American Thyroid Association Risk Stratification System Research Articles

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Risk Stratification of Differentiated Thyroid Cancer at King Abdullah Specialized Children's Hospital Endocrinology Clinic in Riyadh, Saudi Arabia.

Background Papillary thyroid cancer (PTC), a well-differentiated form of cancer, accounts for the majority of thyroid malignancies, and the incidence of PTC is on the rise. While the rate of PTC recurrence is considered to be low, there are broad spectrums of clinical and biological behavior that can lead to disease recurrence. The American Thyroid Association (ATA) risk stratification system for differentiated thyroid cancer is used as a prognostic tool to guide decision-making and management strategies most likely to achieve a favorable outcome. Aim This study aimed to estimate the prevalence of PTC recurrence in each category of the ATA risk stratification system and determine the appropriate iodine dose to be administered at the King Abdulaziz Medical City Endocrinology Clinic in Riyadh, Saudi Arabia. Methods A cross-sectional retrospective chart review was conducted on adult patients with PTC who underwent thyroidectomy procedures at the King Abdullah SpecializedChildren'sHospital(KASCH) Endocrinology Clinic in Riyadh between 2015 and 2023. IBM SPSS (Statistical Package for the Social Sciences) version 25 (IBM Corp., Armonk, NY) was used for data analysis. Results Of the 697 patients included in the study, 82.4% were females. About 5% had suffered from PTC recurrence, and 54.4% had low-risk stratification. In addition, more than half (52.1%) had received radioactive iodine (RAI). The recurrence of PTC was significantly associated with age (P = 0.019), ATA risk stratification (P = 0.0001), RAI therapy (P = 0.001), and iodine dosage (P = 0.013). Conclusion Both low PTC recurrence rates and low-risk stratification were observed among the PTC patients. The risk factors relating to PTC recurrence included high-risk stratification, advanced age, RAItherapy, and the dosage of RAI administered.

ATA risk stratification in papillary thyroid microcarcinoma has low positive predictive value when identifying recurrence

BackgroundRising incidence of papillary thyroid microcarcinomas (PTMC) has raised concerns for overdiagnosis. Utility of the American Thyroid Association Risk Stratification System (ATA-RSS) 2015 in predicting risk of disease recurrence in patients with PTMC was assessed. MethodsElectronic health records of patients who underwent total thyroidectomy were queried. ATA-RSS 2015 risk stratification was performed on those with PTMC, and validity for predicting disease recurrence was calculated. ResultsWith 10-year median follow up, recurrence was higher in PTMC patients with high/intermediate vs low ATA risk (33 % vs 4 %, p = 0.002). Sensitivity of ATA-RSS for detecting recurrence was 60 %, specificity 90 %, PPV 33.3 %, NPV 96.6 %, and accuracy 88 %. When microscopic extrathyroidal extension (ETE) was excluded as an intermediate risk criterion, PPV improved to 50 % and accuracy improved to 92.5 % ConclusionsATA-RSS 2015 predicts recurrence in PTMC with high NPV but low PPV. Exclusion of microscopic ETE improved PPV, which may help prevent overtreatment.

Comparison of the initial presentation and long-term outcome of differentiated thyroid carcinoma (DTC) between children and adults: A single institution experience in Taiwan.

163 Background: Differentiated thyroid carcinoma (DTC) in children is known to be more aggressive than in adults. However, there are no cohort studies in Asia that have compared the presentation and long-term outcomes of pediatric DTC with adult DTC. In this study, we aimed to compare the clinical characteristics and outcomes of pediatric DTC with a comparison cohort of adult DTC patients. Methods: We reviewed the data of 46 pediatric DTC patients who underwent total thyroidectomy from January 1991 to December 2021, along with a comparison cohort of 350 adult DTC patients at our hospital. All patients received postoperative radioiodine therapy. Clinicopathologic features and surgical outcomes were analyzed retrospectively, and patients were stratified according to the American Thyroid Association (ATA) risk stratification system. Clinical outcomes were classified according to Dynamic Risk Stratification (DRS) at the end of follow-up. Results: Children with DTC had less common papillary thyroid carcinoma (80 vs. 93%) but had larger primary tumors, more multifocal disease, and more lymph node and distant metastasis at presentation compared to adults. Thus, at initial risk stratification, more children had intermediate-to-high risk (62 vs. 49%) than adults. At the end of follow-up, fewer children were classified as having excellent response (no evidence of disease) than adults (48 vs. 79%). Based on the ATA risk stratification system, a higher percentage of high-risk children had structural-persistent disease (60%) compared to high-risk adults (29%), and a lower percentage of low-risk children became no evidence of disease (76%) compared to low-risk adults (93%). Conclusions: Children with DTC present with more extensive disease and have worse outcomes compared to adults. The ATA initial risk stratification system can predict long-term outcomes in both children and adult DTC patients and guide personalized management and follow-up strategies.

