1. Exercise and nutrition interventions for older cancer survivors: What next? Wendy Demark-Wahnefried, PhD, RD Professor and Webb Chair of Nutrition Sciences Associate Director, UAB Comprehensive Cancer Center

2. PubMed Search (Elderly OR Older AND Cancer Survivors) Exercise or Physical Activity = 82 papers - 3 RCTs, 2 – 1 arm feasibility (2 Design Papers) Diet = 30 Papers - No Diet-Specific Clinical Trials or Design Papers - Two Diet and Exercise RCTs

3. Justification for Diet & Exercise Interventions that Target Older Cancer Survivors 11.1% of older adults (n = 15,425) adhere to US guidelines for alcohol, tobacco, dietary fat and fruits & vegetables (F&V), and exercise. Most common lifestyle pattern among elderly is adherence to alcohol & tobacco guidelines, but not those for exercise, F&V and dietary fat. Berrigan et al. Prev Med 36:615,2003 Significantly Higher Physical Function Subscale Scores were observed in survivors with ↑ PA (p<.0001) & F&V Intake (p=.0049) & Low Fat Diets (p<.0001) (688 Breast & Prostate Cancer Survivors) Demark-Wahnefried et al. Intl J Behav Nutr Phys Activ. 2004;1(1):16, 2004 In a mixed sample of 190 older survivors, 60% reported distress due to weight change, 64% due to balance or mobility issues & 79% due to fatigue Schlairet & Benton J Cancer Educ. 27:21, 2012 In 753 older breast, prostate & CRC survivors, diet quality associated with ↑Physical QoL & higher BMI associated with ↓ QoL Mosher et al. Cancer. 115:4001, 2009. Older female survivors (n=2,017) who practice 6-8 vs 0-4 WCRF/ AICR Recommendations have 33% lower all cause mortality Inoue-Choi et al. CEBP 22:792, 2013 Higher BMI ↑ odds of frailty by 12% (p=.003); higher PA ↓ odds of frailty by 10% (p <0.001) in 261 older BCS. Bennett et al. Oncol Nurs Forum 40:E126, 2013

4. Interventions – Main Outcomes Team (yr)SampleInterventionResults Benton (2014) 40 Breast (half 40-59 v 60-80) 8-week, 2x/week resistance training Improved chest (p <.001) & press (p <.001); arm curls (p <.05); & chair stands (p <.001) in both groups. Older ♀ more barriers, less improvement in QoL. Campo (2014) 40 Prostate (58-93 yr) 12-week, 2x/week Qigong v stretch Qigong arm greater improvements in FACIT-Fatigue (p = 0.02) & distress (BSI-18, p's < 0.05), signif. better attendance (p=.04) Demark- Wahnefried Project LEAD (2006) 182 Breast & Prostate (65+ yrs) 6M mailings + phone counseling (diet + exercise vs general health) Baseline to 6M change scores in intervention v control: PF= +3.1 v - 0.5 (P =.23); physical activity +111 kcal/wk v -400 kcal/wk (P =.13); diet quality index, +2.2 v -2.9 (P =.003). LaStayo (2010) RENEW 1 Lymphoma, 10 Breast, 5 Prostate, 4 CRC (60+ yrs) 12-week, 3x/week resistance exercise on negative eccen- tric ergometer Signif. improvements in knee extension peak torque production (↑11%)(P =.02) & up-and-go test (↓14%) (P <.001) Morey (2009) RENEW 641 Obese/ Overweight Breast, CRC, Prostate, (age 65+) 1-yr tailored mail + phone counsel on diet+exercise (wait-list v immediate) Intervention vs waitlist ∆’s PF -2.15 vs -4.84 (P =.03); basic lower extremity function +0.34 vs -1.89 (P =.005), & weight PA, diet quality, & overall QoL ↑ significantly in intervention vs control, and weight loss greater (2.06 kg [95% CI, 1.69 to 2.43 kg] vs 0.92 kg [95% CI, 0.51 to 1.33 kg], P <.001). Winters- Stone (2012) POWIR 106 Breast Cancer (age 50+) 1-year, 3x/week (2 clinic, 1 home) resistance + impact exercise vs stretch signif improvements in max. leg (p <0.02) & bench (p <0.02) press strength in intervention v control Winters- Stone (2015) 51 Prostate (on ADT) As aboveSignif. improvements in max. leg (P=.032) & bench press strength (P=.027), & PF (P=.016) in POWIR v control. Disability lessened more with resistance training v stretching (P=.018). Change in leg press strength mediated change in self-reported disability (P<.05).

5. Findings from Secondary Analysis Behavior change is mediated through traditional constructs, such as self efficacy Loprinzi & Cardinal Breast Cancer 20:251,2012 & Loprinzi et al. Support Cancer Care 20:2511,2012 Resistance training exercise improves bone mineral density, but Older (age 65+) vs. younger (50-65) BCS less likely to ↑ BMD in response to mechanical loading Winters-Stone et al. Arch Osteoporosis 7:301,2012. Light physical activity increases PF, especially advanced lower extremity functioning. Blair et al. MSSE 46:1375, 2014 The RENEW mailed material + phone counseling intervention resulted replicable findings in the wait-listed arm and in durable improvements in PA, diet quality and weight loss at 2-year follow-up. But, physical functioning resumed downward trajectory post-intervention. Demark- Wahnefried et al. J Clin Oncol 30:2354, 2012

6. Preferences & Concerns of the Older Cancer Survivor Unaware of increased risk status Increased cumulative disease burden Lower health literacy Transportation issues More likely to view cancer as “beyond their control” Functional/sensory deficits (low vision/hearing impairment) Value preferences favoring more immediate gratification Some data suggest less likely to change behavior & to maintain change Interventions tailored to limitations, holistic & involve others (BCS) Patterson et al. JADA 103:323, 2003; Courneya et al. Crit Rev Oncol/Hematol 51: 249, 2004; Rao & Demark-Wahnefried Crit Rev Oncol Hematol 60:131, 2006; Whitehead & Lavelle Qual Health Res 19:894, 2009; Klepin Interdisc Topics Gerontol. 2013;38:146-157.

7. What Next? Population: Interventions in survivors of other cancers besides breast & prostate Outcomes: - Select biomarkers (mechanisms associated with successful aging) - Co-morbidity & symptoms - Cost Interventions: - Rethink (test) content & strategy (i.e., older individuals may require different dosing or schedule) - Multi-Component-Holistic Approaches that address barriers to participation or dissemination - Crossing the “Valley of Death”