Actualización en carcinoma diferenciado de tiroides refractario a radioyodo / Update on iodine-refractory differentiated thyroid carcinoma

La terapia con radioyodo constituye un pilar fundamental en la terapia adyuvante de rutina de los pacientes con carcinoma diferenciado de tiroides de alto riesgo. Sin embargo, un porcentaje no despreciable de estos pacientes desarrollaran un estado de refractariedad a este tratamiento, mostrando un peor pronóstico, disminuyendo la supervivencia y la esperanza de vida, lo que demuestra una clara necesidad de explorar distintos abordajes terapéuticos. El tratamiento de los pacientes refractarios al radioyodo sigue siendo un desafío, disponiendo en la actualidad de distintas opciones terapéuticas novedosas que deben ser conocidas por las distintas especialidades relacionadas con el carcinoma diferenciado de tiroides (CDT). El objetivo del presente trabajo es hacer una revisión del CDT refractario al tratamiento con yodo radiactivo, centrándose especialmente en la definición de yodorrefractariedad, destacando su importancia por su elevada mortalidad, e introducir las diferentes opciones terapéuticas disponibles para estos pacientes (AU)

Radioiodine therapy represents a fundamental pillar in the routine adjuvant therapy of patients with high-risk differentiated thyroid carcinoma. However, a non-negligible percentage of these patients will develop iodine refractoriness, showing a worse prognosis, as well a lower survival, which demonstrates a clear need to explore different therapeutic approaches. Iodine refractory patient treatment continues to be a challenge, currently having different novel therapeutic options that should be known by the different specialties related to differentiated thyroid carcinoma (DTC). The aim of this work is to review iodine refractory thyroid carcinoma treatment, focusing especially on the definition of iodine refractoriness, highlighting its importance due to its high mortality, and introducing the different therapeutic options available for these patients (AU)

Update on iodine-refractory differentiated thyroid carcinoma.

Radioiodine therapy represents a fundamental pillar in the routine adjuvant therapy of patients with high-risk differentiated thyroid carcinoma. However, a non-negligible percentage of these patients will develop iodine refractoriness, showing a worse prognosis, as well a lower survival, which demonstrates a clear need to explore different therapeutic approaches. Iodine refractory patient treatment continues to be a challenge, currently having different novel therapeutic options that should be known by the different specialties related to differentiated thyroid carcinoma (DTC). The aim of this work is to review iodine refractory thyroid carcinoma treatment, focusing especially on the definition of iodine refractoriness, highlighting its importance due to its high mortality, and introducing the different therapeutic options available for these patients.

Evolution of suppressing TSH therapy at diagnosis and in the long-term follow-up in a cohort of differentiated thyroid cancer.

INTRODUCTION: To evaluate the adequacy of TSH suppression therapy (TSHst) at the first disease assessment and the last follow-up visit. METHODS: Retrospective observational study of those patients under follow-up of DTC in a reference hospital. RESULTS: 216 patients (79.2% women) were evaluated, with a mean age 59.0 ±â€¯13.1 years-old and a mean follow-up of 6.9 ±â€¯4.3 years. 88.4% were papillary carcinomas. At diagnosis, 69.2% had a low risk of recurrence (RR) compared to 13.6% with a high RR. Dynamic risk stratification (DRS) classified patients at first disease assessment and the last visit as excellent response (ER) in 60.0% and 70.7%, respectively. Those patients with ER in the first and last follow-up control maintained TSHst in 30.7% and 16.3% of the cases, respectively (p < 0.001). The factors associated with maintaining TSHst at the last control were younger age, higher RR at diagnosis, DRE at follow-up, presence of multifocality and histological vascular invasion (p < 0.05). In a logistic regression analysis adopting tsTSH at follow-up as the dependent variable, exclusively age (ß = -0.062; p < 0.001), RR at diagnosis (ß = 1.074; p < 0.05) and EDR during follow-up (ß = 1.237; p < 0.05) maintained statistical significance. CONCLUSIONS: Despite the current recommendations, 30.7% of patients with low RR and initial ER are under TSHst. This percentage reduced to 16.3% in those patients with ER after a mean follow-up of 6.9 years. Age, baseline RR, and DRE during follow-up were associated to maintaining tsTSH.

Evolución del tratamiento con radioyodo en el carcinoma diferenciado de tiroides / Evolution of radioiodine treatment in differentiated thyroid carcinoma

En marzo de 2021 se ha celebrado el 80 aniversario de la primera aplicación terapéutica del radioyodo (RAI) por Saúl Hertz a una paciente con hipertiroidismo el 31 de marzo de 1936. El éxito alcanzado impulsó su utilización en el tratamiento del carcinoma diferenciado de tiroides (CDT) y supuso un cambio de paradigma en el manejo de las enfermedades tiroideas. Desde entonces, han cambiado las estrategias de administración de RAI a pacientes con CDT y aún hoy día existen controversias. En esta revisión vamos a comentar las diferentes estrategias adoptadas en la administración de RAI a pacientes con CDT a lo largo de estas 8 décadas y cuáles son las controversias actuales en cuanto a qué pacientes con CDT hay que administrar RAI y qué actividad de RAI se debe administrar. (AU)

March 2021 has marked the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine (RAI) to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. Success with hyperthyroidism fueled a seamless, almost intuitive transition to the use of RAI in thyroid carcinoma and marked the beginning of a new paradigm for thyroid cancer diagnosis and management. Since then, several therapeutic strategies have been adopted in the management of patients with differentiated thyroid cancer (DTC) and there are still controversies today regarding which patients with DTC should be administered RAI and what RAI activity should be administered, issues that will be commented in this review. (AU)

Role of 18F-FDG-PET/CT in patients with differentiated thyroid cancer with biochemical incomplete or indeterminate response to treatment.

