TY  - BOOK
AU  - Burman, Kenneth D
TI  - Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer
SN  - 2324-7096
PY  - 2019///
KW  - *CDC2 Protein Kinase/ge [Genetics]
KW  - *Enhancer of Zeste Homolog 2 Protein/ge [Genetics]
KW  - *Molecular Targeted Therapy
KW  - *Proto-Oncogene Proteins B-raf/ge [Genetics]
KW  - *Thyroid Carcinoma, Anaplastic/ge [Genetics]
KW  - *Thyroid Neoplasms/ge [Genetics]
KW  - Aged
KW  - Autopsy
KW  - CDC2 Protein Kinase/ai [Antagonists & Inhibitors]
KW  - Enhancer of Zeste Homolog 2 Protein/ai [Antagonists & Inhibitors]
KW  - Fatal Outcome
KW  - Humans
KW  - Imidazoles
KW  - Male
KW  - Mutation
KW  - Oximes
KW  - Positron Emission Tomography Computed Tomography
KW  - Protein Kinase Inhibitors/tu [Therapeutic Use]
KW  - Proto-Oncogene Proteins B-raf/ai [Antagonists & Inhibitors]
KW  - Pyridones
KW  - Pyrimidinones
KW  - Thyroid Carcinoma, Anaplastic/dt [Drug Therapy]
KW  - Thyroid Neoplasms/dt [Drug Therapy]
KW  - MedStar Washington Hospital Center
KW  - Medicine/Endocrinology
KW  - Journal Article
N2  - 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
UR  - https://dx.doi.org/10.1177/2324709619890942
ER  -