Prognostic Utility of Tumor Stage versus American Thyroid Association Risk Class in Thyroid Cancer.

To evaluate the prognostic strengths of American Joint Committee on Cancer (AJCC) staging and American Thyroid Association (ATA) risk classification in well-differentiated thyroid cancer (DTC), and their implications in guiding medical decision-making and epidemiological study designs. The 2004-2017 National Cancer Database was queried for DTC patients. Cox proportional hazards (CPH) and Kaplan-Meier analyses modeled patient mortality and overall survival, respectively. Each CPH model was evaluated by its concordance index, measure of explained randomness (MER), Akaike information criterion (AIC), and area under receiver operating characteristic curve (AUC). Overall, 134,226 patients were analyzed, with an average age of 48.1 ± 15.1 years (76.9% female). Univariate CPH models using AJCC staging demonstrated higher concordance indices, MERs, and AUCs than those using ATA risk classification (all p < 0.001). Multivariable CPH models using AJCC staging demonstrated higher concordance indices (p=0.049), MERs (p=0.046), and AUCs (p=0.002) than those using ATA risk classification. The AICs of multivariable AJCC staging and ATA risk models were 7.564 × 104 and 7.603 × 104 , respectively. AJCC stage I tumors were associated with greater overall survival than those classified as ATA low risk, whereas AJCC stages II-III and stage IV tumors demonstrated worse survival than ATA intermediate- and high-risk tumors, respectively (all p < 0.001). AJCC staging may be a more predictive system for patient survival than ATA risk. The prognostic utility of these two systems converges when additional demographic and clinical factors are considered. AJCC staging was found to classify patients across a wider range of survival patterns than the ATA risk stratification system. 4 Laryngoscope, 133:205-211, 2023.

Restratification of Patients with Intermediate-Risk Papillary Thyroid Carcinoma.

Long-term management and follow-up strategies in patients with intermediate-risk papillary thyroid carcinoma (PTC) according to the American Thyroid Association (ATA) are still controversial due to the paucity of data on unique risk factors or a risk stratification system predictive of long-term outcomes. This study included 649 patients with PTC who underwent an initial surgical treatment. Retrospectively enrolled patients were categorized according to the ATA risk stratification system. Intermediate-risk patients were further categorized into subgroups by the number of ATA intermediate risk factors. The recurrence-free survival (RFS) rates of these subgroups were compared with those of low- and high-risk patient groups. Additionally, the patients were classified according to their response to the initial therapy using the dynamic risk stratification (DRS) system, and the percentages of patients in each category were compared among the subgroups. The median follow-up period was 102 months. Structural recurrence occurred in 9.2% of all enrolled patients (60/649) and in 13.0% of intermediate-risk patients (40/308). Patients with two or more current intermediate risk factors had a poorer RFS than patients with only one risk factor (p < 0.001) and showed a comparable RFS to high-risk patients (p > 0.050). The percentages of patients with an excellent response category for DRS significantly decreased with an increase in the number of intermediate risk factors. Subclassification according to the number of intermediate risk factors may be useful to better predict the RFS and the response to initial therapy in patients with intermediate-risk PTC.

The Diagnostic Efficacy of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) and the American Thyroid Association (ATA) Risk Stratification Systems for Thyroid Nodules.

