1. Surveillance and screening for new neoplasms in adult survivors of childhood cancer A report from the Childhood Cancer Survivor Study (CCSS) Paul Nathan MD, MSc The Hospital for Sick Children Toronto, Canada

2. 5-year cancer survival in children ~80% Over 325,000 childhood cancer survivors alive in United States Over 40% of survivors will develop a severe or life threatening late effect of therapy Background The childhood cancer survivor population

3. 30-year cumulative incidence of SMN = 9.3% 30-year cumulative incidence of non-melanoma skin cancer = 6.9% Leading cause of death in 20+ year survivors Standardized incidence ratio = 9.0 Standardized mortality ratio = 15.2 Meadows et al. JCO, 2009; Mertens et al. JNCI, 2008 SMN in the CCSS cohort Second malignant neoplasms (SMN) in childhood cancer survivors

4. 1.To assess adherence to published cancer surveillance guidelines by survivors at high risk for breast, colorectal or skin cancer as a result of their therapy 2.To compare non-high risk survivors’ adherence to national screening guidelines for breast, colorectal and cervical cancer with the general population Study Aims

5. Retrospective cohort study 26 centers: USA and Canada Diagnosis 1970-1986 < 21 years at diagnosis Alive at 5 years Selected malignancies Childhood Cancer Survivor Study

6. Coordinating Center Contributing Institutions Resource Center Participating Centers

7. Study participants

8. Eligible n=20,602 Eligible n=20,602 Contacted n=17,567 Contacted n=17,567 Participants in Baseline Survey n=14,370 Participants in Baseline Survey n=14,370 Participants in Follow-up 2000 n=10,388 Participants in Follow-up 2000 n=10,388 Participants in Follow-up 2003 n=9,308 Participants in Follow-up 2003 n=9,308 Eligible for Current Analysis n=8,318 Eligible for Current Analysis n=8,318 Lost to Follow-up n=3,035 Lost to Follow-up n=3,035 Declined Participation n=3,197 Declined Participation n=3,197 Deceased Cases n=1,541 Deceased Cases n=1,541 Exclusions n=990 Developed SMN (n=960) Race/ethnicity unknown (n=29) Other (n=1) Exclusions n=990 Developed SMN (n=960) Race/ethnicity unknown (n=29) Other (n=1)

9. Survivors (8,318) Population control (8,318)* Gender (male)51.9% Race (White, non-Hispanic)88.7% Mean age at diagnosis (SD), years 7.8 (5.7)- Mean age at interview (SD), years 31.2 (7.3)32.7 (10.6) Cancer center visit in last 2 years 12.5%- *Matched 1:1 by age, gender, race/ethnicity from 2003 National Health Interview Survey Demographics of Study Population

10. Cancer Diagnosis in 8,318 Survivors

11. Specific Aim 1 Adherence to published cancer surveillance guidelines by survivors at high risk for breast, colorectal or skin cancer

13. Risk Definitions and Recommended Surveillance COLORECTALBREASTSKIN HIGH-RISK >30 Gy to abdomen, pelvis or spine N=794 Female, >20 Gy to breast N=521 Any radiation therapy N=4,833 RECOMMENDED SURVEILLANCE Colonoscopy every 5 years starting at age 35 Annual mammogram starting at later of 8 years after radiation or age 25 Annual dermatologic exam of irradiated areas

14. Compliance with Recommended Surveillance Tests

15. Predictors of Adherence Multivariable Logistic Regression Models Covariates Sex Race/ethnicity Age at diagnosis and interview Employment, education, insurance Chronic disease, mental health, physical impairment, concern about future health Survivor or doctor has cancer treatment summary Medical care in last 2 years, care at a cancer center

16. Significant Predictors of Adherence Multivariable Logistic Regression Models Colonoscopy Older age at interview RR=1.08 (1.00-1.17) Mammogram Older age at interview RR=1.09 (1.04-1.13) Care at cancer center RR=1.70 (1.04-2.76) Skin exam Non-white RR=0.63 (0.42-0.95) Care at cancer center RR=1.55 (1.22-1.96) Survivor has treatment summary RR=1.30 (1.07-1.58)

