American Thyroid Association Risk Research Articles

Predictors of recurrence after total thyroidectomy in 1,611 patients with papillary thyroid carcinoma: postoperative stimulated serum thyroglobulin and ATA initial and dynamic risk assessment.

Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-riskto high-risk patients with postoperative s-Tg > 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based ondynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.

Low Mitotic Activity in Papillary Thyroid Cancer: A Marker for Aggressive Features and Recurrence.

The significance of low mitotic activity in papillary thyroid cancer (PTC) is largely undefined. We aimed to determine the behavioral landscape of PTC with low mitotic activity compared to that of no- and high-mitotic activity. A single-institution consecutive series of PTC patients from 2018-2022 was reviewed. Mitotic activity was defined as no mitoses, low (1-2 mitoses/2 mm2) or high (≥3 mitoses/2 mm2) per the World Health Organization. The 2015 American Thyroid Association risk stratification was applied to the cohort, and clinicopathologic features were compared between groups. For patients with ≥6 months follow-up, Cox regression analyses for recurrence were performed. 640 PTCs were included - 515 (80.5%) no mitotic activity, 110 (17.2%) low mitotic activity, and 15 (2.3%) high mitotic activity. Overall, low mitotic activity exhibited rates of clinicopathologic features including vascular invasion, gross extrathyroidal extension, and lymph node metastases in between those of no- and high-mitotic activity. PTCs with low mitotic activity had higher rates of intermediate- and high-risk ATA risk stratification compared to those with no mitotic activity (p < 0.001). Low mitotic activity PTCs also had higher recurrence rates (15.5% vs. 4.5%, p < 0.001). Low mitotic activity was associated with recurrence, independent of the ATA risk stratification (HR 2.96; 95% CI 1.28-6.87, p = 0.01). Low mitotic activity is relatively common in PTC and its behavior lies within a spectrum between no- and high-mitotic activity. Given its association with aggressive clinicopathologic features and recurrence, low mitotic activity should be considered when risk stratifying PTC patients for recurrence.

The effect of COVID-19 pandemic restrictions on the management of differentiated thyroid cancer in Turkey: a single tertiary centre experience.

Many countries have implemented unprecedented health measures since the World Health Organisation declared the novel coronavirus disease 2019 (COVID-19) a global pandemic. These measures have resulted in delays in the diagnosis of differentiated thyroid cancer (DTC). However, there is limited data on the impact of restrictions imposed during the pandemic on DTC management. Thus, the aim of this study is to analyse the clinicopathological and follow-up data of DTC patients diagnosed before and during the COVID-19 outbreak. This retrospective study included 191 DTC patients that were diagnosed between December 2018 and June 2021. The patients were divided into two groups: patients diagnosed before (December 2018 to February 2020) and during (March 2020 to June 2021) the COVID-19 pandemic. The clinicopathological and follow-up data between the two groups were compared. Similar preoperative cytology results were obtained from the two groups. No difference with regard to tumour size, lymphovascular invasion and extrathyroidal invasion was observed between the two groups. While the American Thyroid Association risk stratification was similar between the two groups, radioactive iodine (RAI) therapy was applied less during the COVID-19 period. Although RAI therapy was administered at a lower rate during the COVID-19 period, the recurrence rates among patients after two years of follow-up were similar to those during the pre-COVID-19 period. Although the COVID-19 pandemic restrictions during the pandemic period caused difficulties in the management of DTC patients, this did not negatively affect their prognosis. These findings can confirm the applicability of active surveillance in DTC patients and may help change the real-life treatment practices in selected low-risk DTC patients.

Improved cancer risk stratification of isoechoic thyroid nodules to reduce unnecessary biopsies using quantitative ultrasound.

Gray-scale ultrasound (US) is the standard-of-care for evaluating thyroid nodules (TNs). However, the performance is better for the identification of hypoechoic malignant TNs (such as classic papillary thyroid cancer) than isoechoic malignant TNs. Quantitative ultrasound (QUS) utilizes information from raw ultrasonic radiofrequency (RF) echo signal to assess properties of tissue microarchitecture. The purpose of this study is to determine if QUS can improve the cancer risk stratification of isoechoic TNs. Patients scheduled for TN fine needle biopsy (FNB) were recruited from the Thyroid Health Clinic at Boston Medical Center. B-mode US and RF data (to generate QUS parameters) were collected in 274 TNs (163 isoechoic, 111 hypoechoic). A linear combination of QUS parameters (CQP) was trained and tested for isoechoic [CQP(i)] and hypoechoic [CQP(h)] TNs separately and compared with the performance of conventional B-mode US risk stratification systems. CQP(i) produced an ROC AUC value of 0.937+/- 0.043 compared to a value of 0.717 +/- 0.145 (p >0.05) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.589 +/- 0.173 (p >0.05) for the American Thyroid Association (ATA) risk stratification system. In this study, CQP(i) avoids unnecessary FNBs in 73% of TNs compared to 55.8% and 11.8% when using ACR TI-RADS and ATA classification system. This data supports that a unique QUS-based classifier may be superior to conventional US stratification systems to evaluate isoechoic TNs for cancer and should be explored further in larger studies.