OBJECTIVES: To assess the value of 18F-FDG-PET/CT for detecting recurrent/persistent disease in patients with biochemical incomplete (BIR) or indeterminate response (IR) and to assess the impact of 18F-FDG-PET/CT on the therapeutic management of these patients. METHODS: The study included patients with BIR, in whom 18F-FDG PET/CT was used within the diagnostic algorithm from our database. Patients with IR referred to our hospital with the 18F-FDG PET/CT already performed were also enrolled. All patients had neck ultrasonography with no structural changes. A change in therapeutic approach was defined as repeat surgery; administration of external beam radiotherapy; and/or the start of systemic therapy. RESULTS: Sixty patients (85% women) aged 18-86 years were enrolled in this retrospective study. Of these, 75% had BIR and 25% IR. Increased FDG uptake suggesting locoregional lesions was seen in 40% of patients. Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT to detect local disease were 95%, 87.5% and 90% respectively. The therapeutic approach was modified in 50% of patients with locoregional lesions. CONCLUSIONS: Our study confirmed that 18F-FDG-PET/CT is a useful tool for detecting locoregional recurrence in thyroid cancer patients with BIR or IR with conflicting findings in standard diagnostic procedures. In 50% of patients with locoregional lesions, there was an immediate change in the treatment approach.

El cáncer diferenciado de tiroides: experiencia clínica frente a un panorama cambiante / Differentiated thyroid cancer: clinical experience in a changing scenario

Antecedentes: el cáncer de tiroides es el cáncer endocrino más frecuente, ha aumentado significativamente su incidencia y se han producido importantes cambios en su tratamiento. Objetivos: analizar una población de pacientes con cáncer diferenciado de tiroides tratados en el Hospital Universitario Austral, evaluar sus resultados y discutir las nuevas tendencias en su manejo. Material y métodos: revisión retrospectiva de una serie de 344 pacientes operados entre mayo de 2001 y mayo de 2015; se realizaron 331 tiroidectomías totales y 13 lobectomías, con linfadenectomía central en el 82% y lateral en el 9 %, según hallazgos clínicos o ultrasonográficos. El 80% correspondieron al sexo femenino y el 95% fueron carcinomas papilares. De acuerdo con TNM, el 65 % fueron T1, 41% T1a (microcarcinomas) y, según ATA, el 87 % tenían bajo riesgo de recurrencia. El 34 % de los vaciamientos centrales y todos los laterales presentaron metástasis ganglionares, y solo el 1,8% presentó metástasis a distancia. El 73% de los pacientes recibieron I131 en dosis de 30 a 150 mCi (milicurios). Resultados: la supervivencia global fue del 99,2% con seguimiento promedio de 40,2 meses, con 0,8% de hipoparatiroidismo definitivo y 0,8% de parálisis recurrencial definitiva. Conclusiones: 1) casi el 80% de la población operada correspondía a estadios tempranos con bajo riesgo de recurrencia, 2) más del 40% correspondió a microcarcinomas, 3) los resultados obtenidos son similares a los comunicados por centros de alto volumen, 4) las conductas terapéuticas coincidieron con las recomendaciones de las guías en vigencia y con las nuevas tendencias en el manejo del cáncer diferenciado de tiroides.

Background: Thyroid cancer is the most common type of endocrine cancer with an incidence that is significantly increasing and with important treatment changes. Objectives: The aim of this study was to analyze a population of patients with differentiated thyroid cancer treated at the Hospital Universitario Austral, evaluate the outcomes and discuss the new trends in thyroid cancer management. Material and methods: A series of 344 patients undergoing thyroid surgery between May 2001 and May 2015 were retrospectively reviewed: 331 total thyroidectomies and 13 lobectomies. Central lymph node dissection was performed in 82% of the cases and lateral lymph node dissection in 9%, based on clinical and ultrasound findings. Most patients were women (80%) and 95% were papillary thyroid cancers. According to the TNM classification, 65% were T1, 41% T1a (microcarcinomas) and 87% corresponded to the ATA low risk of recurrence category. Lymph node metastases were present in 34% of the central neck lymph nodes and in all the lateral lymph nodes dissected, and only 1.8% presented distant metastasis. Radioactive iodine was used in 73% of the patients in doses between 30 and 150 mCi. Results: Overall survival was 99.2% with a mean follow-up of 40.2 months; 0.8% presented permanent hypoparathyroidism and 0.8% of the patients presented permanent recurrent laryngeal nerve palsy. Conclusions: 1) almost 80% of the patients undergoing surgery corresponded to early stages of the disease with low risk of recurrence; 2) more than 40% were microcarcinomas; 3) the results obtained are similar to those reported by high-volume centers; and 4) the review of this experience is similar to that reported by current practice guidelines, and the therapeutic approaches are in line with the recommendations of the current practice guidelines and with the new trends in the management of differentiated thyroid cancer.

Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study. / Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM.

OBJECTIVE: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha. PATIENTS AND METHODS: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015. RESULTS: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up. CONCLUSIONS: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations.

