1. Prevalence and Predictors of Posttraumatic Stress Disorder in Adult Survivors of Childhood Cancer A report from the Childhood Cancer Survivor Study Margaret L. Stuber, M.D. Jonsson Cancer Center David Geffen School of Medicine University of California, Los Angeles

2. Co-Investigators Kathleen Meeske, Children's Hospital, Los Angeles Kevin Krull, St. Jude Children’s Research Hospital Wendy Leisenring, Fred Hutchinson Cancer Research Center Kayla Stratton, Fred Hutchinson Cancer Research Center Anne E. Kazak, Children’s Hospital of Philadelphia Marc Huber, SAS Consulting Brad Zebrack, University of Michigan Sebastian H. Uijtdehaage, UCLA Ann C Mertens, Emory University Leslie L. Robison, St. Jude Children’s Research Hospital Lonnie K. Zeltzer, Jonsson Cancer Center, UCLA

3. 5-year cancer survival in children across diagnostic groups is approximately 80% Over 325,000 childhood cancer survivors now alive in United States, and growing Functional and emotional outcomes of survivors as they enter adulthood a concern Background The childhood cancer survivor population

4. Some childhood cancer survivors report symptoms of Posttraumatic Stress Disorder (PTSD) many years after successful treatment PTSD symptoms are associated with functional impairment and emotional distress in young adult survivors of childhood cancer Background Previous studies of PTSD

5. Compare the prevalence of PTSD in young adult childhood cancer survivors to a sibling control group Examine the association of PTSD with demographic variables, including gender, ethnicity, level of education, employment, marital status, and income Assess the association of PTSD with cancer- related variables Study Aims

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

7. Eligible n=20,691 Eligible n=20,691 Contacted n=17,633 Contacted n=17,633 Participants in Baseline Survey n=14,357 Participants in Baseline Survey n=14,357 Participants in Follow-up 2003 n=11,576 Participants in Follow-up 2003 n=11,576 Completed surveys of interest n=9,308 Completed surveys of interest n=9,308 Eligible for Current Analysis n=6, 542 Eligible for Current Analysis n=6, 542 Lost to Follow-up n=3,058 Lost to Follow-up n=3,058 Declined or deceased n=3,276 Declined or deceased n=3,276 Exclusions n=2,766 Currently under 18 Proxy reporter Exclusions n=2,766 Currently under 18 Proxy reporter Study Population Not invited to complete surveys of interest N=2,268 Not invited to complete surveys of interest N=2,268

8. Survivors n=6,542 Siblings n=368 *Statistically significant differences between groups at < 0.01 Male 47.7% 47.6% Race ( non-Hispanic white) 87.5% 93.8%* Employed ( yes) 78.0% 84.2%* Education (college grad+) 48.3% 51.1% Marital status (single) 41.2% 28.0%* Income <$20,000 42.2% 34.1%* Study Population

9. Study Population (n=6,542) Bone 9% CNS 11% Hodgkin 14% NHL 8% Leukemia 33% Wilms 10% Soft-tissue 9% Neuroblastoma 6% Mean age at diagnosis = 8.2 years (range 0-20) Mean age at survey = 31.9 years (range 18-53)

10. Composite dichotomous variable: PTSD Self reported symptoms of PTSD using Foa PDS (reexperiencing, avoidance, hyper-arousal) Self-report of emotional distress (Brief Symptom Inventory) Functional impairment (SF-36)

11. Composite dichotomous variable: Intensity of treatment Combined modality therapy Radiation (TBI, cranial, mantle, pelvic, lung, abdomen) Recurrence, transplant, high dose anthracycline or alkylating agent Major surgery within two years of diagnosis (except nephrectomy)

12. N PTSD Siblings 368 8 (2.2%) Survivors 6542 589 (9.0%) Odds ratio* = 4.36 Odds ratio= 4.36 95% CI = 2.19-8.66 P-value < 0.0001 *(adjusted for age at interview, gender, within-family correlations) Prevalence of PTSD

13. Diagnosis Number with PTSD % with PTSD Bone cancer 6711% CNS 7811% Hodgkin Disease 9310% Leukemia195 9% NHL 41 8% Soft tissue sarcoma 48 8% Wilms 43 7% Neuroblastoma 24 6% Prevalence of PTSD

14. Results: Variables Statistically Significantly Associated with PTSD Age at interview 30-39 yrs Not employed Education <high school Personal Income <$20,000 Single, never married Intensive treatment 1.0 1.5 2.0 2.5 3.0 Odds Ratio (95% CI)

15. Increased risk of PTSD by age at diagnosis by radiation exposure Age at Diagnosis RadiationOdds Ratio* (95% CI) P-value 0-4 years Cranial RT2.05 (1.41 -2.97 )<.001 RT other site1.57 (1.02 -2.43 )0.04 5-9 yearsCranial RT1.25 (0.76 -2.04 )0.39 RT other site1.83 (1.09 -3.06 )0.02 10-14 yearsCranial RT0.58 (0.34 -1.00 )0.05 RT other site1.10 (0.69 -1.75 )0.69 15-20 yearsCranial RT0.82 (0.42 -1.59 )0.56 RT other site1.09 (0.67 -1.77 )0.74 *Odds ratio were calculated using “No RT” as the reference

16. Variables NOT associated with PTSD Gender ( usually women report more symptoms) Race/ethnicity Year of diagnosis (not a “generational” effect) Recurrence or second malignancy (except when combined into treatment intensity variable) Age at diagnosis (except in interaction with CRT)

17. Clinical Implications Although most childhood cancer survivors are resilient, a subset meet full criteria for PTSD Survivors are at significantly greater risk for PTSD than their siblings Survivors with PTSD are generally not doing well with developmental tasks of young adults More intense treatment increases risk of PTSD and functional difficulties

18. Which came first, PTSD or poor function? Because the diagnosis of PTSD included self- reported functional impairment and clinically significant distress, it is not surprising that these survivors were not doing well Survivors were less likely to be married or employed and had lower income than siblings as a group, despite similar education Perhaps marriage, employment, and higher income are protective

19. Conclusions While survivors of childhood cancer are at significantly higher risk of PTSD compared to siblings, only 9% are effected. Younger age at cranial radiation and more intensive therapy are significant predictors of risk for PTSD. While PTSD is associated with a spectrum of psychosocial outcomes, the relationship needs to be clarified.

20. 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 Mattel Children’s Hospital at UCLA Miller Children’s Hospital Long Beach Children’s Hospital of Orange County Riley Hospital for Children – Indiana University UAB/Children’s Hospital of Alabama University of Michigan – Mott Children’s Fred Hutchinson Cancer Research Center

21. 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