Hamidi Sarah, Dadu Ramona, Iyer Priyanka C, Busaidy Naifa L, Maniakas Anastasios, Wang Jennifer R, Banuchi Victoria E, Hosseini S Mohsen, Williams Michelle D, Zafereo Mark E, Cabanillas Maria E
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer, Houston, TX.
Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer, Houston, TX.
JCO Precis Oncol. 2025 Jun;9:e2500067. doi: 10.1200/PO-25-00067. Epub 2025 Jun 26.
Anaplastic thyroid cancer (ATC) is a highly lethal malignancy in which early detection of progression could allow timely treatment modifications and potentially improve outcomes. Novel circulating tumor DNA (ctDNA) assays allow the detection of molecular residual disease. We aimed to investigate the utility of ctDNA as a biomarker in ATC.
Retrospective cohort study of patients with ATC and at least one ctDNA drawn before systemic therapy start (referred to as baseline) between February 2021 and August 2024. ctDNA was correlated with concomitant imaging and/or pathologic results. Patients with ≥1 additional ctDNA on systemic therapy were included in a secondary analysis to evaluate the detection of ctDNA as a molecular evidence of disease recurrence/progression. These patients were divided into two subgroups: recurrence detection after curative-intent therapy (group 1) or treatment response monitoring if known residual disease (group 2).
Forty-five patients met the inclusion criteria. At baseline, ctDNA result correlated with disease status in 93% of patients (75% true positives, 18% true negatives, 7% false negatives [FNs], 0% false positive). Thirty-one patients had ≥1 follow-up ctDNA on systemic therapy, with a total of 130 evaluable results. In group 1(n = 60), ctDNA had 77% sensitivity, 100% specificity, 92% negative predictive value (NPV), and 100% positive predictive value (PPV). In group 2 (n = 70), ctDNA had 78% sensitivity, 100% specificity, 84% NPV, and 100% PPV. Potential reasons for FN ctDNA included low tumor burden, lung-only/brain-only metastatic disease, and heterogeneous molecular profiles in ATC.
ctDNA is a promising tumor biomarker for disease monitoring in ATC, with a high specificity and PPV. It should be considered in addition to standard-of-care surveillance methods to better inform treatment decision making.
间变性甲状腺癌（ATC）是一种高度致命的恶性肿瘤，早期发现病情进展有助于及时调整治疗方案并可能改善预后。新型循环肿瘤DNA（ctDNA）检测方法可检测分子残留病灶。我们旨在研究ctDNA作为ATC生物标志物的效用。
对2021年2月至2024年8月期间接受全身治疗前（称为基线）至少采集过一次ctDNA的ATC患者进行回顾性队列研究。将ctDNA与同期的影像学和/或病理结果进行关联分析。全身治疗期间有≥1次额外ctDNA检测结果的患者纳入二次分析，以评估ctDNA检测作为疾病复发/进展分子证据的情况。这些患者分为两个亚组：根治性治疗后复发检测（第1组）或已知残留病灶时的治疗反应监测（第2组）。
45例患者符合纳入标准。在基线时，93%的患者ctDNA结果与疾病状态相关（75%为真阳性，18%为真阴性，7%为假阴性[FN]，0%为假阳性）。31例患者在全身治疗期间有≥1次ctDNA随访检测结果，共有130个可评估结果。在第1组（n = 60）中，ctDNA的敏感性为77%，特异性为100%，阴性预测值（NPV）为92%，阳性预测值（PPV）为100%。在第2组（n = 70）中，ctDNA的敏感性为78%，特异性为100%，NPV为84%，PPV为100%。ctDNA出现FN的潜在原因包括肿瘤负荷低、仅肺/仅脑转移疾病以及ATC分子谱的异质性。
ctDNA是一种很有前景的用于ATC疾病监测的肿瘤生物标志物，具有高特异性和PPV。除了标准的监测方法外，还应考虑使用ctDNA，以更好地为治疗决策提供信息。