Diagnóstico clínico, ultrasonográfico y citohistológico del carcinoma diferenciado del tiroides / Clinical, ultrasonographic and cytohistological diagnosis of differentiated thyroid carcinoma

Introducción: el carcinoma diferenciado del tiroides representa la neoplasia maligna más frecuente en Endocrinología. Su presentación clínica y su diagnóstico se han modificado gracias a la disponibilidad de herramientas diagnósticas, tales como, el ultrasonido tiroideo y la biopsia aspirativa con aguja fina. Objetivos: describir las características clínicas, ultrasonográficas y citohistológicas de los pacientes intervenidos quirúrgicamente por enfermedad tiroidea maligna, y evaluar en ellos la prevalencia de hipocalcemia crónica y el valor de la hormona estimulante del tiroides. Métodos: se realizó un estudio descriptivo retrospectivo, en el cual se revisaron los informes consecutivos de Anatomía Patológica de todos los pacientes intervenidos quirúrgicamente por enfermedad tiroidea nodular en el Hospital General Provincial Camilo Cienfuegos en el periodo comprendido de enero de 2012 a diciembre 2014. La muestra estuvo conformada por 118 historias clínicas de pacientes operados por enfermedad tiroidea nodular que reunieron los criterios siguientes: datos clínicos, resultados según los criterios de Bethesda de la punción aspirativa con aguja fina, del ultrasonido del tiroides y la biopsia. A estos pacientes se les citó para una evaluación clínica y se les determinó en ayunas, la hormona estimulante del tiroides y en 2 días diferentes, la calcemia. Los pacientes fueron clasificados en portadores de: enfermedad tiroidea maligna (n= 39) y enfermedad tiroidea benigna (n= 79). Resultados: clínicamente solo el 15,4 por ciento de los pacientes con enfermedad tiroidea maligna presentaron dolor o molestia espontánea y/o a la palpación de la glándula del tiroides. La enfermedad tiroidea maligna se diagnosticó en todas las categorías del citodiagnóstico: I: 1/1 (100 por ciento), II: 8/83 (9,6 pòr ciento), III: 4/6 (66,7 por ciento), IV: 2/2 (100 por ciento), V: 18/20 (90 por ciento), VI: 6/6 (100 por ciento). El carcinoma papilar representó la neoplasia más frecuentemente diagnosticada (37/39 pacientes), el 33,3 por ciento de estos enfermos mostraron cifras de hormona estimulante del tiroides por encima de 2,0 mU/L, y hubo un 46,15 por ciento de hipocalcemia crónica. Conclusiones: el carcinoma papilar fue la neoplasia más frecuentemente diagnosticada en los pacientes operados por enfermedad tiroidea maligna. La mayoría de estos pacientes tuvieron un comportamiento subclínico, un tercio de valores no óptimos de la hormona estimulante del tiroides y una prevalencia alta de hipocalcemia crónica(AU)

ntroduction: differentiated thyroid carcinoma represents the most frequent malignant neoplasia in Endocrinology. Its clinical presentation and diagnosis have been modified thanks to the availability of diagnostic tools, such as thyroid ultrasound and fine needle aspiration biopsy. Objectives: to describe the clinical, ultrasonographic and cytohistological characteristics of patients undergoing surgery for malignant thyroid disease, and to evaluate in them the prevalence of chronic hypocalcemia and the value of the thyroid´s stimulating hormone. Methods: a retrospective descriptive study was carried out, in which consecutive reports of Pathological Anatomy of all patients surgically treated for nodular thyroid disease at Camilo Cienfuegos Provincial General Hospital in the period from January 2012 to December 2014 were reviewed. The sample consisted of 118 medical records of patients operated on for nodular-thyroid disease that met the following criteria: clinical data, results according to the Bethesda criteria of fine needle aspiration, thyroid ultrasound and biopsy. These patients were called for a clinical evaluation and they were indicated to be fasting. The patients were classified into carriers of: ETM (n=. 39) and benign thyroid disease (n= 79). Results: in clinical terms, only 15.4 percent of the patients with malignant thyroid disease presented spontaneous pain or discomfort, and / or during palpation of the thyroid glands. Malignant thyroid disease was diagnosed in all categories of cytodiagnosis: I: 1/1 (100 percent), II: 8/83 (9.6 percent), III: 4/6 (66.7 percent), IV: 2/2 (100 percent), V: 18/20 (90 percent), VI: 6/6 (100 percent). Papillary carcinoma represented the most frequently diagnosed neoplasm (37/39 patients); 33.3 percent of these patients showed thyroid stimulating hormone levels above 2.0 mU / L, and there was 46.15 percent of chronic hypocalcemia. Conclusions: papillary carcinoma was the most frequently diagnosed neoplasm in patients operated of malignant thyroid disease. The majority of these patients had a subclinical behavior, a third of non-optimal values of the thyroid stimulating hormone and a high prevalence of chronic hypocalcemia(AU)

Diagnóstico clínico, ultrasonográfico y citohistológico del carcinoma diferenciado del tiroides / Clinical, ultrasonographic and cytohistological diagnosis of differentiated thyroid carcinoma

