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

IF 3.3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2026-06-23 DOI:10.1007/s12020-026-04672-x

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

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引用次数: 0

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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液体活检对间变性甲状腺癌BRAF V600E的评估和监测：三级癌症中心的现实世界研究

背景：复发/转移性间变性甲状腺癌（R/M ATC）与不良预后相关。大约40%的ATCs携带BRAFV600E突变，可用于靶向治疗。然而，brafv600e突变型与野生型ATC的临床特征以及液体活检（LB）在分子评估和监测中的作用仍未完全确定。方法：在三级转诊中心连续治疗的R/M ATCs患者被分层为BRAF野生型（队列a）或brafv600e突变型（队列B）。患者接受化疗、达非尼和曲美替尼（BRAF/MEKi）、免疫检查点抑制剂（ICI）或最佳支持治疗。采用RT-PCR和/或下一代测序（NGS）分析肿瘤组织（TB）。在两个队列的基线和纵向队列b中，通过液滴数字PCR （ddPCR）和/或52基因NGS小组对LB进行循环无细胞DNA评估。评估TB和LB的临床特征、治疗结果和一致性。结果：在2018年至2021年期间，纳入了24例患者（13例队列A， 11例队列B）。BRAFV600E肿瘤在诊断时更常表现为转移性疾病（81.8%比15.4%,p = 0.003）。总体而言，79%接受了一线治疗，41.6%接受了二线治疗。队列B的所有患者均接受BRAF/MEK抑制剂治疗，中位无进展生存期为3.2个月（95% CI 1.2-17.5）。ddPCR检测TB和LB之间BRAFV600E状态的一致性为93.7%（特异性100%，敏感性85.7%）。在12对TB/LB NGS分析中，总体突变一致性为30%。在纵向评估中，LB预测了6例中3例的疾病进展，其中1例在BRAF/MEK抑制剂治疗期间发现了新出现的继发性改变。结论：brafv600e突变ATC在接受靶向治疗时表现出明显的临床特征和生存率提高；基于ddpcr的液体活检为BRAFV600E的检测提供了快速、灵敏的方法，可能支持及时的治疗决策。连续LB分析可能有助于选定患者的疾病监测和耐药机制检测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.