Challenges in treating radioiodine-refractory thyroid cancer: a global perspective with a focus on developing nations in Latin America.

PURPOSE: This article aims to comprehensively analyze the unique challenges in managing patients with metastatic Differentiated Thyroid Cancer (DTC) that develop radioiodine-refractory disease, especially in developing countries in Latin America. We discuss key contentious aspects of their treatment, such as the optimal timing for initiating systemic therapy, the choice of first-line medications, the appropriate timing for requesting molecular interrogation, and the challenges associated with accessing these drugs and molecular panels. METHODS: To illustrate these challenges and enhance understanding, we present five real clinical cases from the authors' experiences. RESULTS: Patients with Differentiated Thyroid Cancer (DTC) generally have an excellent prognosis, with an overall 10-year survival rate exceeding 97%. However, approximately 5% of DTC patients, especially those with distant metastases, may develop radioiodine-refractory disease, reducing survival rates. Access to medications remains difficult and time-consuming, particularly for patients within the public healthcare system. Urgent discussions on drug pricing involving all stakeholders are imperative. To break free from complacency, stakeholders must prioritize patient well-being by advocating for evidence-based drug pricing, increased participation in clinical trials, and streamlined regulatory processes. CONCLUSION: Beyond the recognized need for prospective randomized clinical trials to determine the optimal first-line drug and the timing of molecular testing, this type of manuscript plays a pivotal role in stimulating discussions and disseminating comprehensive knowledge about the challenges associated with treating and monitoring patients with radioiodine-refractory thyroid carcinoma, especially in developing countries.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1alpha After Treatment: A Cell Regulation Study / Observación del Efecto Clínico de Apatinib Combinado con 131I para el Cáncer de Tiroides Diferenciado Resistente al Yodo Radiactivo y Análisis de Importancia Pronóstica de la Proteína Inflamatoria 1alfa de Macrófagos Después del Tratamiento: Un Estudio de Regulación Celular

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Stimulated thyroglobulin and diagnostic 131-iodine whole-body scan as a predictor of distant metastasis and association with response to treatment in pediatric thyroid cancer patients.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is a rare oncological disease in the pediatric population, presenting with a more aggressive form. Stimulated thyroglobulin (sTg) and the 131-iodine whole-body scans (WBSs) are known adult markers related to the presence of distant metastasis. Little is known about their roles in the pediatric population. PURPOSE: To evaluate sTg levels and diagnostic WBS (DxWBS) as predictors of distant metastasis after thyroidectomy and to correlate with the response to treatment at the end of follow-up in pediatric DTC. MATERIALS AND METHODS: Patients under 19 years old diagnosed with DTC from 1980 to 2022 were retrospectively evaluated. sTg values and WBS were assessed after thyroidectomy and prior radioiodine treatment (RIT) and correlated with the possibility of finding distant metastasis and response to treatment at the end of follow-up. RESULTS: In a total of 142 patients with a median age of 14.6 (4-18) years who were followed for 9.5 ± 7.2 years and classified according to the ATA risk of recurrence as low (28%), intermediate (16%), and high risk (56%), 127 patients had their sTg evaluated. A sTg value of 21.7 ng/dl yielded a sensitivity of 88% compared to 30% for DxWBS in predicting distant metastasis. Specificity was 60% and 100% respectively. 42% of patients obtained discordant results between DxWBS and RxWBS. In high-risk patients, sTg levels were particularly able to differentiate those who would have distant metastasis with better diagnostic accuracy than the WBSs. CONCLUSIONS: The sTg level had better performance in detecting distant metastases in pediatric DTC than the DxWBS. DxWBS's low performance suggests that caution should be taken in interpreting their findings in terms of the underdiagnosis for metastatic disease, especially when the sTg level already suggests distant disease.

Management of radioiodine refractory differentiated thyroid cancer: the Latin American perspective.

