Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort

Abstract

Childhood cancer survivors are at increased risk for subsequent neoplasms (SNs), but the incidence beyond age 40 and associations with therapeutic exposures have not been well- described. Among 14,364 childhood cancer survivors diagnosed between 1970 and 1986, 3,171 had an attained age ≥40 years at the time of last contact. Cumulative incidence of SNs, standardized incidence ratios (SIRs) and excess absolute risk of subsequent malignant neoplasms (SMNs), and relative risks (RR) for SMNs and non-melanoma skin cancers (NMSCs), were calculated. In total, 679 SNs were diagnosed ≥40 years of age, including 196 SMNs, 419 NMSCs, 21 non-malignant meningiomas, and 43 other benign neoplasms. At age 55, the cumulative incidence of new SNs and SMNs occurring beyond age 40 was 34.6% (95% CI 28.7-40.6) and 16.3% (95% CI 11.7-20.9), respectively. Survivors were twice as likely as the general population to be diagnosed with a SMN after age 40 (SIR=2.2, 95% CI 1.9-2.5). Among SMNs, risk was increased for breast cancer (SIR=5.5, 95% CI 4.5-6.7), renal cancer (SIR=3.9, 95% CI 2.0-7.5), soft tissue sarcoma (SIR=2.6, 95% CI 1.5-4.4), and thyroid cancer (SIR=1.9, 95% CI 1.0-3.5). Female sex (RR=1.9, 95% CI 1.3-2.6, P<0.001) and therapeutic radiation exposure (RR=2.2, 95% CI 1.4-3.3, P<0.001) were associated with higher risk for SMN in multivariable analysis. Even beyond 40 years of age, survivors of childhood cancer remain at increased risk for treatment-related SNs. These data suggest the need for lifelong monitoring and should inform anticipatory guidance provided to childhood cancer survivors.