Rehabilitation in OncologyGetting to Better Outcomes

/ Nicole L. Stout DPT, CLT-LANA, FAPTAResearch Assistant ProfessorWVU Cancer InstituteSchool of MedicineDepartment of Hematology and OncologyCancer Prevention and ControlWest Virginia UniversityNicole.stout@hsc.wvu.eduwvucancer.org/cpc

University of Pittsburgh2nd Annual Cancer Rehabilitation ConferenceApril 2021

Disclosures• I have financial relationships with commercial interests for

continuing education webinars with: • Survivorship Solutions LLC

• Medbridge Inc.

In the presence of a confluence of circumstances known to escalate the risk of an adverse outcome…

Are you proactive?OrAre you reactive?

PROACTIVE

REACTIVE

Diagnosis Treatment Survivorship End of Life

Cancer Care

Continuum

Trajectory of Function

Cancer TX

RISK INTRODUCEDOnset of

Impairment

Onset of

Symptoms

Chronic condition

mgmtDisability

No Disability

Functional

Continuum

Diagnosis Treatment Survivorship End of Life

Cancer Care

Continuum

Trajectory of Function

Cancer TX

RISK INTRODUCEDOnset of

Impairment

Onset of

Symptoms

Chronic condition

mgmtDisability

No Disability

Functional

Continuum

Clinical Phase

Intervention

Continuum

Impairment

progressionRehabilitation

Services

Alleviate

Impairment

Ongoing reassessment

& condition

management as neededRISK

REDUCTIONEarly Detection

& Intervention

Sub Clinical Phase

NCI Office of Cancer Survivorship

> 1 Impairment

Intermittent Impairment

N/A

Impairment Impacting Function

Assistance with ADLAssistance with IADLN/A

Activity Limitations

Neo et al 2017 Cancer Treatment Revs, Cheville et al 2008 Supportive Care in Cancer, Pergolotti et al 2015 J Geriatric Oncology

30%

50%

60%30%

2 - 9 % receive rehab referrals within 12 months of self-reported deficits

Most commonly reported deficits were difficulty with ambulation and balanceMost commonly reported symptoms were pain, weight loss, and fatigue

So much evidence….So much needwhy are we so disconnected?

Rehabilitation Oncology

Functional performanceReturn to workParticipation CommunicationLength of stay, number

of visitsAdherence to prescribed

programSelf-care capabilityBehavior change

Overall survivalDrug effectivenessTolerability to

treatmentTreatment reductionsHospitalizationsInfectionsSymptom toxicityDistress

Convergent Strategies to Demonstrate Value

How do our interventions change/improveTolerability to cancer treatmentsToxicity profile Survival ratesDisease progression ratesPatient distress during treatmentAdverse eventsClinical trial eligibility Financial toxicity

Rehabilitation Program Cost Effectiveness OutcomesModel for Delivery Interventions

Outcomes

Multidimensional Oncology Rehabilitation ProgramsSystematic Review

• Improvements in QOL• Cost-effectiveness ratios for multidimensional rehabilitation >

unidimensional programs• Economic benefit of rehabilitation

Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (PACES)

• Home-based low intensity program (Onco-Move) and moderate intensity, supervised program (On-Track) improved physical fitness and reduced fatigue

• Onco-move was more cost effective than On-Track• Preliminary findings of down-stream costs suggest On-Track may be cost-

effective in preventing adverse effects compared to usual care

Mewes, J. C., Steuten, L. M., IJzerman, M. J., & Van Harten, W. H. (2012). Effectiveness of multidimensional cancer survivor rehabilitation and cost-effectiveness of cancer rehabilitation in general: a systematic review. The oncologist, 17(12), 1581.van Waart, H., Van Dongen, J. M., Van Harten, W. H., Stuiver, M. M., Huijsmans, R., Hellendoorn-van Vreeswijk, J. A., ... & Aaronson, N. K. (2018). Cost–utility and cost-effectiveness of physical exercise during adjuvant chemotherapy. The European Journal of Health Economics, 19(6), 893-904.

