Physical Activity and Endometrial Cancer Survival Janet Hildebrand Joanne Kim

Background - Physical activity in cancer Physical activity is associated with lower risk of breast, colon, and gynecologic cancers in women. Evidence from clinical and observational studies suggests that physical activity improves survival after cancer diagnosis. Most of the existing evidence comes from breast cancer studies.1 Physical activity in endometrial cancer is associated with improvement in quality of life,2 but studies on survival are lacking.3 American Cancer Society recommends exercise during and after treatment for those who are able. 4 ≈150 minutes/week of moderate-vigorous activity + strength training 2 days/week Exercise programs should be tailored to the survivor’s capabilities. Exercise can hasten recovery from side effects of treatment and prevent long-term side effects. Studies from breast cancer show that exercise lowers risk of death (24-67%) and risk of cancer recurrence (~50%). Results similar for colorectal cancer. Observed benefits include improvement in fatigue, anxiety, depression, self-esteem, happiness, QOL. Studies in endometrial cancer suggest improved sleep quality (Ref: Ambruster et al, Gynecologic oncology 2018), and QOL (Rossi et al Supportive Care in Cancer 2017) 1 Bouillet et al, Crit Rev Oncol Hematol 2015 2 Rossi et al, Supportive Care in Cancer 2017 3 Armbruster et al, Gynecologic Oncology 2017 4 Cancer Facts & Figures 2018

Endometrial Cancer Facts 4th most commonly diagnosed cancer in women after breast, lung, colorectal (7% of all incident cases) New cases in 2018 63,230 US (920 expected in SC) Rates are increasing (>1% in Whites, 2.5% in African Americans, annually) Obesity is a strong risk factor (70% of endometrial cancer patients are obese) Median age at diagnosis = 62 Expected deaths N=11,350 5-year survival 82% (62% among Black women vs 84% among Whites) Treatment by stage Early stage (I, II) Surgery alone Surgery + radiation, hormonal, and/or chemo Late stage (III, IV) Surgery, radiation, chemo Stage at Diagnosis Siegel et al., Cancer Statistics, 2018

Question ― Hypothesis Does post-diagnosis physical activity improve overall survival or progression-free survival in women with endometrial cancer? We think so! Based on results from other hormonally-driven cancer such as breast and CRC, it is plausible that PA would improve outcomes in endom cancer patients too. Results from this study would fill a gap in the literature on outcomes after endometrial cancer diagnosis.

Study Design Prospective cohort of women newly diagnosed with stage 1 and 2 endometrial cancer in South Carolina   Coordinated enrollment and clinical data collection with participating oncology practices statewide 3-year enrollment period   Pilot study among 2-3 oncology practices before full roll-out  Baseline data collection / exposure assessment within 90 days of diagnosis; follow-up at every year to update exposure Access to medical record by consent for tumor factors (stage) and treatment Additional covariables of interest: demographic, pre-diagnosis physical activity, BMI, and smoking history Follow-up to 5-years (maybe 10 years) Questions – how many participants can we reasonably expect from approximately ~1800 new cases in 2 years? Should we have a pilot among 2-3 centers? Include multiple states?

Exposure and Outcome Assessment Baseline physical activity and other information collected via in-clinic interview / health assessment administered by study coordinator Physical activity and sedentary behavior assessed by accelerometry 1 Accelerometer worn for 7 days Both physical activity and sedentary time captured  Analysis of cumulative weekly activity assessed (continuous and categorical minutes/week and metabolic energy expenditure; referent = lowest PA category) Sedentary behavior (e.g. sitting time) also captured Outcome Overall and progression-free survival ascertained through linkage with NDI (death from any cause) and SC registry (tumor progression) at 5-years Accerlerometer is lightweight and worn on a strap around the waist or hip continuously for 1 week. Issue accelerometer at each clinical visit (beginning at 6 months) along with mail-in return envelope. We will assess if they are meeting standard PA recommendation of 150 min/week moderate-vigorous physical activity (MVPA) (yes/no). 1 Broderick, Support Care Cancer (2014) 22:1121–1130

Timeline Enrollment 5-years 6 months 18 months 3 years Diagnosis Baseline data collection (within 90 days) Survival analysis NDI (death from any cause) SC Tumor Registry (disease progression) Ideally, follow-up will continue beyond 5 years so additional studies can be conducted for median survival and progression-free survival according to physical activity (and potentially other exposures) periodically (every 2 years, for example) – the study has the potential to be resource for studying many associations with endometrial cancer outcome. Enrollment 5-years 6 months 18 months 3 years 7-day accelerometer ― mailed questionnaire

Does not meet PA guidelines Power Sample size for prospective cohort study  Assume 80% power  Assume 20% of patients engage in ANY physical activity 1 Assume ratio of unexposed to exposed : 4:1 Meets PA guidelines Does not meet PA guidelines Total Sample Size  RR 0.70 30% Reduction in mortality 535 2,137 2,672 RR 0.60 40% Reduction in mortality 302 1,207 1,509 RR 0.50 50% Reduction in mortality 189 755 944 According to National Health Statistics, about 15% of women in SC meet the PA guideline. Here, we’re assuming at least 20% do some ANY physical activity (conservative). 1 Blackwell et al, Ntnl Health Stats Rep 2018 www.openepi.com/Power/PowerCohort.htm accessed 26 Nov 2018

Limitations Logistically challenging recruitment and enrollment design Depends upon engagement and support of clinicians across the state Timing of physical activity exposure assessment may be complicated by treatment and recovery Time intensive (3 years of active enrollment + 5 years follow-up) Exposure may be overestimated in this cohort – endometrial cancer survivors have high rates of obesity and inactivity Need Money!

Thanks! Questions? Comments?