Zhang Hui, Hu Yi, Wang Yan, Song Xia, Hu Ying, Ma Li, Yang Xinjie, Li Kun, Qin Na, Wang Jinghui, Lv Jialin, Li Xi, Zhang Xinyong, Zhang Quan, Wu Yuhua, Yao Guangyin, Zhang Shucai
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Department of Medical Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
Front Oncol. 2023 Jan 26;12:942123. doi: 10.3389/fonc.2022.942123. eCollection 2022.
BACKGROUND/OBJECTIVE: The third-generation epidermal growth factor receptor () -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of T790M, was approved as the first-line therapy for advanced -mutated non-small cell lung cancer (NSCLC). Thus, detection of the T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs.
A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples.
The results showed that the sensitivity and the specificity of T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% ( = 0.016) or average value of 3.16% ( = 0.010).
Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of T790M in the plasma samples of NSCLC patients.
背景/目的：第三代表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs），如奥希替尼，旨在靶向EGFR T790M获得性耐药突变，被批准作为晚期EGFR突变非小细胞肺癌（NSCLC）的一线治疗药物。因此，检测NSCLC患者的EGFR T790M突变至关重要。然而，组织样本往往难以获取，尤其是在晚期患者中。本研究评估了液滴数字聚合酶链反应（ddPCR）和下一代测序（NGS）在检测NSCLC患者血浆循环肿瘤DNA（ctDNA）样本中EGFR T790M状态和丰度方面的性能。我们还探讨了EGFR T790M状态和丰度与对第三代EGFR-TKIs反应之间的关联。
本研究共纳入201例有匹配组织的血浆样本、821例血浆样本以及56例接受第三代EGFR-TKIs治疗并进行反应评估的患者。采用ddPCR和NGS检测组织和/或血液样本中EGFR T790M的突变状态和丰度。
结果显示，与组织样本相比，ddPCR检测血浆样本中EGFR T790M突变状态的敏感性和特异性分别为81.82%和91.85%，一致性系数为0.740。在821例血浆样本中，ddPCR和NGS检测到的EGFR T790M阳性率分别为34.2%（281/821）和22.5%（185/821）。以NGS结果为参照，ddPCR的敏感性和特异性分别为100%和84.91%，两种方法的一致性系数为0.717。此外，我们发现无论以0.43%的中位数（P = 0.016）还是3.16%的平均值（P = 0.010）分类，较高的EGFR T79M丰度与对第三代EGFR-TKIs的较高治疗反应率相关。
综合这些数据，本研究表明ddPCR是检测NSCLC患者血浆样本中EGFR T790M的一种有效替代方法。