Background This study is aimed at evaluating the diagnostic efficacy of ultrasound-based risk stratification for thyroid nodules in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) risk stratification systems. Methods 286 patients with thyroid cancer were included in the tumor group, with 259 nontumor cases included in the nontumor group. The ACR TI-RADS and ATA risk stratification systems assessed all thyroid nodules for malignant risks. The diagnostic effect of ACR and ATA risk stratification system for thyroid nodules was evaluated by receiver operating characteristic (ROC) analysis using postoperative pathological diagnosis as the gold standard. Results The distributions and mean scores of ACR and ATA rating risk stratification were significantly different between the tumor and nontumor groups. The lesion diameter > 1 cm subgroup had higher malignant ultrasound feature rates detected and ACR and ATA scores. A significant difference was not found in the ACR and ATA scores between patients with or without Hashimoto's disease. The area under the receiver operating curve (AUC) for the ACR TI-RADS and the ATA systems was 0.891 and 0.896, respectively. The ACR had better specificity (0.90) while the ATA system had higher sensitivity (0.92), with both scenarios having almost the same overall diagnostic accuracy (0.84). Conclusion Both the ACR TI-RADS and the ATA risk stratification systems provide a clinically feasible thyroid malignant risk classification, with high thyroid nodule malignant risk diagnostic efficacy.

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China.

ObjectiveAntithyroglobulin antibody (TgAb) is a potential tumour marker for detecting differentiated thyroid cancer (DTC) recurrence, but insufficient data have supported its clinical applications. Our study aimed to describe the changing trend of TgAb after surgery and identify the relationship between this trend and clinical outcomes.Patients and MethodsWe reviewed the electronic records of 1,686 DTC patients who had undergone total thyroidectomy (TT) and radioactive iodine (131I) therapy at West China Hospital of Sichuan University from January 2015 to December 2017. Finally, 289 preoperative TgAb-positive DTC patients were included and divided into four subgroups depending on the clinical outcome: Group A (tumour free), Group B (uncertain), Group C (incomplete biochemical response), and Group D (structural disease). The patient demographics, tumour characteristics, operations, pathology reports, and all serological biomarkers were reviewed and compared, and the prognostic efficacy of TgAb was evaluated.ResultsAmong all 1,686 patients, 393 (23.65%) were TgAb positive (>40 IU/ml) preoperatively. The TgAb level in Group A decreased significantly after surgery and 131I therapy and stabilised at a low level after 1–2 years of 131I therapy. However, in the other three groups, the decrease in TgAb was not significant after treatment. Conversely, TgAb declined slowly and remained stable or increased. The variations in TgAb relative to the preoperative level of Group A were significantly larger than those of Groups B, C, and D at most time points of follow-up (p < 0.001). By receiver operating characteristic (ROC) analyses, the variations of TgAb > −77.9% at 6 months after 131I therapy (area under the curve (AUC) = 0.862; p < 0.001) and TgAb > −88.6% at 2 years after 131I therapy (AUC = 0.901; p < 0.001) had good prognostic efficacy in tumour-free survival. When the variation in TgAb > −88.6% at 2 years after 131I therapy was incorporated as a variable in the American Thyroid Association (ATA) categories, both intermediate- and high-risk patients also had a significantly increased chance of being tumour free (from 75.68% to 93.88% and 42.0% to 82.61%, respectively).ConclusionsFor preoperative TgAb-positive DTC patients, variations in TgAb > −77.9% at 6 months after 131I therapy and TgAb > −88.6% at 2 years after 131I therapy had good prognostic efficacy. Their incorporation as variables in the ATA risk stratification system could more accurately predict disease-free survival.

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study

ObjectiveAlthough the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up. MethodsIn this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons. ResultsThis study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease. ConclusionApplying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

The influence of age on disease outcome in 2015 ATA high-risk differentiated thyroid cancer patients.

Recent research suggests that the addition of age improves the 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC). The aim of our study was to investigate the influence of age on disease outcome in ATA-high risk patients with a focus on differences between patients with papillary (PTC) and follicular thyroid cancer (FTC). We retrospectively studied adult patients with high-risk DTC from a Dutch University hospital. Logistic regression and Cox proportional hazards models were used to estimate the effects of age (at diagnosis) and several age cutoffs (per 5 years increment between 20 and 80 years) on (i) response to therapy, (ii) developing no evidence of disease (NED), (iii) recurrence, and (iv) disease-specific mortality (DSM). We included 236 ATA high-risk patients (32% FTC) with a median follow-up of 6 years. Age, either continuously or dichotomously, had a significant influence on having an excellent response after initial therapy, developing NED, recurrence, and DSM for PTC and FTC. For FTC, an age cutoff of 65 or 70 years showed the best statistical model performance, while this was 50 or 60 years for PTC. In a population of patients with high-risk DTC, older age has a significant negative influence on disease outcomes. Slightly different optimal age cutoffs were identified for the different outcomes, and these cutoffs differed between PTC and FTC. Therefore, the ATA Risk Stratification System may further improve should age be incorporated as an additional risk factor.