The significance of the presence of extranodal extension in the metastatic node of differentiated thyroid cancer: a proposal for modification in the American Thyroid Association (ATA) risk stratification.

Multiple factors contribute to recurrences in differentiated thyroid cancers (DTC). Though the nodal size and number of positive nodes along with the presence of extranodal extension (ENE) have been mentioned in the present ATA risk stratification, the weightage given for ENE seems inadequate compared to the former two. Factors predicting recurrences were analysed in this retrospective study of patients with DTC operated in a tertiary care centre. Based on our findings, we propose a modification in the present risk stratification. We have done so by comparing with existing risk stratification for fit and discrimination of this system. Out of 1428 patients, 859 (60.2%) patients had pathological nodal metastases (pN +) with ENE being present in 26.8% of these. The recurrence rate was 6.4% (92 patients). Recurrence rates in patients with ≤ 5 nodes without ENE, > 5 nodes without ENE, ≤ 5 nodes with ENE and > 5 nodes with ENE were 2.7%, 1.3%, 8.3% and 10.3%, respectively. Recurrence rates in patients with 0.2-3cm without ENE, 0.2-3cm with ENE and > 3cm with/without ENE were 1.8%, 8.5% and 13.4%, respectively. A modified risk stratification incorporating ENE and excluding the number of metastatic nodes was proposed. The modified risk stratification had a better fit than the present system in terms of higher C index and lower AIC. Extranodal extension in differentiated thyroid cancer had the maximum influence on recurrence risk (recurrence-free survival) in our cohort. The prognostic impact of ENE supersedes the number of positive nodes in the risk of recurrence.

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects

IntroductionPatients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies.Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. Material and methodsPatients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy.Patients were reclassified in the following 6–18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels.The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. ResultsSixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses.A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). ConclusionsIn selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

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.

Retracted: 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

Retracted: 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

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects

IntroductionPatients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies.Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. Material and methodsPatients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy.Patients were reclassified in the following 6–18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels.The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. ResultsSixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses.A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). ConclusionsIn selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

The American Thyroid Association risk stratification and long-term outcomes of differentiated thyroid cancer: a 20-year follow-up of patients in Saudi Arabia.

Studies have reported differing factors associated with poor outcomes in patients with differentiated thyroid cancer (DTC). We aimed to describe our 20 years of experience in the management of thyroid cancer (TC) and identify predictors of treatment outcomes. We conducted a retrospective review of medical records of patients with TC seen in the Thyroid Center at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia, between the years 2000 and 2020. Demographic and clinical data including pathological characteristics were collected. The American Thyroid Association (ATA) risk stratification was determined for all patients at the postoperative period as well as the response to therapy at the final follow-up visit. A total of 674 patients (mean age: 47.21 years) with TC, 571 (84.7%) of which were women, were included. There were 404 (60.0%) patients with ATA low risk, 127 (18.8%) with intermediate risk, and 143 (21.2%) with high-risk histology. Overall, 461 patients (68.4%) had an excellent response to treatment, 65 (9.6%) had an indeterminate response, 83 (12.3%) had a biochemical incomplete response, and 65 (9.6%) had a structural incomplete response. Patients who had an excellent response were mostly ATA low risk (n = 318 of 431, 68.1%), whereas 40 of 65 patients (61.5%) of those with ATA high-risk histology had a structural incomplete response to treatment. There were significantly more women who had an excellent response compared with men. Obesity, lymphovascular invasion, and size of the tumor were significant predictors of worse outcomes to therapy. Tumor size, lymphovascular invasion, and obesity are strong predictors of a worse response to therapy among patients with TC. Patients with obesity should be carefully followed up regardless of their risk stratification in light of the recent compelling evidence associating obesity with thyroid cancer and its higher risk of a worse disease outcome. ATA risk stratification is well correlated with patient long-term outcomes.

