Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
Guardant Health, Inc., Redwood City, California, USA.
Thyroid. 2024 Feb;34(2):197-205. doi: 10.1089/thy.2023.0204. Epub 2023 Dec 22.
The limited availability of targeted therapies in thyroid cancer (TC) has challenged conventional treatment algorithms and has established urgency for the identification of targetable genomic abnormalities. In addition to widely adopted tissue-based next-generation sequencing (NGS), plasma-based circulating tumor DNA (ctDNA) NGS is rapidly emerging as a genomic biomarker detection method and is steadily gaining utility across solid tumors. To date, plasma-based genomic alterations in TC have not been determined. Herein, we profile potential actionable mutations detected through ctDNA in patients with TC subtypes. A retrospective data analysis of the Guardant Health, Inc. database was performed using the commercially available Guardant360 plasma-NGS test on TC samples from adult patients collected between 2016 and 2021. The landscape of genomic alterations and blood tumor mutation burden (bTMB) were analyzed in patients with different types of TC: anaplastic TC (ATC), papillary TC (PTC), follicular TC (FTC), oncolytic carcinoma of the thyroid (OCA), poorly differentiated TC (PDTC), medullary TC (MTC), and TC not otherwise specified (TC NOS). Of the 1094 patients included most of the patients = 876 had TC NOS, and 20% had a specific diagnosis (92 ATC, 62 PTC, 14 FTC, 16 OCA, 2 PDTC, and 32 MTC patients). The median age was 65 (range 10-98) and 47.3% were male. 78.3% of patients had one or more genomic alteration detected by ctDNA NGS. (46.9%) was the most common mutation detected among all TC. was detected in 27.2% of ATC, 35.7% of PTC, and in none of FTC. was detected in 18.5% of ATC, 11.9% of PTC, and 62.5% of FTC. , , and fusions were seen in 1.1%, 0.5%, and 0.2% of all TC, respectively. mutations were detected in 66.7% of MTC. bTMB analysis was performed on 159 patients. The mean bTMB was higher in ATC compared with other types of TC ( = 0.0011, 0.0557, and <0.0001, respectively). Plasma-based comprehensive NGS is a promising NGS method in TC; however, future validation of the clinical utility by analysis of paired tumor and plasma samples is needed.
甲状腺癌（TC）中靶向治疗的有限可用性挑战了传统的治疗方案，并迫切需要确定可靶向的基因组异常。除了广泛采用的基于组织的下一代测序（NGS）外，基于血浆的循环肿瘤 DNA（ctDNA）NGS 作为一种基因组生物标志物检测方法迅速崭露头角，并在实体瘤中得到了稳定的应用。迄今为止，TC 中基于血浆的基因组改变尚未确定。在此，我们对 TC 亚型患者通过 ctDNA 检测到的潜在可治疗突变进行了分析。使用 Guardant Health，Inc. 数据库中的回顾性数据分析，对 2016 年至 2021 年间采集的成年 TC 患者的 Guardant360 血浆-NGS 检测进行了商业检测。对不同类型 TC 患者的基因组改变和血液肿瘤突变负荷（bTMB）进行了分析：间变性 TC（ATC）、乳头状 TC（PTC）、滤泡性 TC（FTC）、甲状腺溶瘤癌（OCA）、低分化 TC（PDTC）、髓样 TC（MTC）和未特指的 TC（TCNOS）。在 1094 名纳入患者中，大多数患者为 876 名 TC NOS，20%有明确诊断（92 名 ATC、62 名 PTC、14 名 FTC、16 名 OCA、2 名 PDTC 和 32 名 MTC 患者）。中位年龄为 65 岁（范围 10-98 岁），47.3%为男性。78.3%的患者通过 ctDNA NGS 检测到一种或多种基因组改变。（46.9%）是所有 TC 中最常见的突变。在 27.2%的 ATC、35.7%的 PTC 中检测到突变，在 FTC 中未检测到。在 18.5%的 ATC、11.9%的 PTC 和 62.5%的 FTC 中检测到突变。在 1.1%、0.5%和 0.2%的所有 TC 中分别检测到、和融合。在 66.7%的 MTC 中检测到突变。对 159 名患者进行了 bTMB 分析。与其他类型的 TC 相比，ATC 的平均 bTMB 更高（ = 0.0011、0.0557 和 <0.0001）。基于血浆的综合 NGS 是 TC 中一种很有前途的 NGS 方法；然而，需要通过分析配对的肿瘤和血浆样本来验证其临床实用性。