Prognostic Implications of Preablation Stimulated Tg: A Retrospective Analysis of 2500 Thyroid Cancer Patients.

The risk of persistent and recurrent disease in patients with differentiated thyroid cancer (DTC) is a continuum that ranges from very low to very high, even within the 3 primary risk categories. It is important to identify independent clinicopathological parameters to accurately predict clinical outcomes. To examine the association between pre-ablation stimulated thyroglobulin (ps-Tg) and persistent and recurrent disease in DTC patients and investigate whether incorporation of ps-Tg could provide a more individualized estimate of clinical outcomes. Medical records of 2524 DTC patients who underwent total thyroidectomy and radioiodine ablation between 2006 and 2018 were retrospectively reviewed. Ps-Tg was measured under thyroid hormone withdrawal before remnant ablation. Association of ps-Tg and clinical outcomes. In multivariate analysis, age, American Thyroid Association (ATA) risk stratification, distant metastasis, ps-Tg, and cumulative administered activities were the independent predictive factors for persistent/recurrent disease. Receiver operating characteristic analysis identified ps-Tg cutoff (≤10.1 ng/mL) to predict disease-free status with a negative predictive value of 95%, and validated for all ATA categories. Integration of ps-Tg into ATA risk categories indicated that the presence of ps-Tg ≤ 10.1 ng/mL was associated with a significantly decreased chance of having persistent/recurrent disease in intermediate- and high-risk patients (9.9% to 4.1% in intermediate-risk patients, and 33.1% to 8.5% in high-risk patients). The ps-Tg (≤10.1 ng/mL) was a key predictor of clinical outcomes in DTC patients. Its incorporation as a variable in the ATA risk stratification system could more accurately predict clinical outcomes.

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer.

Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.

Analysis of BRAF and TERT Expressions in Papillary Thyroid Carcinoma Cases Based on ATA Risk Stratification

BackgroundPapillary thyroid carcinoma (PTC) is the most common malignancy in thyroid, accounting for more than 80% of all thyroid cancer.Rrecurrences of the disease reach 30% cases. It has been widely observed that BRAF and TERT is associated with aggressivenessbehaviors in human cancer. Both are involved in the pathogenesis of PTC that may be used as targets for new therapies. AmericanThyroid Association (ATA) risk stratification can define the risk of recurrence in PTC. No marker has been found to determine therisk of PTC recurrence. The purpose of this study is to analyzed BRAF and TERT expression in ATA risk stratification system inPTC classic variant samples.MethodsThe methods of this study is an analytical observational study with cross sectional approach, conducted on 56 samples of PTCclassic variant selected from Department of Anatomical Pathology Dr. Soetomo General Hospital between January 2015-December2017 by determined criteria in ATA risk stratification groups of low risk, intermediate risk and high risk. The expression BRAF andTERT observed using immunohistochemical staining of Santa Cruz monoclonal antibody.ResultsThe result for each group based on ATA risk stratification groups of low risk were 13 samples (23.20%), intermediate risk were 25samples (44.62%) and high risk were 18 samples (32.12%).The correlation was assessed with Spearman’s rho correlation test. There is significant correlation BRAF (p=0.004) with a value ofr=0.374 and TERT(p=0.032) with a value of r=0.287 for ATA risk stratification.ConclusionBRAF and TERT expression showed significant correlation to ATA risk stratification in classic variant PTC.

The BRAFV600E mutation analysis and risk stratification in papillary thyroid carcinoma.

