions – Lynn Gerber,
MD
Clinical consequences of debility and physical
deconditioning – Sam Shahpar, MD
An exercise prescription for cancer survivors:
Mitigating late effects and overall survival – Kim
Barker, MD
Exercise value in advanced cancer and at end of
life care – Andrea Cheville, MD
Panel for questions
Session 2: Exercise as primary cancer
intervention and personalized medicine:
Changing the culture of cancer care





Introduction – Gail Gamble, MD
The role of exercise as a prevention and treatment
strategy for cancer – Donald McKenzie, MD, PhD
Functional screening tools: Incorporating patientcentered outcomes research into cancer care –
Sarah Eickmeyer, MD
Exercise adherence in the cancer population:
Innovative strategies for behavioral change and
the role of technology – Andrea Cheville, MD
Round Table Q&A: Strategies to integrate a culture
of exercise into cancer – What is the physiatrist’s
role?
Session 1: Exercise treats cancer comorbidity across the spectrum of disease:
An evidence-based discussion






Introduction – Gail Gamble, MD
Exercise and cancer-related fatigue: Evidence
base and future research directions – Lynn Gerber,
MD
Clinical consequences of debility and physical
deconditioning – Sam Shahpar, MD
An exercise prescription for cancer survivors:
Mitigating late effects and overall survival – Kim
Barker, MD
Exercise value in advanced cancer and at end of
life care – Andrea Cheville, MD
Panel for questions
Exercise for Fatigue
Effective Treatment for
Breast Cancer Survivors
Lynn Gerber, MD
College of Health and Human
Services
Center for Chronic Illness and
Disability
CRF: Definition
•
Fatigue lasting >2 weeks, each day
•
Associated with distress and functional
loss
•
Clinical association with cancer diagnosis
and/or chemotherapy
•
Not explained by primary psychiatric
diagnosis (eg depression)
– http://www.nccn.com/files/cancerguidelines/breast/index.html#/110/
Features
• Clinical expression of CRF is multidimensional
• Fatigue may be experienced and reported differently
by each individual
• May occur as an isolated symptom or as one
component within a cluster (pain, fatigue, depression,
sleep disturbances)
• Qualitative studies of fatigue show:
– CRF experience is unlike other fatigue
– Unpredictability and refractoriness to self-management
contributes to distress
• Personality and coping style may also influence the
experience of CRF
ICD-10 Criteria for Cancer-Related Fatigue1
A. Six (or more) of the following symptoms have been present
every day or nearly every day during the same two-week
period in the past month, and at least one of the symptoms
is significant fatigue (A1).
– A1. Significant fatigue, diminished energy, or increased need to rest,
disproportionate to any recent change in activity level
– A2. Complaints of generalized weakness or limb heaviness
– A3. Diminished concentration or attention
– A4. Decreased motivation or interest to engage in usual activities
– A5. Insomnia or hypersomnia
– A6. Experience of sleep as unrefreshing or nonrestorative
– A7. Perceived need to struggle to overcome inactivity
– A8. Marked emotional reactivity (e.g., sadness, frustration, irritability) to
feeling fatigued
– A9. Difficulty completing daily tasks attributed to feeling fatigued
– A10. Perceived problems with short-term memory
– A11. Postexertional malaise lasting several hours
1.
Cella, D., Davis, K., Bretibart, W., Curt, G. (2001). Cancer-related fatigue: Prevalence of proposed diagnostic criteria
in a United States sample of cancer survivors. Journal of Clinical Oncology; 19 (14), 3385-3391
ICD-10 Criteria for Cancer-Related Fatigue
B. The symptoms cause clinically significant distress
or impairment in social, occupational, or other
important areas of functioning.
C. There is evidence from the history, physical
examination, or laboratory findings that the
symptoms are a consequence of cancer or cancer
therapy.
D. The symptoms are not primarily a consequence of
comorbid psychiatric disorders such as major
depression, somatization disorder, somatoform
disorder, or delirium
Fatigue: Classification
• Peripheral Fatigue
– Neuromuscular
– Exercise induced
• Energy production is impaired
• Energy utilization is inefficient
• Central Fatigue
– Mediated by the central nervous system
– Exercise independent, independent of disease severity
• Dysregulation of the neuroendocrine system
– Neuropeptides, catecholamines, cytokines, cortisol
Variability in Manifestations of CRF
• Central features: loss of efficiency, mental fogginess,
inertia, and sleep that is not restorative
• Peripheral features: excessive need to rest, an inability
to recover promptly from exertion, muscle heaviness
and weakness
• Challenging to distinguish CRF from depression,
cognitive dysfunction, or asthenia
– Overlapping symptoms?
– Shared neurophysiologic mechanisms?
Goldstein, D, BMC Cancer, 2006
Scope of the Problem
• Prevalence of fatigue in cancer survivors:
– 30% to 96% of survivors report persistent fatigue
• Fatigue has consequences for physical,
vocational, cognitive and social functioning;
mood; treatment adherence, psychological and
spiritual distress, and possibly for long-term
survival outcomes
•
Stasi, R, 2003
Fatigue – what happens over time
 Increases in fatigue during adjuvant treatment
 Inconsistent evidence relating to what happens
beyond treatment
20-30% up to
2 years ptx
20% (5-34%)
up to 5 years
ptx
It is a persistent problem
Approaches to Measuring CancerRelated Fatigue
• Single items that gauge fatigue severity
• Single items or subscales that measure relevant aspects of the fatigue
experience that have been drawn from measures of quality of life (eg.
FACIT-Fatigue), psychosocial adjustment, mood, or self-reported
health status (eg. vigor, vitality)
• Instruments designed specifically to evaluate CRF from a
multidimensional perspective (eg. Multidimensional Fatigue Inventory;
Piper Fatigue Scale)
• Neurophysiologic and performance-based measurements of fatigue,
including muscle force, endurance time, muscle reserve,
neuromuscular-junction impulse propagation, and functional
performance
,
Minton & Stone (2009); Alexander, Minton & Stone (2009)
Measurement Considerations
• Fatigue is a multidimensional construct:
– sensory dimension (fatigue severity, persistence)
– physiologic dimension (eg. leg weakness, diminished mental
concentration)
– affective dimension (sadness, depression, fear)
– behavioral dimension (reduction in the performance of needed or
valued activities)
• Multidimensional measures provide information about this
full range of characteristics beyond fatigue presence and
intensity
• Weakness, tiredness or the absence of vigor or vitality,
may not necessarily be equated with fatigue
Scale
Features
EORTCfatigue
subscale


Functional

Assessment of
Cancer
Therapy
Fatigue scale
(FACT-F)


Fatigue

Questionnaire
(FQ)


Domain(s)
Measured
Evaluation Comments
Time Frame
3-item uni-dimensional Physical
scale converted to a
fatigue
score/100
Minimal time for
completion
Fatigue over 
past week

13 item uniPhysical
dimensional scale: 5- fatigue
point Likert Scale
Fatigue scale part of a
20-item anemia scale
Higher scores = less
fatigue
5-10 minutes
Fatigue over 
past week