Radioiodine (RAI) refractory differentiated thyroid cancer is an uncommon and challenging situation that requires a multidisciplinary approach to therapeutic strategies. The definition of RAI-refractoriness is usually a clear situation in specialized centers. However, the right moment for initiation of multikinase inhibitors (MKI), the time and availability for genomic testing, and the possibility of prescribing MKI and selective kinase inhibitors differ worldwide.Latin America (LA) refers to the territories of the world that stretch across two regions: North America (including Central America and the Caribbean) and South America, containing 8.5% of the world's population. In this manuscript, we critically review the current standard approach recommended for patients with RAI refractory differentiated thyroid cancer, emphasizing the challenges faced in LA. To achieve this objective, the Latin American Thyroid Society (LATS) convened a panel of experts from Brazil, Argentina, Chile, and Colombia. Access to MKI compounds continues to be a challenge in all LA countries. This is true not only for MKI but also for the new selective tyrosine kinase inhibitor, which will also require genomic testing, that is not widely available. Thus, as precision medicine advances, significant disparities will be made more evident, and despite efforts to improve coverage and reimbursement, molecular-based precision medicine remains inaccessible to most of the LA population. Efforts should be undertaken to alleviate the discrepancies between the current state-of-the-art care for RAI-refractory differentiated thyroid cancer and the present situation in Latin America.

Metastatic differentiated thyroid cancer: worst prognosis in patients with metachronous metastases.

PURPOSE: To describe the overall survival and progression-free survival in patients diagnosed with differentiated thyroid carcinoma with synchronous and metachronous metastatic involvement. MATERIALS AND METHODS: A retrospective cohort study was conducted with 101 patients with differentiated thyroid cancer (DTC) who had metastatic involvement at diagnosis or during follow-up, who were treated at the National Cancer Institute between January 1, 2010 and December 31 of 2015. RESULTS: 81 patients (80.2%) were women and the mean age at diagnosis was 49 years (12-80). Synchronous metastases were detected in 54.5% of patients and metachronous metastasis was diagnosed in 45.5% of patients, in whom the mean time between initial diagnosis and the finding of distant metastases was 5 years. Pulmonary involvement occurred in almost all patients, with 131I uptake in 58% of synchronous metastases and in 21% of metachronous. There were 10 events in the patients with 131I-avid metastases with a median time to progression that was not reached, and there were 23 events in patients with 131I-refractory metastases with a median time to progression of 96 months; The median time to progression was significantly longer in patients with synchronous metastases compared to those with metachronous metastases (Not reached vs 95 months, P = 0.017) The 5-year overall survival rate was 95% to the entire cohort. CONCLUSIONS: The present study contributes to the expansion of the knowledge about this clinical course of DTC with the finding of a worst prognosis in patients with metachronous metastases.

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.

Redox Homeostasis in Thyroid Cancer: Implications in Na+/I- Symporter (NIS) Regulation.

Radioiodine therapy (RAI) is a standard and effective therapeutic approach for differentiated thyroid cancers (DTCs) based on the unique capacity for iodide uptake and accumulation of the thyroid gland through the Na+/I- symporter (NIS). However, around 5-15% of DTC patients may become refractory to radioiodine, which is associated with a worse prognosis. The loss of RAI avidity due to thyroid cancers is attributed to cell dedifferentiation, resulting in NIS repression by transcriptional and post-transcriptional mechanisms. Targeting the signaling pathways potentially involved in this process to induce de novo iodide uptake in refractory tumors is the rationale of "redifferentiation strategies". Oxidative stress (OS) results from the imbalance between ROS production and depuration that favors a pro-oxidative environment, resulting from increased ROS production, decreased antioxidant defenses, or both. NIS expression and function are regulated by the cellular redox state in cancer and non-cancer contexts. In addition, OS has been implicated in thyroid tumorigenesis and thyroid cancer cell dedifferentiation. Here, we review the main aspects of redox homeostasis in thyrocytes and discuss potential ROS-dependent mechanisms involved in NIS repression in thyroid cancer.

Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?

Radioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic 131I whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC. A retrospective analysis of 301 intermediate-risk DTC patients submitted to total thyroidectomy and RAI therapy was performed. Pretherapy sTg and DxWBS and post-therapy WBS (RxWBS) findings were analyzed and compared to outcomes. Fifty-two patients (17.3%) had metastases diagnosed by DxWBS and/or RxWBS. The DxWBS identified 10.6% of patients with functioning metastases, including unexpected distant metastases. If combined with SPECT-CT, DxWBS detected RAI-avid metastases more frequently, particularly lymph node metastases (13.1% vs 4.2% planar WBS, P = 0.015). The DxWBS findings modified patient management in 8.3%. A pretherapy sTg <1 ng/mL was associated with a low false-negative rate for the presence of metastases (5.2%), and its performance in excluding metastasis was improved by a negative DxWBS (2.7% of patients with both negative exams had metastases in RxWBS). A sTg <1 ng/mL predicted statistically significant lower rates of recurrent/persistent disease and biochemical/structural incomplete responses. In conclusion, preablation sTg and DxWBS contribute to the detection of unknown or persistent metastatic disease in intermediate-risk DTC patients. A sTg <1 ng/mL in combination with a negative DxWBS is highly suggestive of the absence of remaining malignant disease, and one may consider deferring RAI ablation if both exams are negative. A stunning effect is rarely observed and it does not impair proper treatment of metastases.

Dacryoendoscopic recanalization of lacrimal passage obstruction/stenosis after radioiodine therapy for differentiated thyroid carcinoma.

PURPOSE: Radioiodine therapy, a standard treatment for differentiated thyroid carcinomas, is associated with several adverse events including lacrimal drainage system obstruction. Herein, we describe the first case of duct lumen recanalization using dacryoendoscopy for lacrimal passage obstruction and stenosis after radioiodine therapy. OBSERVATIONS: A 48-year-old female treated with radioiodine therapy for differentiated thyroid carcinoma 5 years prior presented with epiphora in both eyes. Dacryocystography showed nasolacrimal duct stenosis in the right eye and nasolacrimal duct obstruction in the left eye. Dacryoendoscopic examination revealed right common canalicular polyps, fibrosis in the right lacrimal sac, right nasolacrimal duct stenosis, and left upper and common canaliculus stenosis. Lacrimal passage recanalization with the insertion of a nasolacrimal stent tube using dacryoendoscopy was performed on the right eye. This successfully resolved the epiphora. CONCLUSIONS AND IMPORTANCE: Dacryoendoscopic examination for epiphora after radioiodine therapy may help detect early-stage nasolacrimal passage obstruction/stenosis. This condition can be resolved by recanalization and insertion of a lacrimal tube, without the need for a more invasive surgical approach such as dacryocystorhinostomy.

Clinical pharmaceutical screening in critical situations in a radioiodine therapy management service.

Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to evaluate all health problems and medications used in the pre-radioiodine therapy period and comprehensive medication managementservices can serve as a screening tool in this context. The present study aims to describe critical clinical situations identified during the initial assessments of a comprehensive medication management service offered to differentiated thyroid carcinoma patients pre-radioiodine therapy, and the pharmaceutical interventions performed to solve them. A descriptive study with regard to the initial ten months of a comprehensive medication management service was carried out in a large oncology hospital (Rio de Janeiro, Brazil). Descriptive analysis was used to describe the critical clinical situations identified, as well as the correspondent drug therapy problems and the type, acceptability, and outcomes of the pharmaceutical interventions performed to solve them. Thirty patients with an average of 45.8 years and 5.1 medications were evaluated. Five critical clinical situations were identified; corresponding to drug therapy problems two(needs additional drug therapy - n = 4) and drug therapy problems four (dosage too low - n = 1). All pharmaceutical interventions were accepted. The comprehensive medication management service provision pre-radioiodine therapy is feasible and represents an important screening strategy.

Indication for radioactive iodine in patients with papillary thyroid carcinoma without apparent disease after total thyroidectomy but with elevated antithyroglobulin antibodies.