Introducción: el carcinoma diferenciado del tiroides representa la neoplasia maligna más frecuente en Endocrinología. Su presentación clínica y su diagnóstico se han modificado gracias a la disponibilidad de herramientas diagnósticas, tales como, el ultrasonido tiroideo y la biopsia aspirativa con aguja fina. Objetivos: describir las características clínicas, ultrasonográficas y citohistológicas de los pacientes intervenidos quirúrgicamente por enfermedad tiroidea maligna, y evaluar en ellos la prevalencia de hipocalcemia crónica y el valor de la hormona estimulante del tiroides. Métodos: se realizó un estudio descriptivo retrospectivo, en el cual se revisaron los informes consecutivos de Anatomía Patológica de todos los pacientes intervenidos quirúrgicamente por enfermedad tiroidea nodular en el Hospital General Provincial Camilo Cienfuegos en el periodo comprendido de enero de 2012 a diciembre 2014. La muestra estuvo conformada por 118 historias clínicas de pacientes operados por enfermedad tiroidea nodular que reunieron los criterios siguientes: datos clínicos, resultados según los criterios de Bethesda de la punción aspirativa con aguja fina, del ultrasonido del tiroides y la biopsia. A estos pacientes se les citó para una evaluación clínica y se les determinó en ayunas, la hormona estimulante del tiroides y en 2 días diferentes, la calcemia. Los pacientes fueron clasificados en portadores de: enfermedad tiroidea maligna (n= 39) y enfermedad tiroidea benigna (n= 79). Resultados: clínicamente solo el 15,4 por ciento de los pacientes con enfermedad tiroidea maligna presentaron dolor o molestia espontánea y/o a la palpación de la glándula del tiroides. La enfermedad tiroidea maligna se diagnosticó en todas las categorías del citodiagnóstico: I: 1/1 (100 por ciento), II: 8/83 (9,6 pòr ciento), III: 4/6 (66,7 por ciento), IV: 2/2 (100 por ciento), V: 18/20 (90 por ciento), VI: 6/6 (100 por ciento). El carcinoma papilar representó la neoplasia más frecuentemente diagnosticada (37/39 pacientes), el 33,3 por ciento de estos enfermos mostraron cifras de hormona estimulante del tiroides por encima de 2,0 mU/L, y hubo un 46,15 por ciento de hipocalcemia crónica. Conclusiones: el carcinoma papilar fue la neoplasia más frecuentemente diagnosticada en los pacientes operados por enfermedad tiroidea maligna. La mayoría de estos pacientes tuvieron un comportamiento subclínico, un tercio de valores no óptimos de la hormona estimulante del tiroides y una prevalencia alta de hipocalcemia crónica(AU)

ntroduction: differentiated thyroid carcinoma represents the most frequent malignant neoplasia in Endocrinology. Its clinical presentation and diagnosis have been modified thanks to the availability of diagnostic tools, such as thyroid ultrasound and fine needle aspiration biopsy. Objectives: to describe the clinical, ultrasonographic and cytohistological characteristics of patients undergoing surgery for malignant thyroid disease, and to evaluate in them the prevalence of chronic hypocalcemia and the value of the thyroid´s stimulating hormone. Methods: a retrospective descriptive study was carried out, in which consecutive reports of Pathological Anatomy of all patients surgically treated for nodular thyroid disease at Camilo Cienfuegos Provincial General Hospital in the period from January 2012 to December 2014 were reviewed. The sample consisted of 118 medical records of patients operated on for nodular-thyroid disease that met the following criteria: clinical data, results according to the Bethesda criteria of fine needle aspiration, thyroid ultrasound and biopsy. These patients were called for a clinical evaluation and they were indicated to be fasting. The patients were classified into carriers of: ETM (n=. 39) and benign thyroid disease (n= 79). Results: in clinical terms, only 15.4 percent of the patients with malignant thyroid disease presented spontaneous pain or discomfort, and / or during palpation of the thyroid glands. Malignant thyroid disease was diagnosed in all categories of cytodiagnosis: I: 1/1 (100 percent), II: 8/83 (9.6 percent), III: 4/6 (66.7 percent), IV: 2/2 (100 percent), V: 18/20 (90 percent), VI: 6/6 (100 percent). Papillary carcinoma represented the most frequently diagnosed neoplasm (37/39 patients); 33.3 percent of these patients showed thyroid stimulating hormone levels above 2.0 mU / L, and there was 46.15 percent of chronic hypocalcemia. Conclusions: papillary carcinoma was the most frequently diagnosed neoplasm in patients operated of malignant thyroid disease. The majority of these patients had a subclinical behavior, a third of non-optimal values of the thyroid stimulating hormone and a high prevalence of chronic hypocalcemia(AU)

Fibroelastic pseudotumor elastofibroma dorsi detected by 18F-FDG PET/CT scan and by postherapy radioiodine SPECT/CT. / Seudotumor fibroelástico elastofibroma dorsi detectado por 18F-FDG PET/TC y por 131I SPECT/TC posterapia.

Radioiodine uptake in the thyroid tissue, metastasis of differentiated thyroid cancer (DTC), and in other tissues, depends on the expression of sodium-iodide symporter (NIS). Vascular permeability, effusions, inflammation, and other mechanisms may also play a role in the accumulation of radioactive iodine. A 63-year-old woman underwent radioiodine therapy, as well as a post-therapy whole-body scan, as she was suspected of having lung metastasis from thyroid carcinoma. The scan not only showed uptake at the lung metastasis but also a faint diffuse bilateral uptake in the posterior thorax. On SPECT/CT this uptake was located in a known Elastofibroma Dorsi (ED) previously diagnosed by contrast CT and viewed in a FDG PET/CT. The radioiodine uptake in ED, especially if typical, is not a diagnostic problem in SPECT/CT study, but can be misleading in a study limited to a few planar images, particularly if the uptake occurs asymmetrically, or ED is located in a unsuspected area.

