{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:36:02Z","timestamp":1777671362996,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine High Impact Case Reports"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1177\/2324709619890942","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T03:56:22Z","timestamp":1574740582000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer"],"prefix":"10.1177","volume":"7","author":[{"given":"Sasan","family":"Fazeli","sequence":"first","affiliation":[{"name":"George Washington University Medical Faculty Associates, Washington, DC, USA"},{"name":"Washington DC VA Medical Center, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edina","family":"Paal","sequence":"additional","affiliation":[{"name":"Washington DC VA Medical Center, Washington, DC, USA"},{"name":"George Washington University, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica H.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Washington DC VA Medical Center, Washington, DC, USA"},{"name":"MedStar Georgetown University Medical Center, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth D.","family":"Burman","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Medical Center, Washington, DC, USA"},{"name":"MedStar Washington Hospital Center, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric S.","family":"Nylen","sequence":"additional","affiliation":[{"name":"George Washington University Medical Faculty Associates, Washington, DC, USA"},{"name":"Washington DC VA Medical Center, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shikha 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