Risk of subsequent myeloid neoplasms after radiotherapy treatment for a solid cancer among adults in the United States, 2000–2014

Although increased risk of acute myeloid leukemia (AML) has been observed after chemotherapy and radiotherapy, less is known about radiotherapy-related risks of specific AML subtypes and other specific myeloid neoplasms. We used the US population-based cancer registry data to evaluate risk of myeloid neoplasms among three cohorts of cancer survivors initially treated with radiotherapy only. We included 1-year survivors of first primary thyroid (radioiodine only, stages I–IV; N = 49 879), prostate (excluding stage IV; N = 237 439), or uterine corpus cancers (stage I–II; N = 16 208) diagnosed during 2000–2013. We calculated standardized incidence ratios (SIRs) and excess absolute risks (EARs). Thyroid cancer survivors had significantly elevated risks of total AML (SIR = 2.77, 95% CI: 1.99–3.76), AML with cytogenetic abnormalities (SIR = 3.90, 95% CI: 1.57–8.04), AML with myelodysplasia-related changes (SIR = 2.87, 95% CI: 1.05–6.25), and BCR-ABL1-positive chronic myelogenous leukemia (CML) (SIR = 5.38, 95% CI: 2.58–9.89). Irradiated prostate and uterine corpus cancer survivors were at elevated risk for total AML (SIR = 1.14, 95% CI: 1.03–1.27 and SIR = 1.77, 95% CI: 1.01–2.87, respectively), AML with cytogenetic abnormalities (SIR = 2.52, 95% CI: 1.84–3.37 and SIR = 7.21, 95% CI: 2.34–16.83, respectively), and acute promyelocytic leukemia (SIR = 3.20, 95% CI: 2.20–4.49 and SIR = 8.88, 95% CI: 2.42–22.73, respectively). In addition, prostate cancer survivors were at increased risk of BCR-ABL1-positive CML (SIR = 2.11, 95% CI: 1.52–2.85). Our findings support the importance of diagnostic precision in myeloid neoplasm classification since susceptibility following radiotherapy may vary by myeloid neoplasm subtype, thereby informing risk/benefit discussions in first primary cancer treatment.