Less is More: The Impact of Multidisciplinary Thyroid Conference on the Treatment of Well-Differentiated Thyroid Carcinoma.

BACKGROUND: In 2006, a multidisciplinary thyroid conference (MDTC) was implemented to better plan management of thyroid cancer patients at our institution. This study assessed the clinical impact of a MDTC on radioactive iodine (RAI) treatment patterns. METHODS: A prospective database (2003-2014) collected patient and tumor characteristics, RAI doses, and tumor recurrences. Patients treated with total thyroidectomy for differentiated thyroid carcinoma ≥1 cm were stratified based on American Thyroid Association (ATA) risk classification. RAI regimens were compared before initiation of MDTC (2003-2005, n = 88), after establishment of MDTC (2007-2009, n = 95), and after the release of 2009 ATA guidelines (2011-2014, n = 181). RAI doses were defined as low (≤75 mCi), intermediate (76-150 mCi), and high (>150 mCi). RESULTS: There was a significant decrease in the number of patients who received high-dose RAI after implementation of MDTC compared to before initiation of MDTC in the intermediate and high-risk patient groups (p = 0.04 and p < 0.01) without an associated increase in tumor recurrence (11 vs. 7%, p = 0.74). On multivariable analysis, presentation of a patient at MDTC was a negative predictor for receiving high-dose RAI (p = 0.002). As might be expected, there was also a significant decrease in use of RAI after the 2009 ATA guidelines were issued compared to after implementation of MDTC (p < 0.01). CONCLUSION: In conjunction with implementation of a thyroid malignancy multidisciplinary conference, we observed significantly decreased postoperative dosing of RAI without increased tumor recurrence. The 2009 ATA guidelines were associated with a further decrease in RAI administration. Treatment for patients with thyroid carcinoma is optimized by a multidisciplinary approach.

Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer.

Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms arising after treatment with RET inhibitors, we performed a comprehensive molecular and genomic analysis of a patient with RET-rearranged thyroid cancer. Using a combination of drug screening and proteomic and biochemical profiling, we identified an adaptive resistance to RET inhibitors that reactivates ERK signaling within hours of drug exposure. We found that activation of FGFR signaling is a mechanism of adaptive resistance to RET inhibitors that activates ERK signaling. Combined inhibition of FGFR and RET prevented the development of adaptive resistance to RET inhibitors, reduced cell viability, and decreased tumor growth in cellular and animal models of CCDC6-RET-rearranged thyroid cancer.

American Thyroid Association Scientific Statement on the Use of Potassium Iodide Ingestion in a Nuclear Emergency.

This document serves to summarize the issues and the American Thyroid Association (ATA) position regarding the use of potassium iodide as a thyroid blocking agent in the event of a nuclear accident. The purpose is to provide a review and updated position statement regarding the advanced distribution, stockpiling, and availability of potassium iodide in the event of nuclear radiation emergencies in the United States.

Enhancement of radioiodine treatment of small-pool hyperthyroidism with antithyroid drugs: kinetics and dosimetry.

UNLABELLED: (131)I-Iodide is the treatment of choice in most cases of hyperthyroidism, with a standard 7,000-cGy (rad) thyroid absorbed dose generally resulting in an incidental blood absorbed dose of less than 10 cGy (rad). However, in approximately 15% of patients there is a small, rapidly secreted thyroid iodine pool (small-pool patients) and, based on theoretic calculations, an incidental blood absorbed dose of up to 150 cGy (rad) could result. In such small-pool patients, continuing antithyroid drugs (ATDs) at a reduced dosage during (131)I therapy should inhibit the formation of (131)I-labeled levothyroxine and triiodothyronine and thereby reduce the protein-bound (131)I-iodine concentration in blood and the blood absorbed dose. METHODS: To test this hypothesis, thyroid and blood time-activity data were measured and absorbed doses were calculated for an (131)I tracer administered to small-pool hyperthyroid patients (n = 9) not receiving ATDs (off ATDs) and then receiving ATDs (on ATDs). RESULTS: The blood absorbed dose (cGy/37 MBq [rad/mCi] administered) was reduced from 2.54 +/- 0.91 (mean +/- SD) without ATDs to 1.27 +/- 0.54 with ATDs (P < 0.0001), whereas the thyroid absorbed dose was unchanged (1,870 +/- 700 vs. 2,080 +/- 1,080). The blood absorbed dose for an administered (131)I activity required to deliver a standard prescribed absorbed dose of 7,000 cGy (rad) to the thyroid therefore was reduced by over 50% with ATDs, from 11.3 +/- 6.5 to 4.9 +/- 2.8 cGy (rad) (P < 0.001). CONCLUSION: Continued administration of ATDs during (131)I therapy thus can effectively reduce extrathyroid radiation in small-pool patients without significantly reducing the target tissue (i.e., thyroid) dose.

Managing terrorism or accidental nuclear errors, preparing for iodine-131 emergencies: a comprehensive review.

Chernobyl demonstrated that iodine-131 (131I) released in a nuclear accident can cause malignant thyroid nodules to develop in children within a 300 mile radius of the incident. Timely potassium iodide (KI) administration can prevent the development of thyroid cancer and the American Thyroid Association (ATA) and a number of United States governmental agencies recommend KI prophylaxis. Current pre-distribution of KI by the United States government and other governments with nuclear reactors is probably ineffective. Thus we undertook a thorough scientific review, regarding emergency response to 131I exposures. We propose: (1) pre-distribution of KI to at risk populations; (2) prompt administration, within 2 hours of the incident; (3) utilization of a lowest effective KI dose; (4) distribution extension to at least 300 miles from the epicenter of a potential nuclear incident; (5) education of the public about dietary iodide sources; (6) continued post-hoc analysis of the long-term impact of nuclear accidents; and (7) support for global iodine sufficiency programs. Approximately two billion people are at risk for iodine deficiency disorder (IDD), the world's leading cause of preventable brain damage. Iodide deficient individuals are at greater risk of developing thyroid cancer after 131I exposure. There are virtually no studies of KI prophylaxis in infants, children and adolescents, our target population. Because of their sensitivity to these side effects, we have suggested that we should extrapolate from the lowest effective adult dose, 15-30 mg or 1-2 mg per 10 pounds for children. We encourage global health agencies (private and governmental) to consider these critical recommendations.

Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association.

BACKGROUND: Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. METHODS: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. RESULTS: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. CONCLUSION: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.