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Antineoplastic Effect of Lenvatinib and Vandetanib in Primary Anaplastic Thyroid Cancer Cells Obtained From Biopsy or Fine Needle Aspiration.

ABSTRACT: Anaplastic thyroid carcinoma (ATC) is a malignant tumor of the thyroid gland, infrequent but with a very poor prognosis, as it rapidly causes death (mean survival of about 6 months). ATC treatment includes a multimodal protocol consisting of surgery, chemotherapy (doxorubicin and cisplatin), and hyperfractionated accelerated external beam radiotherapy (median patient survival of 10 months). For this reason, the identification of an effective systemic treatment for ATC would be a major advance in the management of this deadly thyroid cancer. The opportunity to test the sensitivity to different drugs of primary cells from ATC (pATC) cultures, obtained from each patients, could improve the effectiveness of the treatment. Then, the administration of inactive therapeutics could be avoided. Our aim is to investigate the antineoplastic effect of two tyrosine kinase inhibitors (TKIs; lenvatinib, vandetanib) in pATC obtained both from biopsy (biop-pATC), and from fine needle aspiration (FNA-pATC). The antiproliferative activity of lenvatinib and vandetanib was evaluated in 6 ATC patients, on biop-pATC, such as on FNA-pATC. A significant reduction of proliferation (obtained by WST-1 assay) vs. control was shown with lenvatinib and vandetanib in FNA-pATC, as well as in biop-pATC. The percentage of apoptosis in FNA-pATC, or biop-pATC, increased with both compounds dose-dependently. pATC cells from FNA, or biopsy, had a similar sensitivity to lenvatinib and vandetanib. In conclusion, primary cells (biop-pATC or FNA-pATC) have a similar sensitivity to TKIs, and lenvatinib and vandetanib are effective in reducing cell growth, increasing apoptosis in ATC. The possibility to test the sensitivity to different TKIs in each patient could open the way to personalized treatments, avoiding the administration of ineffective, and potentially dangerous, drugs.

SUBMITTER: Ferrari SM

PROVIDER: S-EPMC6305332 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Antineoplastic Effect of Lenvatinib and Vandetanib in Primary Anaplastic Thyroid Cancer Cells Obtained From Biopsy or Fine Needle Aspiration.

Ferrari Silvia Martina SM La Motta Concettina C Elia Giusy G Ragusa Francesca F Ruffilli Ilaria I Quattrini Luca L Paparo Sabrina Rosaria SR Piaggi Simona S Patrizio Armando A Ulisse Salvatore S Baldini Enke E Materazzi Gabriele G Fallahi Poupak P Antonelli Alessandro A

Frontiers in endocrinology 20181218

Anaplastic thyroid carcinoma (ATC) is a malignant tumor of the thyroid gland, infrequent but with a very poor prognosis, as it rapidly causes death (mean survival of about 6 months). ATC treatment includes a multimodal protocol consisting of surgery, chemotherapy (doxorubicin and cisplatin), and hyperfractionated accelerated external beam radiotherapy (median patient survival of 10 months). For this reason, the identification of an effective systemic treatment for ATC would be a major advance in ...[more]

PMID: 30619094

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Project description:Although thyroid fine-needle aspiration (FNA) and core needle biopsy (CNB) are commonly utilized modalities in the evaluation of thyroid nodules, metastatic tumors to the thyroid are only rarely encountered. We aspired to determine the incidence and primary origin of metastases to the thyroid at our institution and to examine their clinicopathologic and cytomorphologic features.A search of our database was undertaken to review all thyroid FNA and/or CNB examined between January 2004 and December 2013.During our 10 year study period, 7497 patients underwent 13,182 FNA and/or CNB. Four hundred sixty one (6%) patients were diagnosed with neoplasms. Only five (1.1%) were found to have metastatic tumors to the thyroid involving three females and two males. Two were diagnosed by FNA, one by CNB, and two by both FNA and CNB, with rapid on-site evaluation (ROSE) employed in all cases. The primary malignancies in the five cases were pulmonary and nasopharyngeal squamous cell carcinomas, renal cell carcinoma, pancreatic adenocarcinoma, and olfactory neuroblastoma. The cytomorphologic features of these metastases to the thyroid aided in their distinction from primary thyroid carcinoma. Two of these metastases, a renal cell carcinoma and pancreatic adenocarcinoma, were the first clinical manifestations of cancer.Metastases to the thyroid diagnosed by FNA and/or CNB are exceedingly rare in our institution, comprising only 0.04% of total FNA/CNB and only 1.1% of all thyroid neoplasms. We report the first known case of metastatic olfactory neuroblastoma to the thyroid diagnosed by aspiration cytology. In addition, an occult primary may present as a thyroid mass on FNA or CNB as occurred with two of our cases. FNA/CNB proved to be highly effective in the diagnosis of metastases to the thyroid, with ROSE proving valuable in assuring specimen adequacy. Thyroid FNA and CNB demonstrated great utility in the setting of metastatic disease, obviating the need for more invasive procedures.

