Abstract
BACKGROUND: Curative therapy places childhood cancer survivors at increased risk for second primary malignancies (SPMs). However, there have been few population-based attempts to characterize differences between outcomes of SPMs in childhood cancer survivors and outcomes of first primary malignancies (FPMs). METHODS: Clinical and demographic information about childhood cancer survivors who developed SPMs and individuals with comparable FPMs was extracted from the Surveillance, Epidemiology, and End Results program. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models comparing the overall survival (OS) of individuals with and without a history of childhood cancer. OS was evaluated both overall and for specific cancers diagnosed in 50 or more childhood cancer survivors. Models accounted for potential confounders, including sex, race, age, treatment decade, histology, and disease stage. RESULTS: Compared with individuals with FPMs (n = 1,332,203), childhood cancer survivors (n = 1409) with an SPM experienced poorer OS (HR, 1.86; 95% CI, 1.72-2.02) after the study had accounted for cancer type, age, sex, race, and decade of diagnosis. A history of childhood cancer remained a poor prognostic factor for all specific cancers evaluated, including breast cancer (HR, 2.07; 95% CI, 1.63-2.62), thyroid cancer (HR, 3.59; 95% CI, 2.08-6.19), acute myeloid leukemia (HR, 2.38; 95% CI, 1.87-3.05), brain cancer (HR, 2.09; 95% CI, 1.72-2.55), melanoma (HR, 2.57; 95% CI, 1.55-4.27), bone cancer (HR, 1.88; 95% CI, 1.37-2.57), and soft-tissue sarcoma (HR, 2.44; 95% CI, 1.78-3.33). CONCLUSIONS: Compared with individuals without a prior cancer diagnosis, survivors of childhood cancer with an SPM experienced inferior outcomes. Survival disparities were observed for the most frequent SPMs diagnosed in childhood cancer survivors.