Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer.
Citation: Journal of Investigative Medicine High Impact Case Reports. 7:2324709619890942, 2019 Jan-Dec.PMID: 31766881Institution: MedStar Washington Hospital CenterDepartment: Medicine/EndocrinologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *CDC2 Protein Kinase/ge [Genetics] | *Enhancer of Zeste Homolog 2 Protein/ge [Genetics] | *Molecular Targeted Therapy | *Proto-Oncogene Proteins B-raf/ge [Genetics] | *Thyroid Carcinoma, Anaplastic/ge [Genetics] | *Thyroid Neoplasms/ge [Genetics] | Aged | Autopsy | CDC2 Protein Kinase/ai [Antagonists & Inhibitors] | Enhancer of Zeste Homolog 2 Protein/ai [Antagonists & Inhibitors] | Fatal Outcome | Humans | Imidazoles | Male | Mutation | Oximes | Positron Emission Tomography Computed Tomography | Protein Kinase Inhibitors/tu [Therapeutic Use] | Proto-Oncogene Proteins B-raf/ai [Antagonists & Inhibitors] | Pyridones | Pyrimidinones | Thyroid Carcinoma, Anaplastic/dt [Drug Therapy] | Thyroid Neoplasms/dt [Drug Therapy]Year: 2019ISSN:- 2324-7096
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
---|---|---|---|---|---|---|
Journal Article | MedStar Authors Catalog | Article | 31766881 | Available | 31766881 |
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.
English