11-item multiPhysical
dimensional scale
and mental
Subscales: 7-item
fatigue
physical fatigue and 4
item mental fatigue
5-10 minutes
Fatigue over 
the last
month vs.

when patient
felt well





Benefit in clinical setting: brief and
simple to administer
Ceiling effect: questionable for use in
palliative setting
Cut point score of 40/100 for clinically
significant CRF suggested
Recommended for use with intervention
studies in research setting
Can be used independently or
administered with the FACT-General
scale
Score of 34/ 52 cut-point for clinically
significant CRF
MCID : 3.0 points for fatigue subscale
Measures both subjective physical and
mental fatigue
Originally developed for use with
chronic fatigue syndrome
Useful for screening for CRF
Cut-point for fatigue: >4.0
(McNeely and Courneya, 2009)
Etiology and Risk Factors
• Advanced/metastatic disease or cancer recurrence
• Cancer treatment (chemotherapy, radiation, surgery, biologic agents,
hormonal agents, molecularly targeted agents)
• Anemia
• Neutropenia
• Hypothyroidism
• Adrenal Insufficiency
• Hypogonadism
• Infection
• Malnutrition
• Depletion of vitamins B1, B 6 and B12
• Electrolyte disturbances (calcium, magnesium, phosphorus)
• Cardiopulmonary, hepatic or renal dysfunction
• Sarcopenia, asthenia, deconditioning
Etiology and Risk Factors
• Proinflammatory cytokine expression/generalized inflammation
• Medications with sedating side effects (eg. narcotics, anxiolytics,
antiemetics, antidepressants), or medications with fatigue as part of
the side effects profile (e.g. beta-blockers) of medications
• Concurrent symptoms (eg. pain, dyspnea, nausea, diarrhea)
• Impaired sleep quality
• Psychological distress (depression, anxiety)
• Accumulating evidence also suggests a role for gene polymorphisms,
altered circadian rhythmicity, immune dysregulation, abnormal cortisol
secretion, elevated body mass index, and metabolic syndrome
• In any one individual, the etiology of CRF likely involves the
interaction of several physiologic and psychobehavioral
mechanisms
Comparison Between Fatigued and Non-Fatigued:
Immune Status Markers
Collado-Hidalgo A, et al
Treatment with Chemotherapy Raises Fat Mass and Lowers
Lean Mass in BrCA
Demark-Wahnefried, W et al, J Clin Oncol, 19:2381, 2001
Organizing
Framework for
Understanding
Cancer-Related
Fatigue
©Berger & Mitchell (In Press) Cancerrelated fatigue and sleep-wake
disturbances. In J Lester and P. Schmitt
(Eds), Personalized Approach to Cancer
Survivorship. Pittsburgh: Oncology Nursing
Society Press, 2011.
What we know about exercise for CRF
• Numerous recent systematic reviews and metaanalyses have evaluated the efficacy of interventions
to reduce CRF in adults with mixed types of cancer.
– Breast cancer patients have participated in most studies.
– These interventions have been categorized in 2 major,
clinically applicable domains:
– physical activity enhancement and psychosocial therapies
• Since fatigue may respond to one/another or combined
treatment, both were searched
Interventions for Cancer Related Fatigue—
General Principles
• More than 170 empiric studies of pharmacologic and nonpharmacologic interventions to reduce or manage CRF, and several
recent meta-analyses or systematic reviews (Cramp & Daniel, 2008; Goedendorp,
Gielissen, Verhagen, & Bleijenberg, 2009; Jacobsen, Donovan, Vadaparampil, & Small, 2007; Kangas, Bovbjerg, &
Montgomery, 2008; Minton, Richardson, Sharpe, Hotopf, & Stone, 2008; Mitchell, Beck, Hood et al, 2007; Mitchell, in
press).
• For some interventions, there is strong and consistent evidence to
support effectiveness, while for other interventions only preliminary
data are available
• Many of the interventions for fatigue have not been studied in HSCT
recipients or long-term survivors of HSCT
Research & Reviews: Exercise
# of
Overall
studies
Other?
Finding
Kangas,
2008
N=17
ES = -.42
(-0.60 to 0.23)
Psychosocial
vs. exercise
No diff. in
psychosocial vs.
exercise
Cramp &
Daniel,
2008
N=16
SMD = -0.36
(-0.49 to 0.23)
Mediators?
Associated with
change in fitness
Speck,
2009
N= 14
WMES = During and
0.54
Post(-.90 to -0.19) treatment
Velthuis,
2010
N=12
SMD = 0.29 Home-based Favour supervised
(0.06 to 0.52) vs. supervised aerobic
Brown,
2011
N=25
WMD = 0.39 Predictors
(0.30 to 0.47)
Favour exercise
(post, but not during
treatment)
> Intensity
(resistance), older,
theoretically driven.
Minto & Stone, BCRT, 2008
• 9 cross-sectional studies
– 8 with comparisons to normal population
– N=49-1957
– Mean time since tx – 4 months – 10 years
• 9 longitudinal studies
– 4 months – 10 years
– N = 88-863
Fatigue – comparison with norms
•
•
•
•
Comparisons up to 29 months post-tx
Variety of methods used
Lack of a priori clinical importance defined
Consistently demonstrated statistical differences in
fatigue in BC group
Minton, Stone; BCRT, 2008, 112:5
Summary for Exercise
• Benefits favored programs with multiple exercise
components, at least partially home-based,
individualized, and >8 weeks long
– Therefore: aerobics and weights,
Interventions With Demonstrated Effectiveness in
Improving Fatigue Outcomes in Cancer Survivors
• Exercise (Shelton et al., 2009; Wiskeman et al., 2008; Coleman et al., 2003;Carlson et al. 2006; Dimeo et
al., 1999; Wilson et al., 2005)
• Physical exercise combined with relaxation breathing (Kim
and Kim, 2005)
• Physical rehabilitation
(Dimeo et al., 1997)
• Exercise, relaxation and psychoeducation (Jarden et al. 2009)
• Coping skills training (preparatory information, cognitive
restructuring, and relaxation with guided imagery) (GastonJohansson et al. 2000)
• Massage/healing touch for family caregivers (Rexilius et al., 2002)
• Massage therapy (Ahles et al., 1999)
Data from Individual Trials
• Courneya et al. 2013: CARE
– 25-30 minutes/session/3x/week (standard aerobic)
– 50-60 minutes/session 3x/week (high intensity)
– Standard aerobic + resistance (2 sets 10-12 reps/3x/week)
High intensity or combined were superior in improving muscles
strength, pain and endocrine symptoms
Data from Individual trials
• Eyigor 2010: Pilates effective in reducing fatigue
• Sprod 2012;and Janelsins 2011: Tai Chi effective in
reducing cytokines, insulin resistance and fatigue
Summary of Cochrane reviews
• McNeely et al.2006: Meta-analysis demonstrated that
exercise had a positive effect on fatigue in breast
cancer patients
• Markes et al. 2006:aerobic and resistive exercise had
a positive effect on fitness, insignificant effect on
fatigue
• Cramp et al 2012:aerobic exercise has a positive
effect on fatigue
• Mishra et al 2012: aerobic exercise has a positive
effect on cardiorespiratory fitness, strength
Guidelines
• Rock et al 2012: Physical Activity Guidelines
• NCCN 2010: Exercise guidelines
Exercise
•Exercise is effective in managing fatigue during and following cancer
treatment in patients with undergoing hematopoietic stem cell
transplantation, HSCT survivors, and patients with breast cancer or solid
tumors
•Possible mechanisms:
•Improves aerobic capacity, and ameliorates muscle loss and
deconditioning
•Favorable effects on sleep, mood, self-efficacy, body composition,
and the immune system and cytokine
•Exercise modalities differ in:
•content (walking, cycling, swimming, resistive exercise, or combined
exercise)
•frequency (ranging from two times per week to two times daily)
•intensity
•degree of supervision (fully supervised group versus self-directed
exercise)
•duration (from two weeks up to one year)
Implications for Practice
• Ongoing periodic screening is an essential component of
care quality
• 10 point scale for screening is efficient and sensitive;
moderate to severe fatigue 4-10 (on 10 point scale) warrants
further evaluation and treatment
• Use national guidelines (NCCN and ONS-PEP) to:
– Examine your practice and expand the repertoire of
interventions recommended for a specific patient based
on efficacy
Implications for Practice
• Screen for correctable contributing factors:
anemia, thyroid dysfunction, hypogonadism,
cardiomyopathy, adrenal insufficiency,
pulmonary dysfunction, sleep disturbance, fluid
and electrolyte imbalances
• Provide patients with anticipatory information
about fatigue prior to initiation of treatment, and
as they transition to survivorship phase
• Develop plan to prevent/manage fatigue
• Systematic evaluation of fatigue at baseline and
prospectively, to evaluate outcome of
intervention
Acknowledgements
Collaborators:
Ali Weinstein
Nicole Stout
Ancha Baranova
Cindy Pfalzer
Aybike Birendinc
Charles McGarvey
Kathryn Doyle
Ellen Levy
Support: PNC Foundation, Dominion Guild
Thanks to Sandy Mitchell, Kristen Campbell for slides
borrowed for this presentation
Session 1: Exercise treats cancer comorbidity across the spectrum of disease:
An evidence-based discussion