Increased incidence of thyroid cancer in Navarra (Spain). Evolution and clinical characteristics, 1986-2010. / Aumento de la incidencia de cáncer de tiroides en Navarra. Evolución y características clínicas, 1986-2010.

INTRODUCTION: The latest published studies show an increased incidence of thyroid cancer worldwide. The aim of this study was to analyze the changes in the incidence of thyroid cancer in Navarra and its clinical presentation regarding sex, histological subtype and size over the last 25 years. METHODS: Thyroid cancer incidence rates were calculated on the basis of data from the Cancer Registry of Navarra during 1986-2010. Clinical data were obtained from the historical cohort of the Hospital Registry of Cancer of Navarra, which includes all the new cases of differentiated thyroid carcinoma diagnosed and treated in the public health network of this Community in that period. RESULTS: The overall incidence of thyroid cancer in Navarra increased over the last 25 years, with an increase in the adjusted rate in men from 2.24 (1986-1990) to 5.85 (2006-2010) per 100,000 population/year (P<.001) and in women from 9.05 to 14.04, respectively (P<.001). This increase occurs only in papillary carcinoma. The clinical characteristics of 739 patients with differentiated thyroid cancer were studied. The mean age at diagnosis increased over the years and the predominance of women (about 80%) remains stable. Mean tumor size decreased over the five-year periods from 30.9 to 22.5mm (P<.001), the proportion of microcarcinomas (T1a) increased from 8.8% to 30% (P<.001) and, despite this increase, there were no statistical differences in the TNM stage at diagnosis during the study period. The distribution of histological variants of papillary and follicular carcinoma did not change over 25 years. CONCLUSIONS: During the period studied, the incidence of thyroid cancer increased in Navarra in both sexes. The increase occurred only in papillary carcinoma, without changes in the distribution of his histological variants. The increase in the proportion of T1a tumors is remarkable, but the TNM stage distribution was maintained. These results suggest an increase in the diagnosis of thyroid microcarcinomas due to changes in clinical practice, without ruling out a real increase in the incidence of papillary carcinoma in Navarra.

Guía práctica para el manejo de efectos adversos por inhibidores multicinasas (sorafenib y vandetanib) en pacientes con cáncer de tiroides avanzado / Practice guidelines for the management of adverse effects due to multikinase inhibitors (sorafenib and vandetanib) in patients with advanced thyroid cancer

El advenimiento de la terapia con inhibidores multicinasas (IMK) representó un cambio radical en el tratamiento de pacientes con carcinoma avanzado de tiroides. Hasta la fecha, 2 fármacos se encuentran aprobados por la Asociación Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) en Argentina: sorafenib, para pacientes con carcinoma diferenciado de tiroides radiorresistente, y vandetanib, para aquellos con carcinoma medular de tiroides (enfermedad progresiva y/o sintomática). Los estudios de fase III han demostrado que estos fármacos aumentan significativamente la supervivencia libre de progresión en este grupo de pacientes. Si bien tienen una indicación precisa, su manejo requiere de un equipo multidisciplinario en contacto estrecho con un paciente involucrado en su tratamiento. Los efectos adversos de sorafenib y vandetanib son frecuentes, sin embargo, muchos de ellos disminuyen con el tiempo y la mayoría puede manejarse a menudo sin disminuir la dosis ni suspender el fármaco. El conocimiento del correcto manejo de los efectos adversos por parte del equipo tratante constituye una herramienta fundamental para poder educar al paciente y, consecuentemente, poder prevenirlos o minimizarlos, y de esta manera evitar complicaciones severas. El objetivo de esta publicación es brindar una guía para el diagnóstico y tratamiento de los efectos adversos de estos IMK y, por otro lado, presentar la iniciativa del Hospital de Clínicas de la Universidad de Buenos Aires en cuanto a la implementación de la misma.

The advent of multikinase inhibitors therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The ANMAT (the Argentinian regulatory health agency) has currently approved sorafenib for patients with radioiodine resistant differentiated thyroid carcinoma, and vandetanib for patients with medullary thyroid carcinoma (progressive and/or symptomatic disease). It has been demonstrated by phase III clinical trials that these drugs improve progression free survival in this group of patients. Although they have a precise indication, an interdisciplinary team in close contact with a committed patient, are required for their effective management. The adverse events of these drugs are common, but many of them may ameliorate over time, and most of them are manageable, even without the need for dose reduction or drug withdrawal. Knowledge of the correct management of the adverse events is a fundamental tool for the medical team and for the patient to prevent or minimise them, to avoid serious complications and to obtain better patient compliance. The primary objective of this article is to provide a guideline for the diagnosis and treatment of the adverse events produced by the multikinase inhibitors, and to present the initiative of the Hospital de Clinicas in order to implement these guidelines.

