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