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Background <p>Relapsed/metastatic anaplastic thyroid carcinoma (R/M ATC) is associated with poor prognosis. Approximately 40% of ATCs harbor the BRAFV600E mutation, for which targeted therapy is available. However, the clinical characteristics of BRAFV600E-mutant versus wild-type ATC and the role of liquid biopsy (LB) for molecular assessment and monitoring remain incompletely defined.</p> Methods <p><?tk 1?>Consecutive patients with R/M ATCs treated at a tertiary referral center were stratified as BRAF wild-type (Cohort A) or BRAFV600E-mutant (Cohort B). Patients received chemotherapy, dabrafenib and trametinib (BRAF/MEKi), immune checkpoint inhibitors (ICI) or best supportive care. Tumor tissue (TB) was analyzed by RT-PCR and/or next-generation sequencing (NGS). Circulating cell-free DNA was assessed by droplet digital PCR (ddPCR) and/or a 52-gene NGS panel on LB at baseline in both cohorts and longitudinally in Cohort B. Clinical characteristics, treatment outcomes, and concordance between TB and LB were evaluated.</p> Results <p><?tk 2?>Between 2018 and 2021, 24 patients were included (13 Cohort A, 11 Cohort B). BRAFV600E tumors more frequently presented with metastatic disease at diagnosis (81.8% vs. 15.4%, <i>p</i> = 0.003). Overall, 79% received first-line therapy and 41.6% second-line treatment. All patients in Cohort B received BRAF/MEK inhibitors, achieving a median progression-free survival of 3.2 months (95% CI 1.2–17.5). Concordance for BRAFV600E status between TB and LB assessed by ddPCR was 93.7% (specificity 100%, sensitivity 85.7%). Among 12 paired TB/LB NGS analyses, overall mutation concordance was 30%. In longitudinal assessment, LB anticipated disease progression in 3 of 6 cases and, in one case, identified emerging secondary alterations during BRAF/MEK inhibitor therapy.</p> Conclusions <p><?tk 2?>BRAFV600E-mutant ATC displays distinct clinical features and improved survival when treated with targeted therapy; ddPCR-based liquid biopsy provides a rapid and sensitive method for BRAFV600E detection and may support timely therapeutic decision-making. Serial LB analysis may contribute to disease monitoring and detection of resistance mechanisms in selected patients.</p>

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Liquid biopsies for BRAF V600E assessment and monitoring in anaplastic thyroid carcinoma: a real-world study of a tertiary cancer center

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Elena Colombo,
  • Elisa Ortolan,
  • Stefano Cavalieri,
  • Elena Tamborini,
  • Federica Perrone,
  • Iolanda Capone,
  • Luca Agnelli,
  • Biagio Paolini,
  • Massimo Milione,
  • Giuseppina Calareso,
  • Monica Salvetti,
  • Francesca Platini,
  • Cristiana Bergamini,
  • Salvatore Alfieri,
  • Carlo Resteghini,
  • Arianna Ottini,
  • Francesca Caspani,
  • Imperia Nuzzolese,
  • Achille Bottiglieri,
  • Giacomo Massa,
  • Daria Maria Filippini,
  • Giancarlo Pruneri,
  • Lisa Licitra,
  • Maria Grazia Daidone,
  • Laura Deborah Locati

摘要

Background

Relapsed/metastatic anaplastic thyroid carcinoma (R/M ATC) is associated with poor prognosis. Approximately 40% of ATCs harbor the BRAFV600E mutation, for which targeted therapy is available. However, the clinical characteristics of BRAFV600E-mutant versus wild-type ATC and the role of liquid biopsy (LB) for molecular assessment and monitoring remain incompletely defined.

Methods

Consecutive patients with R/M ATCs treated at a tertiary referral center were stratified as BRAF wild-type (Cohort A) or BRAFV600E-mutant (Cohort B). Patients received chemotherapy, dabrafenib and trametinib (BRAF/MEKi), immune checkpoint inhibitors (ICI) or best supportive care. Tumor tissue (TB) was analyzed by RT-PCR and/or next-generation sequencing (NGS). Circulating cell-free DNA was assessed by droplet digital PCR (ddPCR) and/or a 52-gene NGS panel on LB at baseline in both cohorts and longitudinally in Cohort B. Clinical characteristics, treatment outcomes, and concordance between TB and LB were evaluated.

Results

Between 2018 and 2021, 24 patients were included (13 Cohort A, 11 Cohort B). BRAFV600E tumors more frequently presented with metastatic disease at diagnosis (81.8% vs. 15.4%, p = 0.003). Overall, 79% received first-line therapy and 41.6% second-line treatment. All patients in Cohort B received BRAF/MEK inhibitors, achieving a median progression-free survival of 3.2 months (95% CI 1.2–17.5). Concordance for BRAFV600E status between TB and LB assessed by ddPCR was 93.7% (specificity 100%, sensitivity 85.7%). Among 12 paired TB/LB NGS analyses, overall mutation concordance was 30%. In longitudinal assessment, LB anticipated disease progression in 3 of 6 cases and, in one case, identified emerging secondary alterations during BRAF/MEK inhibitor therapy.

Conclusions

BRAFV600E-mutant ATC displays distinct clinical features and improved survival when treated with targeted therapy; ddPCR-based liquid biopsy provides a rapid and sensitive method for BRAFV600E detection and may support timely therapeutic decision-making. Serial LB analysis may contribute to disease monitoring and detection of resistance mechanisms in selected patients.