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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.
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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
Selpercatinib, a selective RET kinase inhibitor, has demonstrated remarkable efficacy in treating patients with advanced medullary (MTC) and differentiated thyroid cancer with RET alterations. Primary resistance to selpercatinib is a very uncommon situation, and its underlying mechanisms are poorly understood. We report the case of a 42-year-old female with advanced MTC harboring a somatic M918T RET mutation who exhibited a primary resistance to selpercatinib. Despite prompt treatment initiation after the diagnosis of progressive disease, the patient continued experiencing rapid spread of disease, characterized by the appearance of new metastatic lesions and increased tumor burden. Genomic analysis revealed no additional mutations associated with on-target or off-target resistance. This case highlights a rare clinical scenario of primary resistance to selpercatinib in advanced MTC. While secondary resistance mechanisms have been well-documented, primary resistance remains poorly understood. Possible explanations include tumor heterogeneity and activation of alternative signaling pathways that stills need to be elucidated. Emerging therapies targeting resistance mechanisms and next-generation RET inhibitors offer promising avenues for further investigation.
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PURPOSE: To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications. METHODS: Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011-November 2023). RESULTS: Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034). CONCLUSION: TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients.
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Compostos de Fenilureia , Inibidores de Proteínas Quinases , Quinolinas , Sorafenibe , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Feminino , Masculino , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Sorafenibe/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Resultado do Tratamento , Intervalo Livre de Progressão , Idoso de 80 Anos ou maisRESUMO
Thyroid nodules (TNs) are a common entity, with the majority being benign. Therefore, employing an accurate rule-out strategy in clinical practice is essential. In the thyroid field, the current era is significantly marked by the worldwide diffusion of ultrasound (US)-based malignancy risk stratification systems of TN, usually reported as Thyroid Imaging Reporting And Data System (TIRADS). With the advent of US (and later TIRADS), the role of thyroid scintigraphy (TS) in clinical practice has gradually diminished. The authors of the present paper believe that the role of TS should be reappraised, also considering its essential role in detecting autonomously functioning thyroid nodules and its limited contribution to detecting thyroid cancers. Thus, this document aims to furnish endocrinologists, radiologists, surgeons, and nuclear medicine physicians with practical information to appropriately use TS.
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Cintilografia , Glândula Tireoide , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Cintilografia/métodos , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
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.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , América Latina , Radioisótopos do Iodo/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , BrasilRESUMO
Active Surveillance is a non-invasive strategy designed to identify a minority of patients with low-risk papillary thyroid carcinoma who might experience clinical progression and benefit from additional definitive treatments. Global experience suggests that these tumors typically show minimal changes in size during active surveillance, often demonstrating very slow growth or even size reduction. Moreover, the rate of lymph node metastases is low and can be effectively managed through rescue surgery, without impacting cancer-related mortality. However, despite 30 years of experience demonstrating the safety and feasibility of active surveillance for appropriately selected patients, this approach seems to have limited adoption in specific contexts. This limitation can be attributed to various barriers, including disparities in access to accurate information about the indolent nature of this disease and the prevalence of a maximalist mindset among certain patients and medical settings. This review aims to revisit the experience from the last three decades, provide current insights into the clinical outcomes of active surveillance trials, and propose a systematic approach for its implementation. Furthermore, it intends to emphasize the importance of precise patient selection and provides new perspectives in the field.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Tireoidectomia , Conduta Expectante , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/epidemiologiaRESUMO
Background: The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine needle aspiration (FNA-Ctn) for the diagnosis of medullary thyroid carcinoma (MTC) is currently not established. We evaluated the diagnostic accuracy and clinical utility of FNA-Ctn for the diagnosis and location of MTC in patients with nodular or multinodular goiters. Methods: This was a case-control study nested on a prospective multicenter cohort of patients with nodular or multinodular goiter, normal or elevated serum Ctn, and thyroidectomy indications. Ctn and FNA-Ctn were measured using ECLIA methodology before surgery. From this nested cohort, MTC cases and controls (non-medullary pathology) were identified from the final pathological analysis. Cumulative incidence sampling of controls was randomly performed at a ratio of 1:2. Sensitivity, specificity, and area under the receiver operator curve (AUROC) were calculated for patients and the total number of thyroid nodules. Results: From 1272 patients included in the prospective cohort, 50 MTC cases and 105 controls were included. In this study, 286 thyroid nodules were evaluated (63 MTC and 223 non-MTCs). The median serum Ctn value was significantly higher in cases (525 pg/mL [interquartile range (IQR), 162.5-1.200]) than in controls (1.6 pg/mL [IQR, 0.5-5.6]; p < 0.001). The median FNA-Ctn value was significantly higher in MTC nodules (3.100 pg/mL [IQR, 450-45,200]) than in non-MTC nodules (0.5 pg/mL [IQR, 0.5-0.5]; p < 0.0001). In 11 MTC patients with multinodular goiter, the FNA-Ctn value was significantly higher in non-medullary nodules located in the same lobe where an MTC nodule was diagnosed (p = 0.0002). Overall, the FNA-Ctn AUROC was 0.99 [95% confidence interval, 0.98-1.0], and a threshold of ≥220 pg/mL showed 100% sensitivity and 98% specificity for MTC diagnosis. Conclusions: The use of FNA-Ctn measured by ECLIA showed adequate diagnostic accuracy for MTC diagnosis. Moreover, it may be clinically useful for localization in multinodular goiter when lobectomy is considered. Clinical Trial Registration: Clinicaltrials.gov NCT06067594.