Partial Thyroidectomy With Incidental Metastatic Lymph Nodes

The need for completion thyroidectomy in patients with incidental metastatic lymph nodes after partial thyroidectomy is unclear. To investigate the outcomes of patients with incidental metastatic lymph nodes following partial thyroidectomy. A retrospective review of a prospectively maintained thyroid cancer database from 1985 to 2015 was carried out at a head and neck surgery practice at a tertiary referral cancer center. A total of 74 patients who underwent thyroid lobectomy or thyroid isthmusectomy between 1985 and 2015 and were found to have incidental metastatic lymph nodes on final pathologic analysis and were selected to be observed without immediate completion thyroidectomy were included. A separate group of additional 11 patients who underwent immediate completion thyroidectomy was also identified and reviewed. Analysis took place from February to May 2022. Recurrence-free survival outcomes of patients found to have incidental metastatic lymph nodes on final pathologic analysis following partial thyroidectomy with no immediate completion thyroidectomy. A total of 74 patients were observed, with a median (IQR) age of 39 (28-49) years; 44 (59%) were women. Sixty-four patients underwent thyroid lobectomy and 10 patients had isthmusectomy. Classic papillary thyroid carcinoma was the most common histologic type (34 [46%]). Vascular invasion and microscopic extrathyroidal extension were present in 11 patients (16%) and 22 patients (30%), respectively. Positive margins were identified in 5 patients (7.8%). Size of metastatic lymph nodes ranged between 0.07 cm and 1.2 cm. No extranodal extension was reported. A total of 52 patients (70%) were classified as intermediate risk for recurrence based on the American Thyroid Association risk stratification system. The median (IQR) follow up was 48.15 (15.4-86.1) months, during which only 1 patient had a regional recurrence. Another patient underwent delayed completion thyroidectomy for a contralateral lobe malignant abnormality. Recurrence-free survival, disease-specific survival, and overall survival were 97.4%, 100%, and 96.2%, respectively. A separate group of 11 patients who underwent immediate completion thyroidectomy were reviewed. These patients were more likely to have tall-cell papillary thyroid carcinoma (6 [55%] vs 13 [18%]), multifocality (9 [82%] vs 28 [41%]), microscopic extrathyroidal extension (8 [73%] vs 22 [30%]), and positive margins (3 [30%] vs 5 [7.8%]) compared with patients who were under observation only. Completion thyroidectomy may not be necessary in appropriately selected patients who are found to have incidental metastatic lymph nodes (N1a) after partial thyroidectomy for localized well-differentiated thyroid cancer.

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.

Risk-stratified Distant Metastatic Thyroid Cancer with Clinicopathological Factors and BRAF/TERT Promoter Mutations.

To assess the prognostic value of clinicopathological factors as well as BRAF and TERT promoter mutations in predicting distant metastasis in patients with papillary thyroid cancer. The status of BRAF and TERTp mutations were available in 1,208 thyroid cancer patients who received thyroidectomy at Jiangyuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine from January 2008 to December 2021. Based on inclusion criteria, 99 distant metastasis thyroid cancers (DM-TCs) and 1055 patients without DM (Non-DM-TCs) were retrospectively reviewed. After univariate and multivariate analyses, a risk model was established for DM prediction based on factors: T3/T4 stage, lymph node metastasis (LNM) number over 5, and BRAF/TERT mutations (TLBT). It was defined based on the number of TLBT factors: low risk (no risk factor, n=896), intermediate risk (1 risk factor, n=199), and high risk (≥2 risk factors, n=59). Notably, compared with patients with low and intermediate risks, patients assigned to high TLBT risk have a shorter time of DM disease-free survival. Except for gene mutation, other factors were also included in the 2015 American Thyroid Association (ATA) risk guideline. Comparing with the ATA risk category, this risk model showed a better performance in predicting DM-TCs. This study proposes a TLBT risk classifier consisting of T3/T4 stages, LNM (n>5), and BRAF+TERTp mutations for predicting DM-TCs. TLBT risk stratification may help clinicians make personalized treatment management and follow-up strategies.

[A single-center study on the oncological outcomes of active surveillance of thyroid nodules measuring≤1 cm with highly suspicious ultrasound features].

