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Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer
Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a m...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880026/ https://www.ncbi.nlm.nih.gov/pubmed/31766881 http://dx.doi.org/10.1177/2324709619890942 |
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author | Fazeli, Sasan Paal, Edina Maxwell, Jessica H. Burman, Kenneth D. Nylen, Eric S. Khosla, Shikha G. |
author_facet | Fazeli, Sasan Paal, Edina Maxwell, Jessica H. Burman, Kenneth D. Nylen, Eric S. Khosla, Shikha G. |
author_sort | Fazeli, Sasan |
collection | PubMed |
description | Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy. |
format | Online Article Text |
id | pubmed-6880026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-68800262019-12-05 Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer Fazeli, Sasan Paal, Edina Maxwell, Jessica H. Burman, Kenneth D. Nylen, Eric S. Khosla, Shikha G. J Investig Med High Impact Case Rep Case Report Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy. SAGE Publications 2019-11-26 /pmc/articles/PMC6880026/ /pubmed/31766881 http://dx.doi.org/10.1177/2324709619890942 Text en © 2019 American Federation for Medical Research http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Case Report Fazeli, Sasan Paal, Edina Maxwell, Jessica H. Burman, Kenneth D. Nylen, Eric S. Khosla, Shikha G. Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer |
title | Salutary Response to Targeted Therapy in Anaplastic Thyroid
Cancer |
title_full | Salutary Response to Targeted Therapy in Anaplastic Thyroid
Cancer |
title_fullStr | Salutary Response to Targeted Therapy in Anaplastic Thyroid
Cancer |
title_full_unstemmed | Salutary Response to Targeted Therapy in Anaplastic Thyroid
Cancer |
title_short | Salutary Response to Targeted Therapy in Anaplastic Thyroid
Cancer |
title_sort | salutary response to targeted therapy in anaplastic thyroid
cancer |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880026/ https://www.ncbi.nlm.nih.gov/pubmed/31766881 http://dx.doi.org/10.1177/2324709619890942 |
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