Although the prognostic role of BRAFV600E mutation in papillary thyroid carcinoma (PTC) is controversial, the American Thyroid Association (ATA) includes the mutational status in their risk stratification system. To evaluate the impact of the BRAFV600E mutation status on PTC risk stratification. PTC patients attending a university-based hospital who had the analysis of the BRAFV600E mutation were included. Persistent disease was defined as the presence of biochemical or structural disease. The performance of the ATA risk stratification system on predicting persistent disease with or without the BRAFV600E mutation status information was evaluated. Of the 134 patients evaluated, 44 (32.8%) carried BRAFV600E mutation. The median tumor size was 1.7 cm (P25-75 1.0-3.0), 64 (47.8%) patients had lymph node, and 11 (8.2%) distant metastases. According to the ATA risk stratification system, patients were classified as low, intermediate, and high risk in 55 (41%), 59 (44%), and 20 (14%) patients, respectively. The data on BRAFV600E mutation reclassified 12 (8.9%) patients from low to intermediate risk. After a median follow-up of 8.5 years, the prevalence of persistent disease was similar in patients with and without BRAFV600E mutation (P = 0.42). Multivariate analysis failed to demonstrate an association between the BRAFV600E mutation and persistent disease status (RR 0.96; 95%CI 0.47-1.94). Notably, none of the patients reclassified from low to intermediate risk showed persistent disease on follow-up. Inclusion of BRAFV600E mutational status has a limited impact on risk stratification and does not add to the prediction of outcomes in PTC patients.

Real-World Performance of the American Thyroid Association Risk Estimates in Predicting 1-Year Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study of 2000 Patients.

Background: One of the most widely used risk stratification systems for estimating individual patients' risk of persistent or recurrent differentiated thyroid cancer (DTC) is the American Thyroid Association (ATA) guidelines. The 2015 ATA version, which has increased the number of patients considered at low or intermediate risk, has been validated in several retrospective, single-center studies. The aims of this study were to evaluate the real-world performance of the 2015 ATA risk stratification system in predicting the response to treatment 12 months after the initial treatment and to determine the extent to which this performance is affected by the treatment center in which it is used. Methods: A prospective cohort of DTC patients collected by the Italian Thyroid Cancer Observatory web-based database was analyzed. We reviewed all records present in the database and selected consecutive cases that satisfied inclusion criteria: (i) histological diagnosis of DTC, with the exclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features; (ii) complete data of the initial treatment and pathological features; and (iii) results of 1-year follow-up visit (6-18 months after the initial treatment), including all data needed to classify the estimated response to treatment. Results: The final cohort was composed of 2071 patients from 40 centers. The ATA risk of persistent/recurrent disease was classified as low in 1109 patients (53.6%), intermediate in 796 (38.4%), and high in 166 (8.0%). Structural incomplete responses were documented in only 86 (4.2%) patients: 1.5% in the low-risk, 5.7% in the intermediate-risk, and 14.5% in the high-risk group. The baseline ATA risk class proved to be a significant predictor of structural persistent disease, both for intermediate-risk (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.59-8.43) and high-risk groups (OR 16.48; CI 7.87-34.5). Individual center did not significantly influence the prediction of the 1-year disease status. Conclusions: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability.

OR21-07 The 2015 American Thyroid Association Risk Stratification System Is a Predictor of Persistent Disease in Real-World Clinical Practice

Background. Management and follow-up of differentiated thyroid cancer (DTC) are guided by the likelihood of disease persistence or recurrence. The American Thyroid Association (ATA) practice guidelines provide a risk-estimation system based on data mainly derived by retrospective, single-center, and small cohorts. Aim. To validate the ATA risk-stratification system in predicting persistent structural disease. Methods. We analyzed data from the Italian Thyroid Cancer Observatory’s observational, web-based database, which prospectively enrolls newly diagnosed DTC patients in 40 Italian centers. For the present study we selected consecutive cases satisfying the inclusion criteria: 1) histological diagnosis of DTC, including papillary, follicular, and poorly differentiated tumors; 2) registration in the ITCO database between January 1, 2013 and April 23, 2019; 3) clinical evaluation between 6 and 18 month after primary treatment, including enough data to estimate the response to the initial treatment. Exclusion criteria were: histological diagnosis of NIFTP, medullary, or anaplastic thyroid cancer. The response to the initial treatment was categorized as excellent, biochemical incomplete, structural incomplete, or indeterminate based on imaging findings (neck ultrasound and other imaging studies, if performed), basal or stimulated serum thyroglobulin levels, and anti-Tg antibody levels. To model the response to treatment, we used a cumulative link model; given the hierarchical structure of the data, with patients nested within centers, we used a mixed-effect model, with a center-specific intercept summarizing unobserved center-specific characteristics. Results. Complete data about initial treatment and response to treatment after 6-18 months since initial treatment was available for 2071 patients. According to the ATA system, 1109 patients (53.6%) were classified as low-risk, 796 (38.4%) as intermediate, and 166 (8.0%) as high-risk. Excellent response was recorded in 1576 (76.1%) patients, indeterminate in 376 (18.2%), biochemical incomplete in 33 (1.6%), and structural incomplete in 86 (4.2%).The ATA risk stratification system is a significant predictor of response to treatment after 6-18 months: classification as intermediate- and high-risk increased the likelihood of a response worse than excellent (OR 1.68 [95% confidence intervals, CI 1.34-2.10] and 3.23 [95% CI 2.23-4.67], respectively), and a persistent structural disease (OR 4.67 [95% CI 2.59-8.43] and 16.48 [95% CI 7.87-34.5], respectively. In both analyses, the effect of the center (taking into account center-specific features) was negligible and not statistically significant. Conclusion. The 2015 ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC, also if applied in a real-world setting consisting of several different clinical sites.