Objective: To investigate the oncological outcomes of active surveillance (AS) in patients showing thyroid nodules measuring≤1 cm with highly suspicious ultrasound features. Methods: A prospective single-center cohort study. A total of 534 patients with highly suspicious thyroid nodules (2015 American Thyroid Association Nodule Sonographic Patterns and Risk of Malignancy: High Suspicion) were enrolled in this study, the patients received AS at Peking Union Medical College Hospital between January 2017 and November 2022 to assess oncological outcomes (disease progression, recurrence/metastasis rate, etc). The patients were followed up every 6 months for physical examination and neck ultrasound examination. And the value of tumor volume changes in evaluating tumor enlargement was explored too. Results: There were 413 females and 121 males in this cohort, with a mean age of (42.6±11.8) years. During a median follow-up period of 45.6 months (ranged from 3.5 to 176.0 months), disease progression occurred in 26 patients (4.9%) with highly suspicious thyroid nodules, characterized by a minimum 3-mm increase in tumor diameter in 19 patients (3.6%) and lymph node metastases in 7 patients (1.3%). Forty-seven (8.8%) patients opted for delayed surgery, with 29 patients due to a change in preference. There was no significant differences in pathologic and follow-up outcomes between patients with disease progression and preference change. Patients aged≤40 years had a higher cumulative incidence of 5-year disease progression than those aged>40 years (4.9% vs 1.9%, P=0.060). No patients experienced distant metastases or deaths. Among the 595 high-risk thyroid nodules with continuous volume assessment results and an increase in nodule diameter of less than 3 mm (including all high-risk nodules in patients with single or multiple nodules), 184 (30.9%) and 79 (13.3%) nodules exhibited volume increases of more than 50% and 100%, respectively, in multiple measurements. Among the nodules with volume changes exceeding 50% and 100%, the proportion of nodules with a baseline tumor diameter of≤0.5 cm was significantly higher than those with a diameter of>0.5 cm, at 69.0% vs 31.0% (P<0.001) and 77.2% vs 22.8% (P<0.001), respectively. Conclusions: Active surveillance in patients with highly suspicious subcentimeter thyroid nodules has good short-term oncological outcomes and can be considered a safe alternative to surgery. Due to the large variability in the measurement results of tumor volume, it is not suitable as an indicator for evaluating tumor enlargement.

Risk Stratification of Differentiated Thyroid Cancer: A Single-Center Study in Basrah.

Background Differentiated thyroid cancer is a common endocrine cancer; most of it has an indolent course and favorable outcomes, with a subset of patients having the risk of disease recurrence, which can be assessed using the fixed American Thyroid Association (ATA) risk stratification system or the dynamic response to therapy risk stratification that can be modified during patients follow-up. Aim The aim of this article is to assess the risk stratification of patients having differentiated thyroid cancer. Methods This is aretrospective cross-sectional study in which we evaluated medical records of 75 patients having differentiated thyroid cancer to assess the baseline ATA risk of recurrence and compared it to the results of dynamic risk stratification in response to therapy at 6-12 months post-surgery and at the last visit. Thyroglobulin level, anti-thyroglobulin antibody, thyroid ultrasound, and cytopathological examination were used to determine dynamic response to therapy and divided subjects into four groups: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR), and indeterminate response (IR). Results At baseline, 55 patients had low risk, 14 patients had intermediate risk, and six patients had high risk. At 6-12 months post-surgery, in the low-risk group, ER, BIR, and IR responses were observed in 56.4%, 5.5%, and 38.2% of patients, respectively, and none of them exhibited SIR. In the intermediate-risk group, ER, BIR, and IR responses were observed in 57.1%, 21.4%, and 21.4% of patients, respectively, and none exhibited SIR. Among the high-risk group, two patients had ER, two patients had BIR, one patient had IR, and one patient had SIR. At the last visit, ER, BIR, and IR were observed in 65.5%, 9.1%, and 25.5% of low-risk patients, respectively, and no patient developed SIR. In the intermediate-risk group, ER, BIR, and IR were observed in 50%, 21.4%, and 28.6% of patients, respectively, and no patients developed SIR. Among the high-risk group, three patients achieved ER, one had BIR, one had IR, and one had SIR. Conclusion Most of the differentiated thyroid cancers in this study are low-risk. Dynamic risk stratification appears to be an effective tool in the follow-up of this population of patients having differentiated thyroid cancer.

Prognostic Factors Improving ATA Risk System and Dynamic Risk Stratification in Low- and Intermediate-Risk DTC Patients.

