000			03958nam a22006017a 4500
008			191219s20192019 xxu||||| |||| 00| 0 eng d
022			_a2324-7096
024			_a10.1177/2324709619890942 [doi]
040			_aOvid MEDLINE(R)
099			_a31766881
245			_aSalutary Response to Targeted Therapy in Anaplastic Thyroid Cancer.
251			_aJournal of Investigative Medicine High Impact Case Reports. 7:2324709619890942, 2019 Jan-Dec.
252			_aJ. investig. med. high impact case rep.. 7:2324709619890942, 2019 Jan-Dec.
252			_zJ. investig. med. high impact case rep.. 7:2324709619890942, 2019 Jan-Dec.
253			_aJournal of investigative medicine high impact case reports
260			_c2019
260			_fFY2020
265			_sppublish
266			_d2019-12-17
268			_aJournal of Investigative Medicine High Impact Case Reports. 7:2324709619890942, 2019 Jan-Dec.
520			_aContext. 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.
546			_aEnglish
650			_a*CDC2 Protein Kinase/ge [Genetics]
650			_a*Enhancer of Zeste Homolog 2 Protein/ge [Genetics]
650			_a*Molecular Targeted Therapy
650			_a*Proto-Oncogene Proteins B-raf/ge [Genetics]
650			_a*Thyroid Carcinoma, Anaplastic/ge [Genetics]
650			_a*Thyroid Neoplasms/ge [Genetics]
650			_aAged
650			_aAutopsy
650			_aCDC2 Protein Kinase/ai [Antagonists & Inhibitors]
650			_aEnhancer of Zeste Homolog 2 Protein/ai [Antagonists & Inhibitors]
650			_aFatal Outcome
650			_aHumans
650			_aImidazoles
650			_aMale
650			_aMutation
650			_aOximes
650			_aPositron Emission Tomography Computed Tomography
650			_aProtein Kinase Inhibitors/tu [Therapeutic Use]
650			_aProto-Oncogene Proteins B-raf/ai [Antagonists & Inhibitors]
650			_aPyridones
650			_aPyrimidinones
650			_aThyroid Carcinoma, Anaplastic/dt [Drug Therapy]
650			_aThyroid Neoplasms/dt [Drug Therapy]
651			_aMedStar Washington Hospital Center
656			_aMedicine/Endocrinology
657			_aJournal Article
700			_aBurman, Kenneth D
790			_aBurman KD, Fazeli S, Khosla SG, Maxwell JH, Nylen ES, Paal E
856			_uhttps://dx.doi.org/10.1177/2324709619890942 _zhttps://dx.doi.org/10.1177/2324709619890942
942			_cART _dArticle
999			_c4827 _d4827