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 twice as likely as the general population to receive a diagnosis of SMN after age 40 years (SIR, 2.2; 95% CI, 1.9 to 2.5). Among SMNs, risk was increased for breast cancer (SIR, 5.5; 95% CI, 4.5 to 6.7), renal cancer (SIR, 3.9; 95% CI, 2.0 to 7.5), soft tissue sarcoma (SIR, 2.6; 95% CI, 1.5 to 4.4), and thyroid cancer (SIR, 1.9; 95% CI, 1.0 to 3.5). Female sex (RR, 1.9; 95% CI, 1.3 to 2.6; P < .001) and therapeutic radiation exposure (RR, 2.2; 95% CI, 1.4 to 3.3; P < .001) were associated with an increased for 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.

Fig 1.

Patient flow diagram of eligible survivors from the Childhood Cancer Survivor Study (CCSS) age 40 years or older. SN, subsequent neoplasm.

Fig 2.

Patterns of multiple subsequent neoplasms (SNs) in survivors age 40 years or older. NMSC, nonmelanoma skin cancer; STS, soft tissue sarcoma.

Fig 3.

Cumulative incidence of new subsequent neoplasms (SNs) and subsequent malignant neoplasms (SMNs) diagnosed in survivors from the Childhood Cancer Survivor Study age 40 years or older. Solid lines are calculated cumulative incidence values; dashed lines are 95% CIs.

Fig 4.

Cumulative incidence curves on the basis of previous history of subsequent neoplasm (SN) and radiation therapy (RT). (A) SNs after age 40 years in individuals who did not receive RT for their primary disease. (B) SNs after age 40 years in individuals who did receive RT for their primary disease. (C) Subsequent malignant neoplasms (SMNs) after age 40 years without previous RT. (D) SMNs after age 40 years with previous RT. Solid lines are calculated cumulative incidence values, and dashed lines are 95% CIs.