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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 CenterDavid Geffen School of MedicineUniversity of California, Los Angeles
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
• 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
BackgroundThe childhood cancer survivor population
• 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
BackgroundPrevious studies of PTSD
• 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
• 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
Eligiblen=20,691
Eligiblen=20,691
Contactedn=17,633
Contactedn=17,633
Participants in Baseline Surveyn=14,357
Participants in Baseline Surveyn=14,357
Participants in Follow-up 2003n=11,576
Participants in Follow-up 2003n=11,576
Completed surveys of interestn=9,308
Completed surveys of interestn=9,308
Eligible for Current Analysisn=6, 542
Eligible for Current Analysisn=6, 542
Lost to Follow-upn=3,058Lost to Follow-upn=3,058
Declined or deceasedn=3,276Declined or deceasedn=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 interestN=2,268
Not invited to complete surveys of interestN=2,268
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
Study Population (n=6,542)
Bone9%
CNS11%
Hodgkin14%
NHL8%Leukemia
33%
Wilms10%
Soft-tissue9%
Neuroblastoma6%
Mean age at diagnosis = 8.2 years (range 0-20)Mean age at survey = 31.9 years (range 18-53)
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)
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)
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
DiagnosisNumber with
PTSD % with PTSD
Bone cancer 67 11%
CNS 78 11%
Hodgkin Disease 93 10%
Leukemia 195 9%
NHL 41 8%
Soft tissue sarcoma 48 8%
Wilms 43 7%
Neuroblastoma 24 6%
Prevalence of PTSD
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)
Increased risk of PTSD by age at diagnosis by radiation exposure
Age at Diagnosis
Radiation Odds Ratio*(95% CI)
P-value
0-4 years Cranial RT 2.05 (1.41 -2.97 ) <.001
RT other site 1.57 (1.02 -2.43 ) 0.04
5-9 years Cranial RT 1.25 (0.76 -2.04 ) 0.39
RT other site 1.83 (1.09 -3.06 ) 0.02
10-14 years Cranial RT 0.58 (0.34 -1.00 ) 0.05
RT other site 1.10 (0.69 -1.75 ) 0.69
15-20 years Cranial RT 0.82 (0.42 -1.59 ) 0.56
RT other site 1.09 (0.67 -1.77 ) 0.74
*Odds ratio were calculated using “No RT” as the reference
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)
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
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
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.
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
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