Factores Pronósticos Determinantes de la Sobrevida del Cáncer Diferenciado de Tiroides en el Servicio de Cirugía de Cabeza y Cuello del Hospital Carlos Andrade Marín (HCAM) durante los años 1980 al 2010 / Decisive prognosis factors of survival of differentiated thyroid cancer in the Head and Neck Surgery Department of the Carlos Andrade Marin Hospital (HCAM) during the years 1980 - 2010

Introducción: El cáncer diferenciado de tiroides (CDT) constituye el 80% de los casos de enfermedad maligna de la glándula tiroides. Tiene buen pronóstico y evolución benigna. Varios estudios señalan que factores del paciente y del tipo de tumor influyen en su curso clínico. El objetivo de esta investigación fue determinar la sobrevida de los pacientes con CDT e identificar factores pronóstico. Materiales y Métodos: Se realizó un estudio descriptivo, retrospectivo de pacientes con CDT que acudieron al servicio de Cirugía de Cabeza y Cuello del Hospital Carlos Andrade Marín (HCAM) durante los años 1980 al 2010 y fueron sometidos a cirugía. Se evaluaron variables demográficas, variables dependientes del tumor y tipo de tratamiento. Se utilizó el método de Kapplan Meier para calcular las curvas de sobrevida y la prueba de Log Rank test para establecer su significancia. El modelo de Cox se utilizó para evaluar factores pronóstico. Resultados: De 353 pacientes estudiados, la sobrevida global a 5 años en el tipo folicular fue 65.4% y en el papilar 90.1%; a 10 años, el tipo folicular fue 41.5% y el papilar 76.9%; a 15 años, el tipo follicular fue 33.2% y el papilar 66.5%. El análisis univariado demostró diferencias significativas para factores como edad (p 0,002), extension extratiroidea (EET) (p 0,001) y ganglios cervicales invadidos (p 0,002). Discusión: La edad, la EET y la presencia de ganglios cervicales invadidos fueron factores pronósticos de la sobrevida de pacientes con CDT.

Abstract Introduction: Differenciated thyroid carcinoma (DTC) stand for 80% of malignant disease of the thyroid gland. DTC generally has a good prognosis and benign course. Several studies concluded that specific patient risk factors and tumor type determine their clinical course. The aim of the study was to define global survival and identify risk factors. Methods: We performed a descriptive and retrospective analysis of DTC patients who were surgically treated at the Head and Neck Surgery Service at Carlos Andrade Marin Hospital from 1980 to 2010. Demographic variables, tumor related variables and type of tumor were recorded. Kaplan Meier survival curves and long Rank test were obtained. Cox model was used to assess prognostic factors. Results: Of 353 DTC treated patients, the 5-year overall survival rate for follicular type was 65.4% and for papillary type 90.1%. A 10-year overall survival rate for follicular type was 41.5% and for papillary tipe 76.9 %. Finally, a 15-year overall survival rate for follicular type was 33.2 % and for papillary type 66.5%. Univariate analysis showed that factors like age (p 0,002), ETE ( p 0,001) and histological lymph node invasion (p 0,002) were significant. Discusion: Variables like age, ETE and histological lymph node invasion were found to be significant prognostic survival factors in DTC patients.

Cáncer diferenciado de tiroides de tipo folicular en la infancia y adolescencia: A propósito de un caso / Diferentiated thyroid cancer type folicular in childhood and adolescence: A case report

Objetivo: Presentación de un caso clínico de carcinoma folicular de tiroides en un adolescente, patología infrecuente en la población pediátrica y revisión de su manejo. Caso clínico: Paciente masculino de 14 años de edad que consultó por presentar aumento de volumen en región anterior del cuello de rápido crecimiento, 3 meses de evolución, asociado a dolor persistente, disfonía y disfagia. Examen físico: Peso: 65 kg, Talla: 1,68 m, IMC: 23 kg/m². Macrocefálico. Glándula tiroides aumentada de tamaño: 3x4 cm (3N), a expensas de lóbulo derecho, de consistencia aumentada y superficie lisa. No se palparon adenopatías. El ultrasonido (US) tiroideo reportó nódulo que midió 33 x 33 x 32 mm en el lóbulo derecho. Funcionalmente eutiroideo. El estudio citológico del nódulo mediante PAAF reportó neoplasia folicular. En abril del 2014 se le practicó tiroidectomía total, cuya biopsia reportó carcinoma folicular de tiroides mínimamente invasivo, de 4,7 x 4,6 x 3,8 cm. Esta neoplasia se clasificó como T3N0M0 (St I AJCC 2010 <45años), bajo riesgo de recurrencia (ATA 2009), se administró terapia metabólica con yodo radiactivo (150mCi). Conclusión: El riesgo de recurrencia estimado concuerda con las características del bajo riesgo, sin embargo se decidió el manejo terapéutico tomando en cuenta el tamaño de la lesión (mayor de 4 cm) y la agresividad que muestra el cáncer diferenciado de tiroides en éste grupo etario, donde se observa con mayor frecuencia multifocalidad, invasión a la cápsula y metástasis a ganglios linfáticos regionales o a distancia, al momento del diagnóstico.

Objective: To present a case of follicular thyroid carcinoma in an adolescent, uncommon condition in the pediatric population and management review. Clinical case: Male patient 14 years old who consulted for filing increased volume in anterior neck of rapid growth, 3 months of evolution associated with persistent pain, dysphonia and dysphagia. Physical exam: Weight: 65 kg, Height: 1.68 m, BMI 23 kg/m². Macrocephalic. Enlarged thyroid gland size: 3x4 cm (3N) at the expense of right lobe, increased consistency and smooth surface. No lymph nodes were palpated. Ultrasound (US) reported thyroid nodule that measured 33 x 33 x 32 mm in the right lobe. Functionally euthyroid. The cytological study of the nodule FNA reported follicular neoplasm. In April 2014 he underwent total thyroidectomy whose biopsy reported minimally invasive follicular thyroid carcinoma, 4.7x 4.6x 3.8 cm. This neoplasm was classified as T3N0M0 (St I AJCC 2010 <45 years), low risk of recurrence (ATA 2009). Metabolic radioiodine therapy (150 mCi) was administered. Conclusion: The estimated risk of recurrence is consistent with the characteristics of low risk, however the therapeutic management was decided taking into account the size of the lesion (greater than 4 cm) and aggressivity that shows the differentiated thyroid cancer in this group of age where more frequently is observed multifocality, invasion of the capsule and metastasis to regional lymph nodes or distant, at diagnosis.

