Laura Boucai1, John Falcone2, Jenny Ukena1, Catherine C Coombs3, Ahmet Zehir4, Ryan Ptashkin4, Michael F Berger4,5, Ross L Levine5,6, James A Fagin1,5. 1. Division of Endocrinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York. 2. Weill Cornell Medical College, New York, New York. 3. Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 4. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York. 5. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York. 6. Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
Abstract
Context: Radioactive iodine (RAI) has been epidemiologically associated with the development of hematologic malignancies. Clonal hematopoiesis (CH) is a precursor clonal state that confers increased risk of leukemia and occurs at an elevated rate in patients with thyroid cancer relative to other solid tumors. Objective: We explore if the high prevalence of CH may be a result of RAI exposure and whether CH may be a surrogate in the association between RAI and leukemia. Design: CH, CH-potential driver (CH-PD), and overall survival were evaluated in 279 patients with advanced thyroid carcinoma. Results: The prevalence of CH in patients with thyroid cancer was 37%, and that of CH-PD was 5.2%. Age was the strongest predictor of CH and CH-PD. For every year increase in age, there was a 5% and 13% increase in the odds of CH and CH-PD, respectively. RAI dose was significantly associated with CH and CH-PD, even after adjustment for age, external beam radiation therapy, and chemotherapy. For every 10 mCi increase in the dose of RAI administered, there was a 2% and 4% increase in the odds of CH and CH-PD, respectively. Patients with CH-PD previously exposed to RAI had a significantly poorer survival, even when stratified by age (heart rate = 3.75, 95% CI = 1.23 to 11.5, P = 0.02). Conclusions: RAI was associated with a high prevalence of CH, and CH is a precursor state of hematologic malignancies. The implications of this study may favor identification of CH in patients where the risks might outweigh the benefits of receiving RAI therapy for thyroid cancer.
Context:Radioactive iodine (RAI) has been epidemiologically associated with the development of hematologic malignancies. Clonal hematopoiesis (CH) is a precursor clonal state that confers increased risk of leukemia and occurs at an elevated rate in patients with thyroid cancer relative to other solid tumors. Objective: We explore if the high prevalence of CH may be a result of RAI exposure and whether CH may be a surrogate in the association between RAI and leukemia. Design: CH, CH-potential driver (CH-PD), and overall survival were evaluated in 279 patients with advanced thyroid carcinoma. Results: The prevalence of CH in patients with thyroid cancer was 37%, and that of CH-PD was 5.2%. Age was the strongest predictor of CH and CH-PD. For every year increase in age, there was a 5% and 13% increase in the odds of CH and CH-PD, respectively. RAI dose was significantly associated with CH and CH-PD, even after adjustment for age, external beam radiation therapy, and chemotherapy. For every 10 mCi increase in the dose of RAI administered, there was a 2% and 4% increase in the odds of CH and CH-PD, respectively. Patients with CH-PD previously exposed to RAI had a significantly poorer survival, even when stratified by age (heart rate = 3.75, 95% CI = 1.23 to 11.5, P = 0.02). Conclusions: RAI was associated with a high prevalence of CH, and CH is a precursor state of hematologic malignancies. The implications of this study may favor identification of CH in patients where the risks might outweigh the benefits of receiving RAI therapy for thyroid cancer.
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