1. Mobility Interventions for Older Cancer Patients: Design Issues Heidi D. Klepin, M.D., M.S. Associate Professor of Medicine Comprehensive Cancer Center of Wake Forest University

2. Older cancer patients are at high risk for functional decline:The perfect storm Aging Physiology  Δ body composition  ↓ cardiorespiratory fitness  ↓ strength/flexibility Common Conditions of Aging  Cognitive decline  Mood disorders  Comorbid conditions Cancer Burden  Symptoms  Mood disorder  Physiologic stress Cancer Treatment  Side effects  Physiologic stress  Inactivity  Mood disorders  Secondary comorbidities Physical Function Decline

3. Benefits of intervening upon the functional decline cascade ↑ self-reported functional limitations ↓ strength/balance/endurance physical performance The impact Cancer Burden The insult Cancer Treatment Intervention Disability ↓ Independence ↓ Quality of life ↑ Symptoms Potential consequences Death ↓ Cancer treatment outcomes ↑ Health care utilization

4. Challenges and unanswered questions ChallengesEvidenceLimitations/Gaps/Opportunities SafetyNo adverse safety signalFew elderly represented Comorbidity exclusions/frailty During treatment interventions scarce RecruitmentRanges widely (29-86%)Often not reported Factors associated with successful recruitment largely unknown AdherenceParticipation and attrition problems in high risk populations Not consistently reported Strategies to maximize unknown Age specific issues? InterventionResistance training has consistent positive effects on strength Optimal modality, intensity, frequency and timing? Supervised versus home-based? How to individualize? What outcomes??? DurabilityChange in physical activity behavior persists 2 years post intervention 1 Most interventions <6 months Longer term effects on function unknown Sustainability-resources, social support 1. Demark-Wahnefried et al. J Clin Oncol 2012

5. Gaps in knowledge: Outcomes Optimal interventions should target observed deficits Outcomes are time, population, and treatment specific Which outcomes matter most to patients? How do functional outcomes relate to quality of survivorship, cancer treatment, health care cost? Opportunity: Functional outcomes should be routinely measured in clinical trials

6. Gaps in knowledge: Intervention How do we tailor interventions to meet the needs of patients and caregivers while optimizing safety, participation, and durability of benefits?

7. Example: Physical activity for older adults with AML- 1 st attempt Eligibility ≥ 50 years Newly diagnosed or relapsed Inpatient Intensive induction ECOG 0-3 Intervention 3 sessions per week 4 week duration Multi-modal (30-40 min) –Walking –Strength –flexibility

8. Feasibility? Eligible patients (n=55) Provided informed consent (n=24) Completed baseline assessments (n=21) Did not complete baseline assessments due to: Refused (n=1) Intracranial bleed (n=1) Pneumonia (n=1) Participated in exercise (n=17) Did not participate in exercise due to: GI bleed (n=1) Confusion (n=1) Subdural hematoma (n=1) Pneumonia (n=1) Completed any follow-up assessments (n=11) Exercised but unable to complete follow-up assessments due to: Deceased (n=2) Scheduling conflict (n=3) Refused (n=1) 43% recruitment rate Retention challenges N=24 N=17 N=11

9. Exercise Sessions Attended- not many Feasibility? Klepin et al. J Geriatr Oncol 2011;2:11-17 Exercise sessions Number of participants 77%

10. Lessons learned: Importance of tailoring, flexibility and integration Physical activity intervention: offered 5x/week Behavioral counselling: offered once per week Session TypeDescription Standard (Ward based)Walking Strength and flexibility Balance training Intermediate (Room –based)Strength and flexibility Balance training Upper extremity ergometer Low-intensity (Bed-based)Upper extremity ergometer Progressive resistance Session Content Review participation, trouble shoot barriers, identify short and long term functional goals, relate goals to intervention, set weekly goals for participation

11. Tailoring improved feasibility Outcomes (N=70, mean age 73)% (feasibility target) Recruitment rate (70/98) Recruitment period 10/12-2/15 71 (≥60) Retention rate (follow-up)*95 (≥85) Participation rate (participated in offered sessions)* 83 (≥75) * As of 3/13/15, 2 participants pending FU1, 9 participants pending FU2, 1 participant remains on active PA intervention

12. Gaps in knowledge: Efficacy versus effectiveness Changing the paradigm: Is this a mobility intervention or is this optimal supportive care? Opportunity: Intervention studies which integrate into clinical care are needed

13. Gaps in knowledge: Embracing complexity Klepin et al. Journal of the American Geriatrics Society 2010; 59: 1837-1846 Percent of older AML patients impaired on GA measures

14. The majority of AML patients are impaired in multiple geriatric domains Percent Impaired (%) 63% Number of geriatric domain deficits Klepin et al. JAGS 2010; 59: 1837-1846

15. Relationship between vulnerabilities Patients with symptoms of depression are at greater risk for functional decline during induction) P= 0.0 3 P=0.07 Patients with cognitive impairment are at greater risk for functional decline during induction) SPPB

16. Challenge: Designing trials that address reality Newly diagnosed older adult hospitalized for AML chemotherapy Geriatric Assessment Usual Care Chemotherapy *Algorithm to include psychosocial counselling, pharmacy review, delirium screening, nutrition counselling based on vulnerabilities identified Symptom adapted PA intervention GA directed supportive care* Primary: Physical function (SPPB) Secondary: QOL, symptoms, coping, disease specific, health care utilization

17. Moving forward Measure functional outcomes –Core minimal battery in all clinical trials –Registries Gain perspective –Patients/providers/caregivers Conduct demonstration projects –Test methods of dissemination and integration into practice Emphasize collaboration