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This study aims to evaluate the role of liquid biopsies in assessing and monitoring BRAFV600E mutations in anaplastic thyroid carcinoma.

June 26, 2026Open Access

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

ECElena ColomboUniversity of Insubria EOE. OrtolanFondazione IRCCS Istituto Nazionale dei Tumori SCStefano CavalieriUniversity of Milan

Key Points

This study aims to evaluate the role of liquid biopsies in assessing and monitoring BRAFV600E mutations in anaplastic thyroid carcinoma.
Consecutive patients with relapsed/metastatic anaplastic thyroid carcinoma were divided into BRAF wild-type and BRAFV600E-mutant cohorts.
Patients received various therapies including chemotherapy, BRAF/MEK inhibitors, and immune checkpoint inhibitors.
Tumor tissue and circulating cell-free DNA were analyzed using RT-PCR, NGS, and ddPCR.
BRAFV600E tumors presented with metastatic disease more frequently at diagnosis (81.8% vs. 15.4%, p=0.003).
Patients receiving BRAF/MEK inhibitors had a median progression-free survival of 3.2 months (95% CI 1.2-17.5).
The concordance for BRAFV600E status between tissue and liquid biopsy was 93.7% with ddPCR.

Abstract

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.

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