Introduction – Gail Gamble, MD
Exercise and cancer-related fatigue: Evidence
base and future research directions – Lynn Gerber,
MD
Clinical consequences of debility and physical
deconditioning – Sam Shahpar, MD
An exercise prescription for cancer survivors:
Mitigating late effects and overall survival – Kim
Barker, MD
Exercise value in advanced cancer and at end of
life care – Andrea Cheville, MD
Panel for questions
CLINICAL CONSEQUENCES OF
DEBILITY AND PHYSICAL
DECONDITIONING
Sam Shahpar, MD
Clinical Instructor, Feinberg School of Medicine at Northwestern University
Attending Physician, Cancer Rehabilitation Program at Rehabilitation Institute of
Chicago
40
DEFINITIONS
Debility
• a weakened or enfeebled state; weakness
• feebleness, weakness, or loss of strength
Deconditioning
• multiple, potentially reversible changes in body
systems brought about by physical inactivity and
disuse
41
DECONDITIONING
 Cumulative Multifactorial Phenomenon
 Results in Functional decline due to changes in multiple
body systems
 Occurs across a spectrum
42
MUSCULOSKELETAL EFFECTS – MUSCLE STRENGTH
 Skeletal muscle strength declined by 1% to 1.5% per day after
strict bed rest. 1,2
 Decline in strength up to 1.3%-5.5% per day with cast
immobilization.3,4,5
 Loss of strength was found to be greatest during 1st
week of immobilization, decreasing up to 40% 6,7
1.
2.
3.
4.
5.
6.
7.
Honkonen SE, Kannus P, Natri A, Latvala K, Jarvinen MJ. Isokinetic performance of the thigh muscles after tibial plateau fractures. Int Orthop. 1997;21(5):323-326.
Mueller EA. Influence of training and of inactivity on muscle strength. Arch Phys Med Rehabil.1970;51:449-462.
Botvin JG, Otvin JG, Ditunno JF, Herbison GJ. Mobilization of a patient with progressive neuromuscular disease and lower extremity fractures. Arch Phys Med Rehabil. 1975;56(7): 317-319.
Herbison GJ, Jaweed MM, Ditunno JF. Muscle fiber atrophy after cast immobilization in the rat. Arch Phys Med Rehabil. 1978;59(7):301-305.
Herbison GJ, Jaweed MM, Ditunno JF. Recovery of reinnervating rat muscle after cast immobilization. Exp Neurol. 1984;85(2):239-248.
Bloomfield SA. Changes in musculoskeletal structure and function with prolonged bed rest. Med Sci Sports Exerc. 1997;29(2):197-206.
Fowles JR, Sale DG, MacDougal JD. Reduce strength after passive stretch of the human plantar flexors. J Appl Physiol. 2000;89(3): 1179-1188.
43
MUSCULOSKELETAL EFFECTS – MUSCLE ATROPHY
 Reduction of muscle protein synthesis, whole body protein
production are likely main contributors1,2
• Rate of loss slow initially but increases soon after 1st few
days
• After 10 days, 50% of eventual muscle weight loss
• After 14 days, 50% reduction of muscle protein synthesis
before tapering off to new steady state
1.
2.
Ferrando AA, Lane HW, Stuart CA, et al. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol l996;270:
E627–E663.
Haggmark T, Eriksson E, Lanssom E. Muscle fiber type changes in human skeletal muscle after injury and immobilization. J Orthopaedics
1986;9(2): 181–185.
44
MUSCULOSKELETAL EFFECTS – MUSCLE ATROPHY
 Type I muscle fibers > type II
• 2 months of bedrest, 12% decrease mean size of type I
fibers of soleus
• 4 months of bedrest, 39% decrease mean size of type I
fibers of soleus 1
 Lower limbs more affect than upper limbs
• Leads to rapid reduction in endurance, back pain 2,3
1.
2.
3.
Ohira Y, Yoshinaga T, Ohara M, et al. Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading. J Appl
Physiol 1999;87(5):1776–1785.
Rutherford OM, Jones DA, Round JM. Long-lasting unilateral muscle wasting and weakness following injury and immobilization. Scand J Rehabil
Med 1990;22:33–37.
Botvin JG, Otvin JG, Ditunno JF, Herbison GJ. Mobilization of a patient with progressive neuromuscular disease and lower extremity fractures. Arch
Phys Med Rehabil. 1975;56(7): 317-319.
45
MUSCULOSKELETAL EFFECTS – MUSCLE ATROPHY
 Myostatin (growth factor-beta protein) 1
• Inhibits muscle synthesis
• Increased during bed rest - After 25 days, level increases
12%
• Possible target to prevent muscle atrophy
 Sarcopenia
• Age-related loss of muscle mass and strength
• Inactivity contributing factor
• High-intensity resistive exercise can reverse sarcopenia 2
1.
2.
Zachwieja JJ, Smith SR, Sinka-Hikim I, et al. Plasma myostatin-immunoreactive protein is increased after prolonged bed rest with low-dose T3
administration. Journal of Gravitational Physiology 1999;6(2):11–15.
Rubinoff R. Sarcopenia: a major modifiable cause of fragility in the elderly. J Nutr Health Aging 2000;4(3):140–142
46
MUSCULOSKELETAL EFFECTS - PREVENTION
 Resistive leg exercises performed above 50% of max
every 2nd day can maintain muscle protein synthesis as
healthy subjects engaged in normal activity 1
 Dynamic leg-press training maintained of cross-sectional area
and strength for the knee extensors and flexors but
locomotion necessary to preserve strength in the ankle
plantar and dorsiflexors 2
1.
2.
Ferrando AA, Tipton KD, Bamman MM, Wolfe RR. Resistive exercise maintains skeletal muscle protein synthesis during the bed rest. J Appl Physiol
1997;82(3):807–810.
Akima H, Kubo K, Imai M, et al. Inactivity and muscle: effect of resistance training during bed rest on muscle size in the lower limb. Acta Physiol
Scand 2001;172(4):269–278.
47
MUSCULOSKELETAL EFFECTS – BONE HEALTH
 Non-weight bearing over several weeks can cause a
significant mineral bone loss in the tibia
• Similar to treatment with chronic corticosteroids,
menopausal related osteoporosis.
• May require 1-1.5 years to return to baseline level with
normal activity 1
 Longer duration of immobility  increased time required to
restore bone density to the premorbid levels
1.
Ito M, Matsumoto T, Enomoto H, et al. Effect of non-weight bearing on tibial bone density measured by QCT in patient with hip surgery. J Bone Min
Metab 1999;17(1):45–50.
48
MUSCULOSKELETAL EFFECTS – BONE HEALTH
 Bone mass begins to decline in the 4th and 5th decades of life
 Occurring most rapidly in women in the first 5 to 7 years
after menopause 1,2
 Risk of fracture increases with addition of inactivity and nonweight bearing adding to bone mineral loss.
 Bone mass improves with repeated loading stresses and
decreases with absence of muscle activity/elimination of
gravity 3,4,5
1.
2.
3.
4.
5.
Avioli LV. Hormonal alterations and osteoporotic syndromes. J Bone Miner Res 1993;2[Suppl]:511–514.
Perloff JJ, McDermott MT, Perloff KG, et al. Reduced bone mineral content is a risk factor for hip fractures. Orthop Rev 1991;20:690–698.
Cann CE, Genant HK, Young DR. Comparison of vertebral and peripheral mineral losses in disuse osteoporosis in monkey. Radiology
1980;134:525–559.
Van-Loon JJ, Bervoets DJ, Burger EH, et al. Decreased mineralization and increased calcium release in isolated fetal mouse long bones under near
weightlessness. J Bone Miner Res 1995;10:550–557.
49
Gross TS, Rubin CT. Uniformity of resorptive bone loss induced by disease. J Orthop Res 1995;13:708–714.
CARDIOVASCULAR EFFECTS – HEART RATE
 Immobilization tachycardia
• Resting HR can increases by 1 beat per minute every 2
days
• After 3 weeks of bed rest, the resting pulse increases
10-12 beats per minute 1
 After 3 weeks of bed rest
• HR 165 with submax exercise (HR 129 in active healthy) 2
• 25% decrease in CV performance with 30 min of walking at
3.5 miles per hour up a 10% grade1
1.
2.
Demida BF, Machinski I. Use of rehabilitation measures for restoration of human physical work capacity after the prolonged limitation of motor
activity. Kosmicheskaia biologiiai aviakosmichcskaia meditsina 1979;13:74–75.
