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

Purpose: Anaplastic thyroid cancer (ATC) is a deadly form of thyroid cancer. BRAF V600E is the only actionable mutation for which there is a Food and Drug Administration-approved drug combination. Rapid detection of BRAF 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.
Materials and Methods: The ddPCR assay was evaluated for its sensitivity, specificity for detection of BRAF V600E cfDNA, and concordance with tumor tissue. The assay also was used to evaluate its potential role as a biomarker of response.
Results: Forty-four patients with ATC who were tested for the BRAF mutation by tumor tissue DNA sequencing or immunohistochemistry were included. Sixteen BRAF 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; P < .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 P = .0061). In addition, cfDNA levels by ddPCR were predictive of treatment response in 71% of samples.
Conclusion: 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.
Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Priyanka C. IyerNo relationship to discloseGilbert J. CoteNo relationship to discloseTao HaiNo relationship to discloseMaria Gule-MonroeNo relationship to discloseJacquelin Bui-GriffithNo relationship to discloseMichelle D. WilliamsNo relationship to discloseKenneth HessNo relationship to discloseMarie-Claude HofmannNo relationship to discloseRamona DaduResearch Funding: AstraZeneca, Merck, Eisai, Genentech, Bristol-Myers SquibbMark ZafereoNo relationship to discloseNaifa L. BusaidyConsulting or Advisory Role: Loxo Oncology, Eisai Research Funding: GlaxoSmithKline, NovartisRenata FerrarottoConsulting or Advisory Role: AYALA Research Funding: OncoMed Pharmaceuticals (Inst), G1 Therapeutics (Inst), AstraZeneca (Inst), MedImmune (Inst), EMD Serono (Inst), Genentech (Inst), Roche (Inst), Merck Serono (Inst)Vivek SubbiahConsulting or Advisory Role: MedImmune Research Funding: Novartis (Inst), GlaxoSmithKline (Inst), NanoCarrier (Inst), Northwest Biotherapeutics (Inst), Genentech (Inst), Roche (Inst), BERG (Inst), Bayer AG (Inst), Incyte (Inst), Fujifilm (Inst), PharmaMar (Inst), D3 Oncology Solutions (Inst), Pfizer (Inst), Amgen (Inst), AbbVie (Inst), MultiVir (Inst), Blueprint Medicines (Inst), Loxo Oncology (Inst), Vegenics (Inst), Takeda Pharmaceuticals (Inst), Alfasigma (Inst), Agensys (Inst), Idera (Inst), Boston Biomedical (Inst), Inhibrx (Inst), Exelixis (Inst) Travel, Accommodations, Expenses: PharmaMar, Bayer AGNeil GrossHonoraria: Intuitive Surgical Consulting or Advisory Role: PDS Biotechnology, Verb Surgical (Inst) Research Funding: Regeneron Pharmaceuticals, MedImmune (Inst), Genentech (Inst)Brandon G. GunnNo relationship to discloseHeath D. SkinnerNo relationship to discloseAdam S. GardenConsulting or Advisory Role: Galera TherapeuticsMaria E. CabanillasConsulting or Advisory Role: Loxo Oncology, Blueprint Medicines Research Funding: Kura Oncology, Eisai, Roche, Genentech, Exelixis
(© 2018 by American Society of Clinical Oncology.)