Risk factors for subsequent thyroid neoplasm development in childhood cancer survivors

Subsequent thyroid carcinomas (STCs) are common after childhood cancer treatment and have well-described risk factors, whereas information on subsequent thyroid adenomas (STAs) remains limited. This study compared treatment-related risk factors for STCs and STAs, assessed their associations with other subsequent neoplasms, and evaluated the incidence of STCs relative to that in the age-matched national general population. The study cohort included 4,348 childhood cancer survivors treated between 1975 and 2020; 48% were female, 23% had lymphomas, and 77% had solid tumors. STCs occurred in 44 survivors (59% female), and STAs occurred in 23 (65% female). Compared with the national general population, the risk of STCs was 7.6-fold higher in females and 23.6-fold higher in males. The median age at diagnosis was lower for STCs (25.8 vs 29.8 years). Hodgkin lymphoma was the most frequent primary cancer in both groups (48% vs 57%). The median age at first cancer diagnosis was similar between the groups (9.8 vs 9.4 years). Neck radiotherapy was a major risk factor in both groups (59% vs 83%). Additional subsequent malignant neoplasms occurred in 14% of patients with STCs and 13% of patients with STAs, whereas subsequent benign neoplasms occurred in 20% and 26%, respectively. The incidence of subsequent benign neoplasms was higher in patients with STCs than in patients with other first subsequent malignant neoplasms (P < 0.05). STCs predominated over STAs (66%). Shared risk factors included neck radiotherapy and Hodgkin lymphoma. STCs were diagnosed at a younger age. The frequent occurrence of additional subsequent neoplasms highlights the need for long-term surveillance.