Effects of radioactive iodine on clonal hematopoiesis in patients with thyroid cancer: A prospective study.

[OBJECTIVE] Exposure to therapeutic radioactive iodine (RAI) is associated with an increased relative risk of myeloid malignancies. Clonal hematopoiesis (CH) is a precursor state that can be detected in blood of healthy individuals decades before overt development of leukemia. We prospective studied the effects of RAI on CH.

[DESIGN] Prospective cohort study.

[PATIENTS AND MEASUREMENTS] We examined the effect of RAI on CH in 20 patients exposed to RAI for thyroid carcinoma and 20 age-matched unexposed controls. CH status was determined at baseline, 6, 12, 18 and 24 months. We also examined the effect of CH on structural progression of disease.

[RESULTS] No CH mutations were observed in the patient population that were not present at baseline. Using a variant allelic fraction (VAF) of 2% to define CH, 6/20 older patients (55-80 years old) had CH compared to 2/20 younger patients (20-40 years old) (p = 0.11). Six patients exposed to RAI had CH compared to two patients not exposed to RAI (30% vs. 10%, p = 0.11). There was no significant difference in CH VAF increase in patients treated with RAI compared to untreated age-matched controls (3.8% vs. 1.2%, p = 0.2). CH was significantly associated with somatic BRAFV600E mutations and with worse progression-free survival in the overall cohort as well as among BRAFV600E-mutant tumors.

[CONCLUSIONS] There was no increase in CH in patients treated with RAI over a 2-year follow-up period. Larger studies with longer follow-up periods are needed to investigate the association between RAI and clonal dynamics. The presence of CH is associated with worse structural progression in both BRAFV600E-mutant and wild-type thyroid cancers.