Circulating BRAF V600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma.

Autor:	Lubitz CC; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts.; 2 Institute for Technology Assessment, Massachusetts General Hospital , Boston, Massachusetts., Zhan T; 2 Institute for Technology Assessment, Massachusetts General Hospital , Boston, Massachusetts., Gunda V; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts., Amin S; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts., Gigliotti BJ; 3 Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts., Fingeret AL; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts., Holm TM; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts., Wachtel H; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts., Sadow PM; 4 Department of Pathology, Massachusetts General Hospital , Boston, Massachusetts., Wirth LJ; 3 Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts., Sullivan RJ; 3 Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts., Panka DJ; 5 Department of Medicine, Beth Israel Deaconess Medical Center , Boston, Massachusetts., Parangi S; 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Thyroid : official journal of the American Thyroid Association [Thyroid] 2018 Mar; Vol. 28 (3), pp. 328-339. Date of Electronic Publication: 2018 Feb 27.
DOI:	10.1089/thy.2017.0322
Abstrakt:	Background: BRAF V600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAF V600E assay was reported. The objective of this study was to assess the correlation of BRAF V600E circulating tumor RNA levels with surgical and medical treatment. Methods: Circulating BRAF V600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAF V600E mutation undergoing BRAF V600E -inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAF V600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAF V600E values were assessed and compared to clinical characteristics and response to therapy. Results: In a murine model of anaplastic thyroid carcinoma with BRAF V600E mutation, blood BRAF V600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAF V600E -positive (n = 36) patients undergoing initial surgery for PTC, blood BRAF V600E levels declined postoperatively (median 370.0-178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAF V600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. Conclusions: This study shows the correlation of blood BRAF V600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAF V600E -positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.
Databáze:	MEDLINE
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