Saltin B, Blomqvist G, Mithcell JH, et al. Response to exercise after bed rest and after training. Circulation 1968;38[Suppl VII]:1–78.
50
CARDIOVASCULAR EFFECTS – CO, SV
 Normally, while supine, Cardiac Output (CO) increases by 24% with
blood shifting to thorax with increase in myocardial work
 Bed rest 1
•
•
•
•
After 24 hrs, 5% decrease in plasma volume
After 6 days, 10% decrease in plasma volume
After 14 days, 20% decrease in plasma volume
Correlated drop in CO due to reduced hydrostatic BP, decreased
secretion of ADH
 Stroke volume (SV)
•
•
15% decrease after 2 weeks of bed rest 2,3,4
Up to 30% decrease with submax exercise after 3-4 weeks of bed rest 3
1.
2.
3.
4.
Van Beaumont W, Greenleaf JE, Juhos L. Disproportional changes in hematocrit, plasma volume, and proteins during exercise and bed rest. J Appl
Physiol 1972;33:55–61.
Saltin B, Blomqvist G, Mithcell JH, et al. Response to exercise after bed rest and after training. Circulation 1968;38[Suppl VII]:1–78.
Convertino V, Hung J, Goldwater D, DeBusk RF. Cardiovascular responses to exercise in middle-aged men after 10 days of bed rest. Circulation.
1982;65(1):134-140.
Taylor HL. The effects of rest in bed and of exercise on cardiovascular function. Circulation 1968;38:1016–1017.
51
CARDIOVASCULAR EFFECTS – ORTHOSTASIS
 Normally
• Baroreceptors in R atrium, carotids, aortic arch trigger
adrenergic reflexes  Increase HR, LE and
mesenteric blood vessel vasoconstriction 1,2
 Bed Rest
• Inadequate sympathetic vasopressive response with
limited vasoconstriction
1.
2.
Greenleaf JE, Wade CE, Leftheriotis G. Orthostatic responses following 30-day bed rest deconditioning with isotonic and isokinetic exercise training.
Aviat Space Environ Med 1989;60:537–542.
Melada GA, Goldman RH, Luetscher JA, et al. Hemodynamics, renal function, plasma renin and aldosterone in man after 5 to 14 days of bed rest.
Aviat Space Environ Med 1975;46:1049–1055.
52
CARDIOVASCULAR EFFECTS – ORTHOSTASIS
 Bed Rest
• Decrease in venous return with increased HR limits
ventricular filling during diastole  decrease in SV
• Decrease in SV and CO  Decrease in SBP upon Rising,
difficulties maintaining adequate cerebral perfusion 1,2
 Orthostasis
 Normal response from rise from supine may be completely
lost after 3 weeks of bed rest
 Recovery process make take 3 weeks up to 3 months
1.
2.
Stremel RW, Convetino VA, Bernauer EM, Greenleaf JE. Cardiorespiratory deconditioning with static and dynamic leg exercise during bed rest. J
Appl Physiol 1976;41:905–909.
Robinson BF, Ebstein SE, Beiser GD, et al. Control of heart rate by automatic system: studies in man on the interrelation between baroreceptor
mechanism and exercises. Circ Res 1966;19:400–411.
53
CARDIOVASCULAR FITNESS
 VO2max known key predictor for mortality in all
populations
 Previous research  12% improvement in survival for
men and a reduction of death by 17% in women for every
1 MET increase in aerobic capacity 1,2
1.
2.
Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J
Med. 2002; 346:793-801.
Gulati M, Pandey DK, Arnsdorf MF, et al. Exercise capacity and the risk of death in women: The St. James Women Take Heart Project. Circulation.
2003; 108:1554-1559.
54
CARDIOVASCULAR FITNESS
 Inactivity impairs the function of MSK and CV systems 
significant reduction of maximal oxygen consumption (VO2max)
 After 20 days of bed rest, VO2max may decline by 27%1,2
 Low levels of physical activity can have a beneficial effect on
cardiovascular fitness 3
1.
2.
3.
Taylor HL. The effects of rest in bed and of exercise on cardiovascular function. Circulation 1968;38:1016–1017.
Booth FW, Gordon SE, Carson CJ, Hamilton MT. Waging war on modern chronic disease. J Appl Physiol 2000;88:774–787.
Manson JE, Hu FB, Rich-Edwards JW, et al. A prospective study of waking compared with vigorous exercise in the prevention of
coronary heart disease in women. N Engl J Med 1999;341:650–658.
55
HEMATOLOGIC EFFECTS - THROMBOEMBOLISM
 Virchow’s Triad: Venous stasis, Increased blood
coagulability, Endothelial injury
 Direct relationship between frequency of DVT and
length of bed rest 1
 20% of calf thrombi extend to popliteal and thigh veins
• 50% of these will cause Pulmonary Embolism2
1.
2.
Kudsk KA, Fabian TC, Baum S, et al. Silent deep vein thrombosis in immobilized multiple trauma patients. Am J Surg 1989;158:515–
519.
Hume M, Sevitt S, Thomas LP. Venous thrombosis and pulmonary embolism. Cambridge, MA: Harvard University Press, 1977.
56
NEUROLOGICAL EFFECTS – NEUROLOGIC EFFECTS
 Impaired balance and coordination
•
Due to altered neural control (v. weakness) 1,2
 Sensory deprivation
• Healthy subjects placed on strict bed confinement wearing
gloves, goggles, and earplugs for 3 hours  hallucinations and
disorientation3,4
 Prolonged bed rest + social isolation 5,6
• After 7 days  Perceptual impairment
• After 2 weeks  Restlessness, anxiety, decreased pain
tolerance, irritability, hostility, insomnia, and depression
1.
2.
3.
4.
5.
6.
Haines RF. Effect of bed rest and exercise on body balance. J Appl Physiol 1974;36:323–327.
Trimble RW, Lessard CS. Performance decrement as a function of seven days of bed rest. USAF School of Aerospace Medicine Technical Report
70–56. Alexandria, VA: Aerospace Medical Association, 1970.
Banks R, Cappon D. Effects of reduced sensory input on time perception. Percept Mot Skills 1962;14:74.
Ryback RS, Lewis OF, Lessard CS. Psychobiologic effects of prolonged bed rest (weightlessness) in young healthy volunteers (study 11).
Aerospace Medicine 1971;42:529–535.
57
Downs FS. Bed rest and sensory disturbances. Am J Nurs 1974;74:434–438.
Smith MJ. Changes in judgment of duration with different patterns of auditory information for individuals confined to bed. Nurs Res 1975;24:93–98.
PULMONARY EFFECTS
 Decreased diaphragmatic movement with decreased strength
and endurance of intercostal, axillary respiratory muscles
 Can lead to reduction of Vital Capacity, Functional reserve by
25% to 50% 1
 Poor clearance of secretions with impaired cough (due to
ciliary malfunction, abdominal muscle weakness)
 Leads to Atelectasis and hypostatic pneumonia
1.
Craig DB, Wahba WM, Don HF. Airway closure and lung volume in surgical positions. Can Anaesth Soc J 1971;18:92–99.
58
OTHER EFFECTS
 Genitourinary
•
•
Increased incidence of bladder or renal stones and urinary tract infections.
Urinary retention/Incomplete bladder emptying 1
 Gastrointestinal
•
•
Reflux esophagitis
Decreased peristalsis/Constipation
 Hormonal Disorders
•
•
Significant carbohydrate intolerance with insulin resistance 2,3,4
Increased serum parathyroid hormone 5
1.
2.
3.
4.
5.
Anderson RL, Lefever FR, Francis WR, et al. Urinary and bladder responses to immobilization in male rats. Food Chem Toxicol 1990;28:543–545.
Stuart CA, Shangraw RE, Prince MJ, et al. Bed rest-induced insulin resistance occurs primarily in muscle. Metabolism 1988;37:802–806.
Mikines KJ, Dela F, Tronier B, Galbo H. Effect of 7 days of bed rest on dose-response relation between plasma glucose and insulin secretion. Am J
Physiol 1989;257:43–48.
Seider MJ, Nicholson WF, Booth FW. Insulin resistance for glucose metabolism in disused skeletal muscle of mice. Am J Physiol 1982;242:E12–
18.
Lerman S, Canterbury JM, Reiss E. Parathyroid hormone and the hypercalcemia of immobilization. J Clin Endocrinol Metab 1977;45:425–488.
59
DECONDITIONING TAKE HOME POINTS
 Cumulative Multifactorial Phenomenon, resulting in
decline in multiple body systems
 Decline occur in absence of “illness”
 Can be prevented/attenuated with mobilization, even
with limited participation
60
Session 1: Exercise treats cancer comorbidity across the spectrum of disease:
An evidence-based discussion