17. Specific Aim 2 Comparison of “non-high risk” survivors vs. general population on adherence to national screening guidelines for breast, colorectal and cervical cancer

18. US Preventive Services Task Force Cancer Screening Recommendations Breast Screening mammography every 1-2 years for women aged 40 and older Colorectal Colonoscopy at intervals of 10 years between ages of 50-75 years* Cervix Pap smear beginning within 3 years of onset of sexual activity or age 21 (whichever comes first) and screening at least every 3 years * OR annual fecal occult blood testing OR sigmoidoscopy every 5 years combined with fecal occult blood testing every 3 years

19. US Preventive Services Task Force Cancer Screening Recommendations BreastColonCervix RR=1.29RR=0.97RR=1.17 95% CI, 1.12-1.4895% CI, 0.31-3.0095% CI, 1.14-1.20 P<0.001P=0.95P=<0.001 Compliance with screening Survivor Gen. Pop.

20. Significant Predictors of Adherence Multivariable Logistic Regression Models Breast None Colon Too few survivors over 50 years to analyse in detail Emerging evidence of increased GI malignancies in survivor cohort Cervix Only being “married or living as married” predicted PAP smear compliance (RR 1.17, 1.03-1.34)

21. Conclusions (1) Adherence to Guidelines for Cancer Survivors Rates of colonoscopy, mammography and skin exams in high-risk patients are very low. Care at a cancer center modestly increases surveillance for breast and skin cancer. Patients and their physicians need to be educated about recommended surveillance.

22. Conclusions (2) Adherence to National Screening Guidelines Survivors Cancer survivors are more likely to undergo mammograms and PAP smears than general population. BUT: Compliance rates are very low for colonoscopy and only moderate for mammography. Health care providers must take opportunity to promote early cancer detection strategies in survivors.

23. Study Considerations 1.Self-report data 2.CCSS cohort is a select group – study may overestimate care received 3.Cohort 1970-1986 4.Did not assess all screening/surveillance modalities (e.g. breast MRI, fecal occult blood)

24. Co-Investigators Kevin Oeffinger, Memorial Sloan-Kettering Cancer Center Kirsten Ness, St. Jude Children’s Research Hospital Martin Mahoney, Roswell Park Cancer Institute Zhenghong Li, St. Jude Children’s Research Hospital Melissa Hudson, St. Jude Children’s Research Hospital Jennifer Ford, Memorial Sloan-Kettering Cancer Center Wendy Landier, City of Hope Greg Armstrong, St. Jude Children’s Research Hospital Tara Henderson, University of Chicago Leslie Robison, St. Jude Children’s Research Hospital

25. CCSS Institutions University of Minnesota Denver Children’s Hospital Children’s Hospital of Pittsburgh Stanford University Dana-Farber Cancer Institute Children’s National Medical Center M.D. Anderson Cancer Center Memorial Sloan-Kettering Cancer Center Texas Children’s Hospital University of California, San Francisco Seattle Children’s Hospital Toronto Hospital for Sick Children Children’s Medical Center of Dallas Children’s Hospital of Columbus Emory University St. Jude Children’s Research Hospital Roswell Park Cancer Center Mayo Clinic Children’s Health Care Minneapolis Children’s Hospital of Philadelphia St. Louis Children’s Hospital Children’s Hospital of Los Angeles UCLA Medical Center Miller Children’s Hospital Long Beach Children’s Hospital of Orange County Riley Hospital for Children – Indiana Univ. UAB/Children’s Hospital of Alabama University of Michigan – Mott Children’s Fred Hutchinson Cancer Research Center

26. A Resource for Research The Childhood Cancer Survivor Study is an NCI-funded resource to promote and facilitate research among long-term survivors of cancer diagnosed during childhood and adolescence. Investigators interested in potential uses of this resource are encouraged to visit: www.stjude.org/ccss