Radioactive Iodine Increases Risk of Myeloid Malignancies in Patients with Thyroid Cancer

SUMMARY: The American Cancer Society estimates that about 53,990 new cases of thyroid cancer will be diagnosed in the United States for 2018 and about 2,060 patients will die of the disease. Thyroid cancer is the most prevalent endocrine malignancy and is classified into three histological groups – Well Differentiated Thyroid Cancers (94%) which include Papillary (80%), Follicular (11%) and Hürthle cell (3%) histologies, Medullary Thyroid Carcinoma (MTC) representing 4% and Anaplastic (undifferentiated) Thyroid Carcinoma (ATC) representing about 2%. Patients with WDTC often undergo thyroidectomy followed by adjuvant radioactive iodine (RAI) to ablate residual or unresectable disease. Approximately 20% of the patients with WDTC develop local recurrence and 10% develop metastatic disease at 10 years following surgery, RadioIodine Ablation (RIA) and TSH suppressive therapy. There has been a four-fold increase in the incidence of WDTC over the past 30 years and this has been attributed to improved detection of small, low-risk tumors. Majority of these patients are treated with RAI where patients do not derive therapeutic benefit but are rather exposed to its carcinogenic effects. Although prior studies have shown an increased risk of Secondary Hematologic Malignancies in patients with WDTC treated with RAI, these analyses grouped all types of leukemia under one broad category, which oversimplified risk estimation.

The authors conducted this study to investigate the risk and outcomes of second hematologic malignancies (SHMs) among patients with Well Differentiated Thyroid Cancer (WDTC) treated with RadioActive Iodine (RAI). A total of 183,894 patients with thyroid cancer were identified from 18 registries of the National Cancer Institute SEER (Surveillance, Epidemiology, and End Results) program and 148,215 patients with WDTC were included in this study. Among those included, 53% underwent surgery alone, and 47% underwent surgery and received RAI. Patients were excluded if their thyroid malignancy was not of follicular or papillary histology. Low/Intermediate-risk patients with WDTC were defined per the latest American Thyroid Association guidelines as T1-2, N0 tumors 4 cm or less in size, or T1-3, N1 tumors in patients older than 45 years of age.

The Primary outcome was the development of Second Hematologic Malignancies (SHMs), defined as a non-synchronous Hematologic Malignancies occurring 1 year or more after treatment of WDTC. SHMs included in this study were Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Multiple Myeloma (MM). SHMs occurring less than 1 year after WDTC diagnosis were also excluded. The authors performed a competing risk regression analysis to calculate the risks of SHMs that occurred after WDTC treatment and they assessed the outcomes after SHM diagnosis.

At a median follow up of 6.5 years after WDTC diagnosis, 783 patients developed a Secondary Hematologic Malignancy. In multivariate analysis, when compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing AML (HR=1.79; P=0.01) and CML (HR=3.44; P<0.001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. In those patients with WDTC developing AML, the median Overall Survival was significantly shorter compared with matched controls (8 years versus 31 years; P=0.001). Further, among those developing AML after RAI treatment, median Overall Survival was inferior compared to matched controls with de novo AML (1.2 years versus 2.9 years; P=0.06).

The authors concluded that patients with Well Differentiated Thyroid Cancer (WDTC) treated with RAI are at an increased early risk of developing AML and CML. Patients developing AML following treatment with RAI have a poor prognosis. RAI use in patients with WDTC should therefore be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance. Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer. Molenaar RJ, Sidana S, Radivoyevitch T, et al. J Clin Oncol 2017;36:1831-1839