Introduction – Gail Gamble, MD
Exercise and cancer-related fatigue: Evidence
base and future research directions – Lynn Gerber,
MD
Clinical consequences of debility and physical
deconditioning – Sam Shahpar, MD
An exercise prescription for cancer survivors:
Mitigating late effects and overall survival – Kim
Barker, MD
Exercise value in advanced cancer and at end of
life care – Andrea Cheville, MD
Panel for questions
An Exercise Prescription for Cancer
Survivors:
Mitigating Late Effects and
Impacting Overall Survival
Kim Barker, MD
Assistant Professor
Department of Physical Medicine & Rehabilitation
UT Southwestern Medical Center
Objectives
• Discuss some of the late effects of cancer and
cancer treatment and the effects of exercise
• Discuss how exercise can improve survival and
decrease risk of recurrence in certain cancers
• Discuss ways to integrate exercise for cancer
survivors.
Persistent Changes
American College of Sports Medicine Roundtable on Exercise Guidelines for Cancer Survivors.
Schmitz, Kathryn; PhD, MPH; Courneya, Kerry; Matthews, Charles; PhD, FACSM; Demark-Wahnefried, Wendy; GALVAO, DANIEL; Pinto, Bernardine; IRWIN, Melinda; WOLIN, KATHLEEN; SEGAL,
ROANNE; LUCIA, ALEJANDRO; SCHNEIDER, CAROLE; VON GRUENIGEN, VIVIAN; SCHWARTZ, ANNA
Medicine & Science in Sports & Exercise. 42(7):1409-1426, July 2010.
DOI: 10.1249/MSS.0b013e3181e0c112
Muscle Fatigue and Weakness
• Commonly caused by
– Surgery
– Radiation
– Medications (steroids, hormone therapy)
Muscle Fatigue and Weakness
• Exercise increases lean muscle mass (Speck 2010)
• Prostate cancer survivors
– Chest and leg strength improved by 12kg over 24
weeks of supervised training (Segal, 2009)
• Breast cancer survivors with improved strength
– (Speck 2010, Courneya 2007)
• Early strength improvement is seen in even shortterm training studies (Schmitz 2010)
• ACSM Grade A (Schmitz 2010)
• Less evidence for cancer cachexia
Arthralgias
• Commonly seen with aromatase inhibitors
• Various exercise/physical activity have been
shown to improve pain scores and improve
functioning
– Aerobic and strengthening exercises (DeNysschen
2014)
– Yoga (Galantino 2012)
– Tai Chi (Galantino 2013)
Arthralgias
Arthritis Impact Measure Scale 2
Measure
Before (± SE)
After (± SE)
P value
Arthritic pain
5.6±0.4
2.9 ± 0.5
0.001
Physical activity
3.7 ± 0.7
1.5 ± 0.5
0.001
Dexterity
1.2 ± 0.3
0.4 ± 0.1
0.04
Arm function
0.4 ± 0.1
0.2 ± 0.1
0.02
Self care
0.1 ± 0.1
0.001 ± 0.1
0.5
Mobility
0.4 ± 0.1
0.3 ± 0.1
0.4
House activities
0.3 ± 0.1
0.1 ± 0.1
0.6
Adapted from DeNysschen 2014, Table 2
Cardiovascular
• Numerous complications and etiologies
– Cardiomyopathy (anthracylcines, anthraquinones,
radiation)
• Dose dependent, non-linear
• Up to 33% of breast cancer patients, independent of
chemotherapy (Carver 2007)
– Heart valve disorders (radiation)
– Conduction disorders (variety of chemotherapies,
radiation)
– Hypertension (ifosfamide, cisplatin/carboplatin,
methotrexate, radiation to kidneys, radiation to HPA)
– Hyperlipidemia (cisplatin/carboplatin, radiation to HPA)
(Hudson 2013)
Cardiovascular
• Risk factors:
– Pre-existing cardiac disease
– Pregnancy
– High cumulative dose of therapy
– Combination therapy
– Longer duration of survival
– For those treated with anthracyclines, age (<18,
>65)
(Carver 2007)
Cardiovascular
• Exercise in general improves
–
–
–
–
Maximal aerobic capacity
Lower risk of cardiovascular disease
Improvement in blood pressure
(Schneider 2007, Speck 2010)
• Meta-analysis of heart failure patients
demonstrates that aerobic training significantly
improves:
–
–
–
–
Ejection fraction
End diastolic volume
End systolic volume
(Haykowski 2007)
Cardiovascular
• However, cannot necessarily extrapolate those
results into cancer survivors.
• Animal-based models demonstrate promise of
aerobic training for anthracycline-induced
cardiotoxicity (Scott 2011)
Pulmonary
• Causes include:
– Chemotherapy or medications
– Radiation
– Surgery
• Complications due to
– Restrictive lung disease
– Obstructive lung disease
– (Schmitz 2010)
Pulmonary
• Improvement in lung function at rest and with
exercise
– FVC
– FEV1
– Schneider 2007 x2
• ACSM Grade A (Schmitz 2010)
Neuropathy
• Most commonly caused by chemotherapies, but
can also be caused by radiation treatments.
• Muscular strengthening can translate to better
gait and stability (Woflson 1995)
• Resistance training improved ambulation in
breast cancer patients (Twiss 2009)
• Tai chi can improve balance and functioning in
symmetric peripheral polyneuropathy (Quigley
2014, Xiao 2014)
Osteopenia and Osteoporosis
• Causes include chronic steroid use, treatments
that reduce circulating sex hormones, etc.
• Moderate-intensity, aerobic exercise or
resistance exercise (Winters-Stone 2010)
• However, there is limited trials with conflicting
data regarding efficacy (Schmitz 2010, Saarto
2011)
• Should be used in addition to pharmacological
treatments
Lymphedema
• Most often related to surgery or radiation
• Physical activity and exercise has been found to
be safe (McNeely 2009, Harris 2000)
– Weight lifting and resistance in UE (Cormie 2013,
Chang 2013)
• May be helpful to reducing limb size.
– Aerobic exercise in UE (Letellier 2014, Chang 2013,
Godoy 2013)
– Linear response to aerobic exercise in LE lymphedema
(Brown 2013)
Reducing Recurrence
• Similar to the roles in risk reduction prior to cancer
• Decrease in weight/fat
– Abdominal fat is metabolically active in carcinogenesis
(Friedenreich and Orenstein 2002, Kaaks 2002, Rodriguez
2007)
– Weight and weight gain increases colon, breast
(postmenopausal), endometrium, and ovarian cancers.
(Karim-Kos 2008, Speck 2010)
• Change in metabolic hormones
– Decrease in insulin-like growth factor (IGF-I)
– Increase in insulin growth factor binding proteins (IGFBPs)
– (Nindl 2010, Irwin 2009, Fairey 2003)
Reducing Recurrence
• Change in endogenous sexual hormones
– Alters the level of estrogen, progesterone, and
testosterone in the body
– May increase the level of sex hormone binding globulin
(SHBG)
– (Friedenreich 2010, Galvao 2006)
• Decrease in growth factors
• Decrease in endogenous oxidative stress
• Improvement in immune function
– Change in inflammatory milieu including NK cell, CRP, IL-6,
IL-10, TNF-alpha (Galvao 2008, Miller 2008)
• DNA repair
Reducing Recurrence
• Most of the research has been focused on
breast cancer and colon cancer
• Lack of exercise ≠ Recurrence
– It is somewhat unclear though, whether inactivity