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Carcinoma Neuroendócrino , Bócio , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Calcitonina , Estudos de Casos e Controles , Estudos Prospectivos , Neoplasias da Glândula Tireoide/patologia , Carcinoma Neuroendócrino/patologiaRESUMO
The prevalence of thyroid disease continues to rise. As a consequence, the research in the thyroid field has significantly increased over time. Thus, clinicians, and endocrinologists first, have to be aware of the important continuous progress achieved, in particular of thyroid cancer, to better manage their patients. This themed issue, titled "New Insights in Thyroid Diagnosis and Treatment," delves deep into contemporary hot topics in thyroid field. These papers included in the present issue are focused on several aspects in this area, such as imaging, molecular analysis, machine learning and radiomics, nuclear medicine, clinical, and laboratory. Seven papers centers around thyroid cancer. Three papers review imaging modalities for thyroid nodule/cancer assessment. Two papers report a comprehensive review of metabolic issues involving thyroid gland. Finally, a large overview about genetics of Graves' disease is reported in another study. Clinicians will find this issue very interesting.
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Doença de Graves , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Doença de Graves/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico por imagem , CintilografiaRESUMO
Medullary thyroid carcinoma (MTC) is an infrequent thyroid malignancy that is often diagnosed at advanced stage with consequent poor prognosis. Thus, the earlier the diagnosis of MTC, the better the prognosis. Unfortunately, the preoperative detection of MTC remains challenging in clinical practice. In fact, while ultrasound and fine-needle aspiration cytology have suboptimal performance in this context, measuring serum calcitonin (Ctn), fully recognized as the most reliable test to detect MTC, is not universally accepted as routine test in all patients with thyroid nodule(s). The authors of this paper reappraise critically the matter of Ctn measurement in view of the recent advancements in the literature to point out the essential information to be known, and then to prepare an easy-to-use guide for clinicians to appropriately consider the measurement of serum Ctn during clinical practice.
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Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Calcitonina , Neoplasias da Glândula Tireoide/patologia , Carcinoma Neuroendócrino/patologiaRESUMO
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.
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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
ABSTRACT The incidence of thyroid cancer is increasing globally, but mortality rates have remained steady. Many patients with thyroid cancer have low-risk, nonmetastatic intrathyroidal tumors smaller than 2 cm. Active surveillance has shown benefits in these patients, but the adoption of this approach remains below standard in Latin America. The purpose of this article is to identify ways to improve the incorporation of active surveillance into clinical practice for patients with low-risk thyroid carcinoma in Latin America, taking into consideration cultural and geographic factors. Current recommendations include three steps involving patient participation. The first step, which consists of the initial clinical examination, has eight factors requiring special attention. Anxiety must be managed while considering individual, disease-related, cognitive, and environmental aspects. Terms like "overdiagnosis", "incidentaloma," and "overtreatment" must be explained to the patient. Implementing precise terminology contributes to adequate disease perception, substantially reducing stress and anxiety. Clarifying the nonprogressive nature of thyroid cancer helps dispel myths surrounding the disease. The second step includes advice about procedures and guidelines for patients who choose active surveillance. Flexible monitoring techniques should be implemented, with regular check-ins scheduled based on patient needs. Reasons for adjusting treatment must be clearly communicated to the patient, and changes in preference regarding active surveillance should be considered in advance. The third step includes assistance during follow-up. Patients must be educated about ultrasound results and receive surgical indications from specialized physicians. The effectiveness of active surveillance can be reinforced by explaining to the patients the dynamics of changes in nodule size using clear and concise visual aids.