MON-520 How Does the American Joint Committee on Cancer 8thEdition Tumor, Node, Metastasis Staging System Perform in Patients Evaluated at a Major Middle Eastern Medical Center?

The American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Classification of Cancer 8th edition (AJCC8) was officially introduced in January 2018 as a replacement for the previous version (AJCC7). Validation studies using data obtained from large cancer registries in North America demonstrated the superiority of AJCC8 over AJCC7 for prediction of survival. Subsequent studies from Europe and East Asia have mostly shown similar findings. However, these data may not be generalizable to other parts of the world. In this first study from the Middle East (Saudi Arabia), we compared these two versions of AJCC staging for their concordance and prediction of outcome in a large unselected sample of patients (pts) with DTC managed at a major referral medical center. We also compared the AJCC staging systems with the American Thyroid Association (ATA) Risk Classification.Of 814 consecutive pts seen during this period, 94 were excluded either due to their diagnosis being medullary or anaplastic thyroid cancer (37) or because of deficient data. The remaining 720 pts (149 males (20.7%), 571 females (79.3%) were included. The median age at the diagnosis was 37 yrs (range, 6-83). Total thyroidectomy was performed in 693 pts (96.3%) and central and/or lateral lymph node dissections in 487 pts (67.6%). I-131 was administered to 626 pts (87%). The tumors were classic PTC in 519 pts (72%), follicular variant PTC in 100 (13.9%), Tall cell PTC in 22 (3.1%), diffuse sclerosing PTC in 10 (1.4%), follicular thyroid cancer in 21 (2.9%) and other rare subtypes in 48 pts (6.8%).The number (%) of pts within each stage group by AJCC7 and AJCC8 respectively are as follows: Stage 1: 514 (71.4%) vs. 597 (82.9%), Stage 2: 46 (6.4%) vs. 75 (10.4%), Stage 3: 63 (8.8%) vs. 11 (1.5%), Stage 4: 97 (13.5%) vs. 37 (5.1%).Comparing AJCC8 with the ATA risk stratification system in 709 pts in which data were available, we found a high correlation with 96.8% of ATA low risk group being stage 1 in AJCC8, 2.9% stage 2 and 0.3% stage 3 and none in stage 4. The ATA intermediate risk group was 87.4% AJCC8 stage 1, 12.3% stage 2, 0.4% stage 3 and none in stage 4. The ATA high risk group was 19.1% in AJCC8 stage 1, 33% in stage 2, 9.6% in stage 3 and 38.3% in stage 4.In addition, AJCC8 was more predictive of the outcome with 80% of pts with evidence of disease (biochemically and structurally incomplete) being in AJCC8 stage 3 or 4 compared with 60% in AJCC7. For ATA staging, 8.6%, 22.4% and 67.7% of low, intermediate and high risk groups had evidence of disease at the last follow up, respectively.Conclusion: In this Middle Eastern population, AJCC8 downstaged a significant percentage of pts with DTC from higher stages in AJCC7. It also correlated better with the outcome and with the ATA risk classification system.

Modified risk stratification based on cervical lymph node metastases following lobectomy for papillary thyroid carcinoma.

