Effect of COVID-19 pandemic on diagnosis and treatment of thyroid cancer in Brazil.

Introduction: The COVID-19 pandemic delayed the diagnosis, treatment, and follow-up visits of patients with thyroid cancer. However, the magnitude with which these restrictions affected the Brazilian health care is still unknown. Methods: Retrospective analysis of thyroid cancer-related procedures performed in the Brazilian public health system from 2019 to 2021. Data were retrieved from the Department of Informatics of the Unified Health System (DATASUS). The following procedures were evaluated: fine-needle aspiration biopsies (FNABs), oncologic thyroidectomies, and radioiodine (RAI) therapies for thyroid cancer. The year of 2019 served as baseline control. Results: Compared with 2019, FNABs, oncologic thyroidectomies, and RAI therapies performed in 2020 decreased by 29%, 17% and 28%, respectively. In 2021, compared with 2019, FNABs increased by 2%, and oncologic thyroidectomies and RAI therapies decreased by 5% and 25%, respectively. Most pronounced reductions were observed in the first months of the pandemic. In April 2020, FNABs decreased by 67%, oncologic thyroidectomies by 45%, and RAI therapies by 75%. In 2021, RAI therapies were the only procedure with a statistically significant decrease. Conclusion: The restrictions to public health care during the COVID-19 pandemic resulted in a significant reduction in diagnostic and treatment procedures for thyroid cancer in Brazil. The effects of these transitory gaps in thyroid cancer care, due to COVID-19, are still unclear.

Using an ultrasonography risk stratification system to enhance the thyroid fine needle aspiration performance.

PURPOUSE: The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) is a risk stratification system for thyroid nodules based on their ultrasonography (US) characteristics. Here, we aimed to assess TI-RADS on fine needle aspiration biopsy (FNAB) recommendations and performance in thyroid nodules. METHODS: We performed a retrospective study in a single center. All patients with thyroid nodules who underwent FNAB between 2012 and 2019 were included. TI-RADS data were extracted from medical records. Malignancy rates were defined based on cytological exams. RESULTS: A total of 1,044 nodules (938 patients) were evaluated. TI-RADS classification was as follows: 13 TI-RADS 1, 524 TI-RADS 2, 273 TI-RADS 3, 148 TI-RADS 4, and 85 TI-RADS 5. TI-RADS classification showed a sensitivity of 75% (95 %CI: 63-84.7), a negative predictive value of 97.6% (95 %CI: 96.5-98.5), and accuracy of 73.1% (95 %CI: 70.3-75.8). According to TI-RADS FNAB criteria, only 314 (30%) nodules would have undergone FNAB. Of them, 157 (50%) were classified as benign (Bethesda II), 45 (14.3%) as undetermined (Bethesda III or IV), and 51 (16.2%) as malignant (Bethesda V or VI). Of the remaining 729 nodules that did not meet FNAB criteria, 17 (2.3%) had Bethesda V or VI and underwent surgery. Of them, four (23%) were <1 cm in size (microcarcinomas), and eight (47.0%) remain in follow-up according to the TI-RADS criteria. Seven malignant cases would be missed (0.9%). CONCLUSION: ACR TI-RADS allows a significant decrease in the number of FNAB, increasing its diagnostic accuracy.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Inclusion of BRAFV600E mutational status has a limited impact on risk stratification and does not add to the prediction of outcomes in PTC patients.

New insights into the management of differentiated thyroid carcinoma in children and adolescents (Review).