OBJECTIVE: To evaluate a criterion for the selective indication of radioactive iodine (RAI) based on the short-term behaviour of antithyroglobulin antibodies (TgAb) in patients with papillary thyroid carcinoma (PTC) who have negative thyroglobulin (Tg) and neck ultrasonography (US) without abnormalities after total thyroidectomy but elevated TgAb. DESIGN: This was a prospective study that evaluated 216 patients with low- or intermediate-risk PTC who had nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities but elevated TgAb 3 months after thyroidectomy. RAI was not indicated in patients with negative TgAb or a >50% reduction in TgAb concentrations 6 months after initial assessment followed by a negative test or an additional reduction (also >50%) after 12 months. RESULTS: Only two of the 114 patients who did not receive RAI developed recurrences; another 108 patients met the criterion of an excellent response to therapy in the last assessment and TgAb persisted in four patients but there was an additional reduction in their concentration during follow-up. Among the 102 patients who received RAI, post-therapy whole-body scanning (RxWBS) detected persistent disease in 8 (8%). Two of the 94 patients without persistent disease on RxWBS developed recurrences. In the last assessment, in the absence of additional treatment, 54/92 patients (58.7%) without structural recurrence had negative TgAb. CONCLUSIONS: The indication for RAI can be based on the short-term behaviour of TgAb in patients with PTC and elevated TgAb after thyroidectomy who are not high risk and who do not have apparent disease (nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities).

El tratamiento paciente específico del hipertiroidismo con radioyodo: una oportunidad a la mejora / Radioiodine treatment of hyperthyroidism with patient-specific techniques: an improvement opportunity

Introducción: La aplicación de actividades fijas en el tratamiento del hipertiroidismo con I131 (yoduro de sodio, conocido también como radioyodo), es el método más usado en nuestro país, a pesar de la individualidad morfo-funcional que caracteriza esta afección. Sin embargo, no existe aún, un consenso internacional sobre la dosis más conveniente para cada caso, y por ende, los resultados no siempre son los deseados. Objetivo: Evaluar la aplicabilidad de varios métodos de cálculo de dosis paciente-específica para el tratamiento de hipertiroidismo con yoduro de sodio. Métodos: Se realizó un análisis de los resultados de varios métodos de cálculo de dosis recomendados internacionalmente a partir de la actividad fija prescrita en 10 pacientes, con el empleo de tecnologías y herramientas ya desarrolladas y disponibles en el país. Se evaluó la variabilidad inter-especialista y su impacto en la dosis planificada para el tratamiento. Resultados: El uso de la información incompleta de la biodistribución y farmacocinética del paciente produjo diferencias entre -42 por ciento y 37 por ciento de las dosis para el mismo paciente. El resultado de la comparación del método de cálculo recomendado por la Sociedad Europea de Medicina Nuclear, manejando la masa por gammagrafía-2D / 3D y por ultrasonido, arrojó diferencias no significativas entre sí. La variabilidad inter-especialista de las actividades prescrita mostró diferencias significativas, que arrojan sobre el mismo paciente, discrepancias entre 44Gy y 243Gy de las dosis terapéuticas a recibir, situación que puede comprometer el éxito del tratamiento y producir efectos secundarios no deseados. Conclusiones: Las técnicas dosimétricas paciente-específicas se pueden implementar satisfactoriamente en nuestro país. Las diferencias numéricas encontradas, especialmente la variabilidad inter-especialista, demuestran la no estandarización terapéutica, lo que apoya el uso de la farmacocinética paciente-específica pre terapéutica y la masa por gammagrafía-3D para planificar el tratamiento siempre que sean posible(AU)

Introduction: Despite of its typical morpho-functional individuality, fixed activities remain as the most used method in Cuba for hyperthyroidism treatment with I (sodium iodide, also known as radioiodine). However, there is not yet an international consensus on the most convenient doses for each case, so, the results are not always the desired ones. Objective: To evaluate the applicability of various patient-specific dose calculation methods for the treatment of hyperthyroidism with sodium iodide. Methods: It was carried out an analysis in 10 patients of the results of some methods for dose calculation from the prescribed fixed activity recommended internationally, with the use of technologies and tools already developed and available in the country. The inter-specialist variability and its impact in the planned dose for the treatment were assessed. Results: The use of uncompleted biodistribution and pharmacokinetics information of the patient showed differences between -42 percent and 37 percent in the doses for the same patient. The outcome of the comparison of the calculation method recommended by the European Society of Nuclear Medicine managing the mass by 3D/2D gammagraphy and ultrasound, presented no significant discrepancies among them. The inter-specialist variability of prescribed activity was statistically significant, and it can produce in the same patient differences between 44Gy and 243Gy of the therapeutic doses, which could affect the treatment success and lead to unnecessary side effects. Conclusions: The patient´s personalized calculation methods can be satisfactorily applied in Cuba. The numeric differences found, especially inter-specialist variability, show the lack of therapeutic standardization, which supports the use of pre-therapeutic patient-specific pharmacokinetics and the mass by 3D-gammagraphy to plan the treatment when possible(AU)

