Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma.

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. [ABSTRACT FROM AUTHOR]