Differentiated thyroid carcinoma (DTC) is the most common malignant neoplasm of the endocrine system. In children and adolescents, DTC usually presents as a more aggressive disease than in the adult population, but patients often have a favourable prognosis, even in cases of advanced disease. Nevertheless, certain patients have persistent or recurrent disease leading to increased morbidity. A significant challenge in the management of DTC is identifying the subgroup of patients with a high risk of unfavourable outcomes. Prognostic factors related to the patient, tumour, and stratification systems (Tumor­Node­Metastasis/American Joint Committee on Cancer, American Thyroid Association risk classification and dynamic risk stratification) are used in an attempt to identify the individuals at increased risk. In the present review, the current risk classification systems applied for paediatric thyroid cancer are discussed, highlighting the major differences between paediatric and adult DTC in pathophysiology, clinical presentation and long­term outcomes. In recent years, genetic markers have also been proposed as prognostic factors for children and adolescents with DTC. Advances in the understanding of the molecular profile of paediatric DTC may aid individualized management, potentially improving diagnosis and treatment. This review article aims to critically review and update the current concepts on DTC management in children and adolescents, with an emphasis on clinical presentation, treatment, risk assessment, follow­up and future perspectives.

Patterns of radioiodine use for differentiated thyroid carcinoma in Brazil: insights and a call for action from a 20-year database.

OBJECTIVE: This study aimed to explore the patterns of radioactive iodine (RAI) use for differentiated thyroid cancer (DTC) in Brazil over the past 20 years. METHODS: A retrospective analysis of the DTC-related RAI prescriptions, from 2000 to 2018, retrieved from the Department of Informatics of the Unified Health System (Datasus) and National Supplementary Health Agency (ANS) database was performed. RAI activities prescriptions were re-classified as low (30-50 mCi), intermediate (100 mCi), or high activities (>100 mCi). RESULTS: The number of DTC-related RAI prescriptions increased from 0.45 to 2.28/100,000 inhabitants from 2000 to 2015, declining onwards, closing 2018 at 1.87/100,000. In 2018, population-adjusted RAI prescriptions by state ranged from 0.07 to 4.74/100,000 inhabitants. Regarding RAI activities, in the 2000 to 2008 period, the proportion of high-activities among all RAI prescriptions increased from 51.2% to 74.1%. From 2009 onwards, there was a progressive reduction in high-activity prescriptions in the country, closing 2018 at 50.1%. In 2018, the practice of requesting high-activities varied from 16% to 82% between Brazilian states. Interestingly, variability of RAI use do not seem to be related to RAI referral center volume nor state socio-economic indicators. CONCLUSION: In recent years, there has been a trend towards the lower prescription of RAI, and a reduction of high-activity RAI prescriptions for DTC in Brazil. Also, significative inter-state and inter-institutional variability on RAI use was documented. These results suggest that actions to advance DTC healthcare quality surveillance should be prioritized.

Impact of the updated TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort.

OBJECTIVE: The 8th TNM system edition (TNM-8) released in 2018 presents significant changes when compared to the 7th edition (TNM-7). The aim of this study was to assess the impact of changing the TNM staging criteria on the outcomes in a Brazilian cohort of differentiated thyroid carcinoma (DTC). SUBJECTS AND METHODS: DTC patients, attending a tertiary, University-based hospital, were classified by TNM-7 and TNM-8. Prediction of disease outcomes status of the two systems was compared in a retrospective cohort study design. RESULTS: Four hundred and nineteen DTC patients were evaluated, comprised by 82% (345/419) women, with mean age at diagnosis of 46.4 ± 15.6 years, 89% (372/419) papillary thyroid carcinoma, with a median tumor size of 2.3 cm (P25-P75, 1.3-3.5). One hundred and sixty patients (38%) had lymph node metastases and 47 (11%) distant metastases at diagnosis. Using the TNM-7 criteria, 236 (56%) patients were classified as Stage I, 50 (12%) as Stage II, 75 (18%) as Stage III and 58 (14%) as Stage IV. When evaluated by the TNM-8, 339 (81%) patients were classified as Stage I, 64 (15%) as Stage II, 2 (0.5%) as Stage III and 14(3%) as Stage IV. After a median follow-up of 4.4years (P25-P75 2.6-6.6), the rate of incomplete biochemical and/or structural response was 54% vs. 92% (P = 0.004) and incomplete structural response was 42% vs. 86% (P = 0.009) for patients classified as stage IV by TNM-7 vs TNM-8, respectively. Only 4 (1%) disease-related deaths were recorded. CONCLUSIONS: In our cohort, 37% of DTC patients were down staged with the application of TNM-8 (vs. TNM-7). Additionally, TNM-8 seems to better stratify the risk of structural incomplete response at follow-up.