causes recurrence or lack of/inability to exercise
was due to smoldering cancer
Reducing Recurrence
• Trials that are under way:
– The Exercise and Nutrition to Enhance Recovery
and Good Health for You (ENERGY) Trial
• Multi-center, multi-city, RCT. 24 month follow-up
– The Colon Health and Life-Long Exercise Change
Trial
• Multi-center, multi-nation, RCT. At least annual followup through 10 years.
Clinical Practice
• National Cancer Institute (NCI) has mandated treatment
summaries by 2015
– Includes: surgical history, pathology findings, chemotherapy and
radiation treatment history, any other treatment therapies
(American College of Surgeons 2012, Committee on Cancer
Survivorship: Institute of Medicine and National Research Board
2006, Ganz 2008)
• The Institute of Medicine recommends that all survivors
receive a cancer survivorship plan
• ACSM has specific exercise recommendations for breast,
prostate, colon, hematologic (including s/p SCT), and
gynecologic cancers (Schmitz, 2010)
• Oncologists, primary care physicians, and physiatrists
working together can help bring this to reality
References
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Brown JC, et al. Physical activity and lower limb lymphedema among uterine cancer survivors. Med Sci Sports Exerc. 2013; 45(11):2091-2097.
Carver JR, et al. ASCO Cancer Survivorship Expert Panel. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult
cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007; 25(25):3991-4008.
Chang CJ and Cormier JN. Lymphedema management: Exercise, surgery, and compression garments. Semin Oncol Nurs. 2013; 29(1):28-40.
Committee on Cancer Survivorship: Institute of Medicine and National Research Board. From Cancer Patient to Cancer Survivor: Lost in Transition.
Washing, DC: The National Academic Press, 2006
Cormie J, et al. Is it safe and efficacious for women with lymphedema secondary to breast cancer to lift heavy weights during exercise: a randomized
controlled trial. J Cancer Surviv. 2013; 7(3):413-420.
Courneya KS, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized
controlled trial. 2007; 25(28):4396-4404.
DeNysschen CA, et al. Exercise intervention in breast cancer patients with aromatase inhibitor-associated arthralgia: a pilot study. European Journal
of Cancer Care. 2014; 23:493-501.
Fairey AS, et al. Effects of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin-like growth factor binding
proteins in postmenopausal breast cancer survivors: a randomized controlled trial. Cancer Epidemiol Biomarker Prev. 2003: 12(8):721-727.
Friedenreich CM et al. Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among
postmenopausal women. J Clin Oncol. 2010; 28(9):1458-1466.
Galantino ML, et al. Impact of yoga on functional outcomes in breast cancer survivors with aromatase inhibitor=-associated arthralgias. Intergr
Cancer Ther. 2012; 11(4):313-320.
Galantino ML, eta l. Tai Chi for well-being of breast cancer survivors with aromatase inhibitor-associated arthralgias: a feasability study. Altem Ther
Health med. 2013: 19(6):38-44.
Galvao DA et al. Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer Prostatic Dis. 2008: 11(2):160165.
Godoy MF. Synergy effect of compression therapy and controlled arm exercise using a facilitating device in the treatment of arm lymphedema. Int J
Med Sci. 2012; 9(4):280-284.
Harris SR and Neissen-Vertommen SL. Challenging the myth of exercise-induced lymphedema: a series of case reports. J Surg Oncol. 2000; 74(2):9598.
Haykowsky MJ et al. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on
the type of training performed. J Am Coll Cardiol. 2007; 49(24):2329-2236
Irwin ML et al. Exercise improves body fat, lean mass, and bone mass in breast cancer survivors. Obesity. 2009: 17(8):1534-1541
Karin-Kos HE et al. Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s.
Eur J Cancer. 2008: 44(10):1345-1389.
References
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Letellier ME, et al. Breast-cancer related lymphedema: a randomized controlled pilot and feasibility study. Am J Phys Med Rehil. 2014; 93(9):751763.
McNeely ML, et al. Effect of upper limb volume on breast cancer survivors: a pilot study. Physiother Can. 2009; 61(4):244-251.
Miller AH et al. Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol. 2008; 26(6):971-982.
Nindl BC et al. Insulin-like growth factor I as a biomarker of health, fitness, and training status. Med Sci Sports Exerc. 2010: 42(1):39-49
Quigley PA, et al. Exercise Interventions, Gait, and balance in Older Subjects with Distal Symmetric Polyneuropathy. Am J Phys Med Rehabil
2014;93:1-16.
Saarto T et al. Effect of supervised and home exercise training on bone mineral density among breast cancer patients. A 12-month randomized
controlled trial. Osteoporos Int. 2011
Schmitz KH et al. American college of sports medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc.
2010:42(7):1409-1426
Schneider CM, et al. Effects of supervised exercise training on cardiopulmonary function and fatigue in breast cancer survivors during and after
treatment. Cancer. 2007; 110(4):918-925
Schneider CM, et al. Exercise training manages cardiopulmonary function and fatigue during and following cancer treatment in male cancer
survivors. Integr Cancer Ther. 2007; 6(3):235-241.
Schwartz AL, et al. Effects of a 12-month randomized controlled trial of aerobic or resistance exercise during and following cancer treatment in
women. Phys Sportsmed. 2009: 37(3);62-67.
Scott JM, et al. Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying
mechanisms. Circulation. 2011: 124(5):642-650
Segal RJ, et al. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J Clin Oncol
2009: 27(3):344-351.
Speck RM, et al. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv. 2010;
4(2):87-100.
Twiss JJ, et al. An exercise intervention for breast cancer survivors with bone loss. J Nurs Scholarsh. 2009; 41(1):20-27.
Winters-Stone KM, et al. A review of exercise interventions to improve bone health in adult cancer survivors. J Cancer Surviv. 2010; 4(3):187-201.
Wolfson L, et al. Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol A Biol Sci Med Sci. 1995; 50 (Spec No):64-67.
Xiao CM. Effects of long-term tai chi ball practice on balance performance in older adults. J Am Geriatri Soc. 2014; 62(5):984-5.
Yeh ET, et al. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;
53(24):2231-2247.
Session 1: Exercise treats cancer comorbidity across the spectrum of disease:
An evidence-based discussion






