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Updated: Oct 4, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Circulating BRAF V600E Cell-Free DNA as a Biomarker in the Management of Anaplastic Thyroid Carcinoma
Priyanka C Iyer1, Gilbert J Cote1, Tao Hai1
1The University of Texas MD Anderson Cancer Center, Houston, TX.
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.
Insights
Droplet digital PCR (ddPCR) accurately detects the BRAF V600E mutation in circulating cell-free DNA (cfDNA) from anaplastic thyroid cancer (ATC) patients. This method aids in monitoring treatment response alongside imaging scans.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited therapeutic options.
- The BRAF V600E mutation is the sole actionable target with an FDA-approved drug combination for ATC.
- Timely identification of the BRAF V600E mutation is crucial for initiating effective treatment.
Purpose of the Study:
- To evaluate the efficacy of droplet digital polymerase chain reaction (ddPCR) for detecting BRAF V600E mutations in plasma-based circulating cell-free DNA (cfDNA).
- To assess the sensitivity, specificity, and concordance of the ddPCR assay compared to tumor tissue analysis.
- To explore the utility of cfDNA levels measured by ddPCR as a biomarker for treatment response in ATC patients.
Main Methods:
- The study included 44 patients diagnosed with ATC, with BRAF mutation status previously determined by tumor tissue sequencing or immunohistochemistry.
- Plasma cfDNA was analyzed using a ddPCR assay to detect the BRAF V600E mutation.
- The ddPCR assay's performance was evaluated for sensitivity, specificity, and concordance with tumor tissue results.
- cfDNA levels in 16 BRAF V600E-positive patients were correlated with restaging scans to assess its role as a response biomarker.
Main Results:
- The ddPCR assay demonstrated high concordance (93%) with tumor tissue BRAF mutation status.
- The assay achieved 85% sensitivity and 100% specificity for detecting BRAF V600E in cfDNA.
- Area under the curve was 0.9, indicating strong diagnostic performance (P < .001).
- As a biomarker of treatment response, ddPCR results showed 94% concordance with tumor shrinkage and 47% with tumor growth (P = .0061).
- cfDNA levels detected by ddPCR were predictive of treatment response in 71% of samples.
Conclusions:
- ddPCR is a highly sensitive, specific, and concordant method for detecting BRAF V600E mutations in cfDNA from ATC patients.
- The ddPCR assay shows promise as a tool for monitoring treatment response in conjunction with standard imaging.
- This approach facilitates rapid and non-invasive assessment of therapeutic efficacy in ATC.
