Background: A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. Methods: This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. Results: Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediaterisk, and 68% of the high-risk patients ( p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. Conclusions: Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

A structural incomplete response to initial therapy is associated with significantly worse clinical outcome than a biochemical incomplete response to therapy.

Thyroid cancer bone metastases identified as part of routine clinical follow-up frequently cause significant and recurrent morbidity. The incidence of SRE and median time to first SRE in metastatic thyroid cancer to bone are similar to those reported in other solid tumors. Prospective clinical trials to assess the efficacy of antiresorptive agents in this population are needed.

The optimal management of radioactive iodine (RAI) treatment in patients with metastatic thyroid cancer (TC) is still a matter of debate. We retrospectively analyzed 352 patients with RAI-avid metastatic well-differentiated TC treated withI by an empiric fixed activity of 3.7 GBq at Gustave Roussy (GR, = 231) or by personalized activity (2.7-18.6 GBq) based on whole-body/-blood clearance (WB/BC) dosimetry at Memorial Sloan Kettering Cancer Center (MSKCC, = 121). The primary endpoint was to compare overall survival (OS) in the 2 groups of patients by log-rank test. Patients received a median cumulative activity of 14.8 GBq at GR and 24.2 GBq at MSKCC ( < 0.0001). The median follow-up after the diagnosis of metastases was 7.2 y (0.4-31 y). Five-year OS was 86.8% and 78.8% for patients treated at GR and at MSKCC, respectively ( < 0.01). However, there was no statistical difference in OS after correction for sex, age at the diagnosis of distant metastases, metastases site, and metastases extension between the 2 centers ( = 0.16). OS at 5 y was 96% and 96% for patients younger than 40 y with micrometastases, 70% and 65% for patients older than 40 y with macrometastases or multiple metastases, and 92% and 87% for younger patients with macrometastases or older patients with micrometastases treated at GR and MSKCC, respectively ( = not significant). Routine use of WB/BC dosimetry without lesional dosimetry provided no OS advantage when compared with empiric fixed RAI activity in the management of thyroid cancer patients with RAI-avid distant metastases.

• TIRADS classification allows accurate selection of thyroid nodules requiring biopsy (TIRADS 4-5). • The recognition of benign/possibly benign patterns can avoid unnecessary procedures. • This classification and its sonographic patterns are validated using surgical specimens.

Background: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology.Methods: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies.Results: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64–82% and a negative predictive value of 97–99% in patients with a cancer prevalence range of 20–40%.Conclusions: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.

Background: Low-iodine diet is prescribed before 131I administration in patients with differentiated thyroid cancer, although no study has properly quantified its clinical benefit. Objective: Our study aimed to evaluate the association between urinary iodine excretion (UIE) and 131I ablation by correlating UIE with the rate of successful ablation. Patients: We retrospectively studied 201 differentiated thyroid cancer patients who had received 131I therapy and posttherapy whole-body scan (WBS) for remnant ablation after either thyroid hormone withdrawal (THW group, n = 125) or recombinant human TSH (rhTSH group, n = 76). The outcome of thyroid ablation was assessed using two different criteria: no visible uptake at control WBS 8–12 months after ablation or no visible uptake plus undetectable stimulated serum thyroglobulin (Tg). Results: According to the criterion of no visible uptake, 84.6% of the patients were successfully ablated, with no significant difference between THW and rhTSH groups. Mean UIE at the time of ablation was 132 ± 160 μg/liter, not significantly different between patients of the THW and rhTSH groups. There was no significant difference in UIE between ablated or nonablated patients both in the whole group and the rhTSH or THW groups. According to the criterion of no visible uptake plus undetectable stimulated serum Tg (in anti-Tg negative patients) at control WBS 8–12 months after ablation, UIE was not significantly different in ablated and nonablated patients. Conclusions: Our study indicates that the body iodine content is not an important determinant of thyroid ablation, when preparing the patients with either THW or rhTSH.

No abstract