Introduction – Gail Gamble, MD
Exercise and cancer-related fatigue: Evidence
base and future research directions – Lynn Gerber,
MD
Clinical consequences of debility and physical
deconditioning – Sam Shahpar, MD
An exercise prescription for cancer survivors:
Mitigating late effects and overall survival – Kim
Barker, MD
Exercise value in advanced cancer and at end of
life care – Andrea Cheville, MD
Panel for questions
Session 1: Exercise treats cancer comorbidity across the spectrum of disease:
An evidence-based discussion






Introduction – Gail Gamble, MD
Exercise and cancer-related fatigue: Evidence
base and future research directions – Lynn Gerber,
MD
Clinical consequences of debility and physical
deconditioning – Sam Shahpar, MD
An exercise prescription for cancer survivors:
Mitigating late effects and overall survival – Kim
Barker, MD
Exercise value in advanced cancer and at end of
life care – Andrea Cheville, MD
Panel for questions
Exercise is a
Cancer "Drug":
WHY and HOW
do I use this in
my practice?
Gail Gamble, MD
Moderator
November 14, 2014
AAPMR Annual Assembly
Session 2: Exercise as primary cancer
intervention and personalized medicine:
Changing the culture of cancer care





Introduction – Gail Gamble, MD
The role of exercise as a prevention and treatment
strategy for cancer – Donald McKenzie, MD, PhD
Functional screening tools: Incorporating patientcentered outcomes research into cancer care –
Sarah Eickmeyer, MD
Exercise adherence in the cancer population:
Innovative strategies for behavioral change and
the role of technology – Andrea Cheville, MD
Round Table Q&A: Strategies to integrate a culture
of exercise into cancer – What is the physiatrist’s
role?
Session 2: Exercise as primary cancer
intervention and personalized medicine:
Changing the culture of cancer care





Introduction – Gail Gamble, MD
The role of exercise as a prevention and treatment
strategy for cancer – Donald McKenzie, MD, PhD
Functional screening tools: Incorporating patientcentered outcomes research into cancer care –
Sarah Eickmeyer, MD
Exercise adherence in the cancer population:
Innovative strategies for behavioral change and
the role of technology – Andrea Cheville, MD
Round Table Q&A: Strategies to integrate a culture
of exercise into cancer – What is the physiatrist’s
role?
Session 2: Exercise as primary cancer
intervention and personalized medicine:
Changing the culture of cancer care





