Thyroid : official journal of the American Thyroid Association 2018 01 29() doi 10.1089/thy.2017.0322
BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. We previously reported a highly sensitive blood RNA-based BRAFV600E assay. Our objective was to assess the correlation of BRAFV600E circulating tumor RNA levels with surgical and medical treatment.
We assessed circulating BRAFV600E levels in 1) a murine model of undifferentiated (anaplastic) thyroid carcinoma (ATC) with known BRAFV600E mutation undergoing BRAFV600E-inhibitor (BRAFi) treatment and 2) in 111 patients enrolled prior to thyroidectomy (n=86) or treatment of advanced recurrent or metastatic PTC (n=25). Blood samples were drawn for BRAFV600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAFV600E values were assessed and compared to clinical characteristics and response to therapy.
In a murine model of ATC with BRAFV600E mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAFV600E positive (n=36) patients undergoing initial surgery for PTC, blood BRAF V600E levels declined post-operatively (median 370.0 fg/ng to 178.5 fg/ng, p=0.002). In 4 patients with metastatic or poorly-differentiated thyroid carcinoma receiving targeted therapies, blood BRAFV600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease.
In this study, we show the correlation of blood BRAFV600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAFV600E positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin-Ab (Tg-Ab), and tumors, which do not express Tg.