Evidence for American Thyroid Association (ATA) risk stratification stems largely from studies involving patients undergoing total thyroidectomy. We aimed to assess the risk of recurrence according to the present ATA risk stratification system in patients who underwent lobectomy. Retrospective cohort study. Patients who underwent thyroid lobectomy for 1-4cm-sized papillary thyroid carcinoma (n=571). Disease-free survival (DFS) was compared according to the ATA risk stratification, and specific lymph node (LN) characteristics were evaluated to modify the ATA criteria with a higher predictability for recurrence. Based on the ATA risk stratification, 439 patients (61.1%) were classified into intermediate- or high-risk group, and consideration for completion thyroidectomy is suggested by ATA guidelines for these patients. However, no significant differences were found in DFS among the low-, intermediate- and high-risk groups (P=.9). In contrast, when patients were stratified according solely to the LN criteria from the ATA risk stratification, only 127 patients (22.2%) had intermediate risk (intermediate-N1a) and exhibited significantly poorer DFS than those with N0 disease (P=.035). Modifying the intermediate-N1a criteria by adding the extranodal extension (ENE) status and omitting the clinical nodal disease enabled the subclassification of 19 patients (3%) with a high risk for recurrence. The present study suggests that risk stratification based solely on LN metastases is more reasonable for predicting structural persistence/recurrence following lobectomy than that based on the overall ATA criteria. Considering the ENE status can assist in selecting patients with a high risk of recurrence to minimize further treatments.

Clinical Value of Lymph Node Ratio Integration with the 8th Edition of the UICC TNM Classification and 2015 ATA Risk Stratification Systems for Recurrence Prediction in Papillary Thyroid Cancer

Recently, the 2015 American Thyroid Association (ATA) risk stratification and the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system were released. This study was conducted to assess the clinical value of the lymph node ratio (LNR) as a predictor of recurrence when integrated with these newly released stratification systems, and to compare the predictive accuracy of the modified systems with that of the newly released systems. The optimal LNR threshold value for predicting papillary thyroid cancer (PTC) recurrence was 0.17857 using the Contal and O’Quigley method. The 8th edition of the AJCC/UICC TNM staging system with the LNR and the 2015 ATA risk stratification system with the LNR were significant predictors of recurrence. Furthermore, calculation of the proportion of variance explained (PVE), the Akaike information criterion (AIC), Harrell’s c index, and the incremental area under the curve (iAUC) revealed that the 8th edition of the TNM staging system with the LNR, and the 2015 ATA risk stratification system with the LNR, showed the best predictive performance. Integration of the LNR with the TNM staging and the ATA risk stratification systems should improve prediction of recurrence in patients with PTC.

Evaluating the 2015 American Thyroid Association Risk Stratification System in High-Risk Papillary and Follicular Thyroid Cancer Patients.

Background: The 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Earlier studies evaluating this system evaluated the 2009 edition, comprised a low number of patients with ATA high-risk, had low numbers of patients with follicular thyroid cancer (FTC), or did not distinguish between papillary and FTC. Therefore, we evaluated the prognostic value of the 2015 ATA Risk Stratification System in a large population of high-risk thyroid cancer patients, which included a substantial proportion of FTC patients. Methods: We retrospectively studied adult patients with DTC who were diagnosed and/or treated at a Dutch university hospital between January 2002 and December 2015. All patients fulfilled the 2015 ATA high-risk criteria. Overall survival and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method. Logistic regression and Cox proportional hazards models were used to estimate the effects of DTC subtype and ATA high-risk criteria on response to therapy, recurrence, as well as survival. Results: We included 236 patients with high-risk DTC (32% FTC) with a mean age of 56 years. Median follow-up was 6 years. At final follow-up, 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All high-risk criteria, except large pathologic lymph nodes, were inversely related to excellent response and positively related to structural disease at final follow-up. During follow-up, 14% of the 79 patients who achieved excellent response developed a recurrence. Finally, 10-year DSS was much higher in the initial excellent response than in the initial structural disease group (100% vs. 61%, respectively). Conclusions: In a population of high-risk DTC patients harboring a large subset of FTC patients, the 2015 ATA Risk Stratification System is not only an excellent predictor of persisting disease but also of survival. As much as 14% of the high-risk patients who had an excellent response upon dynamic risk stratification experienced a recurrence during follow-up. Clinicians should thus be aware of the relatively high recurrence risk in these patients, even after an excellent response to therapy.