Health Outcomes in Childhood Cancer Survivors with Congenital Anomalies in the Childhood Cancer Survivor Study

BACKGROUND: Congenital anomalies are associated with an increased risk of childhood cancer. However, there is a knowledge gap about health outcomes for childhood cancer survivors with congenital anomalies. METHODS: We included childhood cancer survivors from the Childhood Cancer Survivor Study (n = 22,247), comparing survivors with and without self-reported anomalies. Using Cox regression, we estimated HR and 95% confidence intervals (CI) of chronic health conditions (CHC) classified per the Common Terminology Criteria for Adverse Events from 1 (mild) to 5 (fatal) and subsequent malignant neoplasms (SMN), comparing survivors by anomaly status. We calculated age-, sex-, and calendar year-specific mortality rates and standardized mortality ratios for survivors compared with the US population. RESULTS: Among survivors, 16.9% (n = 3,880) reported a congenital anomaly. Survivors with anomalies had a higher rate of any CHC (grades 1-5: HR, 1.24; 95% CI, 1.18-1.31), severe CHCs (grades 3-5: HR, 1.29; 95% CI, 1.19-1.40), and multiple CHCs of any grade (≥2 CHCs: HR, 1.31; 95% CI, 1.24-1.39; ≥3 CHCs: HR, 1.42; 95% CI, 1.33-1.52). Survivors with anomalies had an increased rate of soft-tissue sarcomas (HR, 1.96; 95% CI, 1.12-3.44). For deaths related to the original cancer diagnosis, survivors with anomalies (compared with those with no anomalies) had a lower mortality rate (0.64 vs. 0.90 per 1,000 person-years). CONCLUSIONS: We identified an increased rate of CHCs and SMNs among childhood cancer survivors with anomalies and lower mortality directly related to the cancer diagnosis. IMPACT: Future work will focus on the evaluation of genetic pathways that increase the risk of CHCs and SMNs.