Clinical Utility of Circulating Cell-free DNA Mutations in Anaplastic Thyroid Carcinoma.

Background Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid cancer that requires a rapid diagnosis and treatment to achieve disease control. Gene mutation profiling of circulating cell free DNA (cfDNA) in peripheral blood may help to facilitate early diagnosis and treatment selection. The relatively rapid turnaround time compared to conventional tumor mutation testing is a major advantage. The objectives of this study were to examine the concordance of ATC-related mutations detected in cfDNA with those detected in the corresponding tumor tissue, and to determine the prognostic significance of cfDNA mutations in ATC patients. Methods ATC patients who were diagnosed and treated at The University of Texas MD Anderson Cancer Center between January 2015 and February 2018 and who had cfDNA testing were included in this study. cfDNA was collected by blood draw and was analyzed by next generation sequencing (NGS) using the Guardant360- 73 gene platform. Results A total of 87 patients were included in the study. The most frequently mutated genes detected in cfDNA were TP53, BRAF and PIK3CA. In 28 treatment naive ATC patients, the concordance rate of detected mutations in TP53, BRAF V600E and PIK3CA between cfDNA and matched tissue NGS was 82.1%, 92.9% and 92.9% respectively. Patients with a PIK3CA mutation detected on cfDNA had worse overall survival (p=0.03). This association was observed across various treatment modalities including surgery, cytotoxic chemotherapy, radiation and BRAF inhibitor therapy. With regard to treatment, BRAF inhibitor therapy significantly improved ATC overall survival (p=0.003). Conclusions cfDNA is a valuable tool to evaluate a tumor's molecular profile in ATC patients. We identified high concordance rates between the gene mutations identified via cfDNA analysis and those identified from the NGS of the corresponding tumor tissue sequencing. Identified mutations in cfDNA can potentially provide timely information to guide treatment selection and evaluate the prognosis in ATC patients.