[Comparison of differentiated thyroid carcinoma staging systems in a Spanish population]. / Comparación de sistemas de estadificación del carcinoma diferenciado de tiroides en una población española.

BACKGROUND AND OBJECTIVE: Differentiated thyroid carcinoma staging is increasingly important due to the current trends to a less intensive therapy in low-risk patients. The TNM system is most widely used, but other systems based on follow-up of several patient cohorts have been developed. When these systems have been applied to other populations, results have been discordant. Our study evaluates the suitability of several differentiated thyroid carcinoma staging systems in a Spanish population. MATERIAL AND METHOD: 729 patients with differentiated thyroid carcinoma and staging data available were enrolled. Mean follow-up time was 10.8 years. The TNM, EORTC, AMES, Clinical class, MACIS, Ohio, NTCTCS, and Spanish systems were applied to all histological types. The Kaplan-Meier survival curves for each system were analyzed, and compared using the proportion of explained variation (PEV). RESULTS: The demographic and clinical characteristics of our population were similar to those of other Spanish and international cohorts reported. The best systems were NTCTCS, with 74.7% PEV, and TNM (68.3%), followed by the Ohio, MACIS, EORTC, and AMES systems with minimal differences between them, while the least adequate were the Spanish (55.2%) and Clinical class (47.1%) systems. CONCLUSION: The NTCTCS staging system was found to be better than TNM in our population but, because of its simplicity and greater dissemination, the TNM appears to be recommended for staging of patients with differentiated thyroid carcinoma.

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean overall survival has not improved in the past 50 years.

Development, characterization and clinical validation of new sensitive immunofluorometric assay for the measurement of serum thyroglobulin / Desenvolvimento, caracterização e validação clínica de um novo ensaio sensível para a dosagem da tiroglobulina sérica

OBJECTIVE: In the last decade, data published stressed the role of highly-sensitive thyroglobulin (Tg) assays in the follow-up of differentiated thyroid carcinoma (DTC) patients. The present study describes a new, highly-sensitive Tg assay, compares it with an available commercial assay, and validates it in the follow-up of DTC patients. SUBJECTS AND METHODS: The immunofluorometric high-sensitivity Tg assay is based on monoclonal and polyclonal antibodies produced at our laboratories. It was validated in 100 samples of 87 patients with DTC submitted to total thyroidectomy, 87% of whom also received radioiodine. For correlation, all samples were also tested using a commercial Tg assay (Beckman Access) with functional sensitivity (FS) of 0.1 ng/mL. RESULTS: The new method showed FS of 0.3 ng/mL. The correlation between the two methods was good (r = 0.74; p < 0.0001). The diagnostic sensitivity was 88.9%, and it was increased to 100% when combined with neck US. CONCLUSION: This new, high-sensitivity Tg assay presented a good correlation with Beckman Access assay and with the clinical outcome of the patients. The continuous availability of a validated assay is an additional advantage for long term follow-up of DTC patients. Arq Bras Endocrinol Metab. 2012;56(9):658-65.

OBJETIVO: Na última década, estudos mostraram a importância dos ensaios de tiroglobulina (Tg) com melhor sensibilidade funcional no seguimento dos pacientes com carcinoma diferenciado de tiroide (CDT). Neste estudo, descrevemos o desenvolvimento de um novo ensaio de Tg de alta sensibilidade, que foi validado no seguimento de pacientes com CDT e correlacionado com um ensaio comercialmente disponível. SUJEITOS E MÉTODOS: O ensaio imunofluorométrico de Tg baseia-se em anticorpos, um monoclonal e um policlonal desenvolvidos em nosso laboratório. Avaliamos 100 amostras de soro de 87 pacientes com CDT submetidos à tiroidectomia total, sendo que 87% deles também receberam 131I. A Tg foi dosada também em ensaio comercial (Beckman Access). RESULTADOS: A correlação entre os dois métodos foi de 0,74 (p < 0,0001). O novo ensaio mostrou uma sensibilidade funcional de 0,3 ng/mL. A sensibilidade diagnóstica foi de 88,9%, que aumentou para 100% quando associada ao ultrassom cervical (US). CONCLUSÃO: O novo método de dosagem de Tg mostra boa correlação com o ensaio comercial Beckman Access e com a evolução clínica dos pacientes. O novo ensaio será fundamental no seguimento dos nossos pacientes com CDT. Arq Bras Endocrinol Metab. 2012;56(9):658-65.

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop / Doses cumulativas de iodo radioativo no tratamento do carcinoma diferenciado de tireoide: sabendo a hora de parar

OBJECTIVE: Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: The probability of progressive disease according to CDs was evaluated in patients < 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. RESULTS: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs > 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. CONCLUSION: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.

