Circulating <i>BRAF</i> V600E Cell-Free DNA as a Biomarker in the Management of Anaplastic Thyroid Carcinoma.

Abstract

Anaplastic thyroid cancer (ATC) is a deadly form of thyroid cancer. <i>BRAF</i> V600E is the only actionable mutation for which there is a Food and Drug Administration-approved drug combination. Rapid detection of <i>BRAF</i> V600E and initiation of therapy is critical. We explored the ability of droplet digital polymerase chain reaction (ddPCR) to identify this mutation in circulating cell-free DNA (cfDNA) in plasma. The ddPCR assay was evaluated for its sensitivity, specificity for detection of <i>BRAF</i> V600E cfDNA, and concordance with tumor tissue. The assay also was used to evaluate its potential role as a biomarker of response. Forty-four patients with ATC who were tested for the <i>BRAF</i> mutation by tumor tissue DNA sequencing or immunohistochemistry were included. Sixteen <i>BRAF</i> V600E-positive patients had treatment samples to evaluate cfDNA levels as a biomarker of response in correlation with restaging scans. Concordance of ddPCR with tumor tissue was 93%, with a sensitivity of 85% and specificity of 100%. Area under the curve by Wilcoxon rank sum test was 0.9 (95% CI, 0.80 to 0.99; <i>P</i> < .001). As a biomarker of response to treatment, 94% of ddPCR samples were concordant with tumor shrinkage in restaging scans, and 47% were concordant with tumor growth (Fisher's exact test <i>P</i> = .0061). In addition, cfDNA levels by ddPCR were predictive of treatment response in 71% of samples. cfDNA detection by ddPCR is highly sensitive, specific, and concordant with mutation status on ATC tumors. ddPCR also can be used for monitoring cfDNA levels in conjunction with imaging scans in patients with ATC.