Prehabilitation OutcomesCancer Population Exercise Prescription Outcomes

Lung Supervised program3-4 weeks2-3 x/week (30-40 minutes)Moderate intensity exercise

• Improves pulmonary function prior to surgery• Reduction in hospital LOS• Reduced rate of infection• Improved tolerance to chemotherapy

Colorectal and other GI

Supervised program2-3 weeks2-3 x/week (30-40 minutes)Moderate intensity exercise

• Reduced hospitalization and reduced rate of readmission after discharge

• Enhanced physical performance in elderly patients preoperatively

• Improves functional capacity prior to chemotherapy

Gynecological Cancers

Supervised program w/home component2-3 weeks2-3 x/week (40-60 minutes)Moderate intensity exercisePelvic floor muscle training

• Improves time to return to continence• Improves cardiorespiratory fitness• Improves functional walking capacity

Sebio Garcia et al 2016 Interact Cardiovas Thorac Surg, Singh et al 2013, Surg Oncol, Boereboom Tech Coloproctol. 2015 Carli F et al PM&R Clinics NA 2017

Wang Q and Zhou W. Roles and Molecular Mechanisms of Physical Exercise in Cancer Prevention and Treatment. Journ Sport Heal Sci. Online ahead of print, 30 JULY 2020. https://doi.org/10.1016/j.jshs.2020.07.008

Questions?

References

Exercise Guidelines for Cancer SurvivorsStrong Evidence for Exercise Prescription

Symptom or Impairment

Recommendation Other Considerations

Fatigue Aerobic 30 min, 3x/wk x 12 wk @65% HRmax (12 RPE)Resistance 2 sets, 12-15 reps, 2x/wk x 12 wks

Supervised or unsupervisedNo evidence of benefit from low intensity

Health-related Quality of Life

Aerobic 30 min 2-3x/wk x 12 wk @65-85% HRmax (11-13 RPE)Resistance 2-3 sets 8-15 reps, 2-3x/week x 12 wk

A: Supervised more effectiveR: Supervised + home-based

Lymphedema (br cancer)

Resistance 1-3 sets 8-15 reps, 2-3x/wk x 52 wk Supervision for prgm progression

Physical Function Aerobic 30-36 min 3x/wk x 8-12 wk @ 60-85% HRmax (12-13 RPE)Resistance 2 sets 8-12 reps, 2-3 x/wk x 8-12 wk

If unsupervised requires higher weekly threshold

Anxiety Aerobic 30-60 min 3x/wk x 12 wk @60-80% HRmax (13-15 RPE)Resistance efficacy not demonstrated

A + R suggests benefit 2 sets 8-12 reps2-3x/wk x 12 wk

Depression Aerobic 30-60 min 3x/wk x 12 wk @60-80% HRmax (13-15 RPEResistance efficacy not demonstrated

A + R suggests benefit 2 sets 8-12 reps 2-3x/wk x 12 wk

Campbell, K. L., Winters-Stone, K. M., et al . Medicine & Science in Sports & Exercise, 51(11), 2375-2390.

Evidence

Exercise Guidelines for Cancer SurvivorsModerate Evidence for Exercise Prescription

Symptom or Impairment Recommendation Other Considerations

Bone Health Exercise across trials is inconsistentCurrent trials: Breast and Prostate 1 yrsupervised program mod-vig resistance plus high-impact training 2-3x/wk

*results suggest exercise slows bone loss and may have small effect on remodeling

Sleep Findings are mixed across trials- Positive effect of walking identified- No effect of aerobic exercise

No harms in exerciseWalking or mod intensity aerobic: 30-40 min 3-4x/wk x 12 wk can be recommended

Campbell, K. L., Winters-Stone, K. M., et al Medicine & Science in Sports & Exercise, 51(11), 2375-2390.