American Thyroid Association (ATA) guidelines do not consider age at diagnosis as a prognostic factor on the estimation of the risk of persistent/recurrent disease in differentiated thyroid carcinoma (DTC) patients. While age at diagnosis has already been assessed in high-risk patients, it remains to be established in low- and intermediate-risk patients. The aim of our study was to investigate the role of age as a prognostic factor in the short- and long-term outcome of DTC patients classified at low and intermediate risk according to the ATA stratification risk system. We retrospectively evaluated 863 DTC patients (mean follow-up: 10 ± 6.2 years) 52% classified as low (449/863) and 48% as intermediate risk (414/863). For each ATA-risk class patients were divided into subgroups based on age at diagnosis (<55 or ≥55 years). In the intermediate-risk group, patients aged 55 years or older had a higher rate of structural disease (11.6% vs 8.9%), recurrent disease (4.1% vs 0.7%), and death (4.1% vs 1%) when compared with younger patients (<55 years) (P = .007). Multivariate analysis confirmed that older age at diagnosis (odds ratio [OR] = 3.9; 95% CI, 1.9-8.6; P < .001) was an independent risk factor for worse long-term outcome together with response to initial therapy (OR = 13.0; 95% CI, 6.3-27.9; P < .001), and T (OR = 32; 95% CI, 1.4-7.1; P = .005) and N category (OR = 2.3; 95% CI, 1.1-5.0; P = .03). Nevertheless, a negative effect of older age was documented only in the subgroup of intermediate DTC patients with persistent structural disease after initial therapy. Indeed, the rate of worse long-term outcome rose from 13.3% in the whole population of intermediate DTC patients to 47.8% in patients with persistent structural disease after initial therapy (P < .001) and to 80% in patients older than 55 years and persistent structural disease after initial therapy (P = .02). Our results suggest that age at diagnosis further predict individual outcomes in Intermediate-Risk DTC allowing ongoing management to be tailored accordingly.

THU683 TERT Promoter Mutations, But Not BRAFV600EMutation, Correlate With The American Thyroid Association And TNM Staging Systems And Predict Outcome Of Differentiated Thyroid Cancer

Abstract Disclosure: N. Mukhtar: None. K. Alhamoudi: None. M. Alswailem: None. H. Al-Hindi: None. A.K. Murugan: None. B. Alghamdi: None. A.S. Alzahrani: None. Context: The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to predict DTC outcome. Our objectives were to study these molecular markers in terms of their interaction and potential incremental prognostic values over the ATA and TNM staging systems. Patients and Methods: We studied 315 non-selected patients, 229 females, 86 males with a median age of 36 years (IQR 24-49). Data were extracted from medical records. BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Persistent disease (PD) included all patients in structurally or biochemically incomplete and indeterminate response as defined by the 2015 ATA guidelines. Data were analysed using Chi-Square and Fisher Exact test and Kaplan Meier analysis. Results: Of 315 patients tested, 138 (43.8%) had BRAFV600E-positive tumors and 77 (24.5%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of PD (P 0.11). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.01) and in TNM stages III and IV than in lower stages (P &amp;lt;0.001). TERT promoter mutations also predicted the outcome being present in 36.4% of patients with PD compared to only 15.6% in those without evidence of disease (P &amp;lt;0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. TERT promoter mutations alone or TERT promoter + BRAFV600E mutations predicted the development of PD in 100% of patients in TNM stage IV or high-risk ATA stage. Conclusions:TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems. The combination of high-risk ATA or TNM stage IV with TERT promoter mutations is highly predictive of development of PD predicting PD in 100% of cases with these combinations. Presentation: Thursday, June 15, 2023

How do BRAFV600E and TERT promoter mutations interact with the ATA and TNM staging systems in thyroid cancer?

The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to correlate with the histopathological features and outcome of DTC. Our objectives were to study the correlation of these molecular markers with these clinicopathological-staging systems. We studied 296 unselected patients, 214 females and 82 males with a median age of 36 years (IQR 23.3-49.0). BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Data were extracted from medical records and analysed using Chi-Square and Fisher Exact tests and Kaplan Meier analysis. Of 296 patients tested, 137 (46.3%) had BRAFV600E-positive tumors and 72 (24.3%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of persistent disease (PD) (P 0.12). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.006) and in TNM stages III and IV than lower stages (P <0.0001). TERT promoter mutations also predicted the outcome, being present in 37.2% of patients with PD compared to only 15.4% in those without evidence of disease (P <0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems.

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.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.