Impact of the updated TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort

ABSTRACT Objective: The 8th TNM system edition (TNM-8) released in 2018 presents significant changes when compared to the 7th edition (TNM-7). The aim of this study was to assess the impact of changing the TNM staging criteria on the outcomes in a Brazilian cohort of differentiated thyroid carcinoma (DTC). Subjects and methods: DTC patients, attending a tertiary, University-based hospital, were classified by TNM-7 and TNM-8. Prediction of disease outcomes status of the two systems was compared in a retrospective cohort study design. Results: Four hundred and nineteen DTC patients were evaluated, comprised by 82% (345/419) women, with mean age at diagnosis of 46.4 ± 15.6 years, 89% (372/419) papillary thyroid carcinoma, with a median tumor size of 2.3 cm (P25-P75, 1.3-3.5). One hundred and sixty patients (38%) had lymph node metastases and 47 (11%) distant metastases at diagnosis. Using the TNM-7 criteria, 236 (56%) patients were classified as Stage I, 50 (12%) as Stage II, 75 (18%) as Stage III and 58 (14%) as Stage IV. When evaluated by the TNM-8, 339 (81%) patients were classified as Stage I, 64 (15%) as Stage II, 2 (0.5%) as Stage III and 14(3%) as Stage IV. After a median follow-up of 4.4years (P25-P75 2.6-6.6), the rate of incomplete biochemical and/or structural response was 54% vs. 92% (P = 0.004) and incomplete structural response was 42% vs. 86% (P = 0.009) for patients classified as stage IV by TNM-7 vs TNM-8, respectively. Only 4 (1%) disease-related deaths were recorded. Conclusions: In our cohort, 37% of DTC patients were down staged with the application of TNM-8 (vs. TNM-7). Additionally, TNM-8 seems to better stratify the risk of structural incomplete response at follow-up.

Timing of Radioactive Iodine Administration Does Not Influence Outcomes in Patients with Differentiated Thyroid Carcinoma.

BACKGROUND: Radioactive iodine (RAI) is widely used in the management of differentiated thyroid cancer (DTC). The impact of the time interval between total thyroidectomy (TT) and RAI administration on disease outcome remains controversial. The objective of the present study was to evaluate the impact of the time interval between TT and RAI. METHODS: This study evaluated a cohort of DTC patients who received RAI therapy for whom data on disease status were available. Patients were allocated to one of two groups, according to the time interval between TT and RAI. "Disease-free" was defined as no clinical, imaging, or biochemical evidence of thyroid cancer. RESULTS: The study included 545 individuals. The TNM stages were: 322 (59.1%) patients in Stage I, 62 (11.4%) in Stage II, 65 (11.9%) in Stage III, and 82 (15.0%) in Stage IV. The median time interval between TT and RAI was six months (P25-75: 3-10 months). Patients were allocated to one of two groups according to RAI timing administration: group A ≤6 months after TT (median 3 months; n = 295), or group B >6 months after TT (median 10.5 months; n = 250). There were no differences for sex, histological type, tumor size, distant metastasis, or RAI dose between the groups (p > 0.1). Patients in group B were older (47.1 vs. 43.1 years; p = 0.02), had less cervical metastasis (73.6% vs. 59.3%; p = 0.002), and were more commonly classified as low ATA risk (48.0% vs. 36.6%; p = 0.027). One year after initial therapy, 59.3% and 65.6% of patients in groups A and B, respectively, were considered disease-free (p = 0.15). Remarkably, the percentage of patients classified as disease-free was similar, even when analyzing a subgroup of high-risk patients (n = 72; 9.5% vs. 10.0%; p = 1.0). These findings did not change after a median of six years of follow-up. Accordingly, further analysis by multiple logistic regression showed that timing of RAI was not associated with persistent disease (relative risk 0.97 [confidence interval 0.80-1.19]). CONCLUSIONS: Timing of RAI does not seem to interfere with the disease outcomes in DTC and can therefore be safely planned while taking into account the health system logistics.