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We previously described the role of low-density lipoprotein (LDL) in aggressiveness in papillary thyroid cancer (PTC). Moreover, the MAPK signaling pathway in the presence of BRAF V600E mutation is associated with more aggressive PTC. Although the link between MAPK cascade and LDL receptor (LDLR) expression has been previously described, it is unknown whether LDL can potentiate the adverse effects of PTC through it. We aimed to investigate whether the presence of LDL might accelerate the oncogenic processes through MAPK pathway in presence or absence of BRAF V600E in two thyroid cell lines: TPC1 and BCPAP (wild-type and BRAF V600E, respectively). LDLR, PI3K-AKT and RAS/RAF/MAPK (MEK)/ERK were analyzed via Western blot; cell proliferation was measured via MTT assay, cell migration was studied through wound-healing assay and LDL uptake was analyzed by fluorometric and confocal analysis. TPC1 demonstrated a time-specific downregulation of the LDLR, while BCPAP resulted in a receptor deregulation after LDL exposition. LDL uptake was increased in BCPAP over-time, as well as cell proliferation (20% higher) in comparison to TPC1. Both cell lines differed in migration pattern with a wound closure of 83.5 ± 9.7% after LDL coculture in TPC1, while a loss in the adhesion capacity was detected in BCPAP. The siRNA knockdown of LDLR in LDL-treated BCPAP cells resulted in a p-ERK expression downregulation and cell proliferation modulation, demonstrating a link between LDLR and MAPK pathway. The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E.
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Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Fosfatidilinositol 3-Quinases/genética , Mutação , Neoplasias da Glândula Tireoide/patologia , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Receptores de LDL/genética , Lipoproteínas LDL/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Linhagem Celular TumoralRESUMO
Importance: Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval of tropomyosin receptor kinase inhibitors (larotrectinib and entrectinib) for patients with solid tumors, including advanced thyroid carcinomas, harboring NTRK gene fusions. Observations: The relative rarity and diagnostic complexity of NTRK gene fusion events in thyroid carcinoma present several challenges for clinicians, including variable access to robust methodologies for comprehensive NTRK fusion testing and poorly defined algorithms of when to test for such molecular alterations. To address these issues in thyroid carcinoma, 3 consensus meetings of expert oncologists and pathologists were convened to discuss diagnostic challenges and propose a rational diagnostic algorithm. Per the proposed diagnostic algorithm, NTRK gene fusion testing should be considered as part of the initial workup for patients with unresectable, advanced, or high-risk disease as well as following the development of radioiodine-refractory or metastatic disease; testing by DNA or RNA next-generation sequencing is recommended. Detecting the presence of NTRK gene fusions is important to identify patients eligible to receive tropomyosin receptor kinase inhibitor therapy. Conclusions and Relevance: This review provides practical guidance for optimal integration of gene fusion testing, including NTRK gene fusion testing, to inform the clinical management in patients with thyroid carcinoma.
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Neoplasias , Neoplasias da Glândula Tireoide , Humanos , Neoplasias/tratamento farmacológico , Receptor trkA/genética , Receptor trkA/uso terapêutico , Tropomiosina/genética , Tropomiosina/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Proteínas de Fusão Oncogênica/genética , Medicina de Precisão , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Fusão Gênica , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
The detection of low-risk thyroid carcinoma has increased in recent decades, although disease-specific mortality remained without changes. The high prevalence of occult carcinomas in autopsy studies, and hence the underlying indolent course of this entity, prompted the emergence of active surveillance as an alternative approach to these tumors. This strategy aims to recognize the minority group of patients who will develop clinical progression and probably benefit from deferred surgery. Experience around the world has shown that during active surveillance these tumors are mostly unchanged in size, with very-slow growth and even a decrease in diameter. Moreover, the rates of lymph node metastases were low and easily handled by rescue surgery, and distant metastases have not been reported. Given the high prevalence of small thyroid carcinomas and the excellent outcomes for observation, active surveillance provides a safe and feasible alternative in properly selected patients with low-risk thyroid cancer.
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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.
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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
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.
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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
Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.