Evidence

Exercise Guidelines for Cancer SurvivorsInsufficient* Evidence for Exercise PrescriptionSymptom or Impairment What is known

Cardiotoxicity Research in animal models shows protective effect on LV function and vascular function

Chemotherapy-Induced Peripheral Neuropathy

Exercise is safe in current trialsDegree of improvement is variable, endpoints varied from conditioning/strength to balance/mobility

Cognitive Function May have a protective effect when introduced prospectively

Falls No exercise RCTs to date with primary endpoint of falls reduction

Nausea Early study showing benefit has not been replicated in other trials

Pain Lack of high-quality trials. High variability of pain in cancer.Aromatast inhibitor-related joint arthralgia may benefit from aerobic+resist

Sexual Function Few small studies using exercise with sexual function as primary endpoint

Treatment Tolerance Recent SR suggests benefit to chemotherapy completion evidence insufficient

Campbell, K. L., Winters-Stone, K. M., et al Medicine & Science in Sports & Exercise, 51(11), 2375-2390.

*does not mean patient will not benefit

Evidence

Early inclusion of rehabilitation services represents anotherimportant partnership in survivorship care.

Moving Through Cancerhttps://www.exerciseismedicine.org/support_page.php/moving-through-cancer/

Resources: Evidence-based documentsPatient handoutsPhysician prescription pad

templateNational Registry of cancer

exercise programsToolkits for program developmentTraining materials for exercise

health professionals

Support Tools

BibliographyHigh Priority Reads

• Campbell KL, Winters-Stone KM, Wiskemann J, et al. Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable. Medicine & Science in Sports & Exercise. 2019;51(11):2375-2390.

• Schmitz KH, Campbell AM, Stuiver MM, et al. Exercise is medicine in oncology: engaging clinicians to help patients move through cancer. CA: a cancer journal for clinicians. 2019;69(6):468-484.

• Patel AV, Friedenreich CM, Moore SC, et al. American College of Sports Medicine roundtable report on physical activity, sedentary behavior, and cancer prevention and control. Medicine & Science in Sports & Exercise. 2019;51(11):2391-2402.

• Cormie P, Zopf EM, Zhang X, Schmitz KH. The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related Adverse Effects. Epidemiol Rev. 2017;39(1):71-92.

• Maltser S, Cristian A, Silver JK, Morris GS, Stout NL. A Focused Review of Safety Considerations in Cancer Rehabilitation. PM&R. 2017;9(9):S415-S428.

• Mustian KM, Alfano CM, Heckler C, et al. Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis. JAMA Oncol. 2017;3(7):961-968.

• Santa Mina D, Langelier D, Adams SC, et al. Exercise as part of routine cancer care. The Lancet Oncology. 2018;19(9):e433-e436.

• Segal R, Zwaal C, Green E, Tomasone J, Loblaw A, Petrella T. Exercise for people with cancer: a clinical practice guideline. Current Oncology. 2017;24(1):40.

• Stout NL, Baima J, Swisher AK, Winters-Stone KM, Welsh J. A Systematic Review of Exercise Systematic Reviews in the Cancer Literature (2005-2017). PMR. 2017;9(9S2):S347-S384.

Additional References

• Buffart LM, Kalter J, Sweegers MG, et al. Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs. Cancer Treatment Reviews. 2017;52:91-104.

• Boereboom CL, Williams JP, Leighton P, Lund JN, Exercise Prehabilitation in Colorectal Cancer Delphi Study G. Forming a consensus opinion on exercise prehabilitation in elderly colorectal cancer patients: a Delphi study. Tech Coloproctol. 2015;19(6):347-354.

• Bourke L, Smith D, Steed L, et al. Exercise for men with prostate cancer: a systematic review and meta-analysis. European urology. 2016;69(4):693-703.

• Carli F, Silver JK, Feldman LS, et al. Surgical prehabilitation in patients with cancer: state-of-the-science and recommendations for future research from a panel of subject matter experts. Physical medicine and rehabilitation clinics of North America. 2017;28(1):49-64.

• Cavalheri V, Granger C. Preoperative exercise training for patients with non‐small cell lung cancer. Cochrane Database of Systematic Reviews. 2017(6).

• Chen JJ, Wu P-T, Middlekauff HR, Nguyen K-L. Aerobic exercise in anthracycline-induced cardiotoxicity: a systematic review of current evidence and future directions. American Journal of Physiology-Heart and Circulatory Physiology. 2017;312(2):H213-H222.