Low Recurrence Rates in a Cohort of Differentiated Thyroid Carcinoma Patients: A Referral Center Experience.

BACKGROUND: Trends in the epidemiological profiles of differentiated thyroid cancer (DTC) have shifted the disease spectrum. This study aimed to evaluate the recurrence rates and identify factors related to persistent disease in a contemporary cohort of patients with DTC. METHODS: A cohort of DTC patients submitted to total thyroidectomy followed in a referral center were included in the study. "Disease free" was defined as no clinical, imaging, or biochemical evidence of tumors. "Recurrence" was defined as evidence of disease in a patient who had been previously classified as disease free. RESULTS: A total of 786 patients were included. The mean age at diagnosis was 45.8±15.1 years, 81.6% were female, and papillary thyroid cancer accounted for 86.6% of cases. The median tumor size was 2.0 cm, 28.5% had lymph node involvement, and 6.1% had distant metastases. Disease status after the initial therapy was available for 548 patients: 357 (65.1%) were disease free, and 191 (34.9%) had persistent disease (90 biochemical and 101 structural disease). In multivariate model analyses, the variables male sex, lateral lymph nodal involvement, distant metastasis, and 2009 ATA high-risk classification were independent prognostic factors for persist disease. After a four-year follow-up (two to eight years), 97.2% of the patients who had been classified as disease free remained in disease remission status. Of the 10 (2.8%) patients with recurrent disease, eight presented biochemical and two cervical structural disease. CONCLUSIONS: The majority of the DTC patients who were considered to be disease free after the initial treatment remained with this status at long-term follow-up. These data suggest that less intensive follow-up may apply for these patients.

Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases.

OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100%. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.

Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases / Determinação da tireoglobulina no lavado da agulha da punção aspirativa de linfonodos cervicais para detecção de metástases do câncer papilar de tireoide

OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100 percent. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.

OBJETIVO: O objetivo deste estudo foi avaliar a acurácia da dosagem de tireoglobulina no lavado da agulha da punção aspirativa (PAAF-Tg) de linfonodos (LN) cervicais para detecção de metástases do câncer papilar de tireoide (CPT). SUJEITOS E MÉTODOS: Foram incluídos 43 pacientes (51,4 ± 14,6 anos) com diagnóstico de CPT e evidência de LN cervicais aumentados. Os LN suspeitos foram submetidos à punção aspiração com agulha fina guiada por ecografia para análise citológica e dosagem de tireoglobulina (PAAF-Tg). RESULTADOS: A mediana dos valores de PAAF-Tg nos LN metastáticos (n = 5) foi 3.419,0 ng/mL (11,1-25.538), enquanto nos LN não metastáticos (n= 38) a mediana foi de 3,7 ng/mL (0,8-7,4). Utilizando-se o nível de 10 ng/mL como ponto de corte, observaram-se sensibilidade e especificidade de 100 por cento. Os níveis de TSH sérico não interferiram na dosagem de PAAF-Tg (3,3 e 3,8 ng/mL nos grupos com TSH supresso (TSH 0,07 mUI/mL) e hipotireoidismo (TSH 97,4 mUI/mL), respectivamente, P = 0,2). CONCLUSÃO: Os resultados demonstram que a dosagem de PAAF-Tg é uma ferramenta importante no diagnóstico de metástases do CPT, podendo ser utilizada independente do "status" tireoidiano.