High thyroglobulin and negative whole-body scan: no long-term benefit of empiric radioiodine therapy.

PURPOSE: Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. METHODS: A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits. RESULTS: Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). CONCLUSIONS: Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

Fixed 30 mCi (1110 MBq) 131I-iodine therapy in autonomously functioning nodules: Single toxic nodule as a predictive factor of success.

AIMS: The aim of this study is to evaluate the efficacy of a fixed 30 mCi (1110 MBq) 131I-iodine dose for the treatment of hyperthyroidism due to uninodular or multinodular toxic goiter and identify predictors of success. MATERIALS AND METHODS: Fifty-nine patients diagnosed with nonautoimmune toxic goiter were treated with a fixed 30 mCi dose of 131I-iodine and were followed at a tertiary service between 2000 and 2016. The therapy was considered successful if the patient reached euthyroidism or hypothyroidism without needing an extra 131I-iodine dose or antithyroid drugs for at least 1 year after the radioiodine therapy (RIT). RESULTS: Patients with a single toxic nodule were younger at diagnosis (52 vs. 63 years; P = 0.007), presented a shorter disease duration until RIT (2 vs. 3.5 years; P = 0.007), smaller total thyroid volume (20 vs. 82 cm3; P = 0.044), and lower pre-RIT thyroid uptake (P = 0.043) than patients with multinodular goiter. No significant difference was seen with antithyroid drug use, thyroid-stimulating hormone and free thyroxine level, and follow-up after RIT. After RIT, 47 patients (79.66%) met the success criteria, and 12 (20.33%) remained hyperthyroid. Among the success group, 32 (68.08%) reached euthyroidism, while 31.92% developed hypothyroidism after 1 year. Patients with single toxic nodules who achieved success after RIT presented smaller nodules (2.8 vs. 5.75 cm; P = 0.043), while the pre-RIT thyroid uptake was higher among patients with multinodular toxic goiter who achieved success after RIT (5.5% vs. 1.5%; P = 0.007). A higher success rate was observed among patients with a single toxic nodule than those with a toxic multinodular goiter (92.3% vs. 55%; P = 0.001), and a single toxic nodule presentation was found to be an independent predictor of success (P = 0.009). CONCLUSIONS: The fixed 30 mCi 131I-iodine dose was particularly effective in the group of patients with single autonomously functioning nodule rather than the group with multiple nodules. A single toxic nodule was an independent predictor of treatment success.

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.

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

ABSTRACT 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. Materials and 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.

[Long-term survival after small doses of radioiodine therapy for brain metastases of thyroid cancer]. / Supervivencia prolongada luego de pequeñas dosis de terapia con radioyodo en metástasis cerebral de cáncer de tiroides.

Differentiated thyroid cancer is generally accompanied by a long term survival. However, in some cases distant metastases can develop and among them, brain localizations are of poor prognosis. The aim of this presentation is to communicate the clinical case of a 65 year-old woman who consulted for diplopia in vertical gaze which had appeared one month earlier. MRI showed a big mass at the level of the occipital condyle. Diagnosis of primary brain tumor was made so she was operated twice with incomplete tumor resection. The pathological study was confirmatory of a metastatic lesion of thyroid carcinoma. A total thyroidectomy with resection of a papillary cancer of the follicular variant was performed. Then, she was successfully treated with small repetitive radioiodine amounts for a total accumulated dose of 325 mCi 131I, with a long-term survival.

