Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience.

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.

Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level.

PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells. METHODS: The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit. RESULTS: When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05). CONCLUSIONS: Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.

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

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years.

Thyroid leiomyosarcoma: presentation of two cases and review of the literature / Leiomiossarcoma da tireoide: apresentação de dois casos e revisão da literatura

Abstract Introduction: Leiomyosarcoma is a tumor which is rarely seen in the thyroid gland. The diagnosis may be difficult and the treatment is controversial. Objective: The objective of the study is to review the literature about a rare malignant disease of the thyroid gland which has high mortality. Methods: Two cases of thyroid leiomyosarcoma are presented and the previous 23 cases in the current literature are reviewed. Results: A total of 25 cases of thyroid leiomyosarcoma are reviewed; the most common complaint was rapidly growing anterior neck mass, and ten of the 25 patients had distant metastasis at the initial admission. Fifteen of the 25 patients died with the disease in the first 12 months after the diagnosis. Conclusion: The differential diagnosis of thyroid leiomyosarcoma is important and should be performed with other malignancies of the gland, especially with anaplastic carcinoma. The prognosis is poor and there is no consensus regarding the treatment.

Resumo Introdução: Leiomiossarcoma é um tumor raramente observado na glândula tireoide. O diagnóstico pode ser difícil e o tratamento é controverso. Objetivo: O objetivo do estudo foi revisar a literatura sobre um tumor raro da glândula tireoide que possui alto índice de mortalidade. Método: Dois casos de leiomiossarcoma da tireoide são apresentados, e os 23 casos anteriores relatados na literatura atual foram revisados. Resultados: Um total de 25 casos de leiomiossarcoma da tireoide foi revisado. A queixa mais comum foi o rápido crescimento de um tumor cervical anterior; 10 dos 25 pacientes apresentavam metástases distantes no momento da admissão. Quinze dos 25 pacientes foram a óbito nos primeiros 12 meses após o diagnóstico. Conclusão: O diagnóstico diferencial de leiomiossarcoma da tireoide é importante e deve ser feito com outras doenças malignas da glândula, especialmente carcinoma anaplásico. O prognóstico é ruim e não há consenso em relação ao tratamento.

Thyroid leiomyosarcoma: presentation of two cases and review of the literature.

INTRODUCTION: Leiomyosarcoma is a tumor which is rarely seen in the thyroid gland. The diagnosis may be difficult and the treatment is controversial. OBJECTIVE: The objective of the study is to review the literature about a rare malignant disease of the thyroid gland which has high mortality. METHODS: Two cases of thyroid leiomyosarcoma are presented and the previous 23 cases in the current literature are reviewed. RESULTS: A total of 25 cases of thyroid leiomyosarcoma are reviewed; the most common complaint was rapidly growing anterior neck mass, and ten of the 25 patients had distant metastasis at the initial admission. Fifteen of the 25 patients died with the disease in the first 12 months after the diagnosis. CONCLUSION: The differential diagnosis of thyroid leiomyosarcoma is important and should be performed with other malignancies of the gland, especially with anaplastic carcinoma. The prognosis is poor and there is no consensus regarding the treatment.