BACKGROUND: The occurrence of subsequent neoplasms has direct impact on the 
quantity and quality of life in cancer survivors. We have expanded our analysis 
of these events in the Childhood Cancer Survivor Study (CCSS) to better 
understand the occurrence of these events as the survivor population ages.
METHODS: The incidence of and risk for subsequent neoplasms occurring 5 years or 
more after the childhood cancer diagnosis were determined among 14,359 5-year 
survivors in the CCSS who were treated from 1970 through 1986 and who were at a 
median age of 30 years (range = 5-56 years) for this analysis. At 30 years after 
childhood cancer diagnosis, we calculated cumulative incidence at 30 years of 
subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess 
absolute risks (EARs) for invasive second malignant neoplasms, and relative 
risks for subsequent neoplasms by use of multivariable Poisson regression.
RESULTS: Among 14,359 5-year survivors, 1402 subsequently developed 2703 
neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis 
was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent 
neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms 
(excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for 
nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess 
risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% 
CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the 
highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing 
sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable 
analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis 
of Hodgkin lymphoma, and treatment with radiation therapy were associated with 
increased risk of subsequent neoplasm.
CONCLUSIONS: As childhood cancer survivors progress through adulthood, risk of 
subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at 
greatest risk. There is no evidence of risk reduction with increasing duration 
of follow-up.