El cáncer diferenciado de tiroides generalmente se acompaña de una supervivencia a largo plazo. Sin embargo, en algunos casos pueden desarrollarse metástasis a distancia y, entre ellas, las localizaciones cerebrales son de mal pronóstico. El objetivo de esta presentación es comunicar el caso clínico de una mujer de 65 años que consultó por diplopía en la mirada vertical que había aparecido un mes antes. La resonancia magnética mostró una gran masa a nivel del cóndilo occipital. Se realizó el diagnóstico de tumor cerebral primario, por lo que fue operada dos veces con resección tumoral incompleta. El estudio histopatológico confirmó una lesión metastásica de carcinoma de tiroides. Se realizó una tiroidectomía total con resección de un cáncer papilar de la variante folicular. Luego, fue tratada con éxito con pequeñas cantidades repetitivas de yodo radiactivo para una dosis total acumulada de 325 mCi 131I, con una supervivencia a largo plazo.

Supervivencia prolongada luego de pequeñas dosis de terapia con radioyodo en metástasis cerebral de cáncer de tiroides / Long-term survival after small doses of radioiodine therapy for brain metastases of thyroid cancer

Resumen El cáncer diferenciado de tiroides generalmente se acompaña de una supervivencia a largo plazo. Sin embargo, en algunos casos pueden desarrollarse metástasis a distancia y, entre ellas, las localizaciones cerebrales son de mal pronóstico. El objetivo de esta presentación es comunicar el caso clínico de una mujer de 65 años que consultó por diplopía en la mirada vertical que había aparecido un mes antes. La resonancia magnética mostró una gran masa a nivel del cóndilo occipital. Se realizó el diagnóstico de tumor cerebral primario, por lo que fue operada dos veces con resección tumoral incompleta. El estudio histopatológico confirmó una lesión metastásica de carcinoma de tiroides. Se realizó una tiroidectomía total con resección de un cáncer papilar de la variante folicular. Luego, fue tratada con éxito con pequeñas cantidades repetitivas de yodo radiactivo para una dosis total acumulada de 325 mCi 131I, con una supervivencia a largo plazo.

Abstract Differentiated thyroid cancer is generally accompanied by a long term survival. However,in some cases distant metastases can develop and among them, brain localizations are of poor prognosis. The aim of this presentation is to communicate the clinical case of a 65 year-old woman who consulted for diplopia in vertical gaze which had appeared one month earlier. MRI showed a big mass at the level of the occipital condyle. Diagnosis of primary brain tumor was made so she was operated twice with incomplete tumor resection. The pathological study was confirmatory of a metastatic lesion of thyroid carcinoma. A total thyroidectomy with resection of a papillary cancer of the follicular variant was performed. Then, she was successfully treated with small repetitive radioiodine amounts for a total accumulated dose of 325 mCi 131I, with a long-term survival.

Can patients with papillary thyroid carcinoma and low postoperative thyroglobulin in the presence of clinically apparent lymph node metastases (cN1) be spared from radioiodine?

BACKGROUND: The study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and clinically apparent lymph node metastases (LNM) (cN1) who had low thyroglobulin (Tg) after total thyroidectomy and who were not submitted to adjuvant therapy with 131I. METHODS: This was a prospective study. It included 82 cN1 patients (≤3 LNM ≤1.5 cm without macroscopic extracapsular extension) with tumors ≤4 cm without macroscopic extrathyroid invasion (T1-2) and who after thyroidectomy had unstimulated Tg (u-Tg) < 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. The patients were not submitted to therapy with 131I. RESULTS: The time of follow-up ranged from 24 to 156 months (median 84 months). Seventy-nine patients (96.3%) continued to have u-Tg < 0.3 ng/ml and negative US. Three patients (3.6%) exhibited an increase in Tg and structural recurrence was detected in two. After treatment, these patients achieved u-Tg < 1 ng/ml and the imaging methods revealed no apparent tumor. CONCLUSIONS: The results suggest that even cN1 patients, given the absence of extensive LNM or other adverse findings, who have low Tg and neck US showing no anomalies after thyroidectomy do not require radioiodine.