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

Abstract

Purpose Survivors of childhood cancer have an increased risk for subsequent neoplasms (SNs), but the incidence beyond the age of 40 years and associations with therapeutic exposures have not been well described. Patients and Methods Among 14,364 survivors of childhood cancer diagnosed between 1970 and 1986, 3,171 had an attained age of 40 years or older at the time of last contact. Cumulative incidence of SNs, standardized incidence ratios (SIRs), excess absolute risk of subsequent malignant neoplasms (SMNs), and relative risks (RRs) for SMNs and nonmelanoma skin cancers were calculated. Results In total, 679 SNs were diagnosed in patients age 40 years or older. These included 196 SMNs, 419 nonmelanoma skin cancers, 21 nonmalignant meningiomas, and 43 other benign neoplasms. At age 55 years, the cumulative incidence of new SNs and SMNs occurring after age 40 years was 34.6% (95% CI, 28.7 to 40.6) and 16.3% (95% CI, 11.7 to 20.9), respectively. Survivors were four times as likely as the general population to receive a diagnosis of SMN after age 40 years (SIR, 4.4; 95% CI 3.8 to 5.0). Among SMNs, risk was most increased for soft tissue sarcoma (SIR, 12.3; 95% CI, 7.2 to 21.0), breast cancer (SIR, 8.3; 95% CI, 6.9 to 10.0), renal cancer (SIR, 6.1; 95% CI, 3.2 to 11.6), and thyroid cancer (SIR, 5.1; 95% CI, 2.8 to 9.4). Female sex (RR, 1.5; 95% CI, 1.1 to 2.1; P = .008), platinum chemotherapy (RR, 3.4; 95% CI, 1.5 to 7.7; P = .003), epipodophyllotoxins (RR, 2.4; 95% CI, 1.0 to 5.8; P = .05), and therapeutic radiation exposure (RR, 2.0; 95% CI, 1.4 to 3.1; P < .001) were associated with higher risk for SMN in multivariable analysis. Conclusion Even after age 40 years, survivors of childhood cancer remain at increased risk for treatment-related SNs. These data suggest the need for life-long monitoring and should inform anticipatory guidance provided to survivors of childhood cancer.