Project description:BackgroundFine-needle aspiration biopsy (FNAB) is a recognized technique for the basic, preoperative cytological diagnosis of thyroid nodules.Aim of the studyTo analyze the accuracy of FNAB in the diagnosis of thyroid cancer in patients with solitary and multiple thyroid nodules and to compare the demographic, clinical and pathological characteristics of patients with thyroid carcinoma in solitary and multiple tumors.Materials and methodsThe case records of 2,403 patients with solitary and multiple thyroid tumors treated consecutively between 2008 and 2013 were analyzed retrospectively. We selected 1,645 for further analysis. A solitary thyroid nodule was observed in 493 patients, and multiple nodules were detected in 1,152 patients. Further classification of the patients in these two groups was performed on the basis of the FNAB results, type of surgery performed and histopathology. TC was histopathologically confirmed in 166 patients, and benign disease was found in 1,479. The TC patients were assigned to the study group, and those with benign thyroid disease were placed into the control group. The study group was divided into two subgroups according to the presence of cancer in a single thyroid nodule or in multiple nodules. Malignancy in a solitary thyroid nodule was diagnosed in 98 (59.0%) patients, and cancer in multiple nodules was diagnosed in 68 (41.0%). Comparative analyses of the demographic, clinical and histopathological characteristics were performed for both subgroups. The following statistical analyses were performed: comparative characteristic of subgroups, ROC analysis for study group and subgroup of patients, and multivariable logistic regression analysis for study group.ResultsThe rate of prediction of TC by FNAB was three times higher in the patients with a solitary thyroid nodule compared with those with multiple thyroid nodules and it was statistically significant (p<0.001). The rate of total thyroid resection and lack of necessity for reoperation were also significantly higher in the TC patients with a solitary nodule. The histopathological results showed that significantly more patients with a solitary nodule had advanced-stage TC (stage III or IV) and tumor progression (pT3 or pT4) (p = 0.002 for both). ROC analysis demonstrated that the overall accuracy of FNAB as a predictor of thyroid cancer presence was high, especially for the subgroup of patients with a solitary thyroid nodule (AUC = 0.958, p<0.0001). Multivariable logistic regression analysis confirmed that a positive FNAB result was the sole predictor of the performance of total resection in the TC study group (p<0.0001), while a negative FNAB result and the presence of a papillary cancer type were independent predictors of the risk of reoperation (p<0.0001 and p = 0.002, respectively).ConclusionsFNAB often produces false-negative results in patients with multiple malignant thyroid tumors, which results in reoperation in many cases. False-negative FNAB results are rare in patients with a solitary tumor. Because of the low predictive capacity of FNAB for thyroid cancer in patients with multiple thyroid tumors, total thyroid excision should be considered in most cases despite a "negative" (no malignant) FNAB result.

Dataset Information

Antineoplastic Effect of Lenvatinib and Vandetanib in Primary Anaplastic Thyroid Cancer Cells Obtained From Biopsy or Fine Needle Aspiration.

Publications

Antineoplastic Effect of Lenvatinib and Vandetanib in Primary Anaplastic Thyroid Cancer Cells Obtained From Biopsy or Fine Needle Aspiration.

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