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Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Antineoplásicos/uso terapêutico , Estudos de Coortes , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
Background: It has been suggested that small metastatic lymph nodes (LNs) detected after initial surgery in patients with differentiated thyroid cancer (DTC) can be managed with active surveillance (AS). However, there is still concern regarding the clinical outcomes of these patients. The main aims of our study were as follows: (1) to assess the frequency of growth and the need of additional treatment in a group of patients with LN recurrences selected for AS, and (2) to determine predictive factors of LN progression. Methods: We retrospectively reviewed 856 clinical records from our DTC patient's database (May 2010 to January 2022). Eighty patients had suspicious cervical LNs on consecutive ultrasound (US) after initial surgery, but we included 50 patients with cytological confirmation of metastatic disease and at least 12 months follow-up. Exclusion criteria were as follows: any LN ≥2 cm or multiple LNs ≥1.5 cm in size, proximity to vital structures, PET-positive disease (standard uptake value ≥5), aggressive histology, and distant metastasis. Patients were followed with thyroglobulin (Tg) and thyroglobulin antibodies measurements on suppressive therapy and neck US every 6-12 months. LN growth was defined as an increase of ≥3 mm in any of its diameters. Results: A total of 50 patients had a median age of 41 years (range, 18-75). Most patients were women (80%) and had classical papillary thyroid cancer (86%). The mean size of the LNs was 10.1 ± 4.4 mm. After a median follow-up of 29 months (range, 12-144), 12 patients (24%) had an increase in size of the metastatic LN, 7 (58%) of whom were surgically removed. None of these seven patients had a structural incomplete response at the end of follow-up. The only variable that predicted an increase in LN size was a rise in Tg levels ≥0.5 ng/mL (p = 0.016). Based on a multivariate analysis, patients with increase in Tg levels ≥0.5 ng/mL had a significantly higher chance of developing LN growth (odds ratio [OR] 16.2 [confidence interval, CI 1.5-120.2], p = 0.020). The median progression-free survival rate was 6.6 years [CI 5.6-9.5]. Conclusion: AS of small LNs could be a feasible alternative to immediate surgery in properly selected patients.
Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Tireoglobulina/análise , Estudos Retrospectivos , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Conduta Expectante , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgiaRESUMO
After the beginning of COVID-19 vaccination campaigns, several reports of thyroid disease possibly related to the COVID-19 vaccination progressively appeared in the literature, raising the question of whether the thyroid disorder might be a SARS-CoV-2 vaccine complication. The aim of this study was to analyze the data about COVID-19 vaccination and thyroid disease, evaluate the size and quality of related literature, assess the type of these events, and investigate their timing of onset with respect the vaccination. Pubmed/MEDLINE and Cochrane were systematically reviewed until February 2022 to retrieve the largest number of original papers, case reports, and case series articles reporting thyroid disease after SARS-CoV-2 vaccination. Forty-six articles were included with a total of 99 patients aged from 26 to 73 years were described, of whom 74.75% female. Regarding the vaccination received, 49.49% of patients received Comirnaty (Pfizer/BioNTech), 14.14% CoronaVac (Sinovac), 12.12% Vaxzevria (Oxford/Astrazeneca), 11.11% Spikevax (Moderna), 3.03% Ad26.COV2.S (Janssen, Johnson & Johnson), one patient Covaxin (Bharat Biotech) and one patient Convidecia (Cansino). In 7 cases the thyroid disorder developed after the third dose with a combination of different vaccines. Regarding the type of thyroid disorder, 59 were subacute thyroiditis (SAT), 29 Graves' disease (GD), 2 co-occurrence of SAT and GD, 6 painless thyroiditis (PT), and single cases of thyroid eye disease and hypothyroidism associated with mixedema. The timeline between vaccination and thyroid disorder ranged between 0.5 to 60 days, with an average of 10.96 days. Considering the limited follow-up time, a complete remission was reported in most of SAT and PT cases while a persistence was observed in GD. In conclusion, both size and quality of published data about thyroid inconveniences after COVID-19 vaccination are limited; thyroid disorders may occur within 2 months after COVID-19 vaccination; among all thyroid diseases after COVID-19 vaccination, GD and SAT seem to be more frequent.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Doenças da Glândula Tireoide , Adulto , Idoso , Doenças Autoimunes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Doença de Graves , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/epidemiologia , Tireoidite Subaguda , Vacinação/efeitos adversosRESUMO
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.