RESUMO
Los carcinomas de tiroides derivados de células foliculares de alto grado (HGFDTC) son tumores poco frecuentes con un pronóstico intermedio entre carcinomas tiroideos bien diferenciados y anaplásicos. La clasificación de la OMS más reciente identifica dos tipos distintos de HGFDTC: 1) carcinoma de tiroides mal diferenciado (arquitectura sólida, trabecular o insular, falta de características nucleares de núcleos nucleares papilares y contorneados, necrosis mitosis (≥3/2mm2), y 2 ) Diferenciar carcinoma de tiroides de alto grado (recuento mitótico alto (≥5/mm2) y/o necrosis). Estos tumores son frecuentemente refractarios de radioyodo, tienen una alta propensión a metástasis distantes y una mala supervivencia general a largo plazo. Desde un punto de vista molecular, HGFDTC comparten mutaciones del controlador es decir, BRAF) y, con menos frecuencia, las fusiones genéticas (es decir, NTRK, RET) con arcinomas de tiroides diferenciados. A medida que ocurre la desdiferenciación, se adquieren alteraciones secundarias (como el promotor TERT y TP53). En esta revisión, nuestro objetivo es describir las características clínicas, moleculares y patológicas de HGFDTC, así como su gestión e investigación futura
High-grade follicular cell derived thyroid carcinomas (HGFDTC) are infrequent tumors with a prognosis intermediate between well differentiated and anaplastic thyroid carcinomas. The most recent WHO classification identifies two distinct types of HGFDTC: 1) Poorly differentiated thyroid carcinoma (solid, trabecular or insular architecture, lack of nuclear features of papillary nuclear and either convoluted nuclei, necrosis or mitosis (≥3/2mm2), and 2) differentiated high-grade thyroid carcinoma (high mitotic count (≥5/mm2) and/or necrosis). These tumors are frequently radioiodine refractory, have a high propensity for distant metastases, and poor long term overall survival. From a molecular standpoint, HGFDTC share driver mutations (ie BRAF) and, less frequently, gene fusions (ie NTRK, RET) with differentiated thyroid carcinomas. As dedifferentiation occurs, secondary alterations (such as TERT promoter, and TP53) are acquired. In this review, we aim to describe the clinical, molecular and pathological characteristics of HGFDTC, as well as their management and future research
Assuntos
Humanos , Masculino , Feminino , Neoplasias da Glândula Tireoide/diagnóstico , Adenocarcinoma Folicular/patologia , Carcinoma Anaplásico da Tireoide/patologia , Células Epiteliais da Tireoide/patologiaRESUMO
Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.
Assuntos
Terapia Neoadjuvante , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Criança , Tireoidectomia , América Latina , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , QuinolinasRESUMO
Anaplastic thyroid cancer (ATC) is an infrequent thyroid tumor that usually occurs in elderly patients. There is often a history of previous differentiated thyroid cancer suggesting a biological progression. It is clinically characterized by a locally invasive cervical mass of rapid onset. Metastases are found at diagnosis in 50% of patients. Due to its adverse prognosis, a prompt diagnosis is crucial. In patients with unresectable or metastatic disease, multimodal therapy (chemotherapy and external beam radiotherapy) has yielded poor outcomes with 12-month overall survival of less than 20%. Recently, significant progress has been made in understanding the oncogenic pathways of ATC, leading to the identification of BRAF V600E mutations as the driver oncogene in nearly 40% of cases. The combination of the BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) showed outstanding response rates in BRAF-mutated ATC and is now considered the standard of care in this setting. Recently, it was shown that neoadjuvant use of DT followed by surgery achieved 24-month overall survival rates of 80%. Although these approaches have changed the management of ATC, effective therapies are still needed for patients with BRAF wild-type ATC, and high-quality evidence is lacking for most aspects of this neoplasia. Additionally, in real-world settings, timely access to multidisciplinary care, molecular testing, and targeted therapies continues to be a challenge. Health policies are warranted to ensure specialized treatment for ATC.The expanding knowledge of ATC´s molecular biology, in addition to the ongoing clinical trials provides hope for the development of further therapeutic options.
Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Idoso , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Neoplasias da Glândula Tireoide/genética , MutaçãoRESUMO
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.
Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , América Latina , Radioisótopos do Iodo/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , BrasilRESUMO
BACKGROUND: In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes. PURPOSE: To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131I 1.11 GBq (30 mCi). METHODS: Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6-18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography. RESULTS: Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up. CONCLUSIONS: Our findings support the recommendation against routine RA in low-risk DTC patients.
Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Radioisótopos do Iodo/uso terapêutico , Estudos Prospectivos , Seguimentos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
INTRODUCTION: In patients with history of cancer adrenal metastases can be found in up to 70% of adrenal tumors detected during follow-up. Currently, laparoscopic adrenalectomy (LA) is considered the gold standard approach for benign adrenal tumors but is still controversial in malignant disease. Depending on the patient's oncological status, adrenalectomy might be a possible treatment option. Our objective was to analyze the results of LA for adrenal metastasis from solid tumors in two referral centers. METHODS: Retrospective analysis of 17 patients with non-primary adrenal malignancy treated with LA between 2007 and 2019 was performed. Demographic and primary tumor data, type of metastasis, morbidity, disease recurrence and evolution were evaluated. Patients were compared according to type of metastases: synchronous (< 6 months) vs metachronous (≥ 6 months). RESULTS: 17 patients were included. Median metastatic adrenal tumor size was 4 cm (IQR, 3-5.4). We had one conversion to open surgery. Recurrence was found in 6 patients with one recurring in the adrenal bed. The median OS was 24 (IQR, 10.5-60.5) months and 5-year OS was 61.4% (95%CI: 36.7%-81.4%). Patients with metachronous metastases had better overall survival vs. patients with synchronous metastases (87% vs. 14%, p = 0.0037). CONCLUSION: LA for adrenal metastases is a procedure associated with low morbidity and acceptable oncologic outcomes. Based on our results, seems reasonable to offer this procedure to carefully selected patients, mainly those with metachronous presentation. Indication of LA must be done on a case by case evaluation in the context of a multidisciplinary tumor board.
Assuntos
Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Adrenalectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgiaRESUMO
PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.
Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Masculino , Idoso , Feminino , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Argentina , Piridonas/uso terapêutico , Piridonas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , MutaçãoRESUMO
PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.
Assuntos
Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/genética , Argentina/epidemiologia , Humanos , Radioisótopos do Iodo , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genéticaRESUMO
PURPOSE: 18F-DOPA Positron Emission Tomography/Computed Tomography (18F-DOPA PET/CT) is a sensitive functional imaging method (65-75%) for detecting disease localization in medullary thyroid cancer (MTC). We aimed: (i) to assess the clinical usefulness of 18F-DOPA PET/CT in patients with MTC and elevated calcitonin (Ctn) and CEA levels and, (ii) to evaluate changes in disease management secondary to the findings encountered with this methodology. METHODS: Thirty-six patients with MTC and Ctn levels ≥150 pg/ml were prospectively included. Neck ultrasound, chest contrast-enhanced CT, liver magnetic resonance imaging/abdominal three-phase contrast-enhanced CT and bone scintigraphy were carried out up to 6 months before the 18F DOPA PET/CT. RESULTS: Seventy eight percent of patients were female and 27% had hereditary MTC. Median Ctn level was 1450 pg/ml [150-56620], median CEA level 413 ng/ml [2.9-7436]. Median Ctn DT was 37.5 months [5.7-240]; median CEA DT was 31.8 [4.9-180]. 18F-DOPA PET/CT was positive in 33 patients (91.6%); in 18 (56%) uptake was observed in lymph nodes in the neck or mediastinum, in seven cases (22%) distant metastases were diagnosed, and in eight additional patients (24%) both locoregional and distant sites of disease were found. Ctn and CEA levels were higher in patients with ≥3 foci of distant metastases. In 14 patients (38.8%), findings on 18F-DOPA PET/CT led to changes in management; surgery for locoregional lymph nodes was the most frequent procedure in 8 patients (22%). CONCLUSION: 18F-DOPA PET/CT was useful for the detection of recurrent disease in MTC, providing incremental value over conventional imaging procedures that led to modification in treatment strategies in nearly 40% of patients.