Introduction – Gail Gamble, MD
The role of exercise as a prevention and treatment
strategy for cancer – Donald McKenzie, MD, PhD
Functional screening tools: Incorporating patientcentered outcomes research into cancer care –
Sarah Eickmeyer, MD
Exercise adherence in the cancer population:
Innovative strategies for behavioral change and
the role of technology – Andrea Cheville, MD
Round Table Q&A: Strategies to integrate a culture
of exercise into cancer – What is the physiatrist’s
role?
Functional Screening Tools:
Incorporating PatientCentered Outcomes
Research into Cancer Care
Sarah Eickmeyer, MD
Physical Medicine and Rehabilitation
Medical College of Wisconsin
November 14, 2014
Disclosures
• Disclosure of Relevant Financial Relationships
• Grant/Research support from:
– Medical College of Wisconsin Physical Medicine and
Rehabilitation Research Affairs
– Wisconsin Comprehensive Cancer Control Program
Objectives
• What is patient-centered outcomes research?
• What are the research opportunities?
• How can I apply functional screening tools into my
practice?
Patient-Centered Outcomes
Research (PCOR)
• PCOR helps people and their caregivers communicate and
make informed healthcare decisions, allowing their voices
to be heard in assessing the value of healthcare options.
This research answers patient-centered questions, such
as:
– “Given my personal characteristics, conditions, and preferences,
what should I expect will happen to me?”
– “What are my options, and what are the potential benefits and
harms of those options?”
– “What can I do to improve the outcomes that are most important to
me?”
– “How can clinicians and the care delivery systems they work in help
me make the best decisions about my health and health care?”
http://www.pcori.org/content/patient-centered-outcomes-research
Patient-Centered Outcomes
Research Institute (PCORI)
• Nonprofit, nongovernmental organization
• Patient Protection and Affordable Care Act of 2010
• Aims to fund patient-centered research to improve
outcomes for patients, caregivers and stakeholders
http://www.pcori.org/about-us
PCORI Mission Statement
PCORI helps people make informed healthcare decisions
and improves healthcare delivery and outcomes by
producing and promoting high integrity, evidence-based
information that comes from research guided by patients,
caregivers, and the broader health care community.
http://www.pcori.org/about-us
Patient-centeredness
• A perspective on health that is derived
from and directly relevant to the
patient’s experience of illness and of
care.
• Addressing questions that patients and
their families care about in clinical
settings.
What makes PCORI Unique
1. Patient and Stakeholder engagement
throughout research project
– Patients include:
• Person who has lived with/experienced illness or injury
• Caregiver or family of such a person
• Member of relevant advocacy organization
– Stakeholders include: all other members of health
care community
• Hospitals/health systems, Healthcare providers
• Policy makers, purchasers, payers, industry
2. Focus on patient-centered outcomes
– Outcomes that matter to patients
Patient Reported Outcome
Measures (PROs)
• Questionnaire where the responses are collected
directly from the patient
• Examples
– SF-36
– FACT
– PROMIS
http://www.facit.org; http://www.nihpromis.org
PROs = ?Functional Screening Tool
• Can we pair screening for psychosocial distress and
functional needs?
• CoC Standard 3.2: The cancer committee develops and
implements a process to integrate and monitor on-site
psychosocial distress screening and referral for the
provision of psychosocial care.
– NCCN Distress Thermometer
– Minimum 1 time
CoC Standard 3.2 2012
PROs = ?Functional Screening Tool
• Does patient-reported physical function correlate with
performance status?
Abernathy Journ Onc Practice 2011
PROs = ?Functional Screening Tool
• Screening for functional impairments at regular intervals
may prevent disability long-term.
Stout Cancer 2012;8 suppl
PROs = ?Functional Screening Tool
• Can we pair screening for psychosocial distress and
functional needs?
• Does patient-reported physical function correlate with
performance status?
• Screening for functional impairments at regular intervals
may prevent disability long-term.
CoC Standard 3.2 2012; Abernathy Journ Onc Practice 2011; Stout
Cancer 2012;8 suppl
Research examples
• Navigation to rehabilitation services in head and neck
cancer
• Monitoring symptom burden and function in multiple
myeloma after hematopoetic cell transplant (HCT)
Navigation to rehabilitation services in
head and neck cancer
• Background: Despite ample rehab services, head and
neck cancer patients are not referred to rehabilitation at
our center.
• Purpose: Understand unmet rehab needs and pilot
functional screening tools.
• Methods: Focus groups using qualitative methods.
Navigation to rehabilitation
services in head and neck cancer
•
•
•
•
•
•
•
What are the top physical symptoms and limitations you have experienced
since your cancer treatment?
How do you think cancer has affected your day-to-day function and ability to
care for yourself?
What types of activities and social roles do you want to return to now that
cancer treatment is over?
Have you asked for help?
What’s getting in the way of seeking help for your physical limitations?
What has been helpful in recovering physically from your cancer?
What do you think about these measures to identify some of the more
common issues after cancer?
– NCCN Distress Thermometer, PROMIS Physical Function, PROMIS Fatigue,
Cancer Wellness Planner, and locally derived questions
•
How do you think this medical center could better connect you to providers
and services that may help in your recovery from cancer?
Monitoring symptom burden and
function in multiple myeloma (MM)
• Background: After HCT, more MM patients are
getting maintenance chemotherapy with unknown
effects on symptoms and function.
• Purpose: Describe symptom burden, measure
physical function, and define MM cancer-related
disability.
• Methods: Track PROs and clinical measures of
function.
– PROMIS Physical Function and Fatigue
– 10MWT, TUG, 5STS
How can I incorporate this into my
practice?
•
•
•
•
Choose a PRO.
Choose time points.
Decide who will administer and monitor.
Decide on a pathway to rehabilitation.
Session 2: Exercise as primary cancer
intervention and personalized medicine:
Changing the culture of cancer care





Introduction – Gail Gamble, MD
The role of exercise as a prevention and treatment
strategy for cancer – Donald McKenzie, MD, PhD
Functional screening tools: Incorporating patientcentered outcomes research into cancer care –
Sarah Eickmeyer, MD
Exercise adherence in the cancer population:
Innovative strategies for behavioral change and
the role of technology – Andrea Cheville, MD
Round Table Q&A: Strategies to integrate a culture
of exercise into cancer – What is the physiatrist’s
role?
Session 2: Exercise as primary cancer
intervention and personalized medicine:
Changing the culture of cancer care





Introduction – Gail Gamble, MD
The role of exercise as a prevention and treatment
strategy for cancer – Donald McKenzie, MD, PhD
Functional screening tools: Incorporating patientcentered outcomes research into cancer care –
Sarah Eickmeyer, MD
Exercise adherence in the cancer population:
Innovative strategies for behavioral change and
the role of technology – Andrea Cheville, MD
Round Table Q&A: Strategies to integrate a culture
of exercise into cancer – What is the physiatrist’s
role?
Strategies to integrate a
culture of exercise into cancer
 How
do you structure a cancer
rehabilitation program in different
practice settings?
 What is the role of the physiatrist?
 What is the value of the physiatrist?
Exercise and Cancer Rehabilitation
Across Practice Setting
Musculoskeletal
Outpatient
Practice
Academic
Medical Center
CommunityBased Hospital