OBJETIVO: Avaliar a eficácia de doses cumulativas (DCs) da terapia com iodeto-131I (RIT) no câncer diferenciado de tiroide (CDT). SUJEITOS E MÉTODOS: A probabilidade de doença em progressão conforme a DC foi calculada em pacientes com idade < 45 e > 45 anos e correlacionada com o TNM, valores de tiroglobulina sérica, tipos histológicos e variantes, idade e tempo de doença. RESULTADOS: Ao final de um seguimento de 69 ± 56 meses, 85 dos 150 pacientes CDT submetidos a doses fixas de RIT não tinham evidência de doença, 47 tinham doença estável e 18, doença progressiva. DCs mais elevadas foram usadas nas variantes agressivas (p < 0,0001), maior estágio TNM (p < 0,0001) e nos carcinomas foliculares (p = 0,0034). A probabilidade de doença em progressão foi maior com DCs > 600 mCi em pacientes > 45 anos e com DCs > 800 mCi em pacientes < 45 anos. CONCLUSÃO: Apesar de alguns pacientes ainda responderem a altas DCs, o impacto de RITs deve ser cuidadosamente avaliado e outras estratégias terapêuticas devem ser consideradas.

Carcinoma diferenciado de tiroides (CDT) en niños y adolescentes: Evolución clínica y factores pronósticos / Differentiated thyroid carcinoma in children and adolescents: Clinial outcome and prognostic factors

Si bien la forma de presentación del CDT es más agresiva en la edad pediátrica que en los adultos, la tasa de sobrevida es superior al 90%.Objetivo: analizar retrospectivamente las características clínico-patológicas,la evolución y los factores pronósticos en pacientes prepuberales (PP) y puberales (P) con diagnostico de CDT controlados en nuestro servicio. Resultados se incluyeron 43 pacientes seguidos por un tiempo X (±DS) de 5.99 años(a) (3.57) a, rango 1 -14 a. El tratamiento consistió en tiroidectomía con vaciamiento ganglionar, Iodo131 y levotiroxina en dosis inhibitoria de TSH. Al diagnóstico: edad cronológica (EC) X (±DS)10.9 (3.84) a, rango: 4.7 -17a, relación femenino /masculino 2.9. Diecinueve PP y 24 P. El 53.5% (n:23) presentó nódulos confinados a la glándula con o sin extensión ganglionar y el 46.5% (n:20) tenia un estadío tumoral más avanzado con invasión local y metástasis (MTS) pulmonar. Treinta y ocho pacientes (88.4%) tenían MTS ganglionar cervical y 16(37.2%) MTS pulmonar. El grupo PP comparado con el P tenía EC significativamente menor X (±DS) 7.25 (2.03) a vs 13.83a (p <0.001), estadío tumoral más avanzado 84.2 vs16.8% (p<0.001) y mayor ocurrencia de MTS pulmonar 68.4 vs 12.5% (p<0.003). La sobrevida global fue de 92% y libre de enfermedad 78%.Las variables predictoras de persistencia de enfermedad más significativas fueron presencia de MTS pulmonar al diagnóstico y niveles séricos de tiroglobulina superiores a 8.5 ng/ml posterior al tratamiento inicial. Conclusión: el CDT pediátrico tiene una presentación agresiva especialmente en los pacientes prepuberales. El pediatra debería incorporar el examen clínico del cuello para realizar un diagnóstico y tratamiento precoz (AU)

Children-DTC has been found to behave differently than in adults. At diagnosis, children present in a more aggressive way. However the overall survival rates is greater than 90%. The aim of this study was to perform a retrospective analysis of clinicopathologycal features at diagnosis, evolution and prognostic factors for DTC in pre-pubertal (PP)and pubertal (P)children treated at our centre. Results: 43 CDT patients were included. Mean follow up was X (±DS) 5.99 (3.57) years (y) range: 1 -14 y. Treatment consisted on total thyroidectomy with lymph node dissection, radioiodine therapy, and TSH suppressive therapy with L-thyroxine. At diagnosis: chronological age (CA) was (±DS) :10.9 (3.84) y, range: 4.7 - 17y,sex: female/male ratio: 32/11,nineteen were PP and 24 P. Twentythree ( 53.5%) presented intrathyroidal nodes with or without lymph node MTS, Twenty patients (46.5%) had advanced disease, with adjacent tissue invasion and lung MTS. Thirty-eight patients (88.4%) had cervical lymph node MTS, 16 (37.2%) lung MTS.PP group had significant less CA X (±DS) 7.25 (2.03) y vs 13.83 (1.95)y (p <0.001),advanced tumor stage 84.2 vs16.8% (p<0.001) and more lung MTS occurrence 68.4 vs 12.5% (p<0.003). Global survival rate was 92% and disease free survival rate was 78%.Lung metastases (MTS) and serum thyroglobuline levels greater than 8.5 ng\ml post initial treatment were the most significant prognostic factor related to persistent disease. Conclusion: CDT had a more aggressive presentation in children; especially in PP children. Pediatricians should be aware of this in order to realize a precocious diagnosis and treatment (AU)

Carcinoma diferenciado da tiroide / Differentiated thyroid carcinoma

O carcinoma diferenciado da tiroide (CDT) é a neoplasia endocrinológica mais comum. Nos Estados Unidos da América do Norte se estimam que 33.000 pessoas sejam acometidas pela doença. Nos últimos anos se tem observado um aumento progressivo no número de casos por ano em todo o mundo. O CDT tem usualmente uma sobrevida acima de 90% em dez anos, todavia, aproximadamente 20% dos pacientes podem cursar com recorrências locais e a distância, aumentando a mortalidade pelo tumor e reduzindo o tempo livre de doença. Por esses motivos a correta classificação dos indivíduos com CDT, torna-se imprescindível para oferecer o melhor e mais adequado tratamento.