• Cormie P, Zopf EM, Zhang X, Schmitz KH. The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related Adverse Effects.Epidemiol Rev. 2017;39(1):71-92.

• Dalzell MA, Smirnow N, Sateren W, et al. Rehabilitation and exercise oncology program: translating research into a model of care. Curr Oncol. 2017;24(3):e191-e198.

• Dittus KL, Gramling RE, Ades PA. Exercise interventions for individuals with advanced cancer: a systematic review. Preventive medicine. 2017;104:124-132.

• Fuller JT, Hartland MC, Maloney LT, Davison K. Therapeutic effects of aerobic and resistance exercises for cancer survivors: a systematic review of meta-analyses of clinical trials. Br J Sports Med. 2018.

• Heywood R, McCarthy AL, Skinner TL. Efficacy of exercise interventions in patients with advanced cancer: A systematic review. Arch PhysMed Rehabil. 2018.

• Mustian KM, Cole CL, Lin PJ, et al. Exercise Recommendations for the Management of Symptoms Clusters Resulting From Cancer and CancerTreatments. Paper presented at: Seminars in oncology nursing2016.

• Ngo-Huang A, Fontillas RC, Gupta E, et al. Implementing prehabilitation as part of enhanced recovery after surgery (ERAS) efforts at a comprehensive cancer center: A team-based approach. Journal of Clinical Oncology. 2018;36(30_suppl):137-137.

• Padgett LS, Van Dyk K, Kelly NC, Newman R, Hite S, Asher A. Addressing Cancer-Related Cognitive Impairment in Cancer Survivorship. Oncology Issues. 2020;35(1):52-57

• Roberts K, Rickett K, Greer R, Woodward N. Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis. Critical reviews in oncology/hematology. 2017;111:66-80

• Schmitz KH, Ahmed RL, Troxel AB, et al. Weight lifting for women at risk for breast cancer-related lymphedema: a randomized trial. JAMA. 2010;304(24):2699-2705.

• Sebio Garcia R, Yanez Brage MI,et al. Functional and postoperative outcomes after preoperative exercise training in patients with lung cancer: a systematic review and meta-analysis. Interactive cardiovascular and thoracic surgery. 2016;23(3):486-497.

• Singh F, Newton RU, et al. A systematic review of pre-surgical exercise intervention studies with cancer patients. Surg Oncol. 2013;22(2):92-104.

• Silver JK, Baima J, Mayer RS. Impairment-driven cancer rehabilitation: an essential component of quality care and survivorship. CA: a cancer journal for clinicians. 2013;63(5):295-317.

• Sommer MS, Staerkind M, Christensen J, et al. Effect of postsurgical rehabilitation programmes in patients operated for lung cancer: A systematic review and meta-analysis. J Rehabil Med. 2018;50(3):236-245.

• Stout NL, Binkley JM, Schmitz KH, et al. A prospective surveillance model for rehabilitation for women with breast cancer. Cancer. 2012;118(S8):2191-2200.

• Sweegers MG, Altenburg TM, Chinapaw MJ, et al. Which exercise prescriptions improve quality of life and physical function in patients with cancer during and following treatment? A systematic review and meta-analysis of randomised controlled trials. Br J Sports Med. 2017:bjsports-2017-097891

• van der Leeden M, Huijsmans RJ, et al. Tailoring exercise interventions to comorbidities and treatment-induced adverse effects in patients with early stage breast cancer undergoing chemotherapy: a framework to support clinical decisions. Disability and rehabilitation. 2018;40(4):486-496.

• Zerzan S, Smoot B, et al. The Effect of Bone-Loading Exercise on Bone Mineral Density in Women Following Treatment for Breast Cancer: A Systematic Review and Meta-analysis. Rehabilitation Oncology. 2016;34(4):144-155.

• Zhou Y, Zhu J, Gu Z, Yin X. Efficacy of Exercise Interventions in Patients with Acute Leukemia: A Meta-Analysis